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American Macular Degeneration Foundation
... A Search Search Welcome Welcome to the American Macular Degeneration Foundation web site where you can learn about this disease, find valuable resources and help conquer macular degeneration. Macular Degeneration is an incurable eye disease that ...
Accumulating Variation at Conserved Sites in Potyvirus Genomes Is Driven by Species Discovery and Affects Degenerate Primer Design
Unknown and foreign viruses can be detected using degenerate primers targeted at conserved sites in the known viral gene sequences. Conserved sites are found by comparing sequences and so the usefulness of a set of primers depends crucially on how well the known sequences represent the target group including unknown sequences. Methodology\\/Principal Findings: We developed a method for assessing the
Linda Zheng; Paul J. Wayper; Adrian J. Gibbs; Mathieu Fourment; Brendan C. Rodoni; Mark J. Gibbs
Accumulating Variation at Conserved Sites in Potyvirus Genomes Is Driven by Species Discovery and Affects Degenerate Primer Design
Unknown and foreign viruses can be detected using degenerate primers targeted at conserved sites in the known viral gene sequences. Conserved sites are found by comparing sequences and so the usefulness of a set of primers depends crucially on how well the known sequences represent the target group including unknown sequences. Methodology/Principal Findings We developed a method for assessing the apparent stability of consensus sequences at sites over time using deposition dates from Genbank. We tested the method using 17 conserved sites in potyvirus genomes. The accumulation of knowledge of sequence variants over 20 years caused Ĺconsensus decayĺ of the sites. Rates of decay were rapid at all sites but varied widely and as a result, the ranking of the most conserved sites changed. The discovery and reporting of sequences from previously unknown and distinct species, rather than from strains of known species, dominated the decay, indicating it was largely a sampling effect related to the progressive discovery of species, and recent virus mutation was probably only a minor contributing factor. Conclusion/Significance We showed that in the past, the sampling bias has misled the choice of the most conserved target sites for genus specific degenerate primers. The history of sequence discoveries indicates primer designs should be updated regularly and provides an additional dimension for improving the design of degenerate primers.
Wayper, Paul J.; Gibbs, Adrian J.; Fourment, Mathieu; Rodoni, Brendan C.
Single-site resolved studies of a bilayer quantum degenerate gas
NASA Astrophysics Data System (ADS)
Ultracold atoms in optical lattices are a versatile platform for quantum many-body simulation with the promise of insights into quantum magnetism, superconductivity, and superfluidity. In recent years, quantum gas microscopes with single-site resolution have opened the door to local observation and manipulation of strongly correlated two-dimensional quantum gases. Here we present techniques for extending study to two tunnel-coupled planes. Using an axial superlattice we prepare a bilayer system, with full control of the inter-plane tunnel coupling and detuning. We observe coherent inter-plane population transfer with single-site resolution in both planes. A collisional energy blockade in the bilayer system allows us to go beyond parity imaging and unambiguously identify site occupations from zero to three atoms. We have obtained site-resolved images of the ``wedding-cake'' Mott insulator structure and antiferromagnetic ordering in a quantum Ising model. Further applications include spin-dependent readout and in situ phase imaging.
Ma, Ruichao; Preiss, Philipp; Tai, Ming; Bakr, Waseem; Simon, Jonathan; Greiner, Markus
... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.
Precision half-life measurement of the 4-fold forbidden ? decay of V50
NASA Astrophysics Data System (ADS)
A sensitive search of the 4-fold forbidden nonunique decay of V50 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)Î1017 years of the electron capture decay of V50 into the first excited state of Ti50 could be obtained. A photon emission line following the ? decay into the first excited state of Cr50 could not be observed, resulting in a lower limit on the half-life of the ?-decay branch of 1.7Î1018 years. This is not in good agreement with a claimed observation of this decay branch published in 1989.
Dombrowski, H.; Neumaier, S.; Zuber, K.
Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease characterized by behavioral abnormalities, personality changes, language dysfunction, and can co-occur with the development of motor neuron disease. One major pathological form of FTLD is characterized by intracellular deposition of ubiquitinated and phosphorylated TAR DNA binding protein-43 (TDP-43), suggesting that dysregulation in phosphorylation events may contribute to disease progression. However, to date systematic analysis of the phosphoproteome in FTLD brains has not been reported. In this study we employed immobilized metal affinity chromatography (IMAC) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify phosphopeptides from FTLD and age-matched control postmortem human brain tissue. Using this approach we identified 786 phosphopeptides in frontal cortex (control and FTLD), in which the population of phosphopeptides represented approximately 50% of the total peptides analyzed. Label free quantification using spectral counts revealed six proteins with significant changes in the FTLD phosphoproteome. N-myc-downstream regulated gene 2 (NDRG2) and glial fibrillary acidic protein (GFAP) had an increased number of phosphospectra in FTLD, whereas microtubule associated protein 1A (MAP1A), reticulon 4 (RTN4; also referred to as neurite outgrowth inhibitor (Nogo)), protein kinase C gamma (PRKCG), and heat shock protein 90kDa alpha, class A member 1(HSP90AA1) had significantly fewer phosphospectra compared to control brain. To validate these differences, we examined NDRG2 phosphorylation in FTLD brain by immunoblot analyses, and using a phosphoserine-13 (pSer13) GFAP monoclonal antibody we show an increase in pSer13 GFAP levels by immunoblot concomitant with increased overall GFAP levels in FTLD cases. These data highlight the utility of combining proteomic and phosphoproteomic strategies to characterize postmortem human brain tissue.
Herskowitz, Jeremy H.; Seyfried, Nicholas T.; Duong, Duc M.; Xia, Qiangwei; Rees, Howard D.; Gearing, Marla; Peng, Junmin; Lah, James J.; Levey, Allan I.
Pellucid Marginal Corneal Degeneration
Pellucid marginal corneal degeneration (PMCD) is a noninflammatory ectatic corneal disorder mostly involving the inferior\\u000a half of the cornea in a crescentic fashion (Fig. 1). It is a bilateral disease, although one eye may be affected earlier and\\u000a clinically diagnosed, while the other eye has no clinical features (1). Although classically described as an inferor entity, the site of involvement
Jorge L. Aliˇ; Mohamed H. Shabayek; Alberto Artola; Hany El Saftawy
Among the atypical parkinsonian syndromes, corticobasal degeneration (CBD) is probably the most challenging disorder to diagnose antemortem. It can present with multiple phenotypes, none of them specific enough to lead to an unequivocal diagnosis. Alternatively, multiple other neurodegenerative disorders with a different underlying pathology, such as Alzheimer disease (AD), can mimic its clinical course. The ultimate etiology of CBD is unknown; however, current neuropathological and genetic evidence support a role for microtubule-associated protein tau. The classic clinical presentation is corticobasal syndrome, which typically presents as an asymmetric parkinsonism with a variable combination of ideomotor apraxia, rigidity, myoclonus, and dystonia, often associated with the presence of an alien limb phenomenon. Recently, a new set of diagnostic criteria has been developed, but still definite diagnosis requires autopsy confirmation. At the present time, no disease modifying therapies are available, but extensive research is being conducted. PMID:24963675
Grijalvo-Perez, Ana M; Litvan, Irene
Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...
Mitochondria in Degenerating and Regenerating Skeletal Muscle.
National Technical Information Service (NTIS)
Ultrastructural modifications of mitochondria are observed during degeneration and regeneration of myofibers following either acute ischemia in the rabbit or cold injury in the mouse. In the preexisting myofibers near a site of muscle necrosis, vast numbe...
M. Reznik J. L. Hansen
Macular Degeneration Partnership
... meetings. 310-623-4466. Welcome! If you have macular degeneration, or know someone who does, this is the ... caregivers can learn what itĺs like to have macular degeneration and how they can help. In addition to ...
Macular Degeneration: An Overview.
ERIC Educational Resources Information Center
This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.ů
Chalifoux, L. M.
Overlapping T cell antigenic sites on a synthetic peptide fragment from herpes simplex virus glycoprotein D, the degenerate MHC restriction elicited, and functional evidence for antigen-Ia interaction
Analysis of the B10.A T cell response to synthetic peptides representing the NH2-terminal 23 amino acids from the HSV glycoprotein D sequence revealed two antigenic determinants for T cells: one localized between residues 1-16 and the other between residues 8-23. The 1-16 site, which is helical, was recognized in the context of the Ia molecule, whereas the 8-23 site, which is nonhelical, was recognized in the context of the I-E molecule. The I-E-restricted response was found to be highly MHC degenerate in that T cell hybridomas specific for the 8-23 peptide responded to antigen on APCs derived from B10.A, B10.A(5R), and B10.A(9R) mice and showed differences in antigenic fine specificity with APCs of different haplotypes. These data support the idea of antigen-Ia interaction.
Structure shows that a glycosaminoglycan and protein recognition site in factor H is perturbed by age-related macular degeneration-linked single nucleotide polymorphism.
A common single nucleotide polymorphism in the factor H gene predisposes to age-related macular degeneration. Factor H blocks the alternative pathway of complement on self-surfaces bearing specific polyanions, including the glycosaminoglycan chains of proteoglycans. Factor H also binds C-reactive protein, potentially contributing to noninflammatory apoptotic processes. The at risk sequence contains His (rather than Tyr) at position 402 (384 in the mature protein), in the seventh of the 20 complement control protein (CCP) modules (CCP7) of factor H. We expressed both His(402) and Tyr(402) variants of CCP7, CCP7,8, and CCP6-8. We determined structures of His(402) and Tyr(402) CCP7 and showed them to be nearly identical. The side chains of His/Tyr(402) have similar, solvent-exposed orientations far from interfaces with CCP6 and -8. Tyr(402) CCP7 bound significantly more tightly than His(402) CCP7 to a heparin affinity column as well as to defined-length sulfated heparin oligosaccharides employed in gel mobility shift assays. This observation is consistent with the position of the 402 side chain on the edge of one of two glycosaminoglycan-binding surface patches on CCP7 that we inferred on the basis of chemical shift perturbation studies with a sulfated heparin tetrasaccharide. According to surface plasmon resonance measurements, Tyr(402) CCP6-8 binds significantly more tightly than His(402) CCP6-8 to immobilized C-reactive protein. The data support a causal link between H402Y and age-related macular degeneration in which variation at position 402 modulates the response of factor H to age-related changes in the glycosaminoglycan composition and apoptotic activity of the macula. PMID:17360715
Herbert, Andrew P; Deakin, Jon A; Schmidt, Christoph Q; Blaum, Bńrbel S; Egan, Claire; Ferreira, Viviana P; Pangburn, Michael K; Lyon, Malcolm; UhrÝn, Dusan; Barlow, Paul N
Intervertebral Disc Degeneration
Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Mouse models of IVD degeneration were used to investigate the role of the mechanical stress in this process. The application of mechanical overload (1.3 MPa) for 24 hours induced annulus fibrosus cell apoptosis and led to severe degeneration of the mouse disks. Immunostaining revealed cytochrome c release but not Fas-L generation. The role of the caspase-9-dependent mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload was investigated further with the use of cultured rabbit IVD cells in a stretch device. Mechanical overload (15% area change) induced apoptosis with increased caspase-9 activity and decreased mitochondrial membrane potential. Furthermore, Z-LEHD-FMK, a caspase-9 inhibitor, but not Z-IETD-FMK, a caspase-8 inhibitor, attenuated the overload-induced apoptosis. Our results from human samples, mouse models, and annulus fibrosus culture experiments demonstrate that the mechanical overload-induced IVD degeneration is mediated through the mitochondrial apoptotic pathway in IVD cells.
Rannou, Francois; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.
Biomechanics of Disc Degeneration
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 ôgold standardö 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.
Palepu, V.; Kodigudla, M.; Goel, V. K.
Double Degenerate Binary Systems
In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.
Yakut, K. [University of Ege, Department of Astronomy and Space Sciences, 35100-Izmir (Turkey)
Quantitative T2* (T2 star) relaxation times predict site specific proteoglycan content and residual mechanics of the intervertebral disc throughout degeneration.
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. ę 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1083-1089, 2014. PMID:24788830
Ellingson, Arin M; Nagel, Tina M; Polly, David W; Ellermann, Jutta; Nuckley, David J
A 2-dimensional cadmium(II) coordination polymer with the unique 4-fold interpenetrated (4, 4) layered structure from a long bridging ligand
NASA Astrophysics Data System (ADS)
A new 2D Cd(II) coordination polymer was hydrothermally synthesized, which possesses a unique 4-fold interpenetrated (4, 4) layered structure constructed by a long bridging ligand, and has the fluorescent emission with the maximum emission wavelength at 543 nm.
Niu, Cao-Yuan; Zheng, Xian-Fu; Feng, Cao-Ling; Kou, Chun-Hong
Vortices as Degenerate Metrics
NASA Astrophysics Data System (ADS)
We note that the Bogomolny equation for abelian vortices is precisely the condition for invariance of the Hermitian-Einstein equation under a degenerate conformal transformation. This leads to a natural interpretation of vortices as degenerate Hermitian metrics that satisfy a certain curvature equation. Using this viewpoint, we rephrase standard results about vortices and make new observations. We note the existence of a conceptually simple, non-linear rule for superposing vortex solutions, and we describe the natural behaviour of the L 2-metric on the moduli space upon restriction to a class of submanifolds.
Baptista, Joao M.
Intervertebral disc degeneration in dogs
Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting or even preventing IVD degeneration, more basic knowledge of the disease process is
N. Bergknut
What Is Age-Related Macular Degeneration?
... Dry, or atrophic, macular degeneration (also called non-neovascular macular degeneration) with drusen Most people who have ... immediately. Wet, or exudative, macular degeneration (also called neovascular macular degeneration) About 10 percent of people who ...
Degenerate perturbation theory
The algebraic structure of degenerate Rayleigh-Schroedinger perturbation theory is reviewed. There are a number of different but equivalent algorithms which generate this perturbation series; we argue that the frequent need to carry out infinite-order partial summations selects one of these algorithms as the most efficient. Recent developments include coupled-cluster formulations for open shells, a new diagrammatic representation, and the concept of incomplete model subspaces. These subjects are reviewed, as well as some applications.
Brandow, B.
Frontotemporal Lobar Degeneration
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.
Rabinovici, Gil D.; Miller, Bruce L.
Spinocerebellar degenerations: An update
Over the past decade, the spinocerebellar degenerations have gone from a diverse group of loosely defined phenotypes to a\\u000a family of diseases with many identifiable genotypes and the promise of gene-specific treatments. The evaluation of the spinocerebellar\\u000a ataxias has been simplified, and the counseling of patients and families has been enhanced by the growing number of molecular\\u000a diagnostic tests now
Susan L. Perlman
It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may eitherŚ (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to eitherŚ (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more
Klotz, Oskar
Retinal remodeling triggered by photoreceptor degenerations.
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, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) MŘller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed. PMID:12866125
Jones, Bryan W; Watt, Carl B; Frederick, Jeanne M; Baehr, Wolfgang; Chen, Ching-Kang; Levine, Edward M; Milam, Ann H; Lavail, Matthew M; Marc, Robert E
Cortical basal ganglionic degeneration.
In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941
Scarmeas, N; Chin, S S; Marder, K
Cortical Basal Ganglionic Degeneration
In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms.
Scarmeas, Nikolaos; Chin, Steven S.; Marder, Karen
Intracranial Contrast-Enhanced Magnetic Resonance Venography With 6.4-Fold Sensitivity Encoding at 1.5 and 3.0 Tesla
Purpose To prospectively compare vessel conspicuity and diagnostic image quality between three-dimensional intracranial contrast-enhanced MR venography acquired at 1.5 Tesla (T) and 3.0T, with 6.4-fold sensitivity encoding. Materials and Methods Ten healthy volunteers were imaged on 1.5T and 3.0T MR scanners using eight-element head coil arrays. The intracranial venous vasculature was divided into five groups for evaluation based on vessel size and anatomical location. Two radiologists independently assessed vessel conspicuity, level of artifacts, and diagnostic image quality. Informed consent was obtained, and the study was approved by the institutional review board. Results With the exception of large cerebral sinuses where 1.5T and 3.0T results were rated as equivalent, 3.0T images demonstrated superior vessel continuity, sharpness, and signal contrast to background tissue than 1.5T for all other intracranial venous vasculature (P < 0.01). No statistical significance in overall image quality was found between 1.5T and 3.0T venograms, and all data sets were deemed sufficient for diagnostic interpretation. Conclusion Whole brain contrast-enhanced venography with 6.4-fold sensitivity encoding is robust and has the potential to become the method of choice for fast visualization of the intracranial venous vasculature. At 3.0T, demonstration of small cerebral vessels is superior to 1.5T.
Hu, Houchun H.; Haider, Clifton R.; Campeau, Norbert G.; Huston, John; Riederer, Stephen J.
Neural remodeling in retinal degeneration
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
Neural remodeling in retinal degeneration
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
Degenerate Primer Design via Clustering
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 homologous genes. However, when a large collection of sequences is considered, no consensus region may exist in the multiple alignment, making it impossible to design a single pair of primers for the collection. In such
Xintao Wei; David N. Kuhn; Giri Narasimhan
Disc degeneration in Scheuermann disease.
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
Degenerate Quantum Gases of Strontium
NASA Astrophysics Data System (ADS)
Degenerate quantum gases of alkaline-earth-like elements open new opportunities in research areas ranging from molecular physics to the study of strongly correlated systems. These experiments exploit the rich electronic structure of these elements, which is markedly different from the one of other species for which quantum degeneracy has been attained. Specifically, alkaline-earth-like atoms, such as strontium, feature metastable triplet states, narrow intercombination lines, and a nonmagnetic, closed-shell ground state. This review covers the creation of quantum degenerate gases of strontium and the first experiments performed with this new system. It focuses on laser-cooling and evaporation schemes, which enable the creation of Bose-Einstein condensates and degenerate Fermi gases of all strontium isotopes, and shows how they are used for the investigation of optical Feshbach resonances, the study of degenerate gases loaded into an optical lattice, as well as the coherent creation of Sr2 molecules.
Stellmer, Simon; Schreck, Florian; Killian, Thomas C.
Peripheral retinal degenerations and breaks
One-hundred-three patients referred for evaluation of peripheral retinal lesions were reviewed; 56 eyes had peripheral degenerations without breaks, 62 eyes had atrophic holes, and 88 eyes presented retinal tears. Peripheral degenerations of the snail-track and typical lattice-like types occurred with reasonable uniformity throughout the periphery and were seen symmetrically in both eyes. Atrophic retinal holes frequently occurred within these degenerative
M. Kottow
The role of TNF-? during Wallerian degeneration
The role of TNF-? in the course of Wallerian degeneration of the sciatic nerve was studied in control and TNF-? deficient mice. In control animals, the characteristic phenomena of Wallerian degeneration such as axon and myelin degeneration as well as macrophage recruitment with subsequent myelin removal were observed. In TNF-? deficient mice, in contrast, macrophage recruitment into the degenerating nerves
M. Liefner; H. Siebert; T. Sachse; U. Michel; G. Kollias; W. BrŘck
Chondroadherin Fragmentation Mediated by the Protease HTRA1 Distinguishes Human Intervertebral Disc Degeneration from Normal Aging*
Chondroadherin, a member of the leucine-rich repeat family, has previously been demonstrated to be fragmented in some juveniles with idiopathic scoliosis. This observation led us to investigate adults with disc degeneration. Immunoblotting analysis demonstrated that non-degenerate discs from three different age groups show no chondroadherin fragmentation. Furthermore, the chondroadherin fragments in adult degenerate disc and the juvenile scoliotic disc were compared via immunoblot analysis and appeared to have a similar size. We then investigated whether or not chondroadherin fragmentation increases with the severity of disc degeneration. Three different samples with different severities were chosen from the same disc, and chondroadherin fragmentation was found to be more abundant with increasing severity of degeneration. This observation led us to the creation of a neoepitope antibody to the cleavage site observed. We then observed that the cleavage site in adult degenerate discs and juvenile scoliotic discs was identical as confirmed by the neoepitope antibody. Consequently, investigation of the protease capable of cleaving chondroadherin at this site was necessary. In vitro digests of disc tissue demonstrated that ADAMTS-4 and -5; cathepsins K, B, and L; and MMP-3, -7, -12, and -13 were incapable of cleavage of chondroadherin at this site and that HTRA1 was indeed the only protease capable. Furthermore, increased protein levels of the processed form of HTRA1 were demonstrated in degenerate disc tissues via immunoblotting. The results suggest that chondroadherin fragmentation can be used as a biomarker to distinguish the processes of disc degeneration from normal aging.
Akhatib, Bashar; Onnerfjord, Patrik; Gawri, Rahul; Ouellet, Jean; Jarzem, Peter; Heinegard, Dick; Mort, John; Roughley, Peter; Haglund, Lisbet
Age-related macular degeneration
Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration.
Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y
Vascular degeneration in Parkinson's disease.
Vascular degeneration plays a significant role in contributing to neurodegenerative conditions such as Alzheimer's disease. Our understanding of the vascular components in Parkinson's disease (PD) is however limited. We have examined the vascular morphology of human brain tissue from both PD and the control cases using immunohistochemical staining and image analysis. The degenerative morphology seen in PD cases included the formation of endothelial cell "clusters," which may be contributed by the fragmentation of capillaries. When compared to the control cases, the capillaries of PDs were less in number (P < 0.001), shorter in length (P < 0.001) and larger in diameter (P < 0.01) with obvious damage to the capillary network evidenced by less branching (P < 0.001). The level of degeneration seen in the caudate nucleus was also seen in the age-matched control cases. Vessel degeneration associated with PD was, however, found in multiple brain regions, but particularly in the substantia nigra, middle frontal cortex and brain stem nuclei. The data suggest that vascular degeneration could be an additional contributing factor to the progression of PD. Thus, treatments that prevent vascular degeneration and improve vascular remodeling may be a novel target for the treatment of PD. PMID:22897695
Guan, Jian; Pavlovic, Darja; Dalkie, Nicholas; Waldvogel, Henry J; O'Carroll, Simon J; Green, Colin R; Nicholson, Louise F B
Light and inherited retinal degeneration.
Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summarises the clinical evidence for a modifying role of light exposure in retinal degeneration and experimental evidence from animal models, focusing on retinitis pigmentosa with regional degeneration, Oguchi disease, and Stargardt macular dystrophy. These cases illustrate distinct pathophysiological roles for light, and suggest that light restriction may benefit carefully defined subsets of patients. PMID:16707518
Paskowitz, D M; LaVail, M M; Duncan, J L
Pellucid marginal degeneration and scleroderma.
Systemic scleroderma is a progressive multi-system connective tissue disease. Ocular involvement includes keratoconjunctivitis sicca, progressive shallowing of conjunctival fornices, peripheral ulcerative keratitis and eyelid tightness. No association has been reported between scleroderma and pellucid marginal degeneration, which is a rare bilateral corneal ectasia. Pellucid marginal degeneration is characterised by non-inflammatory and progressive peripheral corneal thinning inferiorly, often with high against-the-rule astigmatism. We report a case of a 55-year-old woman with systemic scleroderma who presented with rapidly progressing against-the-rule astigmatism. The differential diagnosis of peripheral corneal thinning and the challenge of the surgical management of pellucid marginal degeneration are briefly discussed. PMID:15186210
Sii, Freda; Lee, Graham A; Sanfilippo, Paul; Stephensen, David C
Diagnostic dilemma in Broad Ligament Leiomyoma with Cystic Degeneration
Fibroids are smooth muscle benign tumors; most commonly arise from uterus but may also rise from extra uterine sites like broad ligament. This case report of broad ligament myoma with extensive cystic degeneration is presented for its rarity and diagnostic challenges as they mimic pelvic adenexal tumors. Mrs. X, 43 years old p5+2, asymptomatic women with no co-morbids presented with mass in abdomen. The MRI showed mix attenuation mass of 19.7 x 16.8 x 13.7cms arising from right side of uterus extending up to epigastrium, with cystic and solid components and ascitic fluid. Resection of mass with abdominal hysterectomy with bilateral salphingo oophrectomy was done. No local or abdominal organ metastases were seen. Histopathology showed left broad ligament leiomyoma weighing 4000 grams with cystic degeneration. Conclusion: Huge broad ligament leiomyoma with cystic degeneration and abdominal ascites may cause diagnostic dilemma with ovarian malignancy. This differential diagnosis must be considered before surgery.
Naz Masood, Shabeen; Masood, Yasir; Mathrani, Janta
If I Had - Macular Degeneration
MedlinePLUS Videos and Cool Tools
... related macular degeneration is one of the most common, and it affects people generally over the age of 50. The risk factors for it are very similar as the risk factors for heart disease, so smoking is really a biggy, itĺs the ...
Superior pellucid marginal corneal degeneration
Purpose To report the clinical features and topographic findings of superior pellucid marginal corneal degeneration (PMCD).Methods Retrospective chart review of 15 eyes of eight patients of superior PMCD. Detailed history, visual acuity at presentation, degree of astigmatism, slit-lamp examination findings, topographic features, and Orbscan findings were noted where available. Improvement in visual acuity with spectacles or contact lens correction, surgical
M S Sridhar; S Mahesh; A K Bansal; G N Rao; Sridhar
Laser therapy and macular degeneration
Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the
Ugo Menchini; Gianni Virgili; Fabrizio Giansanti; Giovanni Giacomelli; Stefania Cappelli
Neuronal Degeneration in Canine Narcolepsy
Narcolepsy is a lifelong illness characterized by persistent sleepiness, hypnagogic hallucinations, and episodes of motor paralysis called cataplexy. We have tested the hypothesis that a transient neurodegenerative process is linked to symptom onset. Using the amino-cupric silver stain on brain sections from canine narcoleptics, we found elevated levels of axonal degeneration in the amygdala, basal forebrain (including the nucleus of
J. M. Siegel; R. Nienhuis; S. Gulyani; S. Ouyang; M. F. Wu; E. Mignot; R. C. Switzer; G. McMurry; M. Cornford
The degenerate primer design problem
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 combina- tions it contains. We study the problem of designing a pair of primers with prescribed degeneracy that match a max- imum number of given input sequences. Such problems occur when studying a
Chaim Linhart; Ron Shamir
[Clinical features of corticobasal degeneration].
Corticobasal degeneration was described in 1968 by Rebeiz, Kolodny and Richardson, who characterized the disease as a syndrome of asymmetric akinesis and rigidity, dystonia of the upper limb, apraxia, myoclonus and dementia. Atrophy of the frontal and parietal lobe, neuronal loss, gliosis and achromatic neurones (and nowadays astrocytic plaques) are the characteristic pathological features of the disease. Corticobasal degeneration is a rare or a rarely recognized disease and it is frequently misdiagnosed as Parkinson's disease. According to the Lang's criteria, corticobasal degeneration can be diagnosed in the presence of rigidity and one cortical symptom (apraxia, cortical sensory loss, alien hand) or in a patient with rigidity, dystonia and focal reflex myoclonus. Exclusion criteria are early dementia (as in primary degenerative dementias), early vertical gaze problems (as in progressive supranuclear palsy), resting tremor and good, sustained therapeutic response to levodopa (as in Parkinson's disease), severe autonomic problems (as in multiple system atrophy) and any pathology on imaging studies which might explain the clinical symptoms. It should be mentioned, that recently early dementia is recognized as an initial symptom of corticobasal degeneration. The authors present a case and review the literature to call attention to this disorder. PMID:15884398
Farsang, Marianna; Takßts, Annamßria; Szirmai, Imre; Kovßcs, Tibor
Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection
Theiler's murine encephalomyelitis virus (TMEV) and other neurotropic virus infections result in degeneration of each component of the neuron: apoptosis of the cell body, axonal (Wallerian) degeneration, and dendritic and synaptic pathology. In general, axonal degeneration is detrimental for hosts. However, axonal degeneration can be beneficial in the case of infection with neurotropic viruses that spread in the CNS using axonal transport. C57BL/WldS (WldS, Wallerian degeneration slow mutant) mice are protected from axonal degeneration. WldS mice infected with the neurovirulent GDVII strain of TMEV are more resistant to virus infection than wild-type mice, suggesting that axonal preservation contributes to the resistance. By contrast, infection with the less virulent Daniels strain of TMEV results in high levels of virus propagation in the CNS, suggesting that prolonged survival of axons in WldS mice favors virus spread. Thus, axonal degeneration might be a beneficial self-destruct mechanism that limits the spread of neurotropic viruses, in the case of less virulent virus infection. We hypothesize that neurons use Ĺbuilt-inĺ self-destruct protection machinery (compartmental neurodegeneration) against neurotropic virus infection, since the CNS is an immunologically privileged site. Early induction of apoptosis in the neuronal cell body limits virus replication. Wallerian degeneration of the axon prevents axonal transport of virus. Dendritic and synaptic degeneration blocks virus transmission at synapses. Thus, the balance between neurodegeneration and virus propagation may be taken into account in the future design of neuroprotective therapy.
Tsunoda, Ikuo
Photos, Images, and Videos (Macular Degeneration)
... dpi (5M, TIFF) Description: A fundus photo showing neovascular age-related macular degeneration. Credit: National Eye Institute, ... Ref#: EDA17 72 dpi (1.1M, TIFF) Description: Neovascular age-related macular degeneration. Credit: National Eye Institute, ...
Retinal remodeling triggered by photoreceptor degenerations
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
Light scattering of degenerate fermions
NASA Astrophysics Data System (ADS)
We report on progress in measuring the suppression of resonant light scattering in a gas of degenerate fermions. A gas of trapped degenerate fermions is expected to exhibit narrower optical linewidths and longer excited state lifetimes than single atoms when the Fermi energy is larger than the photon recoil energy [1-3]. In this case, the number of available states into which a scattered atom can recoil is significantly reduced due to the filling of the Fermi sea. We produce a degenerate gas of 4x10^4 ultra-cold fermionic ^40K atoms by sympathetic cooling with bosonic ^87Rb in a micro-magnetic chip trap. The atoms can then be loaded into a tight dipole trap just above the surface of the chip and probed with a near resonance laser pulse. [1] Th. Busch, J. R. Anglin, J. I. Cirac, and P. Zoller, Europhys. Lett. 44, 1 (1998). [2] B. DeMarco and D. S. Jin, Phys. Rev. A 58, R4267 (1998). [3] J. Javanainen and J. Ruostekosky, Phys. Rev. A 52, 3033 (1995). Work supported by NSERC, CFI, OIT, Research Corporation, and PRO.
Aubin, S.; Leblanc, L. J.; Myrskog, S.; Extavour, M. H. T.; McKay, D.; Stummer, A.; Thywissen, J. H.
Retinal functions in snowflake degeneration.
Retinal functions were studied in 7 patients with snowflake degeneration and correlated with fundus appearance. Despite the presence of vitreous turbidity, scotomatic glare sensitivity was slightly elevated in only one case. Retinal functions were affected more extensively in the late stages of the disease; however, abnormal retinal functions were also detected in some patients who showed only slight fundus changes on ophthalmoscopic examination. Kinetic perimetry showed peripheral defects which were more pronounced in the upper field. Flicker perimetry revealed abnormalities that kinetic perimetry could not detect. Dark-adaptation tests showed elevated rod thresholds except during the early stage of the disease. In all patients, the scotopic b-wave of the electroretinogram elicited by dim white light was low in amplitude. The photopic b-wave and the photopic flicker responses showed decreased amplitudes in some patients. The scotopic b-wave, normally recorded as a second positive peak when deep red light is used, almost disappeared, leaving only a small, single positive peak, photopic in nature, in the late stages. However, no patient had a nonrecordable electroretinogram. The electro-oculographic light peak/dark trough ratio was abnormal in only a few patients. These results indicate that in snowflake degeneration, functional abnormalities of the retina are milder than those in other progressive primary retinal degenerations typically represented by retinitis pigmentosa. PMID:7283319
Hirose, T; Wolf, E; Schepens, C L
Retrograde and Wallerian Axonal Degeneration Occur Synchronously after Retinal Ganglion Cell Axotomy
Axonal injury and degeneration are pivotal pathological events in diseases of the nervous system. In the past decade, it has been recognized that the process of axonal degeneration is distinct from somal degeneration and that axoprotective strategies may be distinct from those that protect the soma. Preserving the cell body via neuroprotection cannot improve function if the axon is damaged, because the soma is still disconnected from its target. Therefore, understanding the mechanisms of axonal degeneration is critical for developing new therapeutic interventions for axonal disease treatment. We combined in vivo imaging with a multilaser confocal scanning laser ophthalmoscope and in vivo axotomy with a diode-pumped solid-state laser to assess the time course of Wallerian and retrograde degeneration of unmyelinated retinal ganglion cell axons in living rats for 4 weeks after intraretinal axotomy. Laser injury resulted in reproducible axon loss both distal and proximal to the site of injury. Longitudinal polarization-sensitive imaging of axons demonstrated that Wallerian and retrograde degeneration occurred synchronously. Neurofilament immunostaining of retinal whole-mounts confirmed axonal loss and demonstrated sparing of adjacent axons to the axotomy site. In vivo fluorescent imaging of axonal transport and photobleaching of labeled axons demonstrated that the laser axotomy model did not affect adjacent axon function. These results are consistent with a shared mechanism for Wallerian and retrograde degeneration.
Kanamori, Akiyasu; Catrinescu, Maria-Magdalena; Belisle, Jonathan M.; Costantino, Santiago; Levin, Leonard A.
Macugen treatment for wet age-related macular degeneration.
Macugen (pegaptanib sodium), manufactured by Eyetech Pharmaceuticals, Inc., and Pfizer, Inc., is the first treatment approved by the U.S. Food and Drug Administration for all forms of wet macular degeneration. Although the cause of wet macular degeneration is not known, it is believed that vascular endothelial growth factor (VEGF) induces angiogenesis, resulting in a neovascular process, the hallmark of wet macular degeneration. Macugen is a VEGF antagonist. In two controlled, double-blinded identical studies, Macugen 0.3 mg was shown to slow the progression of wet macular degeneration. Using strict aseptic technique, Macugen 0.3 mg is administered via intravitreal injection every six weeks for one to two years. Serious adverse reactions include endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. Macugen is administered after a topical anesthetic, a subconjuctival block, or a combination of both is used to numb the injection site on the temporal sclera. Post-procedure patients may initially complain of transient vision loss, burning, pressure, eye pain, or "floaters". At time of discharge, patients should be informed of the signs and symptoms of infection and instructed in the administration of antibiotic drops and in proper follow-up care. Most patients are seen for follow up one week after injection and again in five weeks for additional treatment. PMID:16817567
Tobin, Kathleen A
Microsphere embolization of nerve capillaries and fiber degeneration.
Polystyrene microspheres, the size chosen to plug capillaries and precapillaries, were injected into the arterial supply of rat sciatic nerves. They produced widespread segmental occlusion of capillaries in lower limb nerves. The clinical and pathologic effect was dose-related. One million microspheres produced selective capillary occlusion but no nerve fiber degeneration; approximately 6 million microspheres also produced selective capillary occlusion and associated foot and leg weakness, sensory loss, and fiber degeneration, beginning in a central core of the distal sciatic nerve; 30 million microspheres caused both capillary and arterial occlusion and a greater neuropathologic deficit. From these observations it is inferred that 1) occlusion of isolated precapillaries and capillaries does not produce ischemic fiber degeneration; 2) occlusion of many microvessels results in central fascicular fiber degeneration, indicating that these cores are watershed regions of poor perfusion; and 3) stereotyped pathologic alterations of nerve fibers and Schwann cells are related to dose, anatomic site, and time elapsed since injection. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10
Nukada, H.; Dyck, P. J.
Molecular genetics of retinal degeneration
Inherited retinal degeneration in Drosophila has been explored for insights into similar processes in humans. Based on the mechanisms, I divide these mutations in Drosophila into three classes. The first consists of genes that control the specialization of photoreceptor cells including the morphogenesis of visual organelles (rhabdomeres) that house the visual signaling proteins. The second class contains genes that regulate the activity or level of the major rhodopsin, Rh1, which is the light sensor and also provides a structural role for the maintenance of rhabdomeres. Some mutations in Rh1 (NinaE) are dominant due to constitutive activity or folding defects, like autosomal dominant retinitis pigmentosa (ADRP) in humans. The third class consists of genes that control the Ca2+ influx directly or indirectly by promoting the turnover of the second messenger and regeneration of PIP2, or mediate the Ca2+-dependent regulation of the visual response. These gene products are critical for the increase in cytosolic Ca2+ following light stimulation to initiate negative regulatory events. Here I will focus on the signaling mechanisms underlying the degeneration in norpA, and in ADRP-type NinaE mutants that produce misfolded Rh1. Accumulation of misfolded Rh1 in the ER triggers the unfolded protein response (UPR), while endosomal accumulation of activated Rh1 may initiate autophagy in norpA. Both autophagy and the UPR are beneficial for relieving defective endosomal trafficking and the ER stress, respectively. However, when photoreceptors fail to cope with the persistence of these stresses, a cell death program is activated leading to retinal degeneration.
Strongly Interacting Degenerate Fermi Gases
NASA Astrophysics Data System (ADS)
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 rich new system to study the interplay between quantum statistics and atomic interactions, with the ultimate goal being the achievement of different regimes of fermionic superfluidity. We have created large samples of degenerate fermionic lithium and prepared suitable conditions of spin composition and magnetic field to probe a regime of strong interactions in the vicinity of a Feshbach Resonance. Experimental results from these investigations will be reported and discussed.
Gupta, Subhadeep
Degeneration of the intervertebral disc
The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.
Urban, Jill PG; Roberts, Sally
Ultraviolet spectrophotometry of degenerate stars
NASA Technical Reports Server (NTRS)
Observations of one helium- and three hydrogen-atmosphere degenerates made with the International Ultraviolet Explorer are discussed. Fluxes in the UV give temperatures in good accordance with those determined from the ground and from the ANS satellite data. Profiles of the strong L-alpha absorption in two DA's fit predictions for the expected temperatures. Gravity determination is vitiated by their steep temperature dependence. If one accepts that theoretical predictions should be correct, corrections to the absolute IUE calibration derived are an upward shift of 3-5%, with irregular residuals attaining + or - 7%.
Greenstein, J. L.; Oke, J. B.
Age-related macular degeneration
Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection
Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H
Programmed cell death in intervertebral disc degeneration
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
Advances in the management of macular degeneration
Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.
Bilateral Hypertrophic Olivary Degeneration in Wilson Disease
Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease.
Guenther, Peter; Hoffmann, Karl-Titus
[Age-related macular degeneration].
Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956
Garcia Layana, A
Degeneration and regeneration of interneuronal synapses
Summary 1.Degeneration of synapses in the cat superior cervical ganglion after division of preganglionic fibers was expressed under the optical microscope by argyrophilia or argyrophobia, hypertrophy, and lysis. Under the electron microscope, two types of changes were observed during this process (ôdarkö and ôlightö degeneration of synapses).2.The structure of the synaptic endings in sections impregnated with silver remains similar at
V. P. Babmindra; L. N. D'yachkova
Genetics of Frontotemporal Lobar Degeneration
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.
Galimberti, Daniela; Scarpini, Elio
Ceramide Signaling in Retinal Degeneration
Retinal degenerations (RD) are a complex heterogeneous group of diseases in which retinal photoreceptors and the supporting retinal pigment epithelial cells die irreversibly, causing visual loss for millions of people. Mutations on more than 150 genes have been discovered for RD and there are many forms that possess complex etiology involving more than one gene and environmental effect. For years many have searched for some common intracellular second messenger for these many forms of cell death which could be targeted for therapy. Ceramide is a novel cellular second messenger which signals for apoptosis. Several lines of evidence suggest an integral role of ceramide in photoreceptor apoptosis and cell death. Understanding their role in the pathogenic pathways of retinal degenerative diseases is important for development of targeted therapeutics.
Chen, Hui; Tran, Julie-Thu A.; Brush, Richard S.; Saadi, Anisse; Rahman, Abul K.; Yu, Man; Yasumura, Douglas; Matthes, Michael T.; Ahern, Kelly; Yang, Haidong; LaVail, Matthew M.; Mandal, Md Nawajes A.
Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG
Chronic loose constriction of the sciatic nerve produces mechanoallodynia and thermal hyperalgesia in rats and mice, and the behaviour develops during the time in which the nerve distal to the ligature site is undergoing Wallerian degeneration. There is a sympathetic component to the pain generated by this and other rodent models of neuropathic pain, yet the site at which this
Matt S Ramer; Gavin D French; Mark A Bisby
Gelatinous degeneration presenting as a preleukaemic syndrome.
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
Arranz, R; Gil-Fernandez, J J; Acevedo, A; Tomas, J F; Alegre, A; Fernandez-Ranada, J M
Etiology of Disc Degeneration Related to Low Back Pain.
National Technical Information Service (NTIS)
An animal model of stress-induced intervertebral disc degeneration was developed to verify whether degeneration changes morphological, physiological and material properties of the disc, and to verify whether degeneration causes painful disability. The ani...
S. D. Smith J. F. Lafferty W. G. Winter
A Monte Carlo algorithm for degenerate plasmas
A procedure for performing Monte Carlo calculations of plasmas with an arbitrary level of degeneracy is outlined. It has possible applications in inertial confinement fusion and astrophysics. Degenerate particles are initialised according to the FermiľDirac distribution function, and scattering is via a Pauli blocked binary collision approximation. The algorithm is tested against degenerate electronľion equilibration, and the degenerate resistivity transport coefficient from unmagnetised first order transport theory. The code is applied to the cold fuel shell and alpha particle equilibration problem of inertial confinement fusion.
Turrell, A.E., E-mail: email@example.com; Sherlock, M.; Rose, S.J.
Diagnostic dilemma in Broad Ligament Leiomyoma with Cystic Degeneration.
Fibroids are smooth muscle benign tumors; most commonly arise from uterus but may also rise from extra uterine sites like broad ligament. This case report of broad ligament myoma with extensive cystic degeneration is presented for its rarity and diagnostic challenges as they mimic pelvic adenexal tumors. Mrs. X, 43 years old p5+2, asymptomatic women with no co-morbids presented with mass in abdomen. The MRI showed mix attenuation mass of 19.7 x 16.8 x 13.7cms arising from right side of uterus extending up to epigastrium, with cystic and solid components and ascitic fluid. Resection of mass with abdominal hysterectomy with bilateral salphingo oophrectomy was done. No local or abdominal organ metastases were seen. Histopathology showed left broad ligament leiomyoma weighing 4000 grams with cystic degeneration. Conclusion: Huge broad ligament leiomyoma with cystic degeneration and abdominal ascites may cause diagnostic dilemma with ovarian malignancy. This differential diagnosis must be considered before surgery. PMID:24772162
Naz Masood, Shabeen; Masood, Yasir; Mathrani, Janta
Mouse models for cone degeneration.
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
Degeneration of Biogenic Superparamagnetic Magnetite
ABSTRACT. Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 hours incubation and 5-year storage were investigated with transmission electron microscopy, M ssbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 hour and 5-year crystals are 8.4164 and 8.3774 , respectively. The M ssbauer spectra indicated that the 265 hour magnetite had excess Fe(II) in its crystal-chemistry (Fe3+1.9901Fe2+ 1.0149O4) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe3+2.3875Fe2+0.4188O4). Such crystal-hemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases(fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.
Li, Dr. Yi-Liang [University of Tennessee, Knoxville (UTK); Pfiffner, Susan M. [University of Tennessee, Knoxville (UTK); Dyar, Dr. M Darby [Mount Holyoke College; Vali, Dr. Hojatolah [McGill University, Montreal, Quebec; Konhauser, Dr, Kurt [University of Alberta; Cole, David R [ORNL; Rondinone, Adam Justin [ORNL; Phelps, Tommy Joe [ORNL
Macular Degeneration Prevention and Risk Factors
... susceptibility gene for age-related macular degeneration. CD36 ľ Cluster of Differentiation 36 (CD36) is a ôscavenger receptor,ö ... your doctor if you notice vision changes. ôVisionö Foods to Include in Your Diet Dark green, yellow, ...
Spectral Asymptotics on Degenerating Hyperbolic 3-Manifolds.
National Technical Information Service (NTIS)
In the paper the authors carry out a systematic study of the spectal theory for degenerating hyperbolic manifolds of finite volume in three dimensions. Contents include: Review of hyperbolic geometry; Convergence of heat kernels; Infinite cylinder estimat...
J. Dodziuk J. Jorgenson
Prevention of disc degeneration with growth factors
Clinically, a large number of patients have persistent low back pain attributable to intervertebral disc (IVD) degeneration.\\u000a After the concept of biologically regenerating the degenerated IVD using growth factor injection was first proposed in early\\u000a 1990, the advancement of molecular technology to produce recombinant proteins, including growth factors, on an industrial\\u000a scale accelerated research in this field. The purpose of
Koichi Masuda; Howard S. An
Molecular basis of intervertebral disc degeneration.
This review will acquaint the reader with normal development, structure, and function of the intervertebral disc. The disc is composed of the vertebral endplate, nucleus pulposus, and annulus fibrosus. These three functional components all serve important purposes for health and function of the disc. Nutrition and biomechanics are also discussed. The molecular basis of disc degeneration is reviewed so that biologic approaches to the reversal and or treatment of disc degeneration may be better understood. PMID:15541661
Walker, Matthew H; Anderson, D Greg
Mirror Symmetry via Logarithmic Degeneration Data II
This paper continues the authors' program of studying mirror symmetry via log geometry and toric degenerations, relating affine manifolds with singularities, log Calabi-Yau spaces, and toric degenerations of Calabi-Yaus. The main focus of this paper is the calculation of the cohomology of a Calabi-Yau variety associated to a given affine manifold with singularities B. We show that the Dolbeault cohomology
Mark Gross; Bernd Siebert
Entropy Solutions for Nonlinear Degenerate Problems
We consider a class of elliptic-hyperbolic degenerate equations $$g(u)-\\\\Delta b(u) +\\\\divg\\\\phi (u) =f$$ with Dirichlet homogeneous boundary conditions and a class of elliptic-parabolic-hyperbolic degenerate equations $$g(u)_t-\\\\Delta b(u) +\\\\divg\\\\phi (u) =f$$ with homogeneous Dirichlet conditions and initial conditions. Existence of entropy solutions for both problems is proved for nondecreasing continuous functions g and b vanishing at zero and for a continuous
JosÚ Carrillo
Peripheral Glia Have a Pivotal Role in the Initial Response to Axon Degeneration of Peripheral Sensory Neurons in Zebrafish
Axon degeneration is a feature of many peripheral neuropathies. Understanding the organismal response to this degeneration may aid in identifying new therapeutic targets for treatment. Using a transgenic zebrafish line expressing a bacterial nitroreductase (Ntr)/mCherry fusion protein in the peripheral sensory neurons of the V, VII, IX, and X cranial nerves, we were able to induce and visualize the pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr larvae to the prodrug metronidazole (Met), which Ntr metabolizes into cytotoxic metabolites, resulted in dose-dependent cell death and axon degeneration. This was limited to the Ntr-expressing sensory neurons, as neighboring glia and motor axons were unaffected. Cell death was rapid, becoming apparent 3ľ4 hours after Met treatment, and was followed by phagocytosis of soma and axon debris by cells within the nerves and ganglia beginning at 4ľ5 hours of exposure. Although neutrophils appear to be activated in response to the degenerating neurons, they did not accumulate at the sites of degeneration. In contrast, macrophages were found to be attracted to the sites of the degenerating axons, where they phagocytosed debris. We demonstrated that peripheral glia are critical for both the phagocytosis and inflammatory response to degenerating neurons: mutants that lack all peripheral glia (foxD3?/?; Ntr) exhibit a much reduced reaction to axonal degeneration, resulting in a dramatic decrease in the clearance of debris, and impaired macrophage recruitment. Overall, these results show that this zebrafish model of peripheral sensory axon degeneration exhibits many aspects common to peripheral neuropathies and that peripheral glia play an important role in the initial response to this process.
Pope, Holly M.; Voigt, Mark M.
Neural remodeling in retinal degeneration.
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 phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, MŘller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in phase 1 or 2 in some animal models, but depletion of all neuronal classes is evident in phase 3. As remodeling progresses over months and years, more neurons are lost and patches of the ganglion cell layer can become depleted. Some survivor neurons of all classes elaborate new neurites, many of which form fascicles that travel hundreds of microns through the retina, often beneath the distal glial seal. These and other processes form new synaptic microneuromas in the remnant inner nuclear layer as well as cryptic connections throughout the retina. Remodeling activity peaks at mid-phase 3, where neuronal somas actively migrate on glial surfaces. Some amacrine and bipolar cells move into the former ganglion cell layer while other amacrine cells are everted through the inner nuclear layer to the glial seal. Remodeled retinas engage in anomalous self-signaling via rewired circuits that might not support vision even if they could be driven anew by cellular or bionic agents. We propose that survivor neurons actively seek excitation as sources of homeostatic Ca(2+) fluxes. In late phase 3, neuron loss continues and the retina becomes increasingly glial in composition. Retinal remodeling is not plasticity, but represents the invocation of mechanisms resembling developmental and CNS plasticities. Together, neuronal remodeling and the formation of the glial seal may abrogate many cellular and bionic rescue strategies. However, survivor neurons appear to be stable, healthy, active cells and given the evidence of their reactivity to deafferentation, it may be possible to influence their emergent rewiring and migration habits. PMID:12892644
Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica
Age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50áyears. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and ?-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. PMID:23580402
Cheung, Lily K; Eaton, Angie
Erythropoietin protects sensory axons against paclitaxel-induced distal degeneration
Paclitaxel causes a sensory polyneuropathy with characteristic features of distal axonal degeneration. Although the exact mechanisms underlying distal axonal degeneration are unknown, paclitaxel-induced axonal degeneration has been shown to be associated with an increase in detyrosinated tubulin. Here we show that recombinant human erythropoietin prevents axonal degeneration in sensory neurons in vitro and this effect is associated with downregulation of
Giorgia Melli; Christelene Jack; George L. Lambrinos; Mathias Ringkamp; Ahmet H÷ke
The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves
BACKGROUND: The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons.
Bogdan Beirowski; Robert Adalbert; Diana Wagner; Daniela S Grumme; Klaus Addicks; Richard R Ribchester; Michael P Coleman
Protection of Mouse Photoreceptors by Survival Factors in Retinal Degenerations
PURPOSE. TO examine the protective effect of a number of survival factors on degenerating photoreceptors in mutant mice with naturally occurring inherited retinal degenerations, including retinal degeneration (rd\\/rd), retinal degeneration slow (rds\\/rds), nervous (nr\\/nr), and Purkinje cell degeneration (pcd\\/pcd), in three different forms of mutant rhodopsin transgenic mice and in light damage in albino mice. METHODS. Various survival factors were
Matthew M. LaVail; Douglas Yasumura; Michael T. Matthes; Cathy Lau-Villacorta; Kazuhiko Unoki; Ching-Hwa Sung; Roy H. Steinberg
Protection of Retina by ?B Crystallin in Sodium Iodate Induced Retinal Degeneration
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 proliferatorľactivator receptorľ? (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.
Zhou, Peng; Kannan, Ram; Spee, Christine; Sreekumar, Parameswaran G.; Dou, Guorui; Hinton, David R.
Variability in Rate of Cone Degeneration in the Retinal Degeneration ( rd\\/rd ) Mouse
The retinas ofrd\\/rdmice with inherited retinal degeneration were examined histologically at postnatal days 60ľ66, an age when most rod cells already have degenerated and disappeared but when a significant number of cones are still present. We observed an unexpected hemispheric asymmetry and large variability in the number of surviving cones. Significantly more cones survived in the inferior than in the
Prospectives for gene therapy of retinal degenerations.
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
A caspase cascade regulating developmental axon degeneration.
Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other "upstream" caspases, prompting us to revisit the role of Caspase-3. In vitro, we show that genetic deletion of Caspase-3 is fully protective against sensory axon degeneration initiated by trophic factor withdrawal, but not injury-induced Wallerian degeneration, and we define a biochemical cascade from prosurvival Bcl2 family regulators to Caspase-9, then Caspase-3, and then Caspase-6. Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. In vivo, Caspase-3 and Caspase-6-knockout mice show a delay in developmental pruning of retinocollicular axons, thereby implicating both Caspase-3 and Caspase-6 in axon degeneration that occurs as a part of normal development. PMID:23223278
Simon, David J; Weimer, Robby M; McLaughlin, Todd; Kallop, Dara; Stanger, Karen; Yang, Jing; O'Leary, Dennis D M; Hannoush, Rami N; Tessier-Lavigne, Marc
Antioxidative nanofullerol prevents intervertebral disk degeneration
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.
Yang, Xinlin; Jin, Li; Yao, Lu; Shen, Francis H; Shimer, Adam L; Li, Xudong
Ill-posedness of degenerate dispersive equations
NASA Astrophysics Data System (ADS)
In this paper we provide numerical and analytical evidence that some degenerate dispersive partial differential equations are ill-posed. Specifically we study the K (2, 2) equation ut = (u2)xxx + (u2)x and the Ĺdegenerate Airyĺ equation ut = 2uuxxx. For K (2, 2) our results are computational in nature: we conduct a series of numerical simulations which demonstrate that data which is very small in H2 can be of unit size at a fixed time which is independent of the data's size. For the degenerate Airy equation, our results are fully rigorous: we prove the existence of a compactly supported self-similar solution which, when combined with certain scaling invariances, implies ill-posedness (also in H2).
Ambrose, David M.; Simpson, Gideon; Wright, J. Douglas; Yang, Dennis G.
Nerve fiber degeneration following a single experimental cerebral concussion in the rat.
This study has demonstrated widespread nerve fiber degeneration (nfd) following experimental cerebral concussion (ECC) in the rat by use of the Fink-Heimer modification of the Nauta--Gygax silver staining method for impregnation of degenerating axons. Beginning approximately 1 mm rostral to the optic chiasm and progressing caudally to the level of the cervical spinal cord and sampling at 600 micrometers intervals, 60 of the most prominent neuronal structures showing nfd have been identified and tend to be associated with 3 sites of injury; the coup, the contrecoup and the craniocervical junction. The duration of ECC was compared to the extent of nfd observed. PMID:7254717
Parsons, L C; Guthrie, M D
Malignant degeneration of multilevel monostotic Paget's disease involving the thoracic spine: an unusual presentation.
Paget's disease is the second most common metabolic bone disease after osteoporosis and is characterized by abnormal bone turnover and remodeling that can lead to pain, pathological fracture, bony deformity and nerve compression syndromes. The lumbar region is the most commonly affected site within the spine followed by the thoracic and cervical spine. Even though the spine is affected very commonly in Paget's disease, malignant degeneration is exceptionally rare. Multilevel monostotic spine involvement due to Paget's disease is very uncommon. An unusual clinico-radiological manifestation of multilevel thoracic Paget's disease with sarcomatous degeneration presenting as a neurosurgical emergency is reported with a pertinent review of the literature. PMID:24411323
Tan, Lee A; Kasliwal, Manish K; Harbhajanka, Aparna; Miller, Ira J; Deutsch, Harel
Pathogenesis of tendinopathies: inflammation or degeneration?
The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies.
Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto
Degenerate quasicrystal of hard triangular bipyramids.
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
Kinematic control of robot with degenerate wrist
NASA Technical Reports Server (NTRS)
Kinematic resolved rate equations allow an operator with visual feedback to dynamically control a robot hand. When the robot wrist is degenerate, the computed joint angle rates exceed operational limits, and unwanted hand movements can result. The generalized matrix inverse solution can also produce unwanted responses. A method is introduced to control the robot hand in the region of the degenerate robot wrist. The method uses a coordinated movement of the first and third joints of the robot wrist to locate the second wrist joint axis for movement of the robot hand in the commanded direction. The method does not entail infinite joint angle rates.
Barker, L. K.; Moore, M. C.
Axillary Schwannoma with Extensive Cystic Degeneration
Schwannoma affect mainly head, neck, and flexor aspect of the limbs. Neurogenic tumors arising from the brachial plexus are rare and axillary schwannoma is extremely uncommon. Cystic degeneration is common in longstanding cases and which when aspirated may yield only macrophages or lymphocytes leading to false diagnosis of the case in spite of strong clinical suspicion. We report one such rare case of a solitary axillary schwannoma with extensive cystic degeneration, which was misdiagnosed on fine needle aspiration cytology and subsequently confirmed by the histopathological examination and immunohistochemistry.
Jadhav, Chaithra R; Angeline, N R; Kumar, Bipin; Bhat, Ramachandra V; Balachandran, G
Perineurial permeability to sodium during Wallerian degeneration in rat sciatic nerve.
In rat sciatic nerves, the effect of Wallerian degeneration on the rate of transperineurial passage of sodium between the endoneurium and the epineurial extracellular space was investigated. In nerves transected and ligated at the sciatic notch, an in situ technique was used to measure the permeability coefficient-surface area product (PS) of the mid-thigh portion of the perineurium to 22Na. Sampling times ranged from one day to sixteen weeks after the lesion. Additionally, endoneurial water content (an indicator of nerve edema) was also measured in transected, degenerating nerves at the same sampling times. Endoneurial water content increased significantly by the fourth day after transection, peaked at four weeks, and then remained elevated through 16 weeks of post-lesion measurement. The PS of the perineurium to 22Na on the 4th day after transection was significantly greater than that of control animals. This increase then declined to normal levels through the 2nd week, and finally increased to values that were 3-fold to 4-fold of control values for the remainder of the observation period. The earlier, short lasting increase in perineurial PS is probably associated with the inflammatory response to nerve section, and proliferation of perineurial layers and cells. The later increase in perineurial permeability is proposed to play a role in the dissipation of endoneurial hydrostatic pressure and clearance of myelin debris from the endoneurium. In view of the complex changes in perineurial permeability described herein, it would seem inappropriate to consider these phenomena merely as passive breakdowns of the barrier properties of the perineurium. PMID:1466671
Weerasuriya, A; Hockman, C H
Driving and Age-Related Macular Degeneration
ERIC Educational Resources Information Center
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,ů
Owsley, Cynthia; McGwin, Gerald, Jr.
The Psychosocial Impact of Macular Degeneration
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
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 disablingů
Casten, Robin; Rovner, Barry
Paraneoplastic neurological degenerations: keys to tumour immunity
Paraneoplastic neurological degenerations (PNDs) are neurological disorders that develop in patients with cancer. PNDs are triggered by an effective antitumour immune response against neuronal antigens that are expressed in cancer cells, which subsequently develops into autoimmune neurodegenerative disease. Studying patients with PND has offered the opportunity to gain unique insights into mechanisms of tumour immunity and has provided the potential
Matthew L. Albert; Robert B. Darnell
Surgical Treatment of Advanced Pellucid Marginal Degeneration
Purpose: To determine the efficacy of simultaneous peripheral crescentic lamellar keratoplasty (LK) and central penetrating keratoplasty (PK) for advanced pellucid marginal degeneration (PMD). Design: Retrospective, noncomparative, interventional case series. Participants: Five patients with advanced PMD. Method: Simultaneous peripheral crescentic LK and central PK followed by selective suture removal and astigmatic keratotomy in the postoperative period. Main Outcome Measures: These included
Karim Rasheed; Yaron S. Rabinowitz
Pellucid corneal marginal degeneration: A review
Pellucid marginal corneal degeneration (PMD) is a rare ectatic disorder which typically affects the inferior peripheral cornea in a crescentic fashion. The condition is most commonly found in males and usually appears between the 2nd and 5th decades of life affecting all ethnicities. The prevalence and aetiology of this disorder remain unknown. Ocular signs and symptoms of patients with PMD
Amit Jinabhai; Hema Radhakrishnan; Clare OĺDonnell
Degenerate KAM theory for partial differential equations
NASA Astrophysics Data System (ADS)
This paper deals with degenerate KAM theory for lower dimensional elliptic tori of infinite dimensional Hamiltonian systems, depending on one parameter only. We assume that the linear frequencies are analytic functions of the parameter, satisfy a weak non-degeneracy condition of RŘssmann type and an asymptotic behavior. An application to nonlinear wave equations is given.
Bambusi, D.; Berti, M.; Magistrelli, E.
Paraneoplastic cerebellar degeneration associated with Hodgkin's disease
A case of paraneoplastic cerebellar degeneration (PCD) associated with Hodgkin's disease is presented. The features that make this case particularly interesting are the simultaneous occurrence of PCD with a relapse of Hodgkin's disease, which has been present for 17 years, and the arrested progression of cerebellar dysfunction after a subacute onset. Cerebellar atrophy was revealed by computed tomography and magnetic
K. Wessel; H. C. Diener; G. Schroth; J. Dichgans
Analysis of optineurin in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) can occur jointly with amyotrophic lateral sclerosis (ALS), and these 2 conditions share a genetic risk factor on chromosome 9. It has been reported that mutations in optineurin (OPTN) can cause ALS. Therefore, we sequenced OPTN in 371 FTLD cases but no mutations were detected, suggesting changes in OPTN do not cause FTLD. PMID:21074902
Rollinson, Sara; Bennion, Janis; Toulson, Greg; Halliwell, Nicola; Usher, Suzanne; Snowden, Julie; Richardson, Anna; Neary, David; Mann, David; Pickering-Brown, Stuart M
The nature of apraxia in corticobasal degeneration.
Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage.
Leiguarda, R; Lees, A J; Merello, M; Starkstein, S; Marsden, C D
Pathogenesis of age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. The inability to prevent the development of AMD and its complications stems from our lack of knowledge of the underlying pathological mechanisms. A recent report described a rodent with chemokine deficiencies that developed retinal changes similar to those frequently observed in AMD and
Tongalp H. Tezel; Nalini S. Bora; Henry J. Kaplan
Progranulin in frontotemporal lobar degeneration and neuroinflammation
Progranulin (PGRN) is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD). Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central
Zeshan Ahmed; Ian RA Mackenzie; Michael L Hutton; Dennis W Dickson
[Retroperitoneal lipoma (with areas of myxoid degeneration)].
Retroperitoneal tumors of lipomatous origin are usually liposarcomas. Only a minority of adipose tumors of the retroperitoneum show histological criteria of benignity. We present the case of a 52-year-old woman, diagnosed of a retroperitoneal lipoma with areas of myxoid degeneration. The tumor involved the left kidney and was resected completely. PMID:1493064
DÝaz de Lia˝o, A; Soriano, P; Monzˇn, F J; Merck, N; Ochoa, L
Macular Degeneration: Questions to Discuss with Your Doctor
... us Macular Degeneration Questions to Discuss with Your Doctor: Have you noticed a change in vision in ... have a family history of macular degeneration? Your Doctor Might Examine the Following Body Structures or Functions: ...
9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.
Code of Federal Regulations, 2010 CFR
...2009-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products... ┬ž 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found to be...
9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.
Code of Federal Regulations, 2010 CFR
...2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products... ┬ž 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found to be...
Family-Specific Degenerate Primer Design: A Tool to Design Consensus Degenerated Oligonucleotides
Designing degenerate PCR primers for templates of unknown nucleotide sequence may be a very difficult task. In this paper, we present a new method to design degenerate primers, implemented in family-specific degenerate primer design (FAS-DPD) computer software, for which the starting point is a multiple alignment of related amino acids or nucleotide sequences. To assess their efficiency, four different genome collections were used, covering a wide range of genomic lengths: Arenavirus (10 Î 104 nucleotides), Baculovirus (0.9 Î 105 to 1.8 Î 105?bp), Lactobacillus sp. (1 Î 106 to 2 Î 106?bp), and Pseudomonas sp. (4 Î 106 to 7 Î 106?bp). In each case, FAS-DPD designed primers were tested computationally to measure specificity. Designed primers for Arenavirus and Baculovirus were tested experimentally. The method presented here is useful for designing degenerate primers on collections of related protein sequences, allowing detection of new family members.
Goni, Sandra Elizabeth; Lozano, Mario Enrique
Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration
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
A novel endogenous erythropoietin mediated pathway prevents axonal degeneration
Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate
Sanjay C. Keswani; Ulas Buldanlioglu; Angela Fischer; Nicole Reed; Michelle Polley; Hong Liang; Chunhua Zhou; Christelene Jack; Gerhard J. Leitz; Ahmet Hoke
Degeneration following Injury from Naturally Occurring Developmental Pruning
Summary Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the de- velopment of proper circuitry in the nervous system from insects to mammals. Developmental axon degen- eration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underly- ing mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds
Eric D. Hoopfer; Todd McLaughlin; Ryan J. Watts; Oren Schuldiner; Dennis D. M. O'Leary; Liqun Luo
Iron homeostasis and toxicity in retinal degeneration
Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels build up with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreichĺs Ataxia, and panthothenate kinase associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age- matched controls. Over the past ten years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter 1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.
He, Xining; Hahn, Paul; Iacovelli, Jared; Wong, Robert; King, Chih; Bhisitkul, Robert; Massaro-Giordano, Mina; Dunaief, Joshua L.
[New aspects in age related macular degeneration].
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
We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. In regions where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.
Bacca, S.; Hally, K. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Liebendoerfer, M.; Perego, A. [Department of Physics, University of Basel, Klingelbergstr. 82, 4056 Basel (Switzerland); Pethick, C. J. [Niels Bohr International Academy, Niels Bohr Institute, Blegdamsvej 17, DK-2100 Copenhagen O (Denmark); Schwenk, A. [ExtreMe Matter Institute EMMI, GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, D-64291 Darmstadt (Germany)
Intacs for early pellucid marginal degeneration
A 42-year-old man had Intacs (Addition Technology Inc.) implantation for early pellucid marginal degeneration (PMD). Two Intacs segments (0.45 mm thickness) were inserted uneventfully in the fashion typically used for low myopia correction (nasalľtemporal). Eleven months after the procedure, the uncorrected visual acuity was 20\\/200, compared with counting fingers preoperatively, while the best spectacle-corrected visual acuity improved to 20\\/25 from
George D Kymionis; Ioannis M Aslanides; Charalambos S Siganos; Ioannis G Pallikaris
Management of pellucid marginal corneal degeneration
Purpose A retrospective study to ascertain the management of pellucid marginal corneal degeneration (PMCD).Method and results Sixteen patients (average age 42.6 years) presented with PMCD. PMCD was bilateral in 13 and unilateral in 3 patients. Eight eyes underwent surgery. Nineteen eyes were managed non-surgically. Surgery involved corneal wedge excision (WE) (6 eyes), penetrating keratoplasty (PK) (3 eyes) and lamellar thermo-keratoplasty
Susmito Biswas; Arun Brahma; Cindy Tromans; Alan Ridgway
Terrien's marginal degeneration: Clinicopathologic case reports
We report the clinicopathologic features of seven cases of Terrien's marginal degeneration. Three specimens studied were lamellar resections and four were full-thickness corneal segments. Of the four full-thickness specimens, three were semilunar and one was an annular (ôdoughnut-shapedö) specimen. All cases had stromal thinning, vascularization, lipid keratopathy and local absence of Bowman's membrane. Descemet's membrane was markedly thickened and the
D. R. Guyer; J. Barraquer; P. J. McDonnell; W. R. Green
Almost Sure Stabilizability of Controlled Degenerate Diffusions
We develop a direct Lyapunov method for the almost sure open-loop stabilizability and asymptotic stabilizability of controlled degenerate dif- fusion processes. The infinitesimal decrease condition for a Lyapunov function is a new form of Hamilton-Jacobi-Bellman partial differential in- equality of 2nd order. We give local and global versions of the First and Second Lyapunov Theorems assuming the existence of a
Martino Bardi; Annalisa Cesaroni
Almost sure stability of controlled degenerate diffusions
We develop a direct Lyapunov method for the almost sure open-loop stabilizability and asymptotic stabilizability of controlled degenerate diffusion processes. The infinitesimal decrease condition for a Lyapunov function is a new form of Hamilton-Jacobi-Bellman partial differential inequality of $2nd$ order. We give local and global versions of the First and Second Lyapunov Theorems assuming the existence of a lower semicontinuous
Martino Bardi; Annalisa Cesaroni
Paraneoplastic cerebellar degeneration associated with ovarian cancer
Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. PCD often precedes the cancer diagnosis by months to years. Here, we report the case of a 64-year-old woman who developed PCD symptoms, associated with high levels of anti-Yo antibodies, one year after a previous diagnosis of ovarian cancer. Clinical features, pathogenesis and treatment of PCD associated with cancer are discussed according to previous studies.
Asymmetrical alien hands in corticobasal degeneration.
There are several forms of alien limb, but alien limb in corticobasal degeneration (CBD) is not well understood. We studied a patient with CBD who demonstrated two different types of alien limb. With his right hand he demonstrated a tactile avoidance response with levitation. With his left hand, he demonstrated continuous tactile pursuit of the examiner's hand ("tactile mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance response and levitation are often associated with parietal dysfunction. PMID:17230447
Fitzgerald, David B; Drago, Valeria; Jeong, Yong; Chang, Yu-Ling; White, Keith D; Heilman, Kenneth M
Prevention of age-related macular degeneration
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
Production of quantum-degenerate strontium gases
NASA Astrophysics Data System (ADS)
We report on an improved scheme to generate Bose-Einstein condensates (BECs) and degenerate Fermi gases of strontium. This scheme allows us to create quantum gases with higher atom number, a shorter time of the experimental cycle, or deeper quantum degeneracy than before. We create a BEC of 84Sr exceeding 107 atoms, which is a 30-fold improvement over previously reported experiments. We increase the atom number of 86Sr BECs to 2.5Î104 (a fivefold improvement) and refine the generation of attractively interacting 88Sr BECs. We present a scheme to generate 84Sr BECs with a cycle time of 2 s. We create deeply degenerate 87Sr Fermi gases with T/TF as low as 0.10(1), where the number of populated nuclear spin states can be set to any value between one and ten. Furthermore, we report on a total of five different double-degenerate Bose-Bose and Bose-Fermi mixtures. These studies prepare an excellent starting point for applications of strontium quantum gases anticipated in the near future.
Stellmer, Simon; Grimm, Rudolf; Schreck, Florian
Mucoid degeneration of the anterior cruciate ligament.
Mucoid degeneration of the anterior cruciate ligament (ACL) is a rare cause of knee pain. We report a case of a patient with mucoid degeneration of the ACL, presenting with posterior knee pain and no history of a major knee trauma. On clinical examination, the active range of motion showed a flexion deficit. The posterior knee pain was induced by passive hyperflexion of the knee. There was no evidence of ligamentary instability. MRI showed a diffuse thickening of the ACL with a nodular mass on the femoral insertion occupying the intercondylar notch, with increased signal intensity on both T1- and T2-weighted images. Arthroscopic evaluation showed a diffuse hypertrophy of the ACL, throughout the entire length of the posterolateral bundle (PLB). A yellowish homogenous mass on the femoral insertion of the ACL impinged on the posterior cruciate ligament (PCL) in flexion and occupied the entire intercondylar notch. We performed an arthroscopic debridement of the hypertrophied tissues as precisely as possible. This resulted in a nearly complete removal of the PLB and immediate relief of symptoms. Examination of knee stability after debridement showed a stable ACL. Arthroscopic debridement of the mucoid degeneration of the ACL proved to be a safe and effective method, without causing ligamentary instability in daily activities. PMID:19089409
Motmans, Robrecht; Verheyden, Frank
Exome Sequencing in Familial Corticobasal Degeneration
Background Corticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described. Objective We aim to characterize the clinical, imaging, pathological and genetic features of two familial cases of CBD. Methods We describe two first cousins with CBD associated with atypical MRI findings. We performed exome sequencing in both subjects and in an unaffected first cousin of similar age. Results The cases include a 79-year-old woman and a 72-year-old man of Native American and British origin. The onset of the neurological manifestations was 74 and 68 years respectively. Both patients presented with a combination of asymmetric parkinsonism, apraxia, myoclonic tremor, cortical sensory syndrome, and gait disturbance. The female subject developed left side fixed dystonia. The manifestations were unresponsive to high doses of levodopa in both cases. Extensive bilateral T1-W hyperintensities and T2-W hypointensities in basal ganglia and thalamus were observed in the female patient; whereas these findings were more subtle in the male subject. Postmortem examination of both patients was consistent with corticobasal degeneration; the female patient had additional findings consistent with mild Alzheimerĺs disease. No Lewy bodies were found in either case. Exome sequencing showed mutations leading to possible structural changes in MRS2 and ZHX2 genes, which appear to have the same upstream regulator miR-4277. Conclusions Corticobasal degeneration can have a familial presentation; the role of MRS2 and ZHX2 gene products in CBD should be further investigated.
Fekete, Robert; Bainbridge, Matthew; Baizabal-Carvallo, Jose Fidel; Rivera, Andreana; Miller, Bradley; Du, Peicheng; Kholodovich, Vladyslav; Powell, Suzanne; Ondo, William
Retinoid receptors trigger neuritogenesis in retinal degenerations
Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented retina and brain regions. Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron neuritogenesis and up-regulated several key elements of retinoic acid (RA) signaling, including retinoid X receptors (RXRs). Exogenous RA initiated neuritogenesis in normal adult retinas and primary retinal cultures and exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly attenuated in retinol dehydrogenase knockout (Rdh12?/?) mice and by aldehyde dehydrogenase inhibitors. We further found that LIRD rapidly increased the expression of glutamate receptor 2 and ? Ca2+/calmodulin-dependent protein kinase II (?CaMKII). Pulldown assays demonstrated interaction between ?CaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR antagonists completely prevented and RXR agonists were more effective than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and may be therapeutic targets to attenuate retinal remodeling and facilitate global intervention methods in blinding diseases and other neurodegenerative disorders.ŚLin, Y., Jones, B. W., Liu, A., Tucker, J. F., Rapp, K., Luo, L., Baehr, W., Bernstein, P. S., Watt, C. B., Yang, J.-H., Shaw, M. V., Marc, R. E. Retinoid receptors trigger neuritogenesis in retinal degenerations.
Lin, Yanhua; Jones, Bryan W.; Liu, Aihua; Tucker, James F.; Rapp, Kevin; Luo, Ling; Baehr, Wolfgang; Bernstein, Paul S.; Watt, Carl B.; Yang, Jia-Hui; Shaw, Marguerite V.; Marc, Robert E.
Can neutrinos be degenerate in mass?
NASA Astrophysics Data System (ADS)
We reconsider the possibility that the masses of the three light neutrinos of the Standard Model might be almost degenerate and close to the present upper limits from Tritium ? decay and cosmology. In such a scenario, the cancellations required by the latest upper limit on neutrinoless double-? decay enforce near-maximal mixing that may be compatible only with the vacuum-oscillation scenario for solar neutrinos. We argue that the mixing angles yielded by degenerate neutrino mass-matrix textures are not in general stable under small perturbations. We evaluate within the MSSM the generation-dependent one-loop renormalization of neutrino mass-matrix textures that yielded degenerate masses and large mixing at the tree level. We find that m?e>m??>m?? after renormalization, excluding MSW effects on solar neutrinos. We verify that bimaximal mixing is not stable, and show that the renormalized masses and mixing angles are not compatible with all the experimental constraints, even for tan? as low as unity. These results hold whether the neutrino masses are generated by a see-saw mechanism with heavy neutrinos weighing ~1013 GeV or by non-renormalizable interactions at a scale ~105 GeV. We also comment on the corresponding renormalization effects in the minimal Standard Model, in which m?e Ellis, John; Lola, Smaragda 1999-07-01
Ellis, John; Lola, Smaragda
The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves
Background The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice. Results In wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37ľ42 h after transection and 40ľ44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all WldS axons were partially fragmented 15ľ25 days after nerve lesion, WldS axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks. Conclusions We conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of trophic or regulatory factors by axonal transport triggers degeneration. WldS axons, once they finally degenerate, do so by a fundamentally different mechanism, indicated by differences in the rate, direction and abruptness of progression, and by different early morphological signs of degeneration. These observations suggest that WldS axons undergo a slow anterograde decay as axonal components are gradually depleted, and do not simply follow the degeneration pathway of wild-type axons at a slower rate.
Beirowski, Bogdan; Adalbert, Robert; Wagner, Diana; Grumme, Daniela S; Addicks, Klaus; Ribchester, Richard R; Coleman, Michael P
Optic disc edema associated with spinocerebellar degeneration.
A 58-year-old man presented with optic disc edema as a rare association with spinocerebellar degeneration (SCD). The patient also had chronic idiopathic intestinal pseudo-obstruction with hypoalbuminemia. No elevation of intraspinal pressure and no intracranial lesion was observed. The hypoalbuminemia reacted promptly to treatment, whereas the optic disc edema regressed gradually. An association between SCD and optic atrophy has often been described, but to our knowledge this is the first report of SCD in association with optic disc edema. PMID:9672220
Nakazawa, T; Abe, T; Hasegawa, T; Tamai, M
Aneutronic Fusion in a Degenerate Plasma
In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot.
S. Son; N.J. Fisch
[Pellucid marginal degeneration: diagnosis and treatment].
Pellucid marginal degeneration is characterized by a progressive stromal thinning of the inferior corneal segment, between 4 and 8 o'clock, with a crescentic shape. The area of corneal thinning has a width of about 1 to 2 mm, and it is separated from the corneoscleral limbus by an area of normal corneal tissue. The initial treatment consists of optical correction. However, when the disease progresses to advanced stages, surgical procedures are necessary such as wedge resection, lamellar crescentic resection, penetrating keratoplasty, lamellar keratoplasty, epikeratoplasty and, recently, intracorneal segments. PMID:16936977
MÚrula, Rafael Vidal; Trindade, Fernando Canšado
Intacs for early pellucid marginal degeneration.
A 42-year-old man had Intacs (Addition Technology Inc.) implantation for early pellucid marginal degeneration (PMD). Two Intacs segments (0.45 mm thickness) were inserted uneventfully in the fashion typically used for low myopia correction (nasal-temporal). Eleven months after the procedure, the uncorrected visual acuity was 20/200, compared with counting fingers preoperatively, while the best spectacle-corrected visual acuity improved to 20/25 from 20/50. Corneal topographic pattern also improved. Although the results are encouraging, concern still exists regarding the long-term effect of this approach for the management of patients with PMD. PMID:14967293
Kymionis, George D; Aslanides, Ioannis M; Siganos, Charalambos S; Pallikaris, Ioannis G
Bladder dysfunction in subacute combined degeneration
Objective\\u000a ááIn 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 ááSACD 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
Degenerate Fermi gas of (87)Sr.
We report quantum degeneracy in a gas of ultracold fermionic (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(F)=0.26(-0.06)(+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(F) ?0.5. PMID:20867747
DeSalvo, B J; Yan, M; Mickelson, P G; Martinez de Escobar, Y N; Killian, T C
[Degeneration and regeneration of the peripheral nerve].
The peripheral nerve's degeneration and regeneration after its injury was described by Waller in 1850. The distal stump and small part of the proximal part of the transected fibre disintegrate. Proliferating Schwann cells create the band of BŘngner for the guiding of the regrowing axon. Even if the suture of the nerve is quickly and well performed, the reinervation is never absolute. Regrowing axons can grow into wrong endoneurial tubes or outside the area of the suture and long-lasting denervation leads to progressive atrophy of the target organs. In the future, the neurotrophic factors might improve the outcome of the reinervation. PMID:22737943
Kaiser, R; Haninec, P
Spin susceptibility of degenerate quark matter
NASA Astrophysics Data System (ADS)
The expression for spin susceptibility ? of degenerate quark matter is derived with corrections up to O(g4lng2). It is shown that, at low density, ?-1 changes sign and turns negative, indicating a ferromagnetic phase transition. To this order, we also calculate sound velocity c1 and incompressibility K with arbitrary spin polarization. The estimated values of c1 and K show that the equation of state of the polarized matter is stiffer than that of unpolarized matter. Finally, we determine the finite temperature corrections to the exchange energy and derive corresponding results for the spin susceptibility.
Pal, Kausik; Dutt-Mazumder, Abhee K.
Genetics and molecular pathology of Stargardt-like macular degeneration
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
Scanning electron microscopy studies of erythrocytes in spinocerebellar degeneration
Spinocerebellar degeneration is a heredofamilial disease of unknown aetiology. The shape of erythrocytes as revealed by scanning electron microscopy was studied in this disease. Echinocytes I, as defined by Bessis, were seen more frequently in spinocerebellar degeneration than in age and sex matched controls (7.2 +\\/- 1.5% in spinocerebellar degeneration, 3.4 +\\/- 1.2% in controls, p less than 0.001), Parkinson's
Y Yasuda; I Akiguchi; H Shio; M Kameyama
Degenerate and Resonant Four-Wave Mixing in Plasmas
The status of degenerate and resonant four-wave mixing in plasmas is reviewed. For the degenerate case in a collisional plasma, the theory predicts and experiments demonstrate that the thermal-force contribution to the signal reflectivity dominates over the ponderomotive-force contribution. In the resonant case, the reflectivity can be enhanced over the degenerate level. Experiments show that collisions can lead to a
C. Joshi; Y. Kitagawa; A. Lal
Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of Inherited Retinal Degeneration
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).
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
Cone Degeneration Following Rod Ablation in a Reversible Model of Retinal Degeneration
Purpose. Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible. Methods. The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F1 tadpoles. Results. NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. MŘller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments. Conclusions. The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration.
Choi, Rene Y.; Engbretson, Gustav A.; Solessio, Eduardo C.; Jones, Georgette A.; Coughlin, Adam; Aleksic, Ilija
In vivo study of response threshold in retinal degenerate model at different degenerate stages
Retinal prostheses are being developed to apply electrical stimulation to the retina in order to restore vision of individuals who suffer from diseases such as retinitis pigmentosa (RP) and aged related macular degeneration (AMD). Various electrical stimulus parameters have been extensively studied in both experimental and clinical settings. Both electrophysiological and psychophysical results have shown that outer retina disease exhibit
L. H. Chan; A. Ray; B. B. Thomas; M. S. Humayun; J. D. Weiland
Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.
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, Robert H; Oh, Joo Youn; 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
Family-specific degenerate primer design: a tool to design consensus degenerated oligonucleotides.
Designing degenerate PCR primers for templates of unknown nucleotide sequence may be a very difficult task. In this paper, we present a new method to design degenerate primers, implemented in family-specific degenerate primer design (FAS-DPD) computer software, for which the starting point is a multiple alignment of related amino acids or nucleotide sequences. To assess their efficiency, four different genome collections were used, covering a wide range of genomic lengths: Arenavirus (10 Î 10(4) nucleotides), Baculovirus (0.9 Î 10(5) to 1.8 Î 10(5)?bp), Lactobacillus sp. (1 Î 10(6) to 2 Î 10(6)?bp), and Pseudomonas sp. (4 Î 10(6) to 7 Î 10(6)?bp). In each case, FAS-DPD designed primers were tested computationally to measure specificity. Designed primers for Arenavirus and Baculovirus were tested experimentally. The method presented here is useful for designing degenerate primers on collections of related protein sequences, allowing detection of new family members. PMID:23533783
Iserte, Javier Alonso; Stephan, Betina Ines; Go˝i, Sandra Elizabeth; Borio, Cristina Silvia; Ghiringhelli, Pablo Daniel; Lozano, Mario Enrique
Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration
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 ôknock-inö 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
Mucoid degeneration of the anterior cruciate Ligament: a case report
We report a case of mucoid degeneration of the anterior cruciate ligament (ACL). Mucoid degeneration of the ACL is a very rare cause of knee pain. There have been only some reported cases of mucoid degeneration of the ACL in the English literature. We reviewed previous reports and summarized clinical features and symptoms, including those found in our case. Magnetic Resonance Imaging is the most useful tool for differentiating mucoid degeneration of the ACL from an intraligamentous ganglion or other lesions in the knee joint. If this disease is considered preoperatively, it can be diagnosed easily based on characteristic findings.
el Kadi, Khalid Ibn; Marcaillou, Florian; Blanc, Stephane; Salloum, Bassam; Dimontagliari, Cyril; Boutayeb, Fawzi
Metabolic anatomy of paraneoplastic cerebellar degeneration
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.
Pleiotropy and GAL pathway degeneration in yeast.
Traits that do not contribute to fitness are expected to be lost during the course of evolution, either as a result of selection or drift. The Leloir pathway of galactose metabolism (GAL) is an extensively studied metabolic pathway that degenerated on at least three independent occasions during the evolutionary diversification of yeasts, suggesting that the pathway is costly to maintain in environments that lack galactose. Here I test this hypothesis by competing GAL pathway deletion mutants of Saccharomyces cerevisiae against an isogenic strain with an intact GAL pathway under conditions where expression of the pathway is normally induced, repressed, or uninduced. These experiments do not support the hypothesis that pleiotropy drives GAL pathway degeneration, because mutations that knock out individual GAL genes do not tend to increase fitness in the absence of galactose. At a molecular level, this result can be explained by the fact that yeast uses inexpensive regulatory proteins to tightly regulate the expression of structural genes that are costly to express. I argue that these results have general relevance for our understanding of the fitness consequences of gene disruption in yeast. PMID:17584228
MacLean, R C
Retinoid receptors trigger neuritogenesis in retinal degenerations.
Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented retina and brain regions. Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron neuritogenesis and up-regulated several key elements of retinoic acid (RA) signaling, including retinoid X receptors (RXRs). Exogenous RA initiated neuritogenesis in normal adult retinas and primary retinal cultures and exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly attenuated in retinol dehydrogenase knockout (Rdh12(-/-)) mice and by aldehyde dehydrogenase inhibitors. We further found that LIRD rapidly increased the expression of glutamate receptor 2 and ? Ca(2+)/calmodulin-dependent protein kinase II (?CaMKII). Pulldown assays demonstrated interaction between ?CaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR antagonists completely prevented and RXR agonists were more effective than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and may be therapeutic targets to attenuate retinal remodeling and facilitate global intervention methods in blinding diseases and other neurodegenerative disorders. PMID:21940995
Lin, Yanhua; Jones, Bryan W; Liu, Aihua; Tucker, James F; Rapp, Kevin; Luo, Ling; Baehr, Wolfgang; Bernstein, Paul S; Watt, Carl B; Yang, Jia-Hui; Shaw, Marguerite V; Marc, Robert E
Progranulin in frontotemporal lobar degeneration and neuroinflammation
Progranulin (PGRN) is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD). Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs). While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.
Ahmed, Zeshan; Mackenzie, Ian RA; Hutton, Michael L; Dickson, Dennis W
Disc degeneration-related clinical phenotypes.
The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components. PMID:23884550
BattiÚ, Michele C; Lazßry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, PÚter Pßl; McCall, Iain
Thermodynamic functions of degenerate magnetized electron gas
The Fermi energy, pressure, internal energy, entropy, and heat capacity of completely degenerate relativistic electron gas are calculated by numerical methods. It is shown that the maximum admissible magnetic field on the order of 10{sup 9} G in white dwarfs increases the pressure by a factor of 1.06 in the central region, where the electron concentration is {approx}10{sup 33} cm{sup -3}, while the equilibrium radius increases by approximately a factor of 1.03, which obviously cannot be observed experimentally. A magnetic field of {approx}10{sup 8} G or lower has no effect on the pressure and other thermodynamic functions. It is also shown that the contribution of degenerate electron gas to the total pressure in neutron stars is negligible compared to that of neutron gas even in magnetic fields with a maximum induction {approx}10{sup 17} G possible in neutron stars. The neutron beta-decay forbiddeness conditions in a superstrong magnetic field are formulated. It is assumed that small neutron stars have such magnetic fields and that pulsars with small periods are the most probable objects that can have super-strong magnetic fields.
Skobelev, V. V., E-mail: email@example.com [Moscow State Industrial University (Russian Federation)
Interleukin-1? Inhibition Prevents Choroidal Neovascularization and Does Not Exacerbate Photoreceptor Degeneration
The pro-inflammatory cytokine IL-1? has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1? in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1? expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1?/? model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1+/+ and Cx3cr1?/? mice (enzyme-linked immunoabsorbent assay) after light injury. IL-1? was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1? significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1? on choroidal endothelial cell proliferation. Inhibition of IL-1? in light- and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1?/? mice. Our results suggest that IL-1? inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.
Lavalette, Sophie; Raoul, William; Houssier, Marianne; Camelo, Serge; Levy, Olivier; Calippe, Bertrand; Jonet, Laurent; Behar-Cohen, Francine; Chemtob, Sylvain; Guillonneau, Xavier; Combadiere, Christophe; Sennlaub, Florian
Morphological characterization of the retinal degeneration in three strains of mice carrying the rd-3 mutation.
Retinal development in 3 strains of rd-3/rd-3 mutant mice, previously shown to have different rates of degeneration, was studied using light, electron, and immunofluorescence microscopy. The time course and phenotype of the degeneration as well as details on the mechanism of massive photoreceptor cell loss are compared with other known retinal degenerations in mice. Up until postnatal day (P) 10, the retinas of all three strains (RBF, 4Bnr, In-30) develop similarly to those of pigmented and nonpigmented controls. TUNEL-positive cells appear in the outer nuclear layer (ONL) by P14, and reach a maximum in all three mutant strains around P21. Scattered rods and cones form a loose, monolayered ONL by 8 weeks in the albino RBF strain, by 10 weeks in the albino 4Bnr strain, and by 16 weeks in the pigmented In-30 strain. Though the initial degeneration begins in the central retina, there is no preferred gradient of cell death between central and peripheral photoreceptors. Rods and cones are present at all ages examined. During development, stacks of outer segments (OS) form in all three strains though they never achieve full adult lengths, and often have disorganized, atypical OS. Rod opsin is expressed in the developing OS but is redistributed into plasma membrane as OS degeneration proceeds. Retinal pigment epithelial (RPE) cells of all mutant strains contain packets of phagocytosed OS, and their apical processes associate with the distal ends of the OS. At their synaptic sites, photoreceptor terminals contain ribbons apposed to apparently normal postsynaptic triads. As photoreceptors are lost, MŘller cells fill in space in the ONL but they do not appear to undergo significant hypertrophy or migration, though during the degeneration, glial fibrillary acidic protein (GFAP) expression is gradually upregulated. Macrophage-like cells are found frequently in the subretinal space after the onset of photoreceptor apoptosis. As OS disappear, the RPE apical processes revert to simple microvilli. Late in the degeneration, some RPE cells die and neighboring cells appear to flatten as if to maintain confluence. In regions of RPE cell loss that happen to lie above retina where the ONL is gone, cells of the inner nuclear layer (INL), wrapped by MŘller cell processes, may front directly on Bruch's membrane. PMID:16469183
Linberg, Kenneth A; Fariss, Robert N; Heckenlively, John R; Farber, Debora B; Fisher, Steven K
ABSTRACT Background/Purpose Cumulative sunlight exposure and cataract surgery are reported risk factors for advanced age-related macular degeneration (AMD). Laboratory studies suggest that accumulation and photochemical reactions of A2E (N-retinylidene-N-retinylethanolamine) and its epoxides, components of lipofuscin, are important in AMD. To relate this data to the clinical setting, we modeled the effects of macular irradiance and spectral filtering on production of A2E and reactive oxygen intermediates (ROIs) in pseudophakic eyes with a clear or ôyellowö intraocular lens (IOL) and in phakic eyes. Methods We calculated relative changes of macular irradiance as a function of light (390 to 700 nm) intensity, pupil size, age, and lens status, and modeled resulting all-trans-retinal concentration and rates of production of A2E-related photochemicals and photon-induced ROIs in rods and retinal pigment epithelium (RPE). We compared these photoproducts following cataract surgery and IOL implantation with and without spectral sunglasses to normal age-related nuclear sclerotic lens changes. Results Following cataract and IOL surgery, all-trans-retinal and lipofuscin photochemistry would theoretically increase average generation of 1) A2E-related photochemicals, 2) ROI in rods and 3) ROI in RPE, respectively, 2.6-, 15- and 6.6-fold with a clear IOL, and 2.1-, 4.1- and 2.6 fold with a yellow IOL, but decrease approximately 30-, approximately 20-and 4-fold with a vermillion filter sunglass and clear IOL compared to an average 70 year old phakic eye. Conclusion Sunglasses that strongly decrease both deep blue light and rod photobleaching, while preserving photopic sensitivity and color perception, would provide upstream protection from potential photochemical damage in subjects at risk for AMD progression after cataract surgery.
Meyers, Sanford M; Ostrovsky, Mikhail A; Bonner, Robert F
Depletion of PtdIns(4,5)P2 underlies retinal degeneration in Drosophila trp mutants
Summary The prototypical transient receptor potential (TRP) channel is the major light-sensitive, and Ca2+-permeable channel in the microvillar photoreceptors of Drosophila. TRP channels are activated following hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by the key effector enzyme phospholipase C (PLC). Mutants lacking TRP channels undergo light-dependent retinal degeneration, as a consequence of the reduced Ca2+ influx. It has been proposed that degeneration is caused by defects in the Ca2+-dependent visual pigment cycle, which result in accumulation of toxic phosphorylated metarhodopsinľarrestin complexes (MPPľArr2). Here we show that two interventions, which prevent accumulation of MPPľArr2, namely rearing under red light or eliminating the C-terminal rhodopsin phosphorylation sites, failed to rescue degeneration in trp mutants. Instead, degeneration in trp mutants reared under red light was rescued by mutation of PLC. Degeneration correlated closely with the light-induced depletion of PtdIns(4,5)P2 that occurs in trp mutants due to failure of Ca2+-dependent inhibition of PLC. Severe retinal degeneration was also induced in the dark in otherwise wild-type flies by overexpression of a bacterial PtdInsPn phosphatase (SigD) to deplete PtdIns(4,5)P2. In degenerating trp photoreceptors, phosphorylated Moesin, a PtdIns(4,5)P2-regulated membraneľcytoskeleton linker essential for normal microvillar morphology, was found to delocalize from the rhabdomere and there was extensive microvillar actin depolymerisation. The results suggest that compromised light-induced Ca2+ influx, due to loss of TRP channels, leads to PtdIns(4,5)P2 depletion, resulting in dephosphorylation of Moesin, actin depolymerisation and disintegration of photoreceptor structure.
Sengupta, Sukanya; Barber, Thomas R.; Xia, Hongai; Ready, Donald F.; Hardie, Roger C.
Transplantation of iris pigment epithelium into the choroid slows down the degeneration of photoreceptors in the RCS rat
Background:Trophic factors [e.g. basic fibroblast growth factor (bFGF)] released by transplanted retinal pigment epithelial (RPE) cells\\u000a are able to slow down the hereditary degeneration of the retina in the Royal College of Surgeons rat in sites distant from\\u000a the site of transplantation where rod outer segment (ROS) phagocytic activity is not reconstituted by the transplants. Methods:To investigate whether iris pigmented
Ulrich Schraermeyer; Peter Kayatz; Gabriele Thumann; Thomas T. Luther; Peter Szurman; Norbert Kociok; Karl U. Bartz-Schmidt
Occupational driving and lumbar disc degeneration: a case- control study
Summary Background Back problems are reported more by occupational drivers than by any other occupational group. One explanation is that whole-body vibration caused by the vehicle leads to accelerated disc degeneration, herniation, and associated symptoms. We aimed to investigate the effects of lifetime driving exposure on lumbar disc degeneration in monozygotic twins with very different histories of occupational driving during
Michele C BattiÚ; Tapio Videman; Laura E Gibbons; Hannu Manninen; Kevin Gill; Malcolm Pope; Jaakko Kaprio
Phase shift behavior at degenerate continuum bound states
A special case of a nonlocal potential which has a degenerate continuum bound state is studied using the Bolsterli criterion for defining the phase shift, and is found to be consistent with Levinson's theorem and the Wigner inequality. NUCLEAR REACTIONS Phase shift behavior for nonlocal potentials, degenerate continuum bound states, Levinson's theorem.
L. L. Foldy
Degenerate matrix method for solving nonlinear systems of differential equations
Degenerate matrix method for numerical solving nonlinear systems of ordinary differential equations is considered. The method is based on an application of special degenerate matrix and usual iteration procedure. The method, which is connected with an implicit Runge?Kutta method, can be simply realized on computers. An estimation for the error of the method is given.
T. Cţrulis; O. Lietuvietis
Senile disciform macular degeneration in the second eye
Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk
Z Gregor; A C Bird; I H Chisholm
Age-Related Macular Degeneration: Etiology, Pathogenesis, and Therapeutic Strategies
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
Weibel instabilities in a completely degenerate electron Fermi gas
NASA Astrophysics Data System (ADS)
Weibel instability in a degenerate Fermi plasma is studied. A new type of quantum Weibel instabilities is disclosed. In particular, a novel oscillatory Weibel instability is found and its growth rate is obtained. A transverse zero sound in a quantum degenerate electron gas, which has no counterpart in the classical consideration, is revealed.
Tsintsadze, Levan N.
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait
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 Ś which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration Ś 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
Tumor-specific killer cells in paraneoplastic cerebellar degeneration
Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood. Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mechanisms underlying tumor immunity to breast and ovarian cancer. Although tumor immunity and autoimmune neuronal degeneration in PCD correlates with a
Matthew L. Albert; Jennifer C. Darnell; Armin Bender; Loise M. Francisco; Nina Bhardwaj; Robert B. Darnell
DPPrimer - A Degenerate PCR Primer Design Tool
Designed degenerate primers unlike conventional primers are superior in matching and amplification of large number of genes, from related gene families. DPPrimer tool was designed to predict primers for PCR amplification of homologous gene from related or diverse plant species. The key features of this tool include platform independence and user friendliness in primer design. Embedded features such as search for functional domains, similarity score selection and phylogebetic tree further enhance the user friendliness of DPPrimer tool. Performance of DPPrimer tool was evaluated by successful PCR amplification of ADP-glucose phosphorylase genes from wheat, barley and rice. Availability DPPrimer is freely accessible at http://18.104.22.168/DGEN_tool/index.html
Gahoi, Shachi; Arya, L; Anil, Rai; Marla, ss
Paraneoplastic cerebellar degeneration in Hodgkin's lymphoma.
Paraneoplastic cerebellar degeneration (PCD) is a rare disorder presenting typically with acute or subacute severe cerebellar ataxia. PCD is most commonly associated with small cell lung cancer followed by adenocarcinoma of breast and ovary, and Hogdkin's lymphoma. We report a case of a 54-year-old male with acute-onset pancerebellar syndrome with underlying Hodgkin's lymphoma. A high index of suspicion of PCD resulted in arriving at an early diagnosis of underlying Hodgkin's disease. The patient was managed with six cycles of chemotherapy, which resulted in clinical stabilization and reversal of magnetic resonance imaging abnormalities. Antitumor therapy appears to have a significant impact on reversing PCD and hence early diagnosis and intervention for the primary remains the corner stone in stabilizing the neurological condition. PMID:22919195
Suri, Vinit; Khan, Nadeem I; Jadhao, Nilesh; Gupta, Rohan
Anterior insula degeneration in frontotemporal dementia
The human anterior insula is anatomically and functionally heterogeneous, containing key nodes within distributed speechľlanguage and viscero-autonomic/socialľemotional 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 ôSalience Networkö 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.
Prevention of age-related macular degeneration
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.
Koo, Simon Chi Yan; Chan, Clement Wai Nang
Prevention of age-related macular degeneration.
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
Transurethral resection and degeneration of bladder tumour
Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ?3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ▒ 23.74 months in TURD-Bt group and 56.28 ▒ 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder.
Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui
The effect of kyphoscoliosis on intervertebral disc degeneration in dogs.
In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann's grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P?0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P?0.0001). Conversely, in older dogs, all IVDs - including the non-adjacents - showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. PMID:24745767
Faller, Kiterie; Penderis, Jacques; Stalin, Catherine; Guevar, Julien; Yeamans, Carmen; Gutierrez-Quintana, Rodrigo
Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of Inherited Retinal Degeneration
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
Gavin W Roddy; Robert H Rosa Jr; Joo Youn Oh; Joni H Ylostalo; Thomas J Bartosh; Hosoon Choi; Ryang Hwa Lee; Douglas Yasumura; Kelly Ahern; Gregory Nielsen; Michael T Matthes; Matthew M LaVail; Darwin J Prockop
Variability in rate of cone degeneration in the retinal degeneration (rd/rd) mouse.
The retinas of rd/rd mice with inherited retinal degeneration were examined histologically at postnatal days 60-66, an age when most rod cells already have degenerated and disappeared but when a significant number of cones are still present. We observed an unexpected hemispheric asymmetry and large variability in the number of surviving cones. Significantly more cones survived in the inferior than in the superior hemisphere in most retinas, although in about 15% of animals the hemispheric asymmetry was absent or was reversed. The number of surviving cones was highly variable from animal to animal, ranging from 3-30, a factor of 10, within the superior hemisphere, and from 7-51, a factor greater than 7, in the inferior hemisphere. If the specific hemisphere was ignored, the number ranged from 3-51, a factor of 17. These findings have significance for the examination of cone survival in the late stages of degeneration in this widely studied mutant, including therapeutic studies using transplantation, gene therapy or survival factors, as well as for the identification of surviving cells using cone-specific markers. PMID:9237863
LaVail, M M; Matthes, M T; Yasumura, D; Steinberg, R H
Disc degeneration after disc herniation: are we accelerating the process?
Study design: ?Systematic review. Study rationale: ?Disc degeneration is a common process starting early in life. Often disc herniation is an early step in disc degeneration, which may cause pain or stenosis. How quickly this subsequent disc degeneration occurs following a disc herniation and subsequent surgical treatment and whether certain spinal procedures increase the rate of degeneration remain unclear. Objectives: ?To investigate the risk of subsequent radiographic disc degeneration following discectomy, discography, and conservative care in patients with a first-time diagnosed herniated nucleus pulpous (HNP) and to ascertain whether this risk in these defined groups changes over time. Methods: ?A systematic review of pertinent articles published up to June 2012. Key articles were searched to identify studies evaluating the risk of subsequent radiographic disc degeneration following treatment for HNP. Studies that included patients undergoing secondary surgery for disc herniation or that did not use a validated classification system to measure the severity of disc degeneration were excluded. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results: ?From a total of 147 possible citations, three cohort studies (class of evidence III) met our inclusion criteria and form the basis for this report. The risk of subsequent lumbar disc degeneration following standard discectomy was significantly greater compared with both microdiscectomy (48.7% vs 9.1%) and asymptomatic controls (90% vs 68%) in two studies with mean follow-ups of 5.5 and 25.3 years, respectively. Following conservative care for first-time HNP in the third study, the risk of progression of lumbar disc degeneration was 47.6% over the first 2 years of follow-up and 95.2% over the next 6 years of follow-up. In the same study, the risk of lumbar disc degeneration was shown to increase incrementally over the course of the 8-year follow-up, with all patients showing signs of degeneration at final examination. Conclusion: ?Standard discectomy in first-time lumbar HNP may increase the risk of subsequent same-level lumbar disc degeneration compared with microdiscectomy as seen in one low-quality study. However, disc degeneration is likely a natural, temporal consequence following HNP, as demonstrated in a second low-quality study. The overall strength of evidence for the conclusions is very low. PMID:23526910
Schroeder, Josh E; Dettori, Joseph R; Brodt, Erika D; Kaplan, Leon
Disc degeneration after disc herniation: are we accelerating the process?
Study design:?Systematic review. Study rationale:?Disc degeneration is a common process starting early in life. Often disc herniation is an early step in disc degeneration, which may cause pain or stenosis. How quickly this subsequent disc degeneration occurs following a disc herniation and subsequent surgical treatment and whether certain spinal procedures increase the rate of degeneration remain unclear. Objectives:?To investigate the risk of subsequent radiographic disc degeneration following discectomy, discography, and conservative care in patients with a first-time diagnosed herniated nucleus pulpous (HNP) and to ascertain whether this risk in these defined groups changes over time. Methods:?A systematic review of pertinent articles published up to June 2012. Key articles were searched to identify studies evaluating the risk of subsequent radiographic disc degeneration following treatment for HNP. Studies that included patients undergoing secondary surgery for disc herniation or that did not use a validated classification system to measure the severity of disc degeneration were excluded. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results:?From a total of 147 possible citations, three cohort studies (class of evidence III) met our inclusion criteria and form the basis for this report. The risk of subsequent lumbar disc degeneration following standard discectomy was significantly greater compared with both microdiscectomy (48.7% vs 9.1%) and asymptomatic controls (90% vs 68%) in two studies with mean follow-ups of 5.5 and 25.3 years, respectively. Following conservative care for first-time HNP in the third study, the risk of progression of lumbar disc degeneration was 47.6% over the first 2 years of follow-up and 95.2% over the next 6 years of follow-up. In the same study, the risk of lumbar disc degeneration was shown to increase incrementally over the course of the 8-year follow-up, with all patients showing signs of degeneration at final examination. Conclusion:?Standard discectomy in first-time lumbar HNP may increase the risk of subsequent same-level lumbar disc degeneration compared with microdiscectomy as seen in one low-quality study. However, disc degeneration is likely a natural, temporal consequence following HNP, as demonstrated in a second low-quality study. The overall strength of evidence for the conclusions is very low.
Schroeder, Josh E.; Dettori, Joseph R.; Brodt, Erika D.; Kaplan, Leon
Potential regenerative treatment strategies for intervertebral disc degeneration in dogs.
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 3-7áyears of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6-8áyears 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
Bach, Frances C; Willems, Nicole; Penning, Louis C; Ito, Keita; Meij, Bj÷rn P; Tryfonidou, Marianna A
Intrinsic axonal degeneration pathways are critical for glaucomatous damage.
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
Establishment of monocular-limited photoreceptor degeneration models in rabbits
Background Numerous rodent models of photoreceptor degeneration have been developed for the study of visual function. However, no viable model has been established in a species that is more closely related to Homo sapiens. Here, we present a rabbit model of monocular photoreceptor degeneration. Methods We tested 2 chemicals, verteporfin and sodium nitroprusside (SNP), for developing a 1-eye limited photoreceptor degeneration model in pigmented rabbits. After the intravenous injection of verteporfin, the retina was exposed to light from a halogen lamp for 0, 10, 30, or 60 min. Alternately, 100 ?L of various concentrations of sodium nitroprusside (0.1 mM, 0.5 mM, and 1 mM) were intravitreously injected into the rabbit eye. Retinal degeneration was evaluated by fundus photography, electroretinogram (ERG), and histological examinations. Results Fundus photographs of animals in the verteporfin- or SNP-treated groups showed evidence of retinal degeneration. The severity of this degradation depended on the duration of light exposure and the concentration of SNP administered. The degeneration was clearly limited to the light-exposed areas in the verteporfin-treated groups. Extensive retinal atrophy was observed in the SNP-treated groups. The a- and b-wave amplitudes were dramatically decreased on the ERGs from SNP-treated groups. Histological examination revealed that either verteporfin or SNP induced severe photoreceptor degeneration. High-dose SNP treatment (1 mM) was also associated with inner retinal layer degeneration. Conclusions Both SNP and verteporfin clearly caused photoreceptor degeneration without any effect on the contralateral eye. These compounds therefore represent valuable tools for the empirical investigation of visual function recovery. The findings will inform guidelines for clinical applications such as retinal prostheses, cell-based therapy, and gene therapy.
Phosphorylated TDP-43 in frontotemporal lobar degeneration and ALS
Objective TDP-43 is deposited as cytoplasmic and intranuclear inclusions in brains of subjects with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Previous studies reported that abnormal phosphorylation takes place in deposited TDP-43. The aim of this study was to identify the phosphorylation sites and responsible kinases, and to clarify the pathological significance of phosphorylation of TDP-43. Methods We generated multiple antibodies specific to phosphorylated TDP-43 by immunizing phosphopeptides of TDP-43, and analyzed FTLD-U and ALS brains by immunohistochemistry, immunoelectron microscopy and immunoblots. Additionally, we performed investigations aimed at identifying the responsible kinases and we assessed the effects of phosphorylation on TDP-43 oligomerization and fibrillization. Results We identified multiple phosphorylation sites in carboxyl-terminal regions of deposited TDP-43. Phosphorylation-specific antibodies stained more inclusions than antibodies to ubiquitin and, unlike existing commercially-available anti-TDP-43 antibodies, did not stain normal nuclei. Ultrastructurally, these antibodies labeled abnormal fibers of 15 nm diameter, and on immunoblots recognized hyperphosphorylated TDP-43 at 45 kDa, with additional 22ľ28 kDa fragments in sarkosyl-insoluble fractions from FTLD-U and ALS brains. The phosphorylated epitopes were generated by casein kinase 1 and 2, and phosphorylation led to increased oligomerization and fibrillization of TDP-43. Interpretation These results suggest that phosphorylated TDP-43 is a major component of the inclusions, and that abnormal phosphorylation of TDP-43 is a critical step in the pathogenesis of FTLD-U and ALS. Phosphorylation-specific antibodies will be powerful tools for the investigation of these disorders.
Hasegawa, Masato; Arai, Tetsuaki; Nonaka, Takashi; Kametani, Fuyuki; Yoshida, Mari; Hashizume, Yoshio; Beach, Thomas G.; Buratti, Emanuele; Baralle, Francisco; Morita, Mitsuya; Nakano, Imaharu; Oda, Tatsuro; Tsuchiya, Kuniaki; Akiyama, Haruhiko
Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons (MNs) that causes skeletal muscle paralysis. Familial forms of ALS are linked to mutations in the superoxide dismutase-1 (SOD1) gene. The mechanisms of human SOD1 (hSOD1) toxicity to MNs are unknown. We hypothesized that skeletal muscle is a primary site of pathogenesis in ALS that triggers MN degeneration. We created transgenic (tg) mice expressing wild-type-, G37R- and G93A-hSOD1 gene variants only in skeletal muscle. These tg mice developed age-related neurologic and pathologic phenotypes consistent with ALS. Affected mice showed limb weakness and paresis with motor deficits. Skeletal muscles developed severe pathology involving oxidative damage, protein nitration, myofiber cell death and marked neuromuscular junction (NMJ) abnormalities. Spinal MNs developed distal axonopathy and formed ubiquitinated inclusions and degenerated through an apoptotic-like pathway involving capsase-3. Mice expressing wild-type and mutant forms of hSOD1 developed MN pathology. These results demonstrate that human SOD1 in skeletal muscle has a causal role in ALS and identify a new non-autonomous mechanism for MN degeneration explaining their selective vulnerability. The discovery of instigating molecular toxicities or disease progression determinants within skeletal muscle could be very valuable for the development of new effective therapies for the treatment and cure of ALS.
Wong, Margaret; Martin, Lee J.
Age-related macular degeneration: choroidal ischaemia?
Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20?MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892▒0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784.
Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul
Nuclear pore complex during neuronal degeneration
In eukaryotic cells, the exchange of molecules between the genetic material within the nucleus and the cytosol occurs through the Nuclear Pore Complex (NPC), which is a large membrane-embedded assembly composed by multiple proteins named nucleoporins arranged around an aqueous channel. The bi-directional passive diffusion and the active transport of factors across the nuclear envelope are responsible for a variety of biological processes and they are controlled respectively by the size of the pore and the interaction between nucleoporins and karyopherins. Thus, it is not surprising that most of the degenerative programs induce cellular stress by altering the NPC composition or the binding between nucleoporins and docking factors. This facilitates the access of nuclear DNA to pro-death factors, amplify the detrimental cascade and finally play a role in the disassembly of the nuclear structure. Recently, we have shown that during calcium-mediated neuronal degeneration NPC components can be degraded with consequent increase of NPC channel permeability. Moreover, we proved that these changes occurred much earlier than the final disassembly of the nuclear envelope and they are mediated by calcium overload. Is the increase of NPC leakiness the executioner of the excitotoxic process or simply a final event of a cell condemned to death? Here we speculate the consequence of the nucleoporin loss, the alteration of nucleocytoplasmic transport and their contribution to neuronal demise.
Hengartner, Michael O
Degenerate interfaces in antigen-antibody complexes.
In most of the work dealing with the analysis of protein-protein interfaces, a single X-ray structure is available or selected, and implicitly it is assumed that this structure corresponds to the optimal complex for this pair of proteins. However, we have found a degenerate interface in a high-affinity antibody-antigen complex: the two independent complexes of the camel variable domain antibody fragment cAb-Lys3 and its antigen hen egg white lysozyme present in the asymmetric unit of our crystals show a difference in relative orientation between antibody and antigen, leading to important differences at the protein-protein interface. A third cAb-Lys3-hen lysozyme complex in a different crystal form adopts yet another relative orientation. Our results show that protein-protein interface characteristics can vary significantly between different specimens of the same high-affinity antibody-protein antigen complex. Consideration should be given to this type of observation when trying to establish general protein-protein interface characteristics. PMID:11676532
Decanniere, K; Transue, T R; Desmyter, A; Maes, D; Muyldermans, S; Wyns, L
Pellucid corneal marginal degeneration: A review.
Pellucid marginal corneal degeneration (PMD) is a rare ectatic disorder which typically affects the inferior peripheral cornea in a crescentic fashion. The condition is most commonly found in males and usually appears between the 2nd and 5th decades of life affecting all ethnicities. The prevalence and aetiology of this disorder remain unknown. Ocular signs and symptoms of patients with PMD differ depending on the severity of the condition. Unless corneal topography is evaluated, early forms of PMD may often be undetected however, in the later stages PMD can often be misdiagnosed as keratoconus. Visual signs and symptoms include longstanding reduced visual acuity or increasing against-the-rule irregular astigmatism leading to a slow reduction in visual acuity. In rare cases, patients may present with a sudden loss of vision and excruciating ocular pain due to corneal hydrops or spontaneous perforation. The vast majority of PMD patients are managed using spectacles and contact lenses. Several surgical procedures have been used in an attempt to improve visual acuity when spectacles and contact lenses do not provide adequate vision correction. Since patients with PMD make poor candidates for laser vision correction, an awareness of the topographical and slit-lamp features of PMD will be useful to clinicians screening for signs of corneal abnormality before corneal refractive surgery. This review describes the clinical features of PMD, its differential diagnosis and various management strategies presently available. PMID:21185225
Jinabhai, Amit; Radhakrishnan, Hema; O'Donnell, Clare
Degenerating Synaptic Boutons in Prion Disease
A growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the hippocampus underpins the first behavioral changes and that there is a selective loss of presynaptic elements. The microglia have an activated morphology at this stage but they have an anti-inflammatory phenotype. We reasoned that the microglia might be involved in synaptic stripping, removing synapses undergoing a degenerative process, and that this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density revealed a progressive loss from 12 weeks post disease initiation. The loss of synapses was not associated with microglia processes; instead, we found that the postsynaptic density of the dendritic spine was progressively wrapped around the degenerating presynaptic element with loss of subcellular components. Three-dimensional reconstructions of these structures from Dual Beam electron microscopy support the conclusion that the synaptic loss in prion disease is a neuron autonomous event facilitated without direct involvement of glial cells. Previous studies described synapse engulfment by developing and injured neurons, and we suggest that this mechanism may contribute to developmental and pathological changes in synapse numbers.
Siskova, Zuzana; Page, Anton; O'Connor, Vincent; Perry, Victor Hugh
Quantitative peptidomics of Purkinje cell degeneration mice.
Cytosolic carboxypeptidase 1 (CCP1) is a metallopeptidase that removes C-terminal and side-chain glutamates from tubulin. The Purkinje cell degeneration (pcd) mouse lacks CCP1 due to a mutation. Previously, elevated levels of peptides derived from cytosolic and mitochondrial proteins were found in adult pcd mouse brain, raising the possibility that CCP1 functions in the degradation of intracellular peptides. To test this hypothesis, we used a quantitative peptidomics technique to compare peptide levels in wild-type and pcd mice, examining adult heart, spleen, and brain, and presymptomatic 3 week-old amygdala and cerebellum. Contrary to adult mouse brain, young pcd brain and adult heart and spleen did not show a large increase in levels of intracellular peptides. Unexpectedly, levels of peptides derived from secretory pathway proteins were altered in adult pcd mouse brain. The pattern of changes for the intracellular and secretory pathway peptides in pcd mice was generally similar to the pattern observed in mice lacking primary cilia. Collectively, these results suggest that intracellular peptide accumulation in adult pcd mouse brain is a secondary effect and is not due to a role of CCP1 in peptide turnover. PMID:23593366
Berezniuk, Iryna; Sironi, Juan J; Wardman, Jonathan; Pasek, Raymond C; Berbari, Nicolas F; Yoder, Bradley K; Fricker, Lloyd D
Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLDS-mediated axon protection independent of axonal mitochondria
Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest a central role for axonal mitochondria in both degeneration and NMNAT/WLDS (Wallerian degeneration slow)-mediated protection. We used dorsal root ganglia (DRG) explants and Drosophila larval motor neurons (MNs) as models to address the role of mitochondria in Wallerian degeneration (WD). We find that expression of Drosophila NMNAT delays WD in human DRG neurons demonstrating evolutionary conservation of NMNAT function. Morphological comparison of mitochondria from WLDS-protected axons demonstrates that mitochondria shrink post-axotomy, though analysis of complex IV activity suggests that they retain their functional capacity despite this morphological change. To determine whether mitochondria are a critical site of regulation for WD, we genetically ablated mitochondria from Drosophila MN axons via the mitochondria trafficking protein milton. Milton loss-of-function did not induce axon degeneration in Drosophila larval MNs, and when axotomized WD proceeded stereotypically in milton distal axons although with a mild, but significant delay. Remarkably, the protective effects of NMNAT/WLDS were also maintained in axons devoid of mitochondria. These experiments unveil an axon self-destruction cascade governing WD that is not initiated by axonal mitochondria and for the first time illuminate a mitochondria-independent mechanism(s) regulating WD and NMNAT/WLDS-mediated axon protection.
Kitay, Brandon M.; McCormack, Ryan; Wang, Yunfang; Tsoulfas, Pantelis; Zhai, R. Grace
Relationship of Facet Tropism with Degeneration and Stability of Functional Spinal Unit
Purpose The authors investigated the effect of lumbar facet tropism (FT) on intervertebral disc degeneration (DD), facet joint degeneration (FJD), and segmental translational motion. Materials and Methods Using kinetic MRI (KMRI), lumbar FT, which was defined as a difference in symmetry of more than 7░ between the orientations of the facet joints, was investigated in 900 functional spinal units (300 subjects) in flexion, neutral, and extension postures. Each segment at L3-L4, L4-L5, and L5-S1 was assessed based on the extent of DD (grade I-V) and FJD (grade 1-4). According to the presence of FT, they were classified into two groups; one with FT and one with facet symmetry. For each group, demographics, DD, FJD and translational segmental motion were compared. Results The incidence of FT was 34.5% at L3-L4, 35.1% at L4-L5, and 35.2% at L5-S1. Age and gender did not show any significant relationship with FT. Additionally, no correlation was observed between DD and FT. FT, however, wasfound to be associated with a higher incidence of highly degenerated facet joints at L4-L5 when compared to patients without FT (p < 0.01). Finally, FT was not observed to have any effects upon translational segmental motion. Conclusion No significant correlation was observed between lumbar FT and DD or translational segmental motion. However, FT was shown to be associated significantly with the presence of high grades of FJD at L4-L5. This suggests that at active sites of segmental motion, FT may predispose to the development of facet joint degeneration.
He, Wubing; Tsai, Yu-Duan; Chen, Nan-Fu; Keorochana, Gun; Do, Duc H.; Wang, Jeffrey C.
[Atypical presentation of pellucid marginal degeneration: case report].
The authors report an unusual clinical presentation of pellucid marginal degeneration with 360 masculine peripheral corneal thinning diagnosed in a younger male patient. We discuss the findings of topographic maps, ultrasound pachymetry and the proposed treatment. PMID:17344988
Santos, Frederico Xavier dos; Mocelin, Sheila; Machado, Renato; Santos, Fernando Henrique Xavier dos; Sousa, Luciene Barbosa de
Bipolar disorder associated with paraneoplastic cerebellar degeneration: a case report.
We Present a case report of a patient who suffers from Paraneoplastic cerebellar degeneration (PCD) secondary to which the patient, a young woman, developed Bipolar Affective Disorder. Here we focus on the mental health aspects of this case. PMID:21057423
Slattery, Catherine; Agius, Mark; Zaman, Rashid
On Fibrinous or Hyaline Degeneration in the Tubercle and Gumma.
National Technical Information Service (NTIS)
Hyaline or fibrinous degeneration is rather frequently found in tubercles; it may occur in tubercles of all organs, but prefers certain organs (spleen, lymph glands, liver), therefore both organs afflicted by cavity formation and those not affected by ulc...
M. Vallat
Hepatic Zonal Degeneration and Necrosis in Reye Syndrome.
National Technical Information Service (NTIS)
Seven pediatric cases with hepatic peripheral zonal degeneration or necrosis in the liver, or both, were studied. From the standpoint of clinicopathological features, these cases fit best into the spectrum of Reye syndrome. Exogenous toxins, such as phosp...
R. E. Brown K. G. Ishak
[Modifiable risk factors for age-related macular degeneration].
The authors present the main modifiable risk factors that may trigger and/or worsen age-related macular degeneration. Mechanisms of action related to these factors as well as preventive measures and intervention effectiveness are discussed. PMID:19668979
Torres, Rogil JosÚ de Almeida; Maia, MaurÝcio; Muccioli, Cristina; Winter, Guilherme; Souza, Greyce Kelly de; Pasqualotto, Luca Rodrigo; Luchini, AndrÚa; PrÚcoma, Dalton Bertolim
Double degenerates from the supernova Ia progenitor survey (SPY)
We report on follow-up observations of double degenerate (DD) white dwarfs\\u000afrom the Supernovae Ia Progenitor Survey (SPY). Orbital parameters of four\\u000asystems, including a massive short period system, are presented.
C. Karl; R. Napiwotzki; U. Heber; T. Lisker; G. Nelemans; N. Christlieb; D. Reimers
Two new types of retinal degeneration in cerebellar mutant mice
HUMAN retinitis pigmentosa represents a class of diseases, the principal characteristic of which is the slow and progressive degeneration of photoreceptor cells. In several human neurological syndromes, photoreceptor degeneration accompanies cerebellar ataxia, deafness, mental retardation or other abnormalities. Some examples of such syndromes are BattenSpielmeyer-Vogt disease, Refsum's disease, Laurence-Moon Biedl syndrome, Bassen-Kornzweig disease, Usher's syndrome and several of the mucopolysaccharidoses1-4.
Richard J. Mullen; Matthew M. Lavail
Risk Factors for Age-related Macular Degeneration
There is an increasing body of evidence as to the risk factors for age-related macular degeneration. Age and genetic make-up are the most important risk factors identified to date. Over the next decade, the different genes that are involved in the development of age-related macular degeneration will be identified. There is reasonably consistent evidence that smoking cigarettes results in increased
Jennifer R. Evans
Rosette-forming glioneuronal tumor of the fourth ventricle with bilateral olivary degeneration.
Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been recognized as a new type of glioneuronal tumor. RGNTs are typically located in the infratentorial midline with involvement of the fourth ventricle. They occasionally involve the aqueduct and/or vermis. RGNTs of unusual anatomical sites or those with unusual findings have been reported. The present case reports describe RGNT of the fourth ventricle with bilateral olivary degeneration. It is important to accumulate imaging findings and biological behaviors of RGNTs given the limited number of cases. PMID:21786101
Fushimi, Yasutaka; Miyasaki, Akihiro; Taki, Hideaki; Aoyama, Kunihiro; Hirato, Junko; Kanagaki, Mitsunori; Togashi, Kaori
Cartilage intermediate layer protein promotes lumbar disc degeneration.
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
N -methyl- N -nitrosourea-induced retinal degeneration in mice.
Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). PMID:24509257
Chen, Yuan-Yuan; Liu, Shi-Liang; Hu, Dan-Ping; Xing, Yi-Qiao; Shen, Yin
Axons degenerate in the absence of mitochondria in C. elegans.
Many neurodegenerative disorders are associated with mitochondrial defects [1-3]. Mitochondria can play an active role in degeneration by releasing reactive oxygen species and apoptotic factors [4-7]. Alternatively, mitochondria can protect axons from stress and insults, for example by buffering calcium [8]. Recent studies manipulating mitochondria lend support to both of these models [9-13]. Here, we identify a C. elegans mutant, ric-7, in which mitochondria are unable to exit the neuron cell bodies, similar to the kinesin-1/unc-116 mutant. When axons lacking mitochondria are cut with a laser, they rapidly degenerate. Some neurons even spontaneously degenerate in ric-7 mutants. Degeneration can be suppressed by forcing mitochondria into the axons of the mutants. The protective effect of mitochondria is also observed in the wild-type: a majority of axon fragments containing a mitochondrion survive axotomy, whereas those lacking mitochondria degenerate. Thus, mitochondria are not required for axon degeneration and serve a protective role in C. elegans axons. PMID:24631238
Rawson, Randi L; Yam, Lung; Weimer, Robby M; Bend, Eric G; Hartwieg, Erika; Horvitz, H Robert; Clark, Scott G; Jorgensen, Erik M
Spatially coordinated kinase signaling regulates local axon degeneration.
In addition to being a hallmark of neurodegenerative disease, axon degeneration is used during development of the nervous system to prune unwanted connections. In development, axon degeneration is tightly regulated both temporally and spatially. Here, we provide evidence that degeneration cues are transduced through various kinase pathways functioning in spatially distinct compartments to regulate axon degeneration. Intriguingly, glycogen synthase kinase-3 (GSK3) acts centrally, likely modulating gene expression in the cell body to regulate distally restricted axon degeneration. Through a combination of genetic and pharmacological manipulations, including the generation of an analog-sensitive kinase allele mutant mouse for GSK3?, we show that the ? isoform of GSK3, not the ? isoform, is essential for developmental axon pruning in vitro and in vivo. Additionally, we identify the dleu2/mir15a/16-1 cluster, previously characterized as a regulator of B-cell proliferation, and the transcription factor tbx6, as likely downstream effectors of GSK3? in axon degeneration. PMID:23015435
Chen, Mark; Maloney, Janice A; Kallop, Dara Y; Atwal, Jasvinder K; Tam, Stephen J; Baer, Kristin; Kissel, Holger; Kaminker, Joshua S; Lewcock, Joseph W; Weimer, Robby M; Watts, Ryan J
Differential charge-transfer cross sections for systems with energetically degenerate or near-degenerate channels
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)
Distinct optical properties of relativistically degenerate matter
NASA Astrophysics Data System (ADS)
In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.
Akbari-Moghanjoughi, M.
Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration
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 mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness.
Karan, G.; Lillo, C.; Yang, Z.; Cameron, D. J.; Locke, K. G.; Zhao, Y.; Thirumalaichary, S.; Li, C.; Birch, D. G.; Vollmer-Snarr, H. R.; Williams, D. S.; Zhang, K.
Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration
Ě 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.?Ě Patients and methods: In 30 eyes the macula was rotated upward by 30ľ50░ following complete\\u000a artificial retinal detachment and a 360░ retinotomy.
Claus Eckardt; Ute Eckardt; Hans-Georg Conrad
Proximal femoral degeneration in growing broiler fowl.
The pathologies in proximal femora of broilers with lameness attributed to disorders of the proximal femur, including so-called 'femoral head necrosis', are described. Samples were collected from a variety of flocks, farms and production systems. Ten 'normal' broilers were also examined. Birds were identified by a characteristic lameness whereby they used a wing for support during locomotion and hip flexion (i.e. whilst sitting down). The appearance of the proximal femora at post mortem was used to place 67 proximal femora in three categories: (a) gross disintegration of the epiphysis, physis and/or metaphysis (43 samples); (b) epiphysiolysis-separation of the cartilaginous epiphysis from the underlying femoral metaphysis (growth plate) (17 samples) and (c) apparently normal (seven samples). Samples from each category were collected for mycoplasmology, virology and bacteriology. All the samples were negative for Mycoplasma, and there was no correlation between pathology and the presence or absence of viruses, but bacteria were cultured from about half the proximal femora and most of these femora showed histological evidence of bacterial infection. Although bacterial culture was negative, evidence of bacterial infections was seen in tissue sections from a further 15 proximal femora. Serial sections were required to find the foci on bacterial lesions. 'Femoral head necrosis' was not considered appropriate to describe the pathologies seen and the term proximal femoral degeneration (PFD) was adopted. Histological examination showed that PFD was most frequently due to a bacterial chondritis and osteomyelitis, with frequent involvement of surrounding tissues. Non-lame controls all had non-bacterial pathologies in the proximal femur which were also seen in many of the lame birds and may have provided a foci for the establishment of bacterial infections. The non-bacterial pathologies when severe were considered the cause of non-infectious PFD which would cause lameness in some cases. Epiphysiolysis was either a post or peri-mortem artefact, traumatic in origin, or could be attributed to underlying growth plate (physeal) pathology which in some cases was due to bacterial infection. PMID:18671021
Thorp, B H; Whitehead, C C; Dick, L; Bradbury, J M; Jones, R C; Wood, A
Theoretical and Uniaxial Experimental Evaluation of Human Annulus Fibrosus Degeneration
Background The highly organized structure and composition of the annulus fibrosus provides the tissue with mechanical behaviors that include anisotropy and nonlinearity. Mathematical models are necessary to interpret and elucidate the meaning of directly measured mechanical properties, to understand the structure-function relationships of the tissue components, namely the fibers and extrafibrillar matrix. This study models the annulus fibrosus as a combination of strain energy functions describing the fibers, matrix, and their interactions. The objective was to quantify the behavior of both nondegenerate and degenerate annulus fibrosus tissue using uniaxial tensile experimental data. Method of Approach Mechanical testing was performed with samples oriented along the circumferential, axial, and radial directions. Results For samples oriented along the radial direction, the toe-region modulus was 2.7X stiffer with degeneration. However, no other differences in measured mechanical properties were observed with degeneration. The constitutive model fit well to samples oriented along the radial and circumferential directions (R2 ? 0.97). The fibers supported the highest proportion of stress for circumferential loading at 60%. There was a 70% decrease in the matrix contribution to stress from the toe- to the linear-region of both nondegenerate and degenerate tissue. The shear fiber-matrix interaction contribution increased 125% with degeneration in the linear-region. Samples oriented along the radial and axial direction behaved similarly under uniaxial tension (modulus = 0.32MPa versus 0.37MPa), suggesting that uniaxial testing in the axial direction is not appropriate for quantifying the mechanics of a fiber reinforcement in the annulus. Conclusions In conclusion, the structurally motivated nonlinear, anisotropic hyperelastic constitutive model help to further understand the effect of microstructural changes with degeneration, suggesting that a remodeling in the subcomponents (i.e. the collagen fibers and FMI) may minimize the overall change in tissue mechanics with degeneration.
O'Connell, Grace D.; Guerin, Heather L.; Elliott, Dawn M.
Endothelin-2-Mediated Protection of Mutant Photoreceptors in Inherited Photoreceptor Degeneration
Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration (IPD). To examine the role of Edn2 in mutant PR survival, we generated Edn2?/? mice carrying homozygous Pde6brd1 alleles or the Tg(RHO P347S) transgene. In the Edn2?/? background, PR survival increased 110% in Pde6brd1/rd1 mice at post-natal (PN) day 15, and 60% in Tg(RHO P347S) mice at PN40. In contrast, PR survival was not increased in retinal explants of Pde6brd1/rd1; Edn2?/? mice. This finding, together with systemic abnormalities in Edn2?/? mice, suggested that the increased survival of mutant PRs in the Edn2?/? background resulted at least partly from the systemic EDN2 loss of function. To examine directly the role of EDN2 in mutant PRs, we used a scAAV5-Edn2 cDNA vector to restore Edn2 expression in Pde6brd1/rd1; Edn2?/? PRs and observed an 18% increase in PR survival at PN14. Importantly, PR survival was also increased after injection of scAAV5-Edn2 into Pde6brd1/rd1 retinas, by 31% at PN15. Together, these findings suggest that increased Edn2 expression is protective to mutant PRs. To begin to elucidate Edn2-mediated mechanisms that contribute to PR survival, we used microarray analysis and identified a cohort of 20 genes with >4-fold increased expression in Tg(RHO P347S) retinas, including Fgf2. Notably, increased expression of the FGF2 protein in Tg(RHO P347S) PRs was ablated in Tg(RHO P347S); Edn2?/? retinas. Our findings indicate that the increased expression of PR Edn2 increases PR survival, and suggest that the Edn2-dependent increase in PR expression of FGF2 may contribute to the augmented survival.
Bramall, Alexa N.; Szego, Michael J.; Pacione, Laura R.; Chang, Inik; Diez, Eduardo; D'Orleans-Juste, Pedro; Stewart, Duncan J.; Hauswirth, William W.; Yanagisawa, Masashi; McInnes, Roderick R.
Radiologic Evaluation of Degeneration in Isthmic and Degenerative Spondylolisthesis
Study Design A cross-sectional imaging study. Purpose The objective was to assess the degree of degeneration and the associated factors through imaging studies of the lesion segment and the adjacent superior and inferior segments of isthmic and degenerative spondylolisthesis. Overview of Literature Few articles existed for degeneration and related factors in isthmic and degenerative spondylolisthesis. Methods The subjects were 95 patients diagnosed with spondylolisthesis. Simple plain radiographs including flexion and extension and magnetic resonance imaging were used to investigate the degree of translation, disc degeneration, high intensity zone (HIZ) lesion, Schmorl's node (SN) and Modic changes. Results Advanced disc degeneration, grade 5, was shown to be significant in the index segment of the isthmic type (p=0.034). Overall, type 2 Modic change was most common in both groups and also, it was observed more in the isthmus group, specifically, the index segment compared to the degenerative group (p=0.03). For the SN, compared to the degenerative type, the isthmus type had a significantly high occurrence in the index segment (p=0.04). For the HIZ lesions, the isthmus type had a higher occurrence than the degenerative type, especially in the upper segment (p=0.03). Conclusions Most advanced disc degeneration, fifth degree, SN and Modic change occurred more frequently in the lesions of the isthmus type. HIZ lesions were observed more in the isthmus type, especially in the segment superior to the lesion.
Jeong, Hyun-Yoon; Sohn, Hong-Moon; Park, Sang-Ha
Degeneration and regeneration of the intervertebral disc: lessons from development
Degeneration of the intervertebral discs, a process characterized by a cascade of cellular, biochemical, structural and functional changes, is strongly implicated as a cause of low back pain. Current treatment strategies for disc degeneration typically address the symptoms of low back pain without treating the underlying cause or restoring mechanical function. A more in-depth understanding of disc degeneration, as well as opportunities for therapeutic intervention, can be obtained by considering aspects of intervertebral disc development. Development of the intervertebral disc involves the coalescence of several different cell types through highly orchestrated and complex molecular interactions. The resulting structures must function synergistically in an environment that is subjected to continuous mechanical perturbation throughout the life of an individual. Early postnatal changes, including altered cellularity, vascular regression and altered extracellular matrix composition, might set the disc on a slow course towards symptomatic degeneration. In this Perspective, we review the pathogenesis and treatment of intervertebral disc degeneration in the context of disc development. Within this scope, we examine how model systems have advanced our understanding of embryonic morphogenesis and associated molecular signaling pathways, in addition to the postnatal changes to the cellular, nutritional and mechanical microenvironment. We also discuss the current status of biological therapeutic strategies that promote disc regeneration and repair, and how lessons from development might provide clues for their refinement.
Smith, Lachlan J.; Nerurkar, Nandan L.; Choi, Kyung-Suk; Harfe, Brian D.; Elliott, Dawn M.
Construction of "small-intelligent" focused mutagenesis libraries using well-designed combinatorial degenerate primers.
Site-saturation mutagenesis is a powerful tool for protein optimization due to its efficiency and simplicity. A degenerate codon NNN or NNS (K) is often used to encode the 20 standard amino acids, but this will produce redundant codons and cause uneven distribution of amino acids in the constructed library. Here we present a novel "small-intelligent" strategy to construct mutagenesis libraries that have a minimal gene library size without inherent amino acid biases, stop codons, or rare codons of Escherichia coli by coupling well-designed combinatorial degenerate primers with suitable PCR-based mutagenesis methods. The designed primer mixture contains exactly one codon per amino acid and thus allows the construction of small-intelligent mutagenesis libraries with one gene per protein. In addition, the software tool DC-Analyzer was developed to assist in primer design according to the user-defined randomization scheme for library construction. This small-intelligent strategy was successfully applied to the randomization of halohydrin dehalogenases with one or two randomized sites. With the help of DC-Analyzer, the strategy was proven to be as simple as NNS randomization and could serve as a general tool to efficiently randomize target genes at positions of interest. PMID:22401547
Tang, Lixia; Gao, Hui; Zhu, Xuechen; Wang, Xiong; Zhou, Ming; Jiang, Rongxiang
Optic nerve degeneration and potential neuroprotection: implications for glaucoma.
In order to study the course of optic nerve degeneration and devise possible ways to achieve neuroprotection, a well-controlled, animal model of partial crush injury of the optic nerve was used. Following the controlled partial crush injury of the rat optic nerve, quantitative morphological and electrophysiological measurements were made of primary and secondary neuronal losses. The neuroprotective effects of NMDA-receptor antagonists and alpha 2-adrenoreceptor agonists were also studied. The results suggested that the ongoing progression of the optic nerve degeneration in glaucoma might be a consequence of the toxic extracellular environment produced by neurons that degenerate as a result of the primary cause of the disease (such as increased IOP). PMID:10230599
Schwartz, M; Yoles, E
Reprogramming of adult rod photoreceptors prevents retinal degeneration
A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration.
Montana, Cynthia L.; Kolesnikov, Alexander V.; Shen, Susan Q.; Myers, Connie A.; Kefalov, Vladimir J.; Corbo, Joseph C.
Hot degenerate dwarfs in a two-phase model
NASA Astrophysics Data System (ADS)
The characteristics of degenerate dwarfs-core radius, mass, and energy, thickness of their outer layers-are calculated based on a mechanical-equilibrium equation in a five-parameter, two-phase compositemodel with an isothermal core and a non-degenerate outer region. An accurate equation of state for the partially degenerate, ideal, relativistic electron gas of the core is used together with a polytropic approximation for the outer layers. The model parameters are determined using the known masses, radii, and luminosities of observed DA white dwarfs. A region where dwarfs can exist is identified in a plot of core temperature vs. the relativity parameter at the center of the star, and the dependence of the core temperature on the effective temperature of the photosphere is constructed.
Vavrukh, M. V.; Smerechinskii, S. V.
Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas
A generalized set of nonlinear electromagnetic quantum hydrodynamic (QHD) equations is derived for a magnetized quantum plasma, including collisional, electron spin-(1/2), and relativistically degenerate electron pressure effects that are relevant for dense astrophysical systems, such as white dwarfs. For illustrative purposes, linear dispersion relations are derived for one-dimensional magnetoacoustic waves for a collisionless nonrelativistic degenerate gas in the presence of the electron spin-(1/2) contribution and for magnetoacoustic waves in a plasma containing relativistically degenerate electrons. It is found that both the spin and relativistic degeneracy at high densities tend to slow down the magnetoacoustic wave due to the Pauli paramagnetic effect and relativistic electron mass increase. The present study outlines the theoretical framework for the investigation of linear and nonlinear behaviors of electromagnetic waves in dense astrophysical systems. The results are applied to calculate the magnetoacoustic speeds for both the nonrelativistic and relativistic electron degeneracy cases typical for white dwarf stars.
Masood, Waqas [TPPD, PINSTECH, P. O. Nilore, Islamabad (Pakistan); Eliasson, Bengt [Department of Physics, Umeaa University, SE-901 87 Umeaa (Sweden); Institut fuer Theoretische Physik IV, Fakultaet fuer Physik und Astronomie, Ruhr-Universitaet Bochum, D-44780 Bochum (Germany); Shukla, Padma K. [Institut fuer Theoretische Physik IV, Fakultaet fuer Physik und Astronomie, Ruhr-Universitaet Bochum, D-44780 Bochum (Germany)
Control of degenerate Hopf bifurcations in three-dimensional maps.
A feedback control method is proposed to create a degenerate Hopf bifurcation in three-dimensional maps at a desired parameter point. The particularity of this bifurcation is that the system admits a stable fixed point inside a stable Hopf circle, between which an unstable Hopf circle resides. The interest of this solution structure is that the asymptotic behavior of the system can be switched between stationary and quasi-periodic motions by only tuning the initial state conditions. A set of critical and stability conditions for the degenerate Hopf bifurcation are discussed. The washout-filter-based controller with a polynomial control law is utilized. The control gains are derived from the theory of Chenciner's degenerate Hopf bifurcation with the aid of the center manifold reduction and the normal form evolution. PMID:12777111
Wen, GuiLin; Xu, Daolin; Xie, JianHua
Control of degenerate Hopf bifurcations in three-dimensional maps
NASA Astrophysics Data System (ADS)
A feedback control method is proposed to create a degenerate Hopf bifurcation in three-dimensional maps at a desired parameter point. The particularity of this bifurcation is that the system admits a stable fixed point inside a stable Hopf circle, between which an unstable Hopf circle resides. The interest of this solution structure is that the asymptotic behavior of the system can be switched between stationary and quasi-periodic motions by only tuning the initial state conditions. A set of critical and stability conditions for the degenerate Hopf bifurcation are discussed. The washout-filter-based controller with a polynomial control law is utilized. The control gains are derived from the theory of Chenciner's degenerate Hopf bifurcation with the aid of the center manifold reduction and the normal form evolution.
Wen, Guilin; Xu, Daolin; Xie, Jianhua
N=2 gauge theories and degenerate fields of Toda theory
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)
Mouse models for studies of retinal degeneration and diseases
Summary Mouse models, with their well-developed genetics and similarity to human physiology and anatomy, serve as powerful tools with which to investigate the etiology of human retinal degeneration. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Here, I describe the tools used in the discoveries of many retinal degeneration models, including indirect ophthalmoscopy (to look at the fundus appearance), fundus photography and fluorescein angiography (to document the fundus appearance), electroretinography (to check retinal function) as well as the heritability test (for genetic characterization).
Chang, Bo
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.
Degenerate photon echoes - Simultaneous storage of multiple optical data
NASA Astrophysics Data System (ADS)
It is shown that simultaneous and spatially overlapping multiple photon echoes can occur following application of a single optical pulse followed by multiple pairs of couterpropagating pulses in various directions (degenerate photon echoes). This scheme has been experimentally verified in Pr(3+):LaF3 for the doubly degenerate case. In the small-pulse-area regime, the two echoes are observed to be independent with no cross talk between them. From the viewpoint of transient optical memory, this makes it possible to store multiple independent optical data in one sample spot and to retrieve any one of them, thereby multiplying the memory capacity of the crystal.
Mitsunaga, M.; Kim, M. K.; Kachru, R.
Selective Rod Degeneration and Partial Cone Inactivation Characterize an Iodoacetic Acid Model of Swine Retinal Degeneration
Purpose. Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP. Methods. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography. Results. IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients. Conclusions. IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention.
Wang, Wei; de Castro, Juan Fernandez; Vukmanic, Eric; Zhou, Liang; Emery, Douglas; DeMarco, Paul J.; Kaplan, Henry J.
Congenital Cerebellar Cortical Degeneration in Holstein Cattle in Southern Brazil
A congenital progressive cerebellar disorder is described in Holstein calves. The clinical signs were progressive and were characterized by ataxia, hypermetria, a wide stance and fine head tremors. When the affected cattle were forced to run, the signs were exacerbated, leading to epileptiform attacks. Histological lesions consisted of a very selective cerebellar cortical degeneration, almost exclusively affecting the Purkinje cells.
A. L. Schild; F. Riet-Correa; E. L. Portiansky; M. C. MÚndez; D. L. Graša
Inflammatory mediators in intervertebral disk degeneration and discogenic pain.
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
Toxic neurofilamentous axonopathies -- accumulation of neurofilaments and axonal degeneration.
A number of neurotoxic chemicals induce accumulation of neurofilaments in axonal swellings that appear at varying distances from the cell body. This pathology is associated with axonal degeneration of different degrees. The clinical manifestation is most commonly that of a mixed motor-sensory peripheral axonopathy with a disto-proximal pattern of progression, as in cases of chronic exposure to n-hexane and carbon disulphide. It has been demonstrated that protein adduct formation is a primary molecular mechanism of toxicity in these axonopathies, but how this mechanism leads to neurofilament accumulation and axonal degeneration remains unclear. Furthermore, little is known regarding the mechanisms of neurofilamentous axonopathy caused by 3,3'-iminodipropionitrile, an experimental toxin that induces proximal axon swelling that is strikingly similar to that found in early amyotrophic lateral sclerosis. Here, we review the available data and main hypotheses regarding the toxic axonopathies and compare them with the current knowledge of the biological basis of neurofilament transport. We also review recent studies addressing the question of how these axonopathies may cause axonal degeneration. Understanding the mechanisms underlying the toxic axonopathies may provide insight into the relationship between neurofilament behaviour and axonal degeneration, hopefully enabling the identification of new targets for therapeutic intervention. Because neurofilament abnormalities are a common feature of many neurodegenerative diseases, advances in this area may have a wider impact beyond toxicological significance. PMID:23331301
Llorens, J
Quantum interference effects in degenerate systems. Spontaneous and stimulated radiation
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
Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain
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 ôdiseasedö 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.
Wuertz, Karin; Haglund, Lisbet
Biomarkers for Age-Related Macular Degeneration (AMD).
National Technical Information Service (NTIS)
Provided are methods of using levels of markers of systemic inflammation, e.g., CRP, to predict a subject's risk of development or progression of Age-Related Macular Degeneration (AMD), and methods of treating, delaying or preventing the development or pr...
J. M. Seddon
Senile macular degeneration: The involvement of immunocompetent cells
Senile macular degeneration (SMD) is a leading cause of legal blindness in western countries. The role of immunocompetent cells in the pathogenesis of this disease has not been widely recognised. In this work specimens were studied by electron microscopy to provide ultrastructural details of the role of immunocompetent cells in early, intermediate and late stages of the disease. Additionally, we
P. L. Penfold; M. C. Killingsworth; S. H. Sarks
Photoreceptor Loss in Age-Related Macular Degeneration
Purpose. The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the
Christine A. Curcio; Nancy E. Medeiros; C. Leigh Millican
The Experience of Age-Related Macular Degeneration
ERIC Educational Resources Information Center
This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation ofů
Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.
Awareness, Knowledge, and Concern about Age-Related Macular Degeneration
ERIC Educational Resources Information Center
Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-relatedů
Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia
Quantum error correction with degenerate codes for correlated noise
We introduce a quantum packing bound on the minimal resources required by nondegenerate error-correction codes for any kind of noise. We prove that degenerate codes can outperform nondegenerate ones in the presence of correlated noise, by exhibiting examples where the quantum packing bound is violated.
Chiribella, Giulio [Perimeter Institute for Theoretical Physics, 31 Caroline St. North, Waterloo, Ontario N2L 2Y5 (Canada); Dall'Arno, Michele; D'Ariano, Giacomo Mauro; Macchiavello, Chiara; Perinotti, Paolo [Quit group, Dipartimento di Fisica 'A. Volta', via Bassi 6, I-27100 Pavia (Italy); INFN Sezione di Pavia, via Bassi 6, I-27100 Pavia (Italy)
Emerging Pharmacologic Therapies for Wet Age-Related Macular Degeneration
As researchers and clinicians are beginning to understand that wet age-related macular degeneration (AMD) is more than simply a vascular disease that includes angiogenic, vascular and inflammatory components, they are exploring new agents with different mechanisms of action addressing multiple targets in this complex pathophysiology. Some of them are already available in human trials or even approved vascular epithelial growth
Zhang Ni; Peng Hui
Topographic analysis in pellucid marginal corneal degeneration and keratoglobus
Pellucid marginal corneal degeneration (PMCD) is an uncommon cause of inferior peripheral corneal ectasia, affecting patients between the ages of 20 and 40 years. Although histopathologically it is considered a variant of keratoconus, it differs in that the marked corneal steepening occurs more inferiorly, above a narrow band of corneal stromal thinning concentric to the inferior limbus. Here we present
C H Karabatsas; S D Cook
Degenerate 1 GHz repetition rate femtosecond optical parametric oscillator.
We report a degenerate femtosecond optical parametric oscillator (OPO) that is synchronously pumped by a mode-locked Ti:sapphire laser at 1 GHz repetition rate. The OPO produces an 85 nm (10 THz) wide frequency comb centered at 1.6 ?m. Stable long-term operation with >100 mW of average output power has been achieved. PMID:23114363
Vainio, Markku; Merimaa, Mikko; Halonen, Lauri; Vodopyanov, Konstantin
T1? MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration
9 asymptomatic subjects and 6 patients underwent T1? MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2ľ3 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1? MRI from which spatial T1? relaxation maps were calculated from segmented T1-weighted images. Median T1? relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1? exceeded asymptomatic articular cartilage median T1? by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1? was elevated in 5, but in all observations, large foci of increased T1? were observed. It was determined that T1? could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes.
Witschey, Walter RT; Borthakur, Arijitt; Fenty, Matt; Kneeland, J Bruce; Lonner, Jess H; McArdle, Erin L.; Sochor, Matt; Reddy, Ravinder
Josephson effect in film structures with degenerate semiconductor bridges
A theoretical analysis is made of a structure formed by two superconducting film strips deposited on a degenerate semiconductor and separated by a small gap. A formula for the critical current is tested against calculations and experimental results for a structure in which niobium is the superconductor and silicon is the semiconductor. A generally good agreement between the theory, calculations,
V. N. Alfeev; A. V. Verbilo; D. P. Kolesnikov; V. A. Ryzhkov
Existence of bounded solutions for some degenerated quasilinear elliptic equations
Summary We prove the existence of bounded solutions in L8 (O) of degenerate elliptic boundary value problems of second order in divergence form with natural growth in the gradient. For the Dirichlet problem our results cover also unbounded domains O.
P. Drßbek; F. Nicolosi
Spectral analysis of linear relations and degenerate operator semigroups
Several problems of the spectral theory of linear relations in Banach spaces are considered. Linear differential inclusions in a Banach space are studied. The construction of the phase space and solutions is carried out with the help of the spectral theory of linear relations, ergodic theorems, and degenerate operator semigroups.
Baskakov, A G [Voronezh State University, Voronezh (Russian Federation); Chernyshov, K I [Voronezh Forestry Engeneering Academy, Voronezh (Russian Federation)
Treatment of dry age-related macular degeneration with dobesilate.
The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337
Cuevas, P; Outeiri˝o, L A; Angulo, J; GimÚnez-Gallego, G
Treatment of dry age-related macular degeneration with dobesilate
The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture.
Cuevas, P; Outeirino, L A; Angulo, J; Gimenez-Gallego, G
Serous Adenocarcinoma of the Uterus Presenting as Paraneoplastic Cerebellar Degeneration
Paraneoplastic cerebellar degeneration is a rare complication of cancer and is most frequently associated with lung, ovary, and breast cancers as well as Hodgkins lymphoma. A 74-year-old female with a past history of breast cancer presented with vomiting, ataxia, slurred speech, and dizziness. Her serum chemistry, thyroid and liver function tests, acetylcholine antibodies, serum cortisol, CT, and MRI imaging were
J. Bram Johns; Kunle O. Odunsi; S. Fleischman; Masoud Azodi; Peter E. Schwartz
Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage
Objective: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal
S Saarakkala; M. S Laasanen; J. S Jurvelin; K T÷rr÷nen; M. J Lammi; R Lappalainen; J T÷yrńs
The Degenerate Primer Design Problem: Theory and Applications
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 combinations it contains We study the problem of designing a pair of primers with prescribed degeneracy that match a maximum number of given input sequences Such problems occur when studying a family
Chaim Linhart; Ron Shamir
PGC-1? regulation of mitochondrial degeneration in experimental diabetic neuropathy.
Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1? and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1? (-/-) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1? (-/-) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1? causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1? in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1? in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1? function may be an attractive approach for treatment of diabetic neuropathy. PMID:24423644
Choi, Joungil; Chandrasekaran, Krish; Inoue, Tatsuya; Muragundla, Anjaneyulu; Russell, James W
Inflammation in Dry Age-Related Macular Degeneration
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
Exact null controllability of degenerate evolution equations with scalar control
Necessary and sufficient conditions for the exact null controllability of a degenerate linear evolution equation with scalar control are obtained. These general results are used to examine the exact null controllability of the Dzektser equation in the theory of seepage. Bibliography: 13 titles.
Fedorov, Vladimir E; Shklyar, Benzion
Genetics Home Reference: Age-related macular degeneration
... and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH gene, contribute to a person's risk of developing age-related macular degeneration. It is unclear how these genetic changes are related to the retinal damage and vision ...
Genetic Factors Associated with Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a complex, multifactorial disease associated with environmental and genetic factors. This review emphasizes the clinical impact of the major genetic factors mainly located in the complement factor H gene and on the 10q26 locus, and their current and future implications for the management of AMD.
Nicolas Leveziel; Julien Tilleul; Nathalie Puche; Jennyfer Zerbib; Franck Laloum; Giuseppe Querques; Eric H. Souied
Control of degenerate Hopf bifurcations in three-dimensional maps
A feedback control method is proposed to create a degenerate Hopf bifurcation in three-dimensional maps at a desired parameter point. The particularity of this bifurcation is that the system admits a stable fixed point inside a stable Hopf circle, between which an unstable Hopf circle resides. The interest of this solution structure is that the asymptotic behavior of the system
Guilin Wen; Daolin Xu; Jianhua Xie
[The utility of voxel-based morphometry in the diagnosis of spinocerebellar degeneration].
We evaluated atrophic sites in the brainstem and cerebellum in the patients with spinocerebellar degeneration by using voxel-based morphometry (VBM). Gray matter atrophy was found extensively in both the cerebellar hemispheres and vermis of subjects presenting the cerebellar variant of multiple system atrophy (MSA-C; n=9). In addition, remarkable white matter atrophy was observed in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. In contrast, gray matter atrophy was not apparent in the cerebellar hemispheres or vermis of subjects in the SCA3 group (n=6), whereas intense white matter atrophy was visible in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. White matter atrophy was also observed in the brainstem and surrounding the dentate nucleus in both cases of dentatorubral-pallidoluysian atrophy (DRPLA) (n=2), whereas gray matter atrophy of the cerebellum was not remarkable. In both the SCA6 group (n=3) and the SCA31 group (n=2), gray matter atrophy was prominent in the cerebellar hemispheres and vermis; however, white matter atrophy was not found in the middle cerebellar peduncle and brainstem, whereas symmetric atrophy of white matter was found in the vicinity of the dentate nucleus. In each of these diseases, VBM findings were consistent with the pathological findings; therefore, VBM can be considered a useful tool for the diagnosis of spinocerebellar degeneration. PMID:24899352
Tanaka, Nobuyuki; Nanri, Kazunori; Taguchi, Takeshi; Tanaka, Noriko; Fujita, Tsuneo; Mitoma, Hiroshi; Kawata, Akihiro; Mizusawa, Hidehiro
Tight constraints on the exchange-correlation potentials of degenerate states.
Identities for the difference of exchange-correlation potentials and energies in degenerate and nondegenerate ground states are derived. The constraints are strong for degenerate ground states, and suggest that local and semilocal approximations to the exchange-correlation energy functional are incapable of correctly treating degenerate ground states. For degenerate states, it is possible to provide both local (pointwise) equality and global inequality constraints for the exchange-correlation potential in terms of the Coulomb potential. PMID:24832345
Ayers, Paul W; Levy, Mel
Tight constraints on the exchange-correlation potentials of degenerate states
NASA Astrophysics Data System (ADS)
Identities for the difference of exchange-correlation potentials and energies in degenerate and nondegenerate ground states are derived. The constraints are strong for degenerate ground states, and suggest that local and semilocal approximations to the exchange-correlation energy functional are incapable of correctly treating degenerate ground states. For degenerate states, it is possible to provide both local (pointwise) equality and global inequality constraints for the exchange-correlation potential in terms of the Coulomb potential.
Ayers, Paul W.; Levy, Mel
Simple Colorimetric Method for Detecting Degenerate Strains of the Cultivated Basidiomycete Flammulina velutipes (Enokitake)
The primary objective of this study was to develop a simple method for detecting degenerate Flammulina velutipes (Eno- kitake) cultures. Cultural degeneration of cultivated strains of Enokitake similar to the degeneration observed for Agaricus bisporus (1, 2) has become a serious problem in Japan. Previ- ous efforts to evaluate the fruiting potential of Enokitake have been made using isozyme electrophoresis
Yumi Magae; Kobun Akahane; Kimiyoshi Nakamura; Shigeyuki Tsunoda
Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy
Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular
Edward E. Morrison; Richard M. Costanzo
Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc
Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs
Daisuke Sakai; Joji Mochida; Toru Iwashina; Akihiko Hiyama; Hiroko Omi; Masaaki Imai; Tomoko Nakai; Kiyoshi Ando; Tomomitsu Hotta
Degenerate configurations, singularities and the non-Abelian nature of loop quantum gravity
Degenerate geometrical configurations in quantum gravity are important to understand if the fate of classical singularities is to be revealed. However, not all degenerate configurations arise on an equal footing, and one must take into account dynamical aspects when interpreting results: while there are many degenerate spatial metrics, not all of them are approached along the dynamical evolution of general
Martin Bojowald
Surface engineering of the retinal Bruch's membrane for treatment of age-related macular degeneration
Age-related macular degeneration (AMD) causes loss of central visual function that ultimately leads to blindness. Prominent in older populations, AMD is the number one cause for blindness in the developed world. The decline in central visual function stems from degeneration of the macula. Early on, the degeneration of the macula is caused by changes in the retinal Bruchĺs membrane (BM)
Rizaldi Sistiabudi
Strong-coupling theory of superconductivity in a degenerate Hubbard model
In order to discuss superconductivity in orbital degenerate systems, a microscopic Hamiltonian is introduced. Based on the degenerate model, a strong-coupling theory of superconductivity is developed within the fluctuation exchange (FLEX) approximation where spin and orbital fluctuations, spectra of electron, and superconducting gap function are self-consistently determined. Applying the FLEX approximation to the orbital degenerate model, it is shown that
Tetsuya Takimoto; Takashi Hotta; Kazuo Ueda
Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration
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
Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia.
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
Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia
Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types AľD). 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.
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.
Severe atrophy and fatty degeneration of the infraspinatus muscle due to isolated infraspinatus tendon tear.
Atrophy of both the supraspinatus and infraspinatus muscles is usually caused by chronic rotator cuff tear, but may also derive from suprascapular nerve entrapment at the spinoglenoid notch. Isolated infraspinatus muscle atrophy is uncommon, and typically associates with suprascapular nerve entrapment occurring distal to the spinoglenoid notch. However, isolated atrophy of the infraspinatus muscle due to insertional tear of the infraspinatus tendon may also occur. We present a case of a 43-year-old male with isolated infraspinatus muscle atrophy and fatty degeneration following an isolated full-thickness infraspinatus tendon tear at the insertion site on the humerus. While it is important to rule out other causes of infraspinatus muscle atrophy, such as concomitant rotator cuff tendon/muscle pathology or suprascapular nerve palsy, we present this case to increase awareness of this uncommon clinical presentation and the potential implications for treatment. PMID:21918868
Kolbe, Amy B; Collins, Mark S; Sperling, John W
Clinical diagnostic criteria and classification controversies in frontotemporal lobar degeneration
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 Ĺphenocopyĺ 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.
Axon retraction and degeneration in development and disease.
The selective elimination of axons, dendrites, axon and dendrite branches, and synapses, without loss of the parent neurons, occurs during normal development of the nervous system as well as in response to injury or disease in the adult. The widespread developmental phenomena of exuberant axonal projections and synaptic connections require both small-scale and large-scale axon pruning to generate precise adult connectivity, and they provide a mechanism for neural plasticity in the developing and adult nervous system, as well as a mechanism to evolve differences between species in a projection system. Such pruning is also required to remove axonal connections damaged in the adult, to stabilize the affected neural circuits, and to initiate their repair. Pruning occurs through either retraction or degeneration. Here we review examples of these phenomena and consider potential cellular and molecular mechanisms that underlie axon retraction and degeneration and how they might relate to each other in development and disease. PMID:16022592
Luo, Liqun; O'Leary, Dennis D M
Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration*
Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2+-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel G?q mutant allele, which has defects in both activation and deactivation. We revealed that Gq modulates the termination of the light response and that metarhodopsin/Gq interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the G?q mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of Gq in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.
Hu, Wen; Wan, Didi; Yu, Xiaoming; Cao, Jinguo; Guo, Peiyi; Li, Hong-sheng; Han, Junhai
Electroreceptors (ampullary organs) of the transparent catfish (Kryptopterus bicirrhus) lie in the epidermis, and contain spherical receptor cells that receive purely afferent innervation from the lateral line nerve. Section of this nerve causes rapid degenerative changes to occur in the receptors. Fine structural alterations occur in the receptor cell synapses and nerve fiber 6ľ12 h postoperatively. Disruption of the receptor cells begins by 18 h and most are lost by 48 h. By 72 h supporting cells and secretory cells also show marked degeneration, and by 96 h they may be totally lost. The rapid degeneration of the electroreceptor organs of Kryptopterus should make them a useful preparation for analysis of neurotrophic functions.
Szamier, R. Bruce; Bennett, Michael V. L.
Optimal Continuous Dependence Estimates for Fractional Degenerate Parabolic Equations
NASA Astrophysics Data System (ADS)
We derive continuous dependence estimates for weak entropy solutions of degenerate parabolic equations with nonlinear fractional diffusion. The diffusion term involves the fractional Laplace operator, {triangle^{?/2}} for {? in (0,2)} . Our results are quantitative and we exhibit an example for which they are optimal. We cover the dependence on the nonlinearities, and for the first time, the Lipschitz dependence on ? in the BV-framework. The former estimate (dependence on nonlinearity) is robust in the sense that it is stable in the limits {? downarrow 0} and {? \\uparrow 2} . In the limit {? \\uparrow 2} , {triangle^{?/2}} converges to the usual Laplacian, and we show rigorously that we recover the optimal continuous dependence result of Cockburn and Gripenberg (J Differ Equ 151(2):231-251, 1999) for local degenerate parabolic equations (thus providing an alternative proof).
Alibaud, NathaŰl; Cifani, Simone; Jakobsen, Espen R.
Structural and functional analysis of Utp23, a yeast ribosome synthesis factor with degenerate PIN domain.
During synthesis of yeast ribosome, a large complex, called the 90S pre-ribosome or the small subunit processome, is assembled on the nascent precursor rRNA and mediates early processing of 18S rRNA. The Utp23 protein and snR30 H/ACA snoRNA are two conserved components of 90S pre-ribosomes. Utp23 contains a degenerate PIN nuclease domain followed by a long C-terminal tail and associates specifically with snR30. Here, we report the crystal structure of the Utp23 PIN domain at 2.5-┼ resolution. The structure reveals a conserved core fold of PIN domain with degenerate active site residues, a unique CCHC Zn-finger motif, and two terminal extension elements. Functional sites of Utp23 have been examined with conservation analysis, mutagenesis, and in vivo and in vitro assays. Mutations in each of three cysteine ligands of zinc, although not the histidine ligand, were lethal or strongly inhibitory to yeast growth, indicating that the Zn-finger motif is required for Utp23 structure or function. The N-terminal helix extension harbors many highly conserved basic residues that mostly are critical for growth and in vitro RNA-binding activity of Utp23. Deletion of the C-terminal tail, which contains a short functionally important sequence motif, disrupted the interaction of Utp23 with snR30 and perturbed the pre-ribosomal association of Utp23. Our data establish a structural framework for dissecting Utp23 function in the assembly and dynamics of 90S pre-ribosomes. PMID:24152547
Lu, Jing; Sun, Mengyi; Ye, Keqiong
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; GarcÝa, Cristˇbal; GinÚ, Jaume
Sarcomatous degeneration in fibrous dysplasia of the rib cage.
Malignant degeneration in fibrous dysplasia is a rare occurrence. Most cases are reported in polyostotic fibrous dysplasia with predisposition of the femur, tibia, maxilla, and mandible. The most commonly observed malignant tumors are osteosarcoma, fibrosarcoma,áand chondrosarcoma. We describe a case of a low-grade osteosarcoma occurring in polyostotic fibrous dysplasia of the rib cage in a 50-year-old man. PMID:24088499
Van Rossem, Carolin; Pauwels, Patrick; Somville, Johan; Camerlinck, Michael; Bogaerts, Peter; Van Schil, Paul E
Measurement of smoke concentration using degenerate four-wave mixing
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
Human lumbar apophyseal joint damage and intervertebral disc degeneration.
OBJECTIVES--To record the extent and location of lumbar apophyseal cartilage damage, and to ascertain if the extent of damage is correlated with the grade of disc degeneration, age, or both. METHODS--The extent and location of fibrillated areas of the apophyseal cartilage of the joint surfaces of 29 lumbar motion segments were examined using computer aided image processing of Indian ink stained areas, and degeneration of the associated intervertebral discs graded using the method of Nachemson. RESULTS--It was found that these joints showed a greater extent and prevalence of cartilage fibrillation than the knee, hip or ankle, with significant damage in specimens younger than 30 years. Damage was predominantly located peripherally, superiorly, and posteriorly in the concave superior apophyseal surfaces, and was predominantly peripheral and posterior in the inferior surfaces, with a tendency to be located inferiorly. There was a weak correlation between apophyseal joint damage and the intervertebral disc degenerative grade, but this was inconclusive, as both increased with age. CONCLUSIONS--The pattern of damage exhibited by superior joint surfaces is most probably caused by tension on collagenous joint capsule fibres which insert into the surfaces posteriorly, so producing an area of fibrocartilage unsuited to loadbearing. Tension on such fibres would be greatest during spinal flexion. The pattern of damage of the inferior surfaces lends some support to the hypothesis that their apices impact the laminae of the lumbar vertebra inferior to them, consequent upon the degeneration and narrowing of the associated intervertebral disc. The predominantly peripheral location of fibrillation of both superior and inferior surfaces may be associated with inadequate mechanical conditioning of marginal joint areas. Disc degeneration cannot be the initial cause of apophyseal fibrillation in most specimens. The study indicates a need for regular spinal exercise, starting at a young age.
Swanepoel, M W; Adams, L M; Smeathers, J E
Ignition Regime for Fusion in a Degenerate Plasma
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.
Noise and dynamic range of CMOS degenerated active inductor resonators
This paper presents a compensation method of active inductor losses, employing passive gyrator degeneration rather than an external negative impedance converter. Theoretical analysis is confirmed by a comparative simulations of two resonators designed for 434 MHz band, using Eldo RF and Spectre and the UMC 0.18 mum 1P6M process. Presented results show that the proposed loss compensation method achieves comparable
Grzegorz Szczepkowski; Ronan Farrell
Utility Values and Age-related Macular Degeneration
Results: The mean utility value for the total group with age-related macular degeneration was 0.72 (95% confi- dence interval (CI), 0.66-0.78) using the time trade-off method and 0.81 (95% CI, 0.76-0.86) using the stan- dard gamble method. Using the time trade-off method correlated with the visual acuity in the better-seeing eye, the results were as follow: group 1, 0.89 (95%
Melissa M. Brown; Jonathan Kistler
Pegaptanib for Neovascular Age-Related Macular Degeneration
background Pegaptanib, an anti-vascular endothelial growth factor therapy, was evaluated in the treatment of neovascular age-related macular degeneration. methods We conducted two concurrent, prospective, randomized, double-blind, multicenter, dose-ranging, controlled clinical trials using broad entry criteria. Intravitreous injec- tion into one eye per patient of pegaptanib (at a dose of 0.3 mg, 1.0 mg, or 3.0 mg) or sham injections were
Evangelos S. Gragoudas; Anthony P. Adamis; Emmett T. Cunningham; Matthew Feinsod; David R. Guyer
Intracorneal rings for the correction of pellucid marginal degeneration
We report a case of Intacs« (KeraVision) implantation for the correction of pellucid marginal degeneration (PMD). Preoperatively, the patientĺs uncorrected visual acuity (UCVA) was 0.05, the best spectacle-corrected visual acuity (BSCVA) was 0.1, and the refraction was ľ2.00 ľ7.00 Î 90 in the right eye. The flattest meridian (K1) measured 43.8@104 and the steepest meridian (K2), 51.3@14. Ultrasound pachymetry revealed
Jose Rodriguez-Prats; Ahmed Galal; Magdalena Garcia-Lledo; Fernando De La Hoz; Jorge L Aliˇ
Differential neuroglycan C expression during retinal degeneration in Rpe65
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
Autophagy Protects the Retina from Light-induced Degeneration*
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.
Chen, Yu; Sawada, Osamu; Kohno, Hideo; Le, Yun-Zheng; Subauste, Carlos; Maeda, Tadao; Maeda, Akiko
Methamphetamine exposure can produce neuronal degeneration in mouse hippocampal remnants
Neuronal cell death in hippocampal remnants was seen after methamphetamine (METH) exposure. Two techniques (Fluoro-Jade labeling and argyrophylia) showed that neuronal degeneration occurred in the indusium griseum, tenia tecta and fasciola cinerea within 5 days post-METH exposure in 70% of the mice. Neurodegeneration also occasionally occurred in the piriform cortex, hippocampus and frontal\\/parietal cortex. This cell death, unlike striatal neurotoxicity,
Larry C Schmued; John F Bowyer
The inverse problem of the theory of degenerate dwarfs
Based on the radii and masses of degenerate dwarfs derived from HIPPARCOS and other observations, we estimate the microscopic\\u000a parameters of a Chandrasekhar model (the relativistic parameter at the stellar center x\\u000a 0, and the chemical-composition parameter Á\\u000a e\\u000a = A\\/Z, where A is the mass number and Z is the nuclear charge). We have obtained analytical expressions for the
M. V. Vavrukh; S. V. Smerechynskyi; N. L. Tyshko
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
Hypertrophic olivary degeneration after resection of a cerebellar tumor
We report a case of hypertrophic olivary degeneration due to cerebellar surgery for a low-grade tumor. A 27-year-old female\\u000a presented with right-sided paresthesias and intermittent leg paresis following a right cerebellar resection of a tumor 2áweeks\\u000a prior. One month later, her symptoms remained stable while her neurological examination demonstrated slight right hemi-body\\u000a hypoesthesia and subtle appendicular ataxia in her right
Serra Akar; Jan Drappatz; Liangge Hsu; Russell A. Blinder; Peter Mc L. Black; Santosh Kesari
CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design
We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3-4
Timothy Rose; Jorja G. Henikoff; Steven Henikoff
Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo
Both proNGF and the neurotrophin receptor p75 (p75NTR) are known to regulate photoreceptor cell death caused by exposure of albino mice to intense illumination. ProNGF-induced apoptosis requires the participation of sortilin as a necessary p75NTR co-receptor, suggesting that sortilin may participate in the photoreceptor degeneration triggered by intense lighting. We report here that light-exposed albino mice showed sortilin, p75NTR, and
Ana M. Santos; Noelia Lˇpez-Sßnchez; David MartÝn-Oliva; Pedro de la Villa; Miguel A. Cuadros; JosÚ M. Frade
Removing degeneration from a WKB explicit formula for bound states
NASA Astrophysics Data System (ADS)
In this paper we improve a previously established three-dimensional WKB formula of asymptotic nature, which holds when the radial quantum number tends to infinity: a more accurate evaluation of the roots of the WKB integrand yields indeed lower order contributions, which depend on the azimuthal quantum number and remove the degeneration of the energy levels. Improvement of the convergence to the usual WKB eigenvalues is also verified in a number of cases.
Paiano, Giulio
Phase conjugate degenerate four-wave mixing in molecular aggregates
We investigate phase conjugate degenerate four-wave mixing (DFWM) in molecular aggregates consisting of N interacting, homogeneously broadened two-level systems in a cyclic configuration with a dimension much smaller than an optical wavelength. The interaction includes both the static dipoleŚdipole coupling and superradiant coupling. We show that, in general the size dependence of ~ is determined by the relative magnitudes of
Francis C. SPANO; Shaul MUKAMEL
Therapy of Nonexudative Age-Related Macular Degeneration
\\u000a Age related macular degeneration (AMD) is the leading cause of blindness among adults over the age of 65 in the Western world.\\u000a The prevalence of AMD is expected to increase dramatically, from 1.75 million in 2000 to 2.95 million in 2020, due to the\\u000a rapidly aging population. Given the large and now increasing burden of disease, the identification of modifiable
Annal D. Meleth; Veena R. Raiji; Nupura Krishnadev; Emily Y. Chew
Delay of photoreceptor degeneration in tubby mouse by sulforaphane.
In this study, the homozygous tubby (tub/tub) mutant mouse, with an early progressive hearing loss and photoreceptor degeneration, was used as a model system to examine the effects of systemic administration of a naturally occurring isothiocyanate, sulforaphane (SF), on photoreceptor degeneration. Several novel observations have been made: (i) the mRNA and protein expression of thioredoxin (Trx), thioredoxin reductase (TrxR) and NF-E2-related factor-2 (Nrf2) were significantly reduced even prior to photoreceptor cell degeneration in the retinas of tub/tub mice, suggesting that retinal expression of the Trx system is impaired and that Trx regulation is involved in the pathogenesis of retinal degeneration in this model, (ii) intraperitoneal injection with SF significantly up-regulated retinal levels of Trx, TrxR, and Nrf2, and effectively protected photoreceptor cells in tub/tub mice as evaluated functionally by electroretinography and morphologically by quantitative histology, and (iii) treatment with PD98059, an inhibitor of extracellular signal-regulated kinases (ERKs), blocked SF-mediated ERKs activation and up-regulation of Trx/TrxR/Nrf2 in the retinas of tub/tub mice. This suggests that ERKs and Nrf2 are involved in the mechanism of SF-mediated up-regulation of the Trx system to protect photoreceptor cells in this model. These novel findings are significant and could provide important information for the development of a unique strategy to prevent sensorineural deafness/retinal dystrophic syndromes and also other forms of inherited neurological disorders. PMID:17394579
Kong, Li; Tanito, Masaki; Huang, Zhong; Li, Feng; Zhou, Xiaohong; Zaharia, Alexander; Yodoi, Junkie; McGinnis, James F; Cao, Wei
Degenerate perturbative treatment of the hydrogenic Zeeman effect
Degenerate perturbation theory is applied to study the first 14 energy levels of the hydrogen atom in a uniform magnetic field up to the second order. The twofold degeneracy of all the levels among them in terms of the oscillator or parabolic states is completely removed. The results obtained with the use of the Pade approximant are compared with those found in the literature. Level crossings are discussed.
Chen, A.C.
Analysis of a degenerated standard model in the piercing process
Purpose: The purpose of this paper is the mathematical description of the impact phenomenon of a bullet of the speed ca. 400 m\\/s, with the use of a degenerated model. Design\\/methodology\\/approach: In the study, an attempt has been made to apply an untypical model for the piercing phenomenon analysis. Basing on the model, the theoretical analysis of the piercing phenomenon
K. Jamroziak
Multilocus analysis of age-related macular degeneration
Age-related macular degeneration (AMD) is a late onset vision disorder. Recent studies demonstrate that alterations in complement cascade genes are associated with AMD. Of the three identified complement loci, variants in complement factor H (CFH) have the highest impact as does an independent locus at 10q26. Our matched caseľcontrol study using the Age-Related Eye Disease Study (AREDS) cohort confirms and
Julie Bergeron-Sawitzke; Bert Gold; Adam Olsh; Sarah Schlotterbeck; Kendal Lemon; Kala Visvanathan; Rando Allikmets; Michael Dean
Resistance to axonal degeneration after nerve compression in experimental diabetes.
To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament. PMID:2928319
Dyck, P J; Engelstad, J K; Giannini, C; Lais, A C; Minnerath, S R; Karnes, J L
Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning.
Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway. PMID:16772170
Hoopfer, Eric D; McLaughlin, Todd; Watts, Ryan J; Schuldiner, Oren; O'Leary, Dennis D M; Luo, Liqun
Glia engulf degenerating axons during developmental axon pruning.
Developmental axon pruning is widely used in constructing the nervous system. Accordingly, diverse mechanisms are likely employed for various forms of axon pruning. In the Drosophila mushroom bodies (MB), gamma neurons initially extend axon branches into both the dorsal and medial MB axon lobes in larvae. Through a well-orchestrated set of developmental events during metamorphosis, axon branches to both lobes degenerate prior to the formation of adult connections. Here, we analyze ultrastructural changes underlying axon pruning by using a genetically encoded electron microscopic (EM) marker to selectively label gamma neurons. By inhibiting axon pruning in combination with the use of this EM marker, we demonstrate a causal link between observed cellular events and axon pruning. These events include changes in axon ultrastructure, synaptic degeneration, and engulfment of degenerating axon fragments by glia for their subsequent breakdown via the endosomal-lysosomal pathway. Interestingly, glia selectively invade MB axon lobes at the onset of metamorphosis; this increase in cell number is independent of axon fragmentation. Our study reveals a key role for glia in the removal of axon fragments during developmental axon pruning. PMID:15084282
Watts, Ryan J; Schuldiner, Oren; Perrino, John; Larsen, Camilla; Luo, Liqun
Stability of trapped degenerate dipolar Bose and Fermi gases
NASA Astrophysics Data System (ADS)
Trapped degenerate dipolar Bose and Fermi gases of the cylindrical symmetry with the polarization vector along the symmetry axis are only stable for the strength of dipolar interaction below a critical value. In the case of bosons, the stability of such a dipolar Bose-Einstein condensate (BEC) is investigated for different strengths of contact and dipolar interactions using a variational approximation and a numerical solution of a mean-field model. In the disc shape, with the polarization vector perpendicular to the plane of the disc, the atoms experience an overall dipolar repulsion and this fact should contribute to the stability. However, a complete numerical solution of the dynamics leads to the collapse of a strongly disc-shaped dipolar BEC due to the long-range anisotropic dipolar interaction. In the case of fermions, the stability of a trapped single-component degenerate dipolar Fermi gas is studied including the Hartree-Fock exchange and Brueckner-Goldstone correlation energies in the local-density approximation valid for a large number of atoms. Estimates for the maximum allowed number of polar Bose and Fermi molecules in the BEC and degenerate Fermi gas are given.
Adhikari, S. K.
Advances in repairing the degenerate retina by rod photoreceptor transplantation.
Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. PMID:24412415
Pearson, Rachael A
Advances in repairing the degenerate retina by rod photoreceptor transplantation?
Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application.
Pearson, Rachael A.
Patterns of White Matter Atrophy in Frontotemporal Lobar Degeneration
Background Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter (WM) alterations in this disease. Objectives To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degenerationŚfronto-temporal dementia (FTD) and semantic dementiaŚand to compare the patterns of WM atrophy with those of gray matter (GM) atrophy in these diseases. Design Structural MRIs were obtained from patients with FTD (n=12) and semantic dementia (n=13) and in cognitively healthy age-matched controls (n=24). Regional GM and WM were classified automatically from high-resolution T1-, T2-, and proton density-weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates. Results Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD. Conclusions These results show that patients with frontotemporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders.
Chao, Linda L.; Schuff, Norbert; Clevenger, Erin M.; Mueller, Susanne G.; Rosen, Howard J.; Gorno-Tempini, Maria L.; Kramer, Joel H.; Miller, Bruce L.; Weiner, Michael W.
Well-posedness results for triply nonlinear degenerate parabolic equations
NASA Astrophysics Data System (ADS)
We study well-posedness of triply nonlinear degenerate elliptic-parabolic-hyperbolic problems of the kind b(-divaś(u,??(u))+?(u)=f, u|=u in a bounded domain with homogeneous Dirichlet boundary conditions. The nonlinearities b,? and ? are supposed to be continuous non-decreasing, and the nonlinearity aś falls within the Leray-Lions framework. Some restrictions are imposed on the dependence of aś(u,??(u)) on u and also on the set where ? degenerates. A model case is aś(u,??(u))=fś(b(u),?(u),?(u))+k(u)a(??(u)), with a nonlinearity ? which is strictly increasing except on a locally finite number of segments, and the nonlinearity a which is of the Leray-Lions kind. We are interested in existence, uniqueness and stability of L entropy solutions. For the parabolic-hyperbolic equation ( b=Id), we obtain a general continuous dependence result on data u,f and nonlinearities b,?,?,aś. Similar result is shown for the degenerate elliptic problem, which corresponds to the case of b?0 and general non-decreasing surjective ?. Existence, uniqueness and continuous dependence on data u,f are shown in more generality. For instance, the assumptions [b+?](R)=R and the continuity of ??[ permit to achieve the well-posedness result for bounded entropy solutions of this triply nonlinear evolution problem.
Andreianov, B.; Bendahmane, M.; Karlsen, K. H.; Ouaro, S.
Transport of Truncated Rhodopsin and Its Effects on Rod Function and Degeneration
Purpose Most transgenic animal models of retinal degeneration caused by rhodopsin mutations express the rhodopsin transgene on a wild-type (WT) genetic background. Previous studies have demonstrated that one mechanism of retinal degeneration is rhodopsin overexpression. To study the effect of C-terminal truncation of rhodopsin without the confounding factors of overexpression, several lines of transgenic mice were generated that expressed a C-terminal rhodopsin mutation on rhodopsin-knockout backgrounds. Methods Two lines of transgenic mice, expressing different levels of C-terminal truncated rhodopsin (S334ter) were mated with heterozygous rhodopsin-knockout (rho+/?) mice to express S334ter rhodopsin on a background with reduced endogenous rhodopsin expression. S334ter mice were mated to homozygous knockout (rho?/?) mice to examine the effect of S334ter rhodopsin on a null rhodopsin background. S334ter rhodopsin expression was estimated by Western blot. Retinal function was assessed by ERG and retinal degeneration by histopathology and morphometry. C-terminal rhodopsin sorting and trafficking was examined by fluorescence immunocytochemistry with detection by electron microscope. Results Expression of S334ter truncated rhodopsin at low levels in the presence of decreased total rhodopsin in rods (S334ter, rho+/?) increased the rate of rod cell death in comparison to rho+/? littermates. In addition, S334ter rhodopsin prolonged the recovery time of the rod ERG to a light flash and diminished the a-wave amplitudes in comparison to their (rho+/?) littermates. Photoreceptors of S334ter mice on a homozygous rhodopsin-knockout background (S334ter+, rho?/?) had a fraction of mutant rhodopsin localized to the ciliary membranes. Conclusions Expression of S334ter rhodopsin without overexpression of total opsin in the rod photoreceptor decreased rod cell contribution to the ERG and compromised rod cell survival in adult mice. The increased cell death may be a consequence of C-terminal truncated rhodopsin mislocalization in membranes of the inner segment. Another possible pathologic mechanism is prolonged activation of phototransduction from the presence of mutant rhodopsin in the outer segment lacking the normal C-terminal binding sites for shutoff by arrestin and phosphorylation. These results suggest that rhodopsin lacking a C-terminal trafficking signal can be transported to the rod outer segment without cotransporting with full-length rhodopsin.
Lee, Edwin S.; Flannery, John G.
Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration
Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.
Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothee; Forster, Valerie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stephane; Jammoul, Firas; Leveillard, Thierry; Benosman, Ryad; Sahel, Jose-Alain; Picaud, Serge
Inhibition of Polyisoprenylated Methylated Protein Methyl Esterase by Synthetic Musks Induces Cell Degeneration
Synthetic fragrances are persistent environmental pollutants that tend to bioaccumulate in animal tissues. They are widely used in personal care products and cleaning agents. Worldwide production of Galaxolide and Tonalide are in excess of 4500 tons annually. Because of their widespread production and use, they have been detected in surface waters and fish in the US and Europe. Consumption of contaminated water and fish from such sources leads to bioaccumulation and eventual toxicity. Since fragrances and flavors bear structural similarities to polyisoprenes, it was of interest to determine whether toxicity by Galaxolide and Tonalide may be linked with polyisoprenylated methylated protein methyl esterase (PMPMEase) inhibition. A concentration-dependent study of PMPMEase inhibition by Galaxolide and Tonalide as well as their effects on the degeneration of cultured cells were conducted. Galaxolide and Tonalide inhibited purified porcine liver PMPMEase with Ki values of 11 and 14 ÁM, respectively. Galaxolide and Tonalide also induced human cancer cell degeneration with EC50 values of 26 and 98 ÁM (neuroblastoma SH-SY5Y cells) and 58 and 14 ÁM (lung cancer A549 cells), respectively. The effects on cell viability correlate well with the inhibition of PMPMEase activity in the cultured cells. Molecular docking analysis revealed that the binding interactions are most likely between the fragrance molecules and hydrophobic amino acids in the active site of the enzyme. These results appear to suggest that the reported neurotoxicity of these compounds may be associated with their inhibition of PMPMEase. Exposure to fragrances may pose a significant risk to individuals predisposed to developing degenerative disorders.
Ayuk-Takem, Lambert; Amissah, Felix; Aguilar, Byron J.; Lamango, Nazarius S.
Neuroprotective effects of IGF-I following kainic acid-induced hippocampal degeneration in the rat.
Insulin-like growth factor I (IGF-I) has been shown to act as a neuroprotectant both in in vitro studies and in in vivo animal models of ischemia, hypoxia, trauma in the brain or the spinal cord, multiple and amyotrophic lateral sclerosis, Alzheimer's and Parkinson's disease. In the present study, we investigated the neuroprotective potential of IGF-I in the "kainic acid-induced degeneration of the hippocampus" model of temporal lobe epilepsy. Increased cell death--as detected by FluoroJade B staining--and extensive cell loss--as determined by cresyl violet staining--were observed mainly in the CA3 and CA4 areas of the ipsilateral and contralateral hippocampus, 7 days following intrahippocampal administration of kainic acid. Kainic acid injection also resulted in intense astrogliosis--as assessed by the number of glial fibrillary acidic protein (GFAP) immunopositive cells--in both hemispheres, forming a clear astroglial scar ipsilaterally to the injection site. Heat-shock protein 70 (Hsp70) immunopositive cells were also observed in the ipsilateral dentate gyrus (DG) following kainic acid injection. When IGF-I was administered together with kainic acid, practically no signs of degeneration were detected in the contralateral hemisphere, while in the ipsilateral, there was a smaller degree of cell loss, reduced number of FluoroJade B-stained cells, decreased reactive gliosis and fewer Hsp70-positive cells. Our present results extend further the cases in which IGF-I is shown to exhibit neuroprotective properties in neurodegenerative processes in the CNS. PMID:19777341
Miltiadous, Panagiota; Stamatakis, Antonios; Stylianopoulou, Fotini
Genetics and molecular pathology of Stargardt-like macular degeneration
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 decade of life (i.e., starting in the teenage years). The clinical profile at any given age among STGD3 patients can be variable suggesting that, although STGD3 is a single gene defect, other genetic or environmental factors may play a role in moderating the final disease phenotype. Genetic studies localized the STGD3 disease locus to a small region on the short arm of human chromosome 6, and application of a positional candidate gene approach identified protein truncating mutations in the elongation of very long chain fatty acids-4 gene (ELOVL4) in patients with this disease. The ELOVL4 gene encodes a protein homologous to the ELO group of proteins that participate in fatty acid elongation in yeast. Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. Mice carrying an Elovl4 mutation developed photoreceptor degeneration and depletion of very long chain fatty acids (VLCFA). ELOVL4 protein participates in the synthesis of fatty acids with chain length longer than 26 carbons. Studies on ELOVL4 indicate that VLCFA may be necessary for normal function of the retina, and the defective protein trafficking and/or altered VLCFA elongation underlies the pathology associated with STGD3. Determining the role of VLCFA in the retina and discerning the implications of abnormal trafficking of mutant ELOVL4 and depleted VLCFA content in the pathology of STGD3 will provide valuable insight in understanding the retinal structure, function, and pathology underlying STGD3 and may lead to a better understanding of the process of macular disease in general.
Vasireddy, Vidyullatha; Wong, Paul; Ayyagaria, Radha
Cerebellar Degeneration Associated with Sj?gren's Syndrome
Background Neurologic manifestations of primary Sj÷gren's syndrome (PSS) have been reported to vary from sensory polyneuropathy to encephalopathy or psychiatric problems. However, marked cerebellar degeneration associated with PSS has rarely been reported. Case Report We describe a patient with Sj÷gren's syndrome who exhibited rapidly progressive cerebellar ataxia, nystagmus, cognitive decline, and psychiatric problems. Brain magnetic resonance imaging revealed marked atrophy of the cerebellum, and 18F-fluorodeoxyglucose positron-emission tomography demonstrated glucose hypometabolism of the cerebellum. Conclusions Our PSS patient exhibited a progressive course of cerebellar syndrome, as evidenced by cerebellar atrophy on serial brain images.
Kim, Mi Jung; Lee, Myoung Chong; Lee, Jae-Hong
Suppression of Myoclonus in Corticobasal Degeneration by Levetiracetam
Myoclonus in corticobasal degeneration (CBD) has often been associated with severe and difficult to treat disabilities. Levetiracetam is a new antiepileptic agent with antimyoclonic effects. Herein, we present a 72-year-old woman with clinically probable CBD and with spontaneous rhythmic myoclonus in the right foot, which was markedly ameliorated through treatment with levetiracetam. The effect of levetiracetam was associated with the decreased amplitude of enlarged cortical somatosensory evoked potentials. This result suggests that the antimyoclonic effect of levetiracetam might be mediated through the suppression of increased cortical excitability.
Cho, Jae Wook; Lee, Jae Hyeok
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
Suppression of myoclonus in corticobasal degeneration by levetiracetam.
Myoclonus in corticobasal degeneration (CBD) has often been associated with severe and difficult to treat disabilities. Levetiracetam is a new antiepileptic agent with antimyoclonic effects. Herein, we present a 72-year-old woman with clinically probable CBD and with spontaneous rhythmic myoclonus in the right foot, which was markedly ameliorated through treatment with levetiracetam. The effect of levetiracetam was associated with the decreased amplitude of enlarged cortical somatosensory evoked potentials. This result suggests that the antimyoclonic effect of levetiracetam might be mediated through the suppression of increased cortical excitability. PMID:24926409
Cho, Jae Wook; Lee, Jae Hyeok
Neuroleptic Malignant Syndrome in a Patient with Corticobasal Degeneration
Parkinsonĺs disease is a principal underlying disease of neuroleptic malignant syndrome (NMS) occurring in parkinsonian disorders, but NMS may occur in patients with progressive supranuclear palsy and multiple system atrophy. We report first patient with corticobasal degeneration (CBD) who developed NMS after abrupt reduction of antiparkinsonian medication and concurrent infection. It should be kept in mind that the prevention of infectious illness, which is common complication in parkinson-plus syndrome, is important, and dose reduction or withdrawal of anti-parkinsonian medications should be carefully performed even in the patients with CBD who are expected to be unresponsive to levodopa treatment.
Lee, Myung Jun; Lyoo, Chul Hyoung; Lee, Myung Sik
Unilateral superior pellucid marginal degeneration in a case with ichthyosis.
A 47-year-old man with ichthyosis vulgaris presented to our hospital complaining of reduced visual acuity and ocular discomfort in the left eye. Slit-lamp biomicroscopy revealed a thinning about 2mm from the superior limbus and superficial punctate corneal lesions in the left eyes. Corneal topography was 'butterfly-like' in an area of increased elevation in the left eye. Although ichthyosis vulgaris and unilateral superior pellucid marginal degeneration are both uncommon conditions, this is first report about these two conditions in studied together. PMID:21084217
Dundar, Huseyin; Kara, Necip; Kaya, Vedat; Bozkurt, Ercument; Yazici, Ahmet Taylan; Hekimhan, Pelin Kaynak
Coupling and degenerating modes in longitudinal-torsional step horns.
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
Quantum fluctuation of nonlinear degenerate optical parametric amplification
NASA Astrophysics Data System (ADS)
An analytical solution of the Fokker Planck equation for the nonlinear degenerate optical parametric amplifier (DOPA) is presented, taking into account the influence of pump depletion on the generation of squeezed light. Results conform to those obtained using perturbation series expansion theory near threshold, and also apply to the whole region far away from threshold. When the nonlinear term(????0) is neglected, the solution transitions naturally to the linear approximation solution; when the nonlinear term is retained (???), in the case ????0, the quantum fluctuations are close to vacuum fluctuations; in the case ????1, squeezing increases, and tends to the result obtained using linear theory, 1/(1?+??).
Zhao, C. Y.; Tan, W. H.
Population control in a degenerate n-level atom.
NASA Astrophysics Data System (ADS)
We show in general how to control the electron population in a degenerate n level atom interacting with a strong external field. Detailed examples are discussed for n=2 (corresponding to a qubit), and n = 3. In both cases the electron population may be fully transferred to a targeted state under by properly adjusting both matrix elements and strength of the external field. For n ? 5 some numerical work is required to find the roots of an n^th order equation. Otherwise the solutions are analytic.
McGuire, J. H.; Shakov, Kh. Kh.; Rakhimov, Kh. Yu.
Coherent Ising machine based on degenerate optical parametric oscillators
NASA Astrophysics Data System (ADS)
A degenerate optical parametric oscillator network is proposed to solve the NP-hard problem of finding a ground state of the Ising model. The underlying operating mechanism originates from the bistable output phase of each oscillator and the inherent preference of the network in selecting oscillation modes with the minimum photon decay rate. Computational experiments are performed on all instances reducible to the NP-hard MAX-CUT problems on cubic graphs of order up to 20. The numerical results reasonably suggest the effectiveness of the proposed network.
Wang, Zhe; Marandi, Alireza; Wen, Kai; Byer, Robert L.; Yamamoto, Yoshihisa
Aetiology of spheroidal degeneration of the cornea in Labrador.
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
Johnson, G J
Genetic and Epigenetic Regulation in Age-related Macular Degeneration
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.
Wei, Lai; Chen, Ping; Lee, Joo Hyun; Nussenblatt, Robert B.
The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective.
Chronic neurodegenerative diseases of the CNS (central nervous system) are characterized by the loss of neurons. There is, however, growing evidence to show that an early stage of this process involves degeneration of presynaptic terminals prior to the loss of the cell body. Synaptic plasticity in CNS pathology has been associated with microglia and the phenomenon of synaptic stripping. We review here the evidence for the involvement of microglia in synaptic stripping and synapse degeneration and we conclude that this is a case of guilt by association. In disease models of chronic neurodegeneration, there is no evidence that microglia play an active role in either synaptic stripping or synapse degeneration, but the degeneration of the synapse and the envelopment of a degenerating terminal appears to be a neuron autonomous event. We highlight here some of the gaps in our understanding of synapse degeneration in chronic neurodegenerative disease. PMID:20967131
Perry, V Hugh; O'Connor, Vincent
Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurements on peripheral nerve. [Rats
Wallerian degeneration of rat sciatic nerves was induced by nerve section. Fifteen days later the degenerated nerves were compared with the intact contralteral nerves from the same animal. Histological sections showed the changes typical of wallerian degeneration: axonal degeneration and secondary demyelination. The freshly dissected nerves were analyzed by magnetic resonance (MR) spectroscopy at 10 MHz, and the water content was determined by dehydration. In the degenerated nerves there was a marked prolongation of both T1 and T2 relaxation times, accompanied by an increase of water content. These results suggest that it should be possible to detect wallerian degeneration in MR images; this will have an important impact on neuropathological diagnosis of central and peripheral nervous system lesions.
Jolesz, F.A.; Polak, J.F.; Ruenzel, P.W.; Adams, D.F.
Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration
Fluoro-Jade is an anionic fluorochrome capable of selectively staining degenerating neurons in brain slices. The histochemical application of Fluoro-Jade results in a simple, sensitive and reliable method for staining degenerating neurons and their processes. The technique will detect neuronal degeneration resulting from exposure to a variety of neurotoxic insults. Fluoro-Jade can be combined with other fluorescent methodologies including immunofluorescence, fluorescent
Larry C. Schmued; Christopher Albertson; William Slikker Jr
Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration
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
Combined corneal lipid and calcium degeneration in a dog with hyperadrenocorticism: a case report.
Corneal degeneration may occur with a deposition of lipids or calcium, or both. Calcareous and lipid degeneration may be either primary or secondary, associated with systemic diseases such as primary hyperlipidemia, hyperlipidemia associated with hyperadrenocorticism, and hypothyroidism. The authors report a case of bilateral corneal lipid and calcium degeneration in a 7-year-old female Poodle with hyperadrenocorticism. The condition worsened with Lysodren therapy but responded to surgical excision. PMID:11940251
Laus, JosÚ L; dos Santos, Cristiane; Talieri, Ivia C; Oriß, Arianne P; Bechara, Gervßsio H
Expression of bioactive bone morphogenetic proteins in the subacromial bursa of patients with chronic degeneration of the rotator cuff.
Degeneration of the rotator cuff is often associated with inflammation of the subacromial bursa and focal mineralization of the supraspinatus tendon. Portions of the supraspinatus tendon distant from the insertion site could transform into fibrous cartilage, causing rotator-cuff tears owing to mechanical instability. Indirect evidence is presented to link this pathology to ectopic production and secretion of bioactive bone morphogenetic proteins (BMPs) from sites within the subacromial bursa. Surgically removed specimens of subacromial bursa tissue from patients with chronic tears of the rotator cuff were analyzed by immunohistochemistry and reverse transcription-PCR. Bioactive BMP was detected in bursa extracts by a bioassay based on induction of alkaline phosphatase in the osteogenic/myogenic cell line C2C12. Topical and differential expression of BMP-2/4 and BMP-7 mRNA and protein was found in bursa tissue. The bioassay of C2C12 cells revealed amounts of active BMP high enough to induce osteogenic cell types, and blocking BMP with specific antibodies or soluble BMP receptors Alk-3 and Alk-6 abolished the inductive properties of the extract. Sufficient information was gathered to explain how ectopic expression of BMP might induce tissue transformation into ectopic bone/cartilage and, therefore, promote structural degeneration of the rotator cuff. Early surgical removal of the subacromial bursa might present an option to interrupt disease progression. PMID:16719933
Neuwirth, Jana; Fuhrmann, RenÚe A E; Veit, Amanda; Aurich, Matthias; StonÔns, Ilmars; Trommer, Tilo; Hortschansky, Peter; Chubinskaya, Susanna; Mollenhauer, Juergen A
Coupled modes in magnetized dense plasma with relativistic-degenerate electrons
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)
Three dimensional electrostatic solitary waves in a dense magnetoplasma with relativistically degenerate electrons
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)
The condition of regular degeneration for singularly perturbed systems of linear differential-difference equations.
NASA Technical Reports Server (NTRS)
Extension of problem of singular perturbation for linear scalar constant coefficient differential- difference equation with single retardation to several retardations, noting degenerate equation solution
Cooke, K. L.; Meyer, K. R.
Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration
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.
Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo
Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration
Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.
Longo, Umile Giuseppe; Papapietro, Nicola; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo
Mesenchymal stem cell for prevention and management of intervertebral disc degeneration.
Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration. PMID:22550520
Longo, Umile Giuseppe; Papapietro, Nicola; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo
Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.
Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0.78, 0.64-0.88). Surgeons as well as radiologists and seniors as well as juniors obtained excellent inter- and intra-rater agreement. The measurement error of the scoring system for cervical facet joint degeneration was 20.1 versus 24.2% of the subjective impression results. This scoring system showed good intra-rater agreement (ICC = 0.71, 0.42-0.89) and fair inter-rater agreement (ICC = 0.49, 0.26-0.74). Both scoring systems fulfilled the criteria for recommendation proposed by Kettler and Wilke. Our scoring systems can be reliable and objective tools for assessing cervical disc and facet joint degeneration. Moreover, the scoring system of cervical disc degeneration was shown to be experience- and discipline-independent. PMID:19005690
Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan
The brain basis of musicophilia: evidence from frontotemporal lobar degeneration
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.
Fletcher, Phillip D.; Downey, Laura E.; Witoonpanich, Pirada; Warren, Jason D.
Symmetry of quantum phase space in a degenerate Hamiltonian system
NASA Astrophysics Data System (ADS)
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? (where ? 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.
Berman, G. P.; Demikhovskii, V. Ya.; Kamenev, D. I.
Diffusion tensor imaging in a child with hypertrophic olivary degeneration.
Hypertrophic olivary degeneration (HOD) is caused by disruptive lesions affecting components of the Guillain-Mollaret triangle (GMT). We present conventional magnetic resonance and diffusion tensor imaging (DTI) findings in a 6-year-old girl with HOD after surgery for a midbrain pilocytic astrocytoma. To our knowledge, this is the first dedicated DTI analysis of GMT in a child with HOD in the literature. In our patient, we found higher fractional anisotropy (FA) and axial diffusivity values of the inferior olivary nucleus (ION) and lower FA, but higher radial diffusivity (RD) values of all other GMT components compared to age-matched controls. Increased FA values of the ION may be explained by increased packing of white matter fibers. However, associated hyperintense T2 signal is contradictory and the association between increased FA values and hyperintense T2 signal remains unclear. Low FA and high RD values of the other GMT components likely reflect demyelination with axonal degeneration and correlate well with histopathological findings. PMID:23307661
Meoded, Avner; Poretti, Andrea; Ilica, A Turan; Perez, Randall; Jallo, George; Burger, Peter C; Huisman, Thierry A G M; Izbudak, Izlem
Imaging corticospinal degeneration in neonatal rats with unilateral cerebral infarction.
Recent human studies indicate that magnetic resonance (MR) imaging, particularly diffusion weighted imaging, detects abnormalities within the descending cortico-spinal tract following stroke. Whether these changes are directly related to processes of axonal degeneration and how MR changes (e.g. apparent diffusion coefficient of water (ADC) and T(2)) vary in their diagnostic utility over time is not known. The present study demonstrates that a commonly used rat model of neonatal transient unilateral hypoxia-ischemia provides similar diffusion weighted and ADC changes in the cerebral peduncle as those observed in human neonates clinically. Imaging the descending cortico-spinal tract in this model at defined acute (1-3 days) and chronic (1 and 4 weeks) time points demonstrates increased T(2) and progressive changes in ADC within the descending cortico-spinal tract in the first days to weeks following hypoxia-ischemia with a normalization by 1 week and further increases in ispilateral cerebral cortex by 4 weeks. These imaging changes are associated with reduced axonal neurofilament staining both at the subacute and more chronic time points. This demonstrates directly the utility of ADC and T(2) MRI to detect acute changes in axons associated with early Wallerian degeneration. PMID:21223967
Lama, S; Qiao, M; Kirton, A; Sun, S; Cheng, E; Foniok, T; Tuor, U I
Symmetry of quantum phase space in a degenerate Hamiltonian system.
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.
Degenerate Frequencies I: Noise Decoupling of Planar Ladder Coils
NASA Astrophysics Data System (ADS)
Degenerate Frequencies I: Noise Decoupling of Planar Ladder Coils Y.-C. N. Cheng, T. P. Eagan, T. K. Kidane and R. W. Brown Department of Physics, Case Western Reserve University The series of closed loops in a radiofrequency (RF) ladder coil is a useful configuration for detecting a magnetic resonance imaging (MRI) signal for the human body. Each loop is especially sensitive to the portion of the body immediately beneath it. To speed up imaging, independent preamplifiers can be tapped into each loop, but it is still important to decouple the noise from loop to loop. For instance, phase-array systems applied to spinal-cord imaging would be advanced by new planar coils with reduced noise coupling. In this talk, we discuss the relation between the inductive decoupling of a coil and its degenerate RF spectrum. In a Kirchoff network analysis, the nearest-neighbor coupling approximation is considered. A general theorem will be presented and can be applied to any number of meshes and order of coupling. Finally, the freedom to choose linearly independent current distributions is highlighted.
Cheng, Yu-Chung; Eagan, Timothy; Kidane, Tesfaye; Brown, Robert
Light damage as a model of retinal degeneration.
The induction of retinal degeneration by light exposure is widely used to study mechanisms of cell death. The advantage of such light-induced lesions over genetically determined degenerations is that light exposures can be manipulated according to the needs of the experimenter. Bright white light exposure can induce a synchronized burst of apoptosis in photoreceptors in a large retinal area which permits to study cellular and molecular events in a controlled fashion. Blue light of high energy induces a hot spot of high retinal irradiance within very short exposure durations (seconds to minutes) and may help to unravel the initial events after light absorption which may be similar for all damage regimens. These initial events may then induce various molecular signaling pathways and secondary effects such as lipid and protein oxidation, which may be varying in different light damage setups and different strains or species, respectively. Blue light lesions also allow to study cellular responses in a circumscribed retinal area (hot spot) in comparison with the surrounding tissue.Here we describe the methods for short-term exposures (within the hours range) to bright full-spectrum white light and for short exposures (seconds to minutes) to high-energy monochromatic blue or green light. PMID:23150362
Grimm, Christian; RemÚ, Charlotte E
Cardiac sympathetic degeneration correlates with olfactory function in Parkinson's disease.
Autonomic and olfactory dysfunctions are considered markers for preclinical diagnosis in Parkinson's disease (PD), because pathological changes in these systems can start before motor symptoms develop. We investigated whether cardiac sympathetic function and olfactory function are associated in PD. Participants comprised 40 nondemented patients with idiopathic PD, and age-matched controls. Cardiac sympathetic function was evaluated by (123) I-metaiodobenzylguanidine (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the washout rate (WR). Olfactory function was evaluated using the Odor Stick Identification Test for Japanese, which evaluates the detection of 12 odorants familiar to Japanese participants. Smell identification scores were significantly lower (P < 0.001) in patients with PD than in controls. Smell identification scores correlated positively with early (P < 0.05) and delayed H/M ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients with early PD (below 5 years of the start of motor symptoms), whereas smell identification scores did not correlate with any parameters of MIBG in the advanced PD (above 5 years of the start of motor symptoms). There was no correlation between motor symptom scores and smell identification scores, H/M ratios, or WR. The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate of speed in advanced PD. PMID:20131383
Iijima, Mutsumi; Osawa, Mikio; Momose, Mitsuru; Kobayakawa, Tatsu; Saito, Sachiko; Iwata, Makoto; Uchiyama, Shinichiro
Structural basis for complement factor H-linked age-related macular degeneration
Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to ?50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonanceľmonitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAGľFH complex.
Prosser, Beverly E.; Johnson, Steven; Roversi, Pietro; Herbert, Andrew P.; Blaum, Barbel S.; Tyrrell, Jess; Jowitt, Thomas A.; Clark, Simon J.; Tarelli, Edward; Uhrin, Dusan; Barlow, Paul N.; Sim, Robert B.; Day, Anthony J.; Lea, Susan M.
Structural basis for complement factor H linked age-related macular degeneration.
Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to approximately 50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance-monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG-FH complex. PMID:17893204
Prosser, Beverly E; Johnson, Steven; Roversi, Pietro; Herbert, Andrew P; Blaum, Bńrbel S; Tyrrell, Jess; Jowitt, Thomas A; Clark, Simon J; Tarelli, Edward; UhrÝn, Dusan; Barlow, Paul N; Sim, Robert B; Day, Anthony J; Lea, Susan M
CNTF Induces Regeneration of Cone Outer Segments in a Rat Model of Retinal Degeneration
Background Cone photoreceptors are responsible for color and central vision. In the late stage of retinitis pigmentosa and in geographic atrophy associated with age-related macular degeneration, cone degeneration eventually causes loss of central vision. In the present work, we investigated cone degeneration secondary to rod loss in the S334ter-3 transgenic rats carrying the rhodopsin mutation S334ter. Methodology/Principal Findings Recombinant human ciliary neurotrophic factor (CNTF) was delivered by intravitreal injection to the left eye of an animal, and vehicle to the right eye. Eyes were harvested 10 days after injection. Cone outer segments (COS), and cell bodies were identified by staining with peanut agglutinin and cone arrestin antibodies in whole-mount retinas. For long-term treatment with CNTF, CNTF secreting microdevices were implanted into the left eyes at postnatal day (PD) 20 and control devices into the right eyes. Cone ERG was recorded at PD 160 from implanted animals. Our results demonstrate that an early sign of cone degeneration is the loss of COS, which concentrated in many small areas throughout the retina and is progressive with age. Treatment with CNTF induces regeneration of COS and thus reverses the degeneration process in early stages of cone degeneration. Sustained delivery of CNTF prevents cones from degeneration and helps them to maintain COS and light-sensing function. Conclusions/Significance Loss of COS is an early sign of secondary cone degeneration whereas cell death occurs much later. At early stages, degenerating cones are capable of regenerating outer segments, indicating the reversal of the degenerative process. Sustained delivery of CNTF preserves cone cells and their function. Long-term treatment with CNTF starting at early stages of degeneration could be a viable strategy for preservation of central vision for patients with retinal degenerations.
Li, Yiwen; Tao, Weng; Luo, Lingyu; Huang, Deqiang; Kauper, Konrad; Stabila, Paul; LaVail, Matthew M.; Laties, Alan M.; Wen, Rong
bcl-2 Overexpression Reduces Apoptotic Photoreceptor Cell Death in Three Different Retinal Degenerations
Apoptosis of photoreceptors occurs infrequently in adult retina but can be triggered in inherited and environmentally induced retinal degenerations. The protooncogene bcl-2 is known to be a potent regulator of cell survival in neurons. We created lines of transgenic mice overexpressing bcl-2 to test for its ability to increase photoreceptor survival. Bcl-2 increased photoreceptor survival in mice with retinal degeneration
Jeannie Chen; John G. Flannery; Matthew M. Lavail; Roy H. Steinberg; Jun Xu; Melvin I. Simon
Simple colorimetric method for detecting degenerate strains of the cultivated basidiomycete Flammulina velutipes (Enokitake).
Degeneration of cultivated strains of Flammulina velutipes is a serious problem. We developed a simple colorimetric method to detect degenerate strains by using a liquid medium supplemented with bromothymol blue and lactose. The ability of a strain to develop normal mushrooms could be determined by the color of the medium. PMID:16204563
Magae, Yumi; Akahane, Kobun; Nakamura, Kimiyoshi; Tsunoda, Shigeyuki
The role of NMDA receptors in the slow neuronal degeneration of Parkinson's disease
Summary Parkinson's disease is a disorder, in which neurons of various neuronal systems degenerate. Furthermore, in such degenerating neurons, the cytoskeleton seems to be affected. In this respect, Parkinson's disease resembles Alzheimer's disease. Since it has been shown, that elevated levels of intracellular calcium can disrupt the cytoskeleton and that the stimulation of glutamate (NMDA) receptors can cause high intracellular
L. D. Loopuijt; W. J. Schmidt
Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration Through Chondrocytic Differentiation and Stimulation of Endogenous Cells
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
Fan Yang; Victor YL Leung; Keith DK Luk; Danny Chan; Kenneth MC Cheung
Disease Sequence from Mutant Rhodopsin Allele to Rod and Cone Photoreceptor Degeneration in Man
Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and
Artur V. Cideciyan; Donald C. Hood; Yijun Huang; Eyal Banin; Zong-Yi Li; Edwin M. Stone; Ann H. Milam; Samuel G. Jacobson
Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons
The causes and effects of neuronal degeneration are of major interest to a wide variety of neuroscientists. Paralleling this growing interest is an increasing number of methods applicable to the detection of neuronal degeneration. The earliest methods employing aniline dyes were methodologically simple, but difficult to interpret due to a lack of staining specificity. In an attempt to circumvent this
Larry C. Schmued; Chris C. Stowers; Andrew C. Scallet; Lulu Xu
Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients
Objective: Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate. Methods: We report ultrastructural changes that support Ca2- mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 char-
Ranjan Dutta; Jennifer McDonough; Xinghua Yin; John Peterson; Ansi Chang; Thalia Torres; Tatyana Gudz; Wendy B. Macklin; David A. Lewis; Robert J. Fox; Richard Rudick; Karoly Mirnics; Bruce D. Trapp
Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL1? and TNF? expression profile
Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF?). However, to date no studies
Christine Lyn Le Maitre; Judith Alison Hoyland; Anthony J Freemont
Spinocerebellar degeneration with prominent involvement of the motor neuron system: Autopsy report of a sporadic case
A sporadic case of spinocerebellar degeneration with prominent involvement of the motor neuron system is reported. A Japanese male without contributing family history, developed cerebellar ataxia at the age of 52, followed by generalized amyotrophy and ophthalmoplegia, and died aged 58. The clinical findings were pathologically verified as degeneration of the spino-ponto-cerebellar system and the motor neuron system, the latter
Y. Hayashi; K. Nagashima; Y. Urano; M. Iwata
Quantitative and qualitative analysis of Wallerian degeneration using restricted axonal labelling in YFP-H mice
We investigated the usefulness of YFP-H transgenic mice [Neuron 28 (2000) 41] which express yellow fluorescent protein (YFP) in a restricted subset of neurons to study Wallerian degeneration in the PNS. Quantification of YFP positive axons and myelin basic protein (MBP) immunocytochemistry revealed that YFP was randomly distributed to approximately 3% of myelinated motor and sensory fibres. Axotomy-induced Wallerian degeneration
Bogdan Beirowski; Livia Berek; Robert Adalbert; Diana Wagner; Daniela S. Grumme; Klaus Addicks; Richard R. Ribchester; Michael P. Coleman
Review of existing grading systems for cervical or lumbar disc and facet joint degeneration
The aim of this literature review was to present and to evaluate all grading systems for cervical and lumbar disc and facet joint degeneration, which are accessible from the MEDLINE database. A MEDLINE search was conducted to select all articles presenting own grading systems for cervical or lumbar disc or facet joint degeneration. To give an overview, these grading systems
Annette Kettler; Hans-Joachim Wilke
Comparison of Electrical Stimulation Thresholds in Normal and Retinal Degenerated Mouse Retina
Purpose To compare the threshold for electrically elicited action potentials of retinal ganglion cells in normal mouse retina and photoreceptor degenerated (rd) mouse retina. Methods Microelectrode recordings were made from retinal ganglion cells of normal and rd mice. Mice with a genetically based retinal degeneration (rd mice) were grown to the age of 16 weeks, when light-evoked responses could no
Satoshi Suzuki; Mark S. Humayun; James D. Weiland; Shih-Jen Chen; Eyal Margalit; Duke V. Piyathaisere; Eugene de Juan Jr
Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration
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 ôknock-inö 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.
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.
Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.
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
Results of lamellar crescentic resection for pellucid marginal corneal degeneration.
Five eyes in four patients with pellucid marginal corneal degeneration were treated by lamellar crescentic resection of the thinned area inferiorly. Normal-thickness stroma was then reapposed to normal-thickness stroma with multiple interrupted 10-0 polypropylene sutures. If excessive central corneal steepening along a vertical meridian was present three months after surgery, selected sutures were cut and removed depending on the slit-lamp appearance, keratometry reading, and photokeratograph pattern. Improvement of visual acuity to 20/40 or better was obtained in four of the five eyes with a follow-up of 27 to 40 months (mean, 31.8 months). Early loosening of sutures resulted in a recurrence of corneal thinning and astigmatism in one eye. Pannus developed inferiorly in all five eyes. PMID:1543223
Cameron, J A
Stem cells as tools in regenerative therapy for retinal degeneration
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.
Enzmann, Volker; Yolcu, Esma; Kaplan, Henry J.; Ildstad, Suzanne T.
Functional consequences of locus coeruleus degeneration in Alzheimer's disease.
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
Radiation Therapy for Neovascular Age-related Macular Degeneration
In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.
Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States)] [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States)] [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: email@example.com [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)
Next generation therapeutic solutions for age-related macular degeneration
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.
Cunnsamy, Khrishen; Ufret-Vincenty, Rafael; Wang, Shusheng
Stopping of relativistic electrons in a partially degenerate electron fluid.
The stopping mechanisms of relativistic electron beams in superdense and partially degenerate electron fluid targets are investigated in the framework of the fast ignitor concept for inertial confinement fusion. In order to comply with specific demands in this area, we focus attention on the target partial degeneracy parameter theta= T(e) / T(f) , in terms of the thermal to Fermi temperature ratio. The target electron fluid is thus modeled very accurately with a random phase approximation dielectric function. The stopping results are shown to be very weakly theta dependent. However, a quantum target description is needed to recover their correct increasing trend with increasing projectile energy. The ranges and effective penetration depths in precompressed thermonuclear fuels are shown to be nearly a factor of 2 shorter than earlier classical estimates in the same conditions. The overall conclusions pertaining to the feasibility of fast ignition thus remain unchanged. PMID:15783429
Starikov, K V; Deutsch, C
Axonal degeneration affects muscle density in older men and women
Using data from InCHIANTI, a prospective population-based survey of older persons, we examined the relationship of peroneal nerve conduction velocity (NCV, a measure of nerve myelination) and compound muscle action potential (CMAP, a measure of axonal degeneration) with calf muscle mass and density, two complementary measures of sarcopenia. NCV and CMAP were assessed by surface electroneurography of the right peroneal nerve conducted in 1162 participants, 515 men and 647 women, age 21ľ96 years, free of major neurological diseases. Cross-sectional muscle area and calf muscle density were measured using peripheral quantitative computerized tomography (pQCT). Both nerve and muscle parameters declined with age although in most cases the decline was not linear. In both sexes, CMAP, but not NCV, was independently and significantly associated with calf muscle density. These findings suggest that intrinsic changes in the muscle tissue are partially caused by a reduction in the number of motor axons.
Lauretani, Fulvio; Bandinelli, Stefania; Bartali, Benedetta; Di Iorio, Angelo; Giacomini, Vittoria; Corsi, Anna Maria; Guralnik, Jack M.; Ferrucci, Luigi
Magnetoresistance in epitaxially grown degenerate ZnO thin films
NASA Astrophysics Data System (ADS)
The magnetoresistance of high-quality epitaxial doped ZnO(:Ga) thin films with various electron concentrations ranging from 3.2Î1018 to 1.3Î1020 cm-3 has been measured. All samples investigated exhibit a negative magnetoresistance at low magnetic fields. Its magnitude systematically depends on carrier concentration and temperature. Low-doped samples switch the sign of the magnetoresistance and the conventional positive component dominates at high fields, whereas highly doped degenerate samples only show a negative component up to fields of 14.5 T. Therefore, the data are analyzed as the sum of a positive and negative contribution to the magnetoresistance applying a semiempirical expression to describe the observed behavior. The model takes into account third-order s-d exchange Hamiltonians describing the negative part and a two-band model for the positive contribution. Least-squares fits to the data are presented. Theory and experiment are in excellent agreement.
Reuss, F.; Frank, S.; Kirchner, C.; Kling, R.; Gruber, Th.; Waag, A.
Intracorneal rings for the correction of pellucid marginal degeneration.
We report a case of Intacs(R) (KeraVision) implantation for the correction of pellucid marginal degeneration (PMD). Preoperatively, the patient's uncorrected visual acuity (UCVA) was 0.05, the best spectacle-corrected visual acuity (BSCVA) was 0.1, and the refraction was -2.00 -7.00 x 90 in the right eye. The flattest meridian (K1) measured 43.8@104 and the steepest meridian (K2), 51.3@14. Ultrasound pachymetry revealed a thin cornea of 420 micrometers. One month postoperatively, the UCVA was 0.2, the BSCVA was 0.5, and the refraction was -8.00 -7.00 x 50. Contact lens best corrected visual acuity was 0.9; 6 months postoperatively, it improved to 1.0. The use of Intacs to treat PMD seems to be viable and improves visual acuity. The residual error can be corrected with contact lenses. PMID:12900254
Rodriguez-Prats, Jose; Galal, Ahmed; Garcia-Lledo, Magdalena; De La Hoz, Fernando; Aliˇ, Jorge L
Macular dystrophies mimicking age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population in the Western world. AMD is a clinically heterogeneous disease presenting with drusen, pigmentary changes, geographic atrophy and/or choroidal neovascularization. Due to its heterogeneous presentation, it can be challenging to distinguish AMD from several macular diseases that can mimic the features of AMD. This clinical overlap may potentially lead to misdiagnosis. In this review, we discuss the characteristics of AMD and the macular dystrophies that can mimic AMD. The appropriate use of clinical and genetic analysis can aid the clinician to establish the correct diagnosis, and to provide the patient with the appropriate prognostic information. An overview is presented of overlapping and distinguishing clinical features. PMID:24291520
Saksens, Nicole T M; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G; den Hollander, Anneke I; Keunen, Jan E E; Boon, Camiel J F; Hoyng, Carel B
Origins of Band-Gap Renormalization in Degenerately Doped Semiconductors
Degenerate n-type doping of semiconductors results in optical band-gap widening through occupation of the conduction band, which is partially offset by the so-called band-gap renormalization. From investigation of the magnitude and origin of these shifts through density-functional band-structure theory, we demonstrate that the key contribution to renormalization arises from the nonparabolic nature of the host conduction band but not the rigid shift of the band edges, as is the current paradigm. Furthermore, the carrier dependence of the band-gap widening is highly sensitive to the electronic states of the dopant ion, which can be involved in a significant reconstruction of the lower conduction band.
Walsh, A.; Da Silva, J.L.F.; Wei, S.-H.
Paraneoplastic cerebellar degeneration associated with lymphoepithelial carcinoma of the tonsil
Background Paraneoplastic cerebellar degeneration (PCD) is a classical tumor-associated, immune-mediated disease typically associated with gynecological malignancies, small-cell lung-cancer or lymphoma. Case presentation Here we present the case of a 38-year old male with an over 12 months rapidly progressive cerebellar syndrome. Extensive diagnostic workup revealed selective hypermetabolism of the right tonsil in whole-body PET. Histological examination after tonsillectomy demonstrated a lymphoepithelial carcinoma of the tonsil and the tongue base strongly suggesting a paraneoplastic cause of the cerebellar syndrome. To the best of our knowledge this is the first case of an association of a lymphoepithelial carcinoma, a rare pharyngeal tumor, with PCD. Conclusions In cases of classical paraneoplastic syndromes an extensive search for neoplasms should be performed including whole-body PET to detect tumors early in the course of the disease.
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.
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
Lattice-cavity solitons in a degenerate optical parametric oscillator
NASA Astrophysics Data System (ADS)
We predict the existence of lattice-cavity solitons for a quadratic nonlinear cavity, where the linear losses are compensated for by the optical pump at second harmonic (degenerate optical parametric oscillator), and which is endowed with a one-dimensional photonic lattice. In the limit of strong discreteness (weak coupling) this kind of soliton solution contains as the subclass the quadratic discrete cavity solitons. The nonlinear coupling between the Bloch waves of different photonics bands allows for the formation of a reach variety of localized solutions. In particular, different types of multiband lattice-cavity solitons can be identified. Most types of lattice-cavity solitons do not have counterparts, neither in conventional planar microresonators nor in genuine discrete systems as an array of weakly coupled cavities. We show that these solitons may destabilize as a consequence of the competition between Bloch waves of different photonic bands.
Egorov, O. A.; Lederer, F.
Pure and mixed states in degenerate parametric oscillation
NASA Astrophysics Data System (ADS)
The degree of purity of the quantum state of electromagnetic field at the output of a degenerate optical parametric oscillator is theoretically analyzed. It is shown that, in the subthreshold and significantly suprathreshold modes, the degree of purity of the state of pairs of waves with frequencies ? s ▒ ? (? s is the signal mode frequency) is unity. Based on this fact, it is concluded that these pairs of waves parametrically develop independent of any other such pairs. At the same time, in the suprathreshold mode near the oscillation threshold, the degree of purity of wave pairs can be much smaller than unity. However, consideration of a tetrad of waves with frequencies ? s ▒ ? and ? p ▒ ? shows that this system is in a pure state, which indicates its independent development.
Golubev, Yu. M.; Golubeva, T. Yu.; Gavrikov, A. A.; Fabre, C.
Bietti's tapetoretinal degeneration with marginal corneal dystrophy crystalline retinopathy.
In 1937 Bietti reported a tapetoretinal degeneration with associated corneal deposits at the limbus. The hallmark of the disease was the crystalline characteristics of the retinal spots as well as those at the corneal limbus. Bagolini and Ioli-Spade in 1968 presented a 30 year follow-up on Bietti's cases and presented six additional cases. The present report delas with this entity in Orientals, a Chinese woman and a Japanese man. Corneal and conjunctival biopsy from the female patient revelaed a lipid deposition in both fibroblasts and epithelium. The term "crystalline retinopathy" has been added to the description of this entity since it defines the most characteristic feature of the syndrome. Images FIGURE 7 A FIGURE 7 B FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 2 C FIGURE 3 FIGURE 4 A FIGURE 4 B FIGURE 5 FIGURE 6 A FIGURE 6 B FIGURE 6 C FIGURE 8
Welch, R B
Today and Future of Age-Related Macular Degeneration
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.
Liu, Kang; Xie, Bolin
New Perspective on Parkinsonism in Frontotemporal Lobar Degeneration
Frontotemporal dementia (FTD) is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20ľ30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17). The genes associated with parkinsonism are microtubule associated protein tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject.
Park, Hee Kyung; Chung, Sun J.
Age-related macular degeneration: Evidence of a major gene
Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.
Bhatt, S.; Warren, C.; Yang, H. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others
Pellucid Marginal Degeneration and Bilateral Corneal Perforation: Case Report and Review of the Literature
Purpose To review corneal perforation cases in pellucid marginal degeneration and report a case of bilateral spontaneous perforation at presentation in rigid gas permeable contact lens wear and pellucid marginal degeneration. Methods Case report and literature review. Results The presentation, clinical course, surgical intervention, pathologic analysis, and postoperative outcome of a case of bilateral spontaneous corneal perforation in pellucid marginal degeneration are detailed. All spontaneous corneal perforation cases associated with pellucid marginal degeneration are reviewed. Conclusions Pellucid marginal degeneration can lead to spontaneous corneal perforation resulting in the need for urgent therapeutic intervention. A potential for severe ocular morbidity should be considered in all patients with this disorder despite a seemingly stable disease and appropriate gas permeable contact lens wear. Unilateral perforation cases should be watched closely for development of complications in the fellow eye.
Barry Lee, William; O'Halloran, Henry S.; Grossniklaus, Hans E.
Protective Effect of Ligustrazine on Lumbar Intervertebral Disc Degeneration of Rats Induced by Prolonged Upright Posture
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.
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
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.
Contribution of disc degeneration to osteophyte formation in the cervical spine: a biomechanical investigation.
Cervical spine disorders such as spondylotic radiculopathy and myelopathy are often related to osteophyte formation. Bone remodeling experimental-analytical studies have correlated biomechanical responses such as stress and strain energy density to the formation of bony outgrowth. Using these responses of the spinal components, the present study was conducted to investigate the basis for the occurrence of disc-related pathological conditions. An anatomically accurate and validated intact finite element model of the C4-C5-C6 cervical spine was used to simulate progressive disc degeneration at the C5-C6 level. Slight degeneration included an alteration of material properties of the nucleus pulposus representing the dehydration process. Moderate degeneration included an alteration of fiber content and material properties of the anulus fibrosus representing the disintegrated nature of the anulus in addition to dehydrated nucleus. Severe degeneration included decrease in the intervertebral disc height with dehydrated nucleus and disintegrated anulus. The intact and three degenerated models were exercised under compression, and the overall force-displacement response, local segmental stiffness, anulus fiber strain, disc bulge, anulus stress, load shared by the disc and facet joints, pressure in the disc, facet and uncovertebral joints, and strain energy density and stress in the vertebral cortex were determined. The overall stiffness (C4-C6) increased with the severity of degeneration. The segmental stiffness at the degenerated level (C5-C6) increased with the severity of degeneration. Intervertebral disc bulge and anulus stress and strain decreased at the degenerated level. The strain energy density and stress in vertebral cortex increased adjacent to the degenerated disc. Specifically, the anterior region of the cortex responded with a higher increase in these responses. The increased strain energy density and stress in the vertebral cortex over time may induce the remodeling process according to Wolff's law, leading to the formation of osteophytes. PMID:11562150
Kumaresan, S; Yoganandan, N; Pintar, F A; Maiman, D J; Goel, V K
Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.
The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. PMID:23582661
Lattante, Serena; Le Ber, Isabelle; Camuzat, AgnŔs; Pariente, JÚrÚmie; Brice, Alexis; Kabashi, Edor
Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal A? accumulation
Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending on the mutant PS1 dosage, we demonstrate a clear aggravation in both plaque-associated and plaque-distant axonal degeneration, despite of an unchanged APP expression level. Amyloid-? (A?) peptides were found to accumulate in axonal swellings as well as in axons and apical dendrites proximate to neurons accumulating intraneuronal A? in their cell bodies. This suggests that A? can be transported within neurites thereby contributing to axonal deficits. In addition, diffuse extracellular A? deposits were observed in the close vicinity of axonal spheroids accumulating intracellular A?, which might be indicative of a local A? release from sites of axonal damage.
Christensen, Ditte Z.; Huettenrauch, Melanie; Mitkovski, Miso; Pradier, Laurent; Wirths, Oliver
Deafness and Retinal Degeneration in A Novel USH1C Knock-In Mouse Model
Usher syndrome is the leading cause of combined deaf-blindness, but the molecular mechanisms underlying the auditory and visual impairment are poorly understood. Usher I is characterized by profound congenital hearing loss, vestibular dysfunction and progressive retinitis pigmentosa beginning in early adolescence. Using the c.216G>A cryptic splice site mutation in exon 3 of the USH1C gene found in Acadian Usher I patients in Louisiana, we constructed the first mouse model that develops both deafness and retinal degeneration. The same truncated mRNA transcript found in Usher 1C patients is found in the cochleae and retinas of these knock-in mice. Absent auditory-evoked brainstem responses indicated that the mutant mice are deaf at one month of age. Cochlear histology showed disorganized hair cell rows, abnormal bundles, and loss of both inner and outer hair cells in the middle turns and at the base. Retinal dysfunction as evident by an abnormal electroretinogram was seen as early as 1 month of age, with progressive loss of rod photoreceptors between 6 and 12 months of age. This knock-in mouse reproduces the dual sensory loss of human Usher I, providing a novel resource to study the disease mechanism and the development of therapies.
Lentz, Jennifer J.; Gordon, William C.; Farris, Hamilton E.; MacDonald, Glen H.; Cunningham, Dale E.; Robbins, Carol A.; Tempel, Bruce L.; Bazan, Nicolas G.; Rubel, Edwin W.; Oesterle, Elizabeth C.; Keats, Bronya J.
Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.
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 familyľbased 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; Mńnnikk÷, Minna; Mńkelń, Pirkka; Karppinen, Jaro; Jńrvelin, 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
Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant
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 familyľbased 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.
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
Rotational vertebral artery occlusion secondary to adjacent-level degeneration following anterior cervical discectomy and fusion.
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
Anecortave acetate in the treatment of age-related macular degeneration
RETAANE« 15mg (anecortave acetate suspension) is under investigation to treat exudative age-related macular degeneration (AMD), the single largest cause of blindness in the Western world, affecting over 15 million people in the USA. RETAANE suspension is a unique synthetic cortisene and has antiangiogenic properties that were established in multiple experimental models of angiogenesis. The molecule acts at multiple sites of the angiogenic cascade. Clinical trials in patients with exudative AMD have demonstrated the excellent safety record of both the drug anecortave acetate and the posterior juxtascleral depot (PJD) administration procedure. A pivotal study comparing RETAANE suspension with placebo showed a significantly higher chance of maintaining vision in the treatment (73%) as compared with placebo (47%). Another study compared RETAANE suspension with Visudyne« photodynamic therapy, revealing no statistically significant differences between the two treatments over 24 months. AMD is a multi-faceted disease and therefore a molecule such as RETAANE suspension with a unique mechanism of action, demonstrated clinical efficacy, and retreatment every six months is an important potential treatment option which should be further investigated both as a monotherapy or in combination with other treatment strategies.
Augustin, Albert
Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy
Sensory polyneuropathies are the most frequent neurological complication of human immunodeficiency virus (HIV) infection. Distal symmetric polyneuropathy (DSP), associated with HIV infection, is characterized by length-dependent axonal degeneration of sensory fibres. In rodent dorsal root ganglia (DRG) cultures, HIV viral envelope protein gp120 results in neurotoxicity and axonal degeneration. Since it is unknown whether the axonal degeneration is a consequence
Giorgia Melli; Sanjay C. Keswani; Angela Fischer; Weiran Chen; Ahmet Hok
Differential proteomic analysis of the mouse retina: The induction of crystallin proteins by retinal degeneration in the rd1 mouse
We have applied proteomic analysis to the degeneration of photoreceptors. In the rd1 mouse, a recessive mutation in the PDE6B gene leads to rapid loss of rods through apoptosis. By 5 wk postnatal, virtually all rod photorecep- tors have degenerated, leaving one row of cones that degenerates secondarily. In order to assess comparative protein expression, proteins extracted from whole retina
Nukhet Cavusoglu; Saddek Mohand-Sa§; Olivier Poch; Alain Van-Dorsselaer; Thierry Leveillard
Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar Degeneration
Objective To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobar degeneration (FTLD). Participants and Design A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases of FTLD with TAR DNA-binding protein of 43-kDa (TDP-43)ľpositive inclusions (FTLD-TDP). We identified 97 individuals with FTLD-TDP with pathogenic GRN mutations (GRN+ FTLD-TDP), assessed their genetic and clinical characteristics, and compared them with 453 patients with FTLD-TDP in which GRN mutations were excluded (GRN? FTLD-TDP). No patients were known to be related. Neuropathologic characteristics were confirmed as FTLD-TDP in 79 of the 97 GRN+ FTLDTDP cases and all of the GRN? FTLD-TDP cases. Results Age at onset of FTLD was younger in patients with GRN+ FTLD-TDP vs GRN? FTLD-TDP (median, 58.0 vs 61.0 years; P<.001), as was age at death (median, 65.5 vs 69.0 years; P<.001). Concomitant motor neuron disease was much less common in GRN+ FTLDTDP vs GRN? FTLD-TDP (5.4% vs 26.3%; P<.001). Fifty different GRN mutations were observed, including 2 novel mutations: c.139delG (p.D47TfsX7) and c.378C>A (p.C126X). The 2 most common GRN mutations were c.1477C>T (p.R493X, found in 18 patients, representing 18.6% of GRN cases) and c.26C>A (p.A9D, found in 6 patients, representing 6.2% of cases). Patients with the c.1477C>T mutation shared a haplotype on chromosome 17; clinically, they resembled patients with other GRN mutations. Patients with the c.26C>A mutation appeared to have a younger age at onset of FTLD and at death and more parkinsonian features than those with other GRN mutations. Conclusion GRN+ FTLD-TDP differs in key features from GRN? FTLD-TDP.
Chen-Plotkin, Alice S.; Martinez-Lage, Maria; Sleiman, Patrick M. A.; Hu, William; Greene, Robert; Wood, Elisabeth McCarty; Bing, Shaoxu; Grossman, Murray; Schellenberg, Gerard D.; Hatanpaa, Kimmo J.; Weiner, Myron F.; White, Charles L.; Brooks, William S.; Halliday, Glenda M.; Kril, Jillian J.; Gearing, Marla; Beach, Thomas G.; Graff-Radford, Neill R.; Dickson, Dennis W.; Rademakers, Rosa; Boeve, Bradley F.; Pickering-Brown, Stuart M.; Snowden, Julie; van Swieten, John C.; Heutink, Peter; Seelaar, Harro; Murrell, Jill R.; Ghetti, Bernardino; Spina, Salvatore; Grafman, Jordan; Kaye, Jeffrey A.; Woltjer, Randall L.; Mesulam, Marsel; Bigio, Eileen; Llado, Albert; Miller, Bruce L.; Alzualde, Ainhoa; Moreno, Fermin; Rohrer, Jonathan D.; Mackenzie, Ian R. A.; Feldman, Howard H.; Hamilton, Ronald L.; Cruts, Marc; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine; Bird, Thomas D.; Cairns, Nigel J.; Goate, Allison; Frosch, Matthew P.; Riederer, Peter F.; Bogdanovic, Nenad; Lee, Virginia M. Y.; Trojanowski, John Q.; Van Deerlin, Vivianna M.
Anterograde Degeneration along the Visual Pathway after Optic Nerve Injury
Purpose To investigate anterograde degenerative changes along the visual pathway in a rat model of optic nerve axotomy. Methods Optic nerve transection was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time intervals and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex (V1). The neuronal cell size and cell density were measured in the dLGN and the V1 using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry. Caspase-3 antibodies were also used to identify apoptotic cells. Neurons and astrocytes were detected using NeuN and glial fibrillary acidic protein (GFAP), respectively. Results An early and sustained loss of Akt phosphorylation was observed after optic nerve transection in both dLGN and V1. At week one, a decrease in the neuronal cell size (50.5▒4.9 vs 60.3▒5.0 Ám2, P?=?0.042) and an increase of TUNEL positive cells (7.9▒0.6 vs 1.4▒0.5 Î102 cells/mm2, P<0.001) were evident in the dLGN but not in V1. A significant decline in neuronal cell number (14.5▒0.1 vs 17.4▒1.3 Î102 cells/mm2, P?=?0.048), cell size (42.5▒4.3 vs 62.1▒4.7 Ám2, P?=?0.001) and an increase in apoptotic cells (5.6▒0.5 vs 2.0▒0.4 Î102 cells/mm2, P<0.001) appeared in V1 initially at one month post-transection. The changes in the visual pathway continued through two months. Both neuronal cells and GFAP-positive glial cells were affected in this anterograde degeneration along the visual pathway. Conclusions Anterograde degeneration along the visual pathway takes place in target relay (LGN) and visual cortex following the optic nerve injury. Apoptosis was observed in both neural and adjacent glial cells. Reduction of Akt phosphorylation preceded cellular and apoptotic changes.
Graham, Stuart L.; Klistorner, Alexander
Exploring the potential of quantum degenerate gases in microgravity
NASA Astrophysics Data System (ADS)
Microgravity is expected to be a decisive ingredient for the next leap in tests in fundamental physics of gravity, relativity and theories beyond the standard model. A promising technique for fundamental tests in the quantum domain are matter-wave sensors based on cold atoms or atom lasers, which use atoms as unperturbed microscopic test bodies for measuring inertial forces or as frequency references. Microgravity is of high relevance for matter-wave interferometers and experiments with quantum matter (Bose-Einstein Condensates or degenerate Fermi gases) as it permits the extension the unperturbed free fall of these test particles in a low-noise environment. Microgravity will also help to establish a new scientific avenue in the research on degenerate quantum gases. Cold quantum gases and, in particular, Bose-Einstein condensates represent a new state of matter which is nowadays established in many laboratories. They offer unique insights into a broad range of fundamental physics as well as prospects for novel quantum sensors. Microgravity will substantially extend the science of quantum gases towards nowadays inaccessible regimes at lowest temperatures, to macroscopic dimensions, and to unequalled durations of unperturbed evolution of these distinguished quantum objects. With the launch of the development of a mobile BEC platform project for microgravity experiments in the drop tower and during parabolic flights within a pilot project, running since January 2004, the DLR took a major first step to establish this field of research in Germany. The group joins the scientific expertise of leading German groups working on various aspects of cold quantum gases with the unique possibilities and technological knowledge offered by the drop tower group at ZARM, University Bremen, to introduce and explore the new field of quantum gases under microgravity. The pilot projects aims for a first technological demonstration of the feasibility of such experiments at the drop tower. The prospects of such an experiment, however, cover the study of quantum gases in the regime of unperturbed evolution with extremely large correlation length and longest unperturbed time of flight. The research will be performed with regard to scientific and technological aspects, from fundamental physical questions with low energy quantum phase transitions and the establishment of quantum correlations to measurements of highest precision in atom interferometric set-ups.
Ertmer, Wolfgang
Integrin - Dependent Mechanotransduction in Mechanically Stimulated Human Annulus Fibrosus Cells: Evidence for an Alternative Mechanotransduction Pathway Operating with Degeneration
Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD ľ peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell« strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS ľ dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS ľ induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.
Gilbert, Hamish T. J.; Nagra, Navraj S.; Freemont, Anthony J.; Millward-Sadler, Sarah J.; Hoyland, Judith A.
Traveling wave solutions in partially degenerate cooperative reaction-diffusion systems
NASA Astrophysics Data System (ADS)
We study the existence of traveling wave solutions for partially degenerate cooperative reaction-diffusion systems that can have three or more equilibria. We show via integral systems that there exist traveling wave solutions in a partially degenerate reaction-diffusion system with speeds above two well-defined extended real numbers. We prove that the two numbers are the same and may be characterized as the spreading speed as well as the slowest speed of a class of traveling wave solutions provided that the linear determinacy conditions are satisfied. We demonstrate our theoretical results by examining a partially degenerate Lotka-Volterra competition model with advection terms.
Li, Bingtuan
Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment.
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 manifestations of folate deficiency would seem to be theoretically advantageous. A case of subacute combined degeneration of the cord due to dietary folate deficiency and associated with an organic brain syndrome is reported. There was striking haematological, neurological and psychiatric response to methyl folate treatment.
Lever, E G; Elwes, R D; Williams, A; Reynolds, E H
Hypertrophic olivary degeneration following surgical excision of brainstem cavernous hemangioma: a case report.
Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubo-olivary pathway. It is distinguished from other types of neuronal degeneration in that hypertrophy, rather than atrophy, takes place in the neurons in the inferior olivary nucleus. Prior to the invention of Magnetic Resonance Imaging (MRI), HOD was difficult to be detected, and a firm diagnosis could only be made at autopsy. We present a case of bilateral HOD following surgical excision of a cavernous hemangioma in the brainstem. The literature and imaging findings of this uncommon condition are reviewed. PMID:10631896
Tsui, E Y; Cheung, Y K; Mok, C K; Yuen, M K; Chan, J H
A Layered Approach to Raising Public Awareness of Macular Degeneration in Australia
Between 2007 and 2011, the Australian Macular Degeneration Foundation conducted a multifaceted campaign to increase public awareness of macular degeneration. Regular national polls conducted by an independent social research company have shown that awareness of macular degeneration increased from 47% to 80% in Australians aged 16 years or older and from 58% to 92% in those aged 50 years or older. The percentage of people aged 50 years or older who reported having had their macula checked in the 2 years prior to the survey increased from 33% to 70% from 2007 to 2011. Other measures, including analysis of Medicare data, have confirmed the success of the campaign.
Heraghty, Julie; Cummins, Robert
Degeneration at the insertion weakens the tensile strength of the supraspinatus tendon: a comparative mechanical and histologic study of the bone-tendon complex.
The purpose of this investigation was to determine the relationship between the degree of degeneration at the supraspinatus insertion, the tensile strength, and the site of failure of this tendon. Thirty-three fresh cadaveric shoulders (average age: 62 years; range: 39-83 years) were examined. A tensile load to failure was applied at a constant crosshead speed of 25.4 mm/min to a 10 mm wide strip of the supraspinatus tendon that remained attached to the bone. Preexisting degenerative changes at the insertion were assessed and scored histologically and compared with the ultimate tensile stress. Twenty tendons failed at the insertion (the insertion group), and 11 failed in the midsubstance (the midsubstance group). The histologic score of degeneration for the insertion group was significantly higher than that for the midsubstance group (p = 0.0026). There was a negative correlation between the ultimate tensile stress at the insertion and the degeneration score for the insertion group (r = -0.60; p = 0.013). Histologic observations revealed that disruptions of tendon fibers were located mostly in the articular half of the tendon and that they enlarged during mechanical testing in 90% of the specimens of the insertion group. It seems that degenerative changes at the supraspinatus insertion reduce the tensile strength of the tendon and constitute a primary pathogenetic factor of rotator cuff tear. PMID:9420602
Sano, H; Ishii, H; Yeadon, A; Backman, D S; Brunet, J A; Uhthoff, H K
Seven new loci associated with age-related macular degeneration.
Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 Î 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 Î 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar 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
Fritsche, Lars G; Chen, Wei; Schu, Matthew; Yaspan, Brian L; Yu, Yi; Thorleifsson, Gudmar; Zack, Donald J; Arakawa, Satoshi; Cipriani, Valentina; Ripke, Stephan; Igo, Robert P; Buitendijk, GabriŰlle H S; Sim, Xueling; Weeks, Daniel E; Guymer, Robyn H; Merriam, Joanna E; Francis, Peter J; Hannum, Gregory; Agarwal, Anita; Armbrecht, Ana Maria; Audo, Isabelle; Aung, Tin; Barile, Gaetano R; Benchaboune, Mustapha; Bird, Alan C; Bishop, Paul N; Branham, Kari E; Brooks, Matthew; Brucker, Alexander J; Cade, William H; Cain, Melinda S; Campochiaro, Peter A; Chan, Chi-Chao; Cheng, Ching-Yu; Chew, Emily Y; Chin, Kimberly A; Chowers, Itay; Clayton, David G; Cojocaru, Radu; Conley, Yvette P; Cornes, Belinda K; Daly, Mark J; Dhillon, Baljean; Edwards, Albert O; Evangelou, Evangelos; Fagerness, Jesen; Ferreyra, Henry A; Friedman, James S; Geirsdottir, Asbjorg; George, Ronnie J; Gieger, Christian; Gupta, Neel; Hagstrom, Stephanie A; Harding, Simon P; Haritoglou, Christos; Heckenlively, John R; Holz, Frank G; Hughes, Guy; Ioannidis, John P A; Ishibashi, Tatsuro; Joseph, Peronne; Jun, Gyungah; Kamatani, Yoichiro; Katsanis, Nicholas; N Keilhauer, Claudia; Khan, Jane C; Kim, Ivana K; Kiyohara, Yutaka; Klein, Barbara E K; Klein, Ronald; Kovach, Jaclyn L; Kozak, Igor; Lee, Clara J; Lee, Kristine E; Lichtner, Peter; Lotery, Andrew J; Meitinger, Thomas; Mitchell, Paul; Mohand-Sa´d, Saddek; Moore, Anthony T; Morgan, Denise J; Morrison, Margaux A; Myers, Chelsea E; Naj, Adam C; Nakamura, Yusuke; Okada, Yukinori; Orlin, Anton; Ortube, M Carolina; Othman, Mohammad I; Pappas, Chris; Park, Kyu Hyung; Pauer, Gayle J T; Peachey, Neal S; Poch, Olivier; Priya, Rinki Ratna; Reynolds, Robyn; Richardson, Andrea J; Ripp, Raymond; Rudolph, Guenther; Ryu, Euijung; Sahel, JosÚ-Alain; Schaumberg, Debra A; Scholl, Hendrik P N; Schwartz, Stephen G; Scott, William K; Shahid, Humma; Sigurdsson, Haraldur; Silvestri, Giuliana; Sivakumaran, Theru A; Smith, R Theodore; Sobrin, Lucia; Souied, Eric H; Stambolian, Dwight E; Stefansson, Hreinn; Sturgill-Short, Gwen M; Takahashi, Atsushi; Tosakulwong, Nirubol; Truitt, Barbara J; Tsironi, Evangelia E; Uitterlinden, AndrÚ G; van Duijn, Cornelia M; Vijaya, Lingam; Vingerling, Johannes R; Vithana, Eranga N; Webster, Andrew R; Wichmann, H-Erich; Winkler, Thomas W; Wong, Tien Y; Wright, Alan F; Zelenika, Diana; Zhang, Ming; Zhao, Ling; Zhang, Kang; Klein, Michael L; Hageman, Gregory S; Lathrop, G Mark; Stefansson, Kari; Allikmets, Rando; Baird, Paul N; Gorin, Michael B; Wang, Jie Jin; Klaver, Caroline C W; Seddon, Johanna M; Pericak-Vance, Margaret A; Iyengar, Sudha K; Yates, John R W; Swaroop, Anand; Weber, Bernhard H F; Kubo, Michiaki; Deangelis, Margaret M; LÚveillard, Thierry; Thorsteinsdottir, Unnur; Haines, Jonathan L; Farrer, Lindsay A; Heid, Iris M; Abecasis, Gonšalo R
Seven New Loci Associated with Age-Related Macular Degeneration
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<5Î10?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<5Î10?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.
Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration
Background Detergent-insoluble protein accumulation and aggregation in the brain is one of the pathological hallmarks of neurodegenerative diseases. Here, we describe the identification of septin 11 (SEPT11), an enriched component of detergent-resistant fractions in frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions (FTLD-U), using large-scale unbiased proteomics approaches. Results We developed and applied orthogonal quantitative proteomic strategies for the unbiased identification of disease-associated proteins in FTLD-U. Using these approaches, we proteomically profiled detergent-insoluble protein extracts prepared from frontal cortex of FTLD-U cases, unaffected controls, or neurologic controls (i.e. Alzheimer's disease; AD). Among the proteins altered specifically in FTLD-U, we identified TAR DNA binding protein-43 (TDP-43), a known component of ubiquitinated inclusions. Moreover, we identified additional proteins enriched in detergent-resistant fractions in FTLD-U, and characterized one of them, SEPT11, in detail. Using independent highly sensitive targeted proteomics approaches, we confirmed the enrichment of SEPT11 in FTLD-U extracts. We further showed that SEPT11 is proteolytically cleaved into N-terminal fragments and, in addition to its prominent glial localization in normal brain, accumulates in thread-like pathology in affected cortex of FTLD-U patients. Conclusions The proteomic discovery of insoluble SEPT11 accumulation in FTLD-U, along with novel pathological associations, highlights a role for this cytoskeleton-associated protein in the pathogenesis of this complex disorder.
Gene Transfer for Neovascular Age-Related Macular Degeneration
Abstract Age-related macular degeneration (AMD) is a complex disease that has two phases: a degenerative phase often referred to as nonneovascular AMD (non-NVAMD) or dry AMD and a phase dominated by growth of new blood vessels in the subretinal space, referred to as NVAMD or wet AMD. Advances in the understanding of the molecular pathogenesis of NVAMD have led to new drug therapies that have provided major benefits to patients. However, those treatments require frequent intraocular injections that in many patients must be continued indefinitely to maintain visual benefits. Gene transfer to augment expression of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term stability in patients with NVAMD. Studies in animal models that mimic aspects of NVAMD have identified several possible transgenes, and a clinical trial in patients with advanced NVAMD has suggested that the approach may be feasible. Many important questions remain, but the rationale and preliminary data are compelling. The results of two ongoing clinical trials may answer several of the questions and help direct future research.
White matter damage in frontotemporal lobar degeneration spectrum.
White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures. PMID:21988828
Agosta, F; Scola, E; Canu, E; Marcone, A; Magnani, G; Sarro, L; Copetti, M; Caso, F; Cerami, C; Comi, G; Cappa, S F; Falini, A; Filippi, M
Genetic & Neuronanatomic Associations in Sporadic Frontotemporal Lobar Degeneration
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.
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
Late degeneration in rabbit tissues after irradiation by heavy ions
NASA Technical Reports Server (NTRS)
Results are presented for investigations of the late effects of heavy-ion irradiation on rabbit tissues which were undertaken to assess the hazards associated with the long-term exposure of humans to heavy ions in space during such activities as the construction of solar power stations or voyages to Mars. White rabbits approximately six weeks old were exposed to various doses of collimated beams of 400-MeV/n Ne ions, 570 MeV/n Ar ions and Co-60 gamma rays directed through both eyes, and the responses of the various tissues (hair follicles, skin, cornea, lens, retina, Harderian glands, bone and forebrain) were examined. Proliferating tissues are found to exhibit high damage levels in the early and late periods following irradiation, while terminally differentiating tissues repond to radiation most intensely in the late period, years after irradiation, with no intermediate recovery. The results obtained from rabbits are used to predict the occurrence of late tissue degeneration in the central nervous system, terminally differentiating systems and stem cells of humans one or more decades following exposure to radiation levels anticipated during long-duration space flights. The studies also indicate that tissues may be prematurely aged in the sense that tissue life spans may be shortened without the development of malignancies.
Lett, J. T.; Cox, A. B.; Keng, P. C.; Lee, A. C.; Su, C. M.; Bergtold, D. S.
A neuroprotective phase precedes striatal degeneration upon nucleolar stress
The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.
Kreiner, G; Bierhoff, H; Armentano, M; Rodriguez-Parkitna, J; Sowodniok, K; Naranjo, J R; Bonfanti, L; Liss, B; Schutz, G; Grummt, I; Parlato, R
Superradiance of Degenerate Fermi Gases in a Cavity
NASA Astrophysics Data System (ADS)
In this Letter we consider spinless Fermi gases placed inside a cavity and study the critical strength of a pumping field for driving a superradiance transition. We emphasize that the Fermi surface nesting effect can strongly enhance the superradiance tendency. Around certain fillings, when the Fermi surface is nearly nested with a relevant nesting momentum, the susceptibility of the system toward a checkboard density-wave ordered state is greatly enhanced in comparison with a Bose gas with the same density, because of which a much smaller (sometime even vanishingly small) critical pumping field strength can give rise to superradiance. This effect leads to interesting reentrance behavior and a topologically distinct structure in the phase diagram. Away from these fillings, the Pauli exclusion principle brings about the dominant effect for which the critical pumping strength is lowered in the low-density regime and increased in the high-density regime. These results open the prospect of studying the rich phenomena of degenerate Fermi gases in a cavity.
Chen, Yu; Yu, Zhenhua; Zhai, Hui
Genetic markers and biomarkers for age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the USA. Although the treatment of AMD has evolved to include laser photocoagulation, photodynamic therapy, surgical macular translocation and antiangiogenesis agents, treatment options for advanced AMD are limited. Furthermore, the dry form of AMD, albeit less devastating than the wet form, has even fewer viable treatment options. This review summarizes the various biomarkers of AMD and analyzes whether or not they may one day be exploited to determine risks of disease onset, measure progression of disease or even assess the effects of treatment of AMD. Potential biomarkers are important to identify since some might be utilized to reflect the disease state of a particular patient and to individualize therapy. Although studies have yielded promising results for nutrient and inflammatory biomarkers, these results have been inconsistent. At present, the best available markers of AMD risk are single nucleotide polymorphisms (SNPs). SNPs in complement factor H (CFH) and PLEKHA1/ARMS2/HtrA1 capture a substantial fraction of AMD risk and permit the identification of individuals at high risk of developing AMD.
Ross, Robert J; Verma, Varun; Rosenberg, Kevin I; Chan, Chi-Chao; Tuo, Jingsheng
Nonlinear analysis of electroencephalogram in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) is a form of dementia characterized by a profound alteration in personality and social behavior and is associated with atrophy in the frontal and temporal brain regions. Despite recent advances, diagnosis of FTLD remains challenging. In the last decade, different studies have combined EEG analysis with mathematical models and theories that consider EEG signals as the result of nonlinear chaotic activity. The aim of the present study was to determine whether new nonlinear dynamic analysis can provide useful information on brain activity in FTLD patients. 19-lead EEG was recorded in patients with clinical diagnosis of FTLD and in healthy controls under two different conditions: closed eyes and open eyes. A nonlinear measure of complexity, correlation dimension (D2), was calculated. Our results show an increase in D2 in healthy individuals when the eyes are open, in keeping with an increase in information processing. Conversely, in FTLD patients, no increase in D2 occurred in the open eyes condition, and D2 was significantly lower than that observed in controls. Our results suggest that the dynamic processes underlying the EEG are less chaotic and complex in FTLD patients compared with normal individuals, thus providing important information on both brain functioning and possible clinical diagnostic applications. PMID:24717666
Carlino, Elisa; Frisaldi, Elisa; Rainero, Innocenzo; Asteggiano, Giovanni; Cappa, Giorgetta; Tarenzi, Luisella; Vighetti, Sergio; Pollo, Antonella; Pinessi, Lorenzo; Benedetti, Fabrizio
Chapter 61: Photoreceptor Cell Degeneration in Abcr?/? Mice
Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency in Abcr is associated with substantial accumulations of lipofuscin pigments in retinal pigment epithelial (RPE) cells. To observe for photoreceptor cell degeneration in these mutant mice, outer nuclear layer (ONL) thickness was measured at 200 ?m intervals superior and inferior to the optic nerve head. ONL width in Abcr?/? mouse was reduced at 8ľ9 month and 11 and 13 months relative to Abcr+/+ mice; thinning was more pronounced centrally and in superior retina. The numbers of photoreceptor nuclei spanning the width of the outer nuclear layer were also reduced. No evidence of age-related ONL thinning was observed in Abcr+/+ mice at these ages. We conclude that albino Abcr?/? mice exhibit progressive photoreceptor cell loss that is detectable at 8 months of age and that has worsened by 11 and 13 months of age. The measurement of ONL thickness is an established approach to assessing photoreceptor cell integrity and can be used in preclinical studies using Abcr?/? mice.
Wu, Li; Nagasaki, Taka; Sparrow, Janet R.
Automatic age-related macular degeneration detection and staging
NASA Astrophysics Data System (ADS)
Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.
van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sßnchez, Clara I.
Review of nutrient actions on age-related macular degeneration.
The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, ?-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. PMID:24461310
Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano
SINGLE-DEGENERATE TYPE Ia SUPERNOVAE WITHOUT HYDROGEN CONTAMINATION
The lack of hydrogen in spectra of type Ia supernovae (SNe Ia) is often seen as troublesome for single-degenerate (SD) progenitor models. We argue that, since continued accretion of angular momentum can prevent explosion of the white dwarf, it may be natural for the donor stars in SD progenitors of SNe Ia to exhaust their envelopes and shrink rapidly before the explosion. This outcome seems most likely for SD SN Ia progenitors where mass transfer begins from a giant donor star and might extend to other SD systems. Not only is the amount of hydrogen left in such a system below the current detection limit, but the donor star is typically orders of magnitude smaller than its Roche lobe by the point when an SD SN Ia occurs, in which case attempts to observe collisions between SN shocks and giant donor stars seem unlikely to succeed. We consider the constraints on this model from the circumstellar structures seen in spectra of SN 2006X and suggest a novel explanation for the origin of this material.
Justham, Stephen, E-mail: firstname.lastname@example.com [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing (China)
Heavy-fermion instability in double-degenerate plasmas
In this work, we study the propagations of normal frequency modes for quantum hydrodynamic waves in the linear limit and introduce a new kind of instability in a double-degenerate plasma. Three different regimes, namely, low, intermediate, and high magnetic field strengths are considered which span the applicability of the work to a wide variety of environments. Distinct behavior is observed for different regimes, for instance, in the laboratory-scale field regime no frequency-mode instability occurs unlike those of intermediate and high magnetic-field strength regimes. It is also found that the instability of this kind is due to the heavy-fermions which appear below a critical effective-mass parameter ({mu}{sub cr}={radical}(3)) and that the responses of the two (lower and upper frequency) modes to fractional effective-mass change in different effective-mass parameter ranges (below and above the critical value) are quite opposite to each other. It is shown that the heavy-fermion instability due to extremely high magnetic field such as that encountered for a neutron-star crust can lead to confinement of stable propagations in both lower and upper frequency modes to the magnetic poles. Current study can have important implications for linear wave dynamics in both laboratory and astrophysical environments possessing high magnetic fields.
Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem, 51745-406 Tabriz (Iran, Islamic Republic of)
Degenerate molecular shuttles with flexible and rigid spacers.
The preparation and dynamic behavior of degenerate rotaxane molecular shuttles are described in which a benzylic amide macrocycle moves back and forth between two naphthalimide-glycine units along a diphenylethyne spacer or an aliphatic spacer consisting of a C(9), C(12), or C(26) alkyl chain. Subtle differences in the (1)H NMR spectra of the rotaxanes can be related to the presence of conformers in which the macrocycle interacts simultaneously with both glycines, especially in the case of the C(9) spacer. The kinetic data of the shuttling behavior in the C(26) rotaxane were obtained from dynamic NMR spectroscopy. The Eyring activation parameters were found to be ?H(ç) = 10 ▒ 1 kcal mol(-1), ?S(ç) = -6.5 ▒ 2.0 cal mol(-1) K(-1), ?G(ç)(298) = 11.9 ▒ 0.2 kcal mol(-1). For the systems with the shorter spacers, the shuttling rates were higher. Also in the diphenylethyne, rotaxane shuttling is rapid on the NMR time scale, indicating that the rigid unit does not impose a large barrier to the translocation of the macrocycle. PMID:22663771
GŘnba?, D Deniz; Brouwer, Albert M
Calcification in human intervertebral disc degeneration and scoliosis.
Calcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs (IVDs). The purpose of this study was to assess the calcification potential of IVDs in degenerative disc disease (DDD) and adolescent idiopathic scoliosis (AIS). For this purpose, 34 IVDs from 16 adult patients with DDD and 25 IVDs from 9 adolescent patients with AIS were obtained at surgery. The concave and convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen (COL X) expression associated with endochondral ossification was measured by immunohistochemistry. Alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential. Results showed the presence of calcium deposits and COL X in degenerative and scoliotic IVDs, but not in control discs, and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in AIS discs might reflect a premature degenerative process. PMID:21590718
Hristova, Gergana I; Jarzem, Peter; Ouellet, Jean A; Roughley, Peter J; Epure, Laura M; Antoniou, John; Mwale, Fackson
Rotator cuff degeneration and lateral epicondylitis: a comparative histological study.
OBJECTIVES--Rotator cuff tendinitis and lateral epicondylitis are common in clinical practice but the underlying pathology is poorly understood. The study examined both normal and biopsy tendon specimens histologically, to determine the mechanisms involved in tendon degeneration. METHODS--Rotator cuff tendons from 83 cadavers aged 11-94 and tendon biopsy specimens from 20 patients with lateral epicondylitis aged 27-56 years were examined histologically. RESULTS--The microscopic changes found in the tendon biopsies from the elbow were similar to those found in the cadaveric rotator cuff tendons. Abnormalities ranged from minor blood vessel wall changes and loss of tenocytes to calcification. The most frequent abnormality was glycosaminoglycan infiltration and fibrocartilaginous transformation. There appeared to be some sequence in the changes observed which were milder in younger patients. Only 17% of cadaver tendons, below the age of 39 were abnormal but abnormalities increase in later life to around 40-50%. CONCLUSIONS--There was an increasing incidence of degenerative changes in tendons with age. The changes observed in biopsy samples of common extensor tendons were the same as those seen in aged supraspinatus tendons, but these changes were not seen in control common extensor tendons. Images
Chard, M D; Cawston, T E; Riley, G P; Gresham, G A; Hazleman, B L
Human embryonic stem cell applications for retinal degenerations.
Loss of vision in severe retinal degenerations often is a result of photoreceptor cell or retinal pigment epithelial cell death or dysfunction. Cell replacement therapy has the potential to restore useful vision for these individuals especially after they have lost most or all of their light-sensing cells in the eye. A reliable, well-characterized source of retinal cells will be needed for replacement purposes. Human embryonic stem cells (ES cells) can provide an unlimited source of replacement retinal cells to take over the function of lost cells in the eye. The author's intent for this review is to provide an historical overview of the field of embryonic stem cells with relation to the retina. The review will provide a quick primer on key pathways involved in the development of the neural retina and RPE followed by a discussion of the various protocols out in the literature for generating these cells from non-human and human embryonic stem cells and end with inávivo application of ES cell-derived photoreceptors and RPE cells. PMID:23880530
Reynolds, Joseph; Lamba, Deepak A
Frequency tunable non-degenerate Josephson amplifier for qubit readout
NASA Astrophysics Data System (ADS)
We have developed a new ultra low noise microwave amplifier based on the Josephson parametric converter (JPC), which overcomes a practical weakness of devices of previous generations: having sufficient frequency tunability to easily match the qubit readout frequency. The JPC consists of two superconducting microwave resonators that are coupled to each other through a ring of four Josephson junctions, threaded by a magnetic flux and providing the non-linearity for the amplification process. The non-linearity is of the trilinear form involving the minimal number of modes, and allows ideal non-degenerate parametric amplification at the quantum limit of noise. In our new tunable version, the junctions responsible for amplification are shunted by a cross of four larger junctions, which for our purpose can be regarded as linear inductors, as in the work of Roch et al.[1]. The JPC has now a unique bias point at any applied flux and is tunable over more than half a gigahertz. We are currently using this amplifier in conjunction with a quantum non-demolition measurement of a transmon qubit and have observed quantum jumps with fidelity larger than 90%. [1] N. Roch, E. Flurin, F. Nguyen, P. Morfin, P. Campagne-Ibarcq, M. H. Devoret, and B. Huard, in preparation.
Schackert, Flavius; Hatridge, Michael; Sliwa, Katrina; Abdo, Baleegh; Frunzio, Luigi; Devoret, Michel
Aspirin and age-related macular degeneration: positives versus negatives.
The anti-inflammatory, analgesic, antipyretic and antithrombotic activities of aspirin confer its wide therapeutic application. The three former activities require higher doses of aspirin, whereas the latter can be achieved through a lower, thus safer dose of the drug. Low-dose, long-term aspirin is used as an antithrombotic therapy to prevent cardiovascular disease. Such therapy is used by millions of people worldwide, including those suffering from age-related macular degeneration (AMD); thus, questions have arisen as to whether such treatment has any impact on the development and course of AMD. This editorial addresses the important issue of possible beneficial and adverse effects of long-term, low-dose aspirin treatment of AMD patients. Special emphasis is given to the ability of aspirin to acetylate cyclooxygenases (especially COX-2) and thus to initiate a biochemical pathway leading to the generation of anti-inflammatory pro-resolving mediators synthesized from both ?-3 and ?-6 long-chain polyunsaturated fatty acids. Such mediators (e.g., resolvins, lipoxins) may be of therapeutic value in retarding the development of dry form AMD. PMID:24783984
Nowak, Jerzy Z
Biomarkers in Frontotemporal Lobar Degenerations - Progress and Challenges
Neuronal and glial changes associated with tau, TAR DNA binding protein of ~43 kD (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.
Hu, William T.; Trojanowski, John Q.; Shaw, Leslie M.
Inflammatory priming predisposes mice to age-related retinal degeneration
Disruption of cellular processes affected by multiple genes and accumulation of numerous insults throughout life dictate the progression of age-related disorders, but their complex etiology is poorly understood. Postmitotic neurons, such as photoreceptor cells in the retina and epithelial cells in the adjacent retinal pigmented epithelium, are especially susceptible to cellular senescence, which contributes to age-related retinal degeneration (ARD). The multigenic and complex etiology of ARD in humans is reflected by the relative paucity of effective compounds for its early prevention and treatment. To understand the genetic differences that drive ARD pathogenesis, we studied A/J mice, which develop ARD more pronounced than that in other inbred mouse models. Although our investigation of consomic strains failed to identify a chromosome associated with the observed retinal deterioration, pathway analysis of RNA-Seq data from young mice prior to retinal pathological changes revealed that increased vulnerability to ARD in A/J mice was due to initially high levels of inflammatory factors and low levels of homeostatic neuroprotective factors. The genetic signatures of an uncompensated preinflammatory state and ARD progression identified here aid in understanding the susceptible genetic loci that underlie pathogenic mechanisms of age-associated disorders, including several human blinding diseases.
Mustafi, Debarshi; Maeda, Tadao; Kohno, Hideo; Nadeau, Joseph H.; Palczewski, Krzysztof
Rare postpartum ruptured degenerated fibroid: a case report.
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 Î 8.6 Î 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