WorldWideScience

Sample records for human degenerative disorders

  1. Degenerative disorders of the spine

    Energy Technology Data Exchange (ETDEWEB)

    Gallucci, Massimo; Puglielli, Edoardo; Splendiani, Alessandra [University of L' Aquila, Department of Radiology, L' Aquila (Italy); Pistoia, Francesca; Spacca, Giorgio [S. Salvatore Hospital, Department of Neuroscience, L' Aquila (Italy)

    2005-03-01

    Patients with back pain and degenerative disorders of the spine have a significant impact on health care costs. Some authors estimate that up to 80% of all adults experience back pain at some point in their lives. Disk herniation represents one of the most frequent causes. Nevertheless, other degenerative diseases have to be considered. In this paper, pathology and imaging of degenerative spine diseases will be discussed, starting from pathophysiology of normal age-related changes of the intervertebral disk and vertebral body. (orig.)

  2. Cancer--a degenerative disorder?

    Science.gov (United States)

    Rew, D A

    1998-10-01

    Cancer is primarily a disease of ageing epithelia, and of ageing individuals. We now possess detailed insights into the changes in cell regulatory genes and DNA repair systems which accumulate with time and which manifest in malignancy. These demonstrate how cancer is frequently characterized by degenerative change in the genotype, from the most subtle base pair mutations to gross aneuploidy, and by deterioration in cell and tissue regulatory control, be it of proliferation, programmed cell death or signalling. Cancer may thus be as much a phenomenon of loss or deterioration of normal genomic control as of the acquisition of new, neoplastic functions. This distinction may be more than semantic, not least because it governs our approach to the search for therapeutic strategies. This essay considers the concept of cancer as a degenerative disease and its implications, and proposes the neologism aldoplasia to describe this phenomenon of cancer biology.

  3. Physiochemical basis of human degenerative disease

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    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  4. Cultured cells of the nervous system, including human neurones, in the study of the neuro-degenerative disorder, Alzheimer's disease: an overview.

    Science.gov (United States)

    De Boni, U

    1985-01-01

    Human nervous-system cells in culture are a suitable model for the study of the degenerative changes associated with Alzheimer's disease. Alzheimer-diseased brain contains a factor which induces the formation of paired helical filaments (PHF) in cultured cells, similar to that seen in Alzheimer's disease. The excitotoxic amino acids, glutamate and aspartate, induce similar PHE formation in cultured cells. The neurotoxic element aluminium is present in high concentrations in the brain in several human neurological disorders, including Alzheimer's disease. In cultured-cell systems, aluminium interacts with acidic nuclear proteins, decreases steroid binding, produces a form of neurofibrillary degeneration and alters nucleoside metabolism.

  5. Degenerative spine disorders in the context of clinical findings

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    Freund, Michael [Institut fuer Radiologie und Neuroradiologie, Klinikum Aschaffenburg, Am Hasenkopf 1, 63739 Aschaffenburg (Germany) and Abteilung fuer Neuroradiologie, Universitaetsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)]. E-mail: michael.freund@klinikum-aschaffenburg.de; Sartor, Klaus [Abteilung fuer Neuroradiologie, Universitaetsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)

    2006-04-15

    Hardly any other structure in the human body is held responsible for so many complaints, pain, and costs as the spine and its degenerative disorders. In the following article, the role of imaging procedures in diagnosing disorders of the spine is presented. Due to the fact that disk herniation represents the most frequent cause for degenerative disorders the anatomy of the intervertebral disk and the pathology of the entities that can cause diseases of the disks are described. In particular, the authors focus on the significance of radiological findings with respect to patient history, subjective symptoms, and objective clinical findings. In addition to presenting the technical procedures and their indications and contraindications also practical tips and tricks in conducting these examinations are presented in this paper.

  6. Consensus Paper: Management of Degenerative Cerebellar Disorders

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    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  7. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Institute of Scientific and Technical Information of China (English)

    Natalie Kaminsky; Ofer Bihari; Sivan Kanner; Ari Barzilai

    2016-01-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to geno-mic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degener-ative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evi-dence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a‘‘hostile”environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  8. The ubiquitin-proteasome system in spongiform degenerative disorders.

    Science.gov (United States)

    Whatley, Brandi R; Li, Lian; Chin, Lih-Shen

    2008-12-01

    Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.

  9. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Directory of Open Access Journals (Sweden)

    Natalie Kaminsky

    2016-06-01

    Full Text Available The DNA damage response (DDR is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes. Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  10. A Single-Use, In Vitro Biosensor for the Detection of T-Tau Protein, A Biomarker of Neuro-Degenerative Disorders, in PBS and Human Serum Using Differential Pulse Voltammetry (DPV).

    Science.gov (United States)

    Dai, Yifan; Molazemhosseini, Alireza; Liu, Chung Chiun

    2017-02-19

    A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet. Both working and counter electrodes were thin gold film, 10 nm in thickness. Laser ablation technique was used to define the size and structure of the biosensor. The biosensor was produced using cost-effective roll-to-roll process. Self-assembled monolayers (SAM) of 3-mercaptopropionic acid (MPA) were employed to covalently immobilize the anti-T-Tau (T-Tau antibody) on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) cross-linked anti-T-Tau to the carboxylic groups on one end of the MPA. A T-Tau protein ladder with six isoforms was used in this study. The anti-T-Tau concentration used was 500,000 pg/mL. The T-Tau protein concentration ranged from 1000 pg/mL to 100,000 pg/mL. DPV measurements showed excellent responses, with a good calibration curve. Thus, a practical tool for simple detection of T-Tau protein, a biomarker of neuro-degenerative disorders, has been successfully developed. This tool could also be extended to detect other biomarkers for neuro-degenerative disorders, such as P-Tau protein and β-amyloid 42.

  11. Use of orthopedic shoes in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, Michiel J.; IJzerman, Maarten J.; Groothuis-Oudshoorn, Karin; Stewart, Roy E.; Groothoff, Johan W.; Lankhorst, Gustaaf J.

    2005-01-01

    Objectives: To study the actual use of orthopedic shoes by patients with degenerative foot disorders and to identify factors associated with use and nonuse, based on the parameters of the International Organization for Standardization definition of usability: effectiveness, efficiency, satisfaction,

  12. Nicotinic systems in central nervous systems disease: degenerative disorders and beyond.

    Science.gov (United States)

    Newhouse, P A; Kelton, M

    2000-03-01

    Advances in the understanding of the structure, function, and distribution of central nervous system (CNS) nicotinic receptors has provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realization that such receptors are changed in degenerative neurologic diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Ongoing investigations of the molecular substructure of CNS nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioral, motor, and sensory functioning. Clues from careful studies of human cognition and behavior are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. Modulation of these receptors with the ultimate goal of producing therapeutic benefits is the goal of these investigations and drug development. This paper will review studies from our laboratory and others that point to the importance of CNS nicotinic mechanisms in normal human cognitive and behavioral functioning as well as their role in disease states. In addition, this paper will examine potential clinical applications of nicotine and/or nicotinic agonists in a variety of CNS disorders with particular emphasis on structural brain disease including: movement disorders such as Parkinson's disease and Tourette's syndrome, cognitive/behavioral disorders such as Alzheimer's disease, attention deficit/hyperactivity disorder, and schizophrenia, and other more speculative applications. Important results from early therapeutic studies of nicotine and/or nicotinic agonists in these disease states are presented. For example, recent studies with nicotine and novel nicotinic agonists such as ABT-418 by our group

  13. Sacroiliac joint motion in patients with degenerative lumbar spine disorders.

    Science.gov (United States)

    Nagamoto, Yukitaka; Iwasaki, Motoki; Sakaura, Hironobu; Sugiura, Tsuyoshi; Fujimori, Takahito; Matsuo, Yohei; Kashii, Masafumi; Murase, Tsuyoshi; Yoshikawa, Hideki; Sugamoto, Kazuomi

    2015-08-01

    OBJECT Usually additional anchors into the ilium are necessary in long fusion to the sacrum for degenerative lumbar spine disorders (DLSDs), especially for adult spine deformity. Although the use of anchors is becoming quite common, surgeons must always keep in mind that the sacroiliac (SI) joint is mobile and they should be aware of the kinematic properties of the SI joint in patients with DLSDs, including adult spinal deformity. No previous study has clarified in vivo kinematic changes in the SI joint with respect to patient age, sex, or parturition status or the presence of DLSDs. The authors conducted a study to clarify the mobility and kinematic characteristics of the SI joint in patients with DLSDs in comparison with healthy volunteers by using in vivo 3D motion analysis with voxel-based registration, a highly accurate, noninvasive method. METHODS Thirteen healthy volunteers (the control group) and 20 patients with DLSDs (the DLSD group) underwent low-dose 3D CT of the lumbar spine and pelvis in 3 positions (neutral, maximal trunk flexion, and maximal trunk extension). SI joint motion was calculated by computer processing of the CT images (voxel-based registration). 3D motion of the SI joint was expressed as both 6 df by Euler angles and translations on the coordinate system and a helical axis of rotation. The correlation between joint motion and the cross-sectional area of the trunk muscles was also investigated. RESULTS SI joint motion during trunk flexion-extension was minute in healthy volunteers. The mean rotation angles during trunk flexion were 0.07° around the x axis, -0.02° around the y axis, and 0.16° around the z axis. The mean rotation angles during trunk extension were 0.38° around the x axis, -0.08° around the y axis, and 0.08° around the z axis. During trunk flexion-extension, the largest amount of motion occurred around the x axis. In patients with DLSDs, the mean rotation angles during trunk flexion were 0.57° around the x axis, 0.01

  14. A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

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    Hyman M. Schipper

    2015-03-01

    Full Text Available Heme oxygenase-1 (HO-1 is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

  15. Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders

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    Chen, Yu; Palczewski, Krzysztof

    2015-01-01

    In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein–coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration–approved pharmacological agents. PMID:25839098

  16. Current concepts on spinal arthrodesis in degenerative disorders of the lumbar spine

    OpenAIRE

    Lykissas, Marios G; Aichmair, Alexander

    2013-01-01

    Back pain is a common chronic disorder that represents a large burden for the health care system. There is a broad spectrum of available treatment options for patients suffering from chronic lower back pain in the setting of degenerative disorders of the lumbar spine, including both conservative and operative approaches. Lumbar arthrodesis techniques can be divided into sub-categories based on the part of the vertebral column that is addressed (anterior vs posterior). Furthermore, one has to ...

  17. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    Science.gov (United States)

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  18. DEGRO guidelines for the radiotherapy of non-malignant disorders. Part II: Painful degenerative skeletal disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ott, Oliver J. [University Hospitals Erlangen, Dept. of Radiation Oncology, Erlangen (Germany); Niewald, Marcus [Saarland University Medical School, Dept. of Radiotherapy and Radiation Oncology, Homburg/Saar (Germany); Weitmann, Hajo-Dirk [Fulda Hospital, Dept. of Radiooncology and Radiotherapy, Fulda (Germany); Jacob, Ingrid [Municipal Hospital Traunstein, Dept. of Radiotherapy, Traunstein (Germany); Adamietz, Irenaeus A. [Marien Hospital Herne/Ruhr University Bochum, Dept. of Radiotherapy and Radiation Oncology, Herne (Germany); Schaefer, Ulrich [Lippe Hospital, Dept. of Radiotherapy, Lemgo (Germany); Keilholz, Ludwig [Bayreuth Hospital, Dept. of Radiotherapy, Bayreuth (Germany); Heyd, Reinhard [Center for Radiosurgery, Frankfurt a. M. (Germany); Muecke, Ralph [Marien Hospital Herne/Ruhr University Bochum, Dept. of Radiotherapy and Radiation Oncology, Herne (Germany); Lippe Hospital, Dept. of Radiotherapy, Lemgo (Germany); Collaboration: German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD)

    2014-09-20

    The purpose of this article is to summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign painful degenerative skeletal disorders with low-dose radiotherapy. This overview reports on the role of low-dose radiotherapy in the treatment of enthesiopathies (shoulder syndrome, trochanteric bursitis, plantar fasciitis, and elbow syndrome) and painful arthrosis (knee, hip, hand, and finger joints). The most relevant aspects of the DEGRO S2e Consensus Guideline Radiation Therapy of Benign Diseases 2014 regarding diagnostics, treatment decision, dose prescription as well as performance of radiotherapy and results are summarized. For all indications mentioned above, retrospective and some prospective analyses have shown remarkable effects in terms of pain relief. Nevertheless, the Level of Evidence (LoE) and the Grade of Recommendation (GR) vary: LoE 1b-4 and GR A-C. Low-dose radiotherapy for painful degenerative skeletal disorders is effective in the majority of the patients and therefore it may be a reasonable therapeutic alternative when simple and non-invasive methods have been used without persistent success. For all discussed entities, single fraction doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy/series applied with 2-3 fractions per week are recommended. (orig.) [German] Zusammenfassung der Empfehlungen der DEGRO-S2e-Leitlinie zur Niedrigdosis-Radiotherapie von gutartigen schmerzhaften degenerativen Skeletterkrankungen. Die vorliegende Zusammenfassung berichtet ueber die Bedeutung der Niedrigdosis-Radiotherapie in der Behandlung von Enthesiopathien (Schultersyndrom, Ellenbogensyndrom, Bursitis trochanterica, Fasciitis plantaris) und schmerzhaften Arthrosen (Knie-, Hueft, Hand- und Fingergelenksarthrosen). Die wichtigsten Aspekte der aktuellen DEGRO-S2e-Konsensus-Leitlinie Strahlentherapie gutartiger Erkrankungen bezueglich Diagnostik, Therapieentscheidungen, Dosisempfehlungen und Durchfuehrung einer Radiotherapie werden

  19. Sagittal balance disorders in severe degenerative spine. Can we identify the compensatory mechanisms?

    Science.gov (United States)

    Barrey, Cédric; Roussouly, Pierre; Perrin, Gilles; Le Huec, Jean-Charles

    2011-09-01

    Aging of the spine is characterized by facet joints arthritis, degenerative disc disease and atrophy of extensor muscles resulting in a progressive kyphosis. Recent studies confirmed that patients with lumbar degenerative disease were characterized by an anterior sagittal imbalance, a loss of lumbar lordosis and an increase of pelvis tilt. The aim of this paper was thus to describe the different compensatory mechanisms which are observed in the spine, pelvis and/or lower limbs areas for patients with severe degenerative spine. We reviewed all the compensatory mechanisms of sagittal unbalance described in the literature. According to the severity of the imbalance, we could identify three different stages: balanced, balanced with compensatory mechanisms and imbalanced. For the two last stages, the compensatory mechanisms permitted to limit consequences of lumbar kyphosis on the global sagittal alignment. Reduction of thoracic kyphosis, intervertebral hyperextension, retrolisthesis, pelvis backtilt, knee flessum and ankle extension were the main mechanisms described in the literature. The basic concept of these compensatory mechanisms was to extend adjacent segments of the kyphotic spine allowing for compensation of anterior translation of the axis of gravity. To avoid underestimate the severity of the degenerative spine disorder, it thus seems important to recognize the different compensatory mechanisms from the upper part of the trunk to the lower limbs. We propose a three steps algorithm to analyse the balance status and determine the presence or not of these compensatory mechanisms: measurement of pelvis incidence, assessment of global sagittal alignment and analysis of compensatory mechanisms successively in the spine, pelvis and lower limbs areas.

  20. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

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    Kamei, Hidekazu (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author).

  1. The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

    Directory of Open Access Journals (Sweden)

    Gao B

    2014-02-01

    Full Text Available Bifeng Gao, An Doan, Brooks M HybertsonDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USAAbstract: Nuclear factor (erythroid-derived 2-like 2 (Nrf2; encoded in humans by the NFE2L2 gene is a transcription factor that regulates the gene expression of a wide variety of cytoprotective phase II detoxification and antioxidant enzymes through a promoter sequence known as the antioxidant-responsive element (ARE. The ARE is a promoter element found in many cytoprotective genes; therefore, Nrf2 plays a pivotal role in the ARE-driven cellular defense system against environmental stresses. Agents that target the ARE/Nrf2 pathway have been tested in a wide variety of disorders, with at least one new Nrf2-activating drug now approved by the US Food and Drug Administration. Examination of in vitro and in vivo experimental results, and taking into account recent human clinical trial results, has led to an opinion that Nrf2-activating strategies – which can include drugs, foods, dietary supplements, and exercise – are likely best targeted at disease prevention, disease recurrence prevention, or slowing of disease progression in early stage illnesses; they may also be useful as an interventional strategy. However, this rubric may be viewed even more conservatively in the pathophysiology of cancer. The activation of the Nrf2 pathway has been widely accepted as offering chemoprevention benefit, but it may be unhelpful or even harmful in the setting of established cancers. For example, Nrf2 activation might interfere with chemotherapies or radiotherapies or otherwise give tumor cells additional growth and survival advantages, unless they already possess mutations that fully activate their Nrf2 pathway constitutively. With all this in mind, the ARE/Nrf2 pathway remains of great interest as a possible target for the pharmacological control of degenerative and

  2. Effectiveness of custom-made orthopaedic shoes in the reduction of foot pain and pressure in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, M.; van Dijk, H.; Ijzerman, M.; Groothuis-Oudshoorn, K.; Groothoff, J.; Lankhurst, G.

    2006-01-01

    Background. Degenerative disorders of the foot often are painful during standing and walking. It is assumed that, because of bone deformity, callus, and deformity of the plantar pads, the plantar pressure distribution changes. Prescription of orthopaedic shoes for patients with degenerative disorder

  3. Questionnaire for usability evaluation of orthopaedic shoes : Construction and reliability in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, MJA; de Vries, J; Stewart, RE; Groothoff, JW; Lankhorst, GJ

    2004-01-01

    Objective: To develop a self-report questionnaire for patients with degenerative disorders of the foot to evaluate the usability of their orthopaedic shoes, and to assess the reproducibility and responsiveness of the instrument. Design: Development of the Questionnaire for Usability Evaluation of or

  4. Questionnaire for usability evaluation of orthopaedic shoes: construction and reliability in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, Michiel J.A.; Vries, de Jaap; Stewart, Roy E.; Groothoff, Johan W.; Lankhorst, Gustaaf J.

    2004-01-01

    Objective: To develop a self-report questionnaire for patients with degenerative disorders of the foot to evaluate the usability of their orthopaedic shoes, and to assess the reproducibility and responsiveness of the instrument. Design: Development of the Questionnaire for Usability Evaluation of or

  5. Quantitative electroencephalography (qEEG to discriminate primary degenerative dementia from major depressive disorder (depression

    Directory of Open Access Journals (Sweden)

    Deslandes Andréa

    2004-01-01

    Full Text Available Electroencephalography (EEG can be a valuable technique to assess electrophysiological changes related to dementia. In patients suspected of having dementia, the EEG is often quite informative. The sensitivity of the EEG to detect correlates of psychiatric disorders has been enhanced by means of quantitative methods of analysis (quantitative EEG. Quantitative features are extracted from, at least, 2 minutes of artifact-free, eyes closed, resting EEG, log-transformed to obtain Gaussianity, age-regressed, and Z-transformed relative to population norms (Neurometrics database. Using a subset of quantitative EEG (qEEG features, forward stepwise discriminant analyses are used to construct classifier functions. Along this vein, the main objective of this experiment is to distinguish profiles of qEEG, which differentiate depressive from demented patients (n = 125. The results showed that demented patients present deviations above the control group in variables associated to slow rhythms: Normed Monopolar Relative Power Theta for Cz and Normed Bipolar Relative Power Theta for Head. On the other hand, the deviation below the control group occurs with the variable associated to alpha rhythm: Normed Monopolar Relative Power Alpha for P3, in dementia. Using this method, the present investigation demonstrated high discriminant accuracy in separating Primary Degenerative Dementia from Major Depressive Disorder (Depression.

  6. Effectiveness of custom-made orthopaedic shoes in the reduction of foot pain and pressure in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, M.J.A.; Jannink, M.J.A.; van Dijk, H; IJzerman, Maarten Joost; Groothuis-Oudshoorn, Catharina Gerarda Maria; Groothuis, C.G.M.; Groothoff, J.W.; Lankhorst, G.J.

    2006-01-01

    Background: Degenerative disorders of the foot often are painful during standing and walking. It is assumed that, because of bone deformity, callus, and deformity of the plantar pads, the plantar pressure distribution changes. Prescription of orthopaedic shoes for patients with degenerative

  7. Effectiveness of custom-made orthopaedic shoes in the reduction of foot pain and pressure in patients with degenerative disorders of the foot

    NARCIS (Netherlands)

    Jannink, M.; van Dijk, H.; Ijzerman, M.; Groothuis-Oudshoorn, K.; Groothoff, J.; Lankhurst, G.

    2006-01-01

    Background. Degenerative disorders of the foot often are painful during standing and walking. It is assumed that, because of bone deformity, callus, and deformity of the plantar pads, the plantar pressure distribution changes. Prescription of orthopaedic shoes for patients with degenerative

  8. CT scanning of the brain and lumbar CSF monoamine metabolites in spinocerebellar degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hidenao; Kanazawa, Ichiro; Nakanishi, Takao; Kuramoto, Kenmei (Tsukuba Univ., Sakura, Ibaraki (Japan))

    1984-08-01

    Eight patients with parenchymatous cerebellar degeneration (PCD) group (3 with late cortical cerebellar atrophy and 5 with Holmes' hereditary ataxia), 14 with olivo-ponto-cerebellar atrophy (OPCA) group (4 with Shy-Drager syndrome, 6 with OPCA without family history and 4 with Menzel type SCS), 15 with Parkinson's disease and 44 control with other neurological diseases were studied. In all the spinocerebellar degenerative disorders (SCD) cases, CVI values corresponding to the cerebellar atrophy were definitely reduced. On the other hand, PVI values corresponding to the pontine atrophy were only significantly decreased in OPCA group. However, since there were several cases showing only questionable pontine atrophy, it seems difficult to clearly differentiate individual OPCA cases from other SCD cases on CT films alone. Concerning monoamine metabolites in CSF, it was noted that a significant reduction of HVA and total MHPG was found in the OPCA group. Among them, the patients with overt autonomic failure showed the lowest HVA level and the cases of Menzel type of SCD showed a slight reduction of HVA but an unexpected elevation of free MHPG values. The cases of Parkinson's disease showed a definite reduction of HVA. On the other hand, the cases of PCD group showed no significant difference against controls. 5-HIAA levels were not significantly different among the SCD subgroups.

  9. Validation of the clinical diagnostic criteria for temporomandibular disorders for the diagnostic subgroup of degenerative joint disease.

    Science.gov (United States)

    Brandlmaier, I; Grüner, S; Rudisch, A; Bertram, S; Emshoff, R

    2003-04-01

    Research is needed to assess the validity of the Clinical Diagnostic Criteria for Temporomandibular Disorders (CDC/TMD). The purpose of this study was to test the reliability of the clinical diagnosis of temporomandibular joint (TMJ) degenerative joint disease (DJD) as compared with the magnetic resonance imaging (MRI) 'gold standard'. The TMJ DJD group comprised 48 joints in 24 consecutive patients who were assigned a clinical bilateral diagnosis of TMJ DJD. The TMJ non-DJD group consisted of 82 joints in 41 consecutive patients without a TMJ-related diagnosis of TMD. Bilateral sagittal and coronal MR images were obtained subsequently to establish the corresponding diagnosis of degenerative joint changes. An MRI diagnosis of osteoarthrosis (OA) was defined by the presence of flattening, subchondral sclerosis, surface irregularities, and erosion of the condyle or presence of condylar deformities associated with flattening, subchondral sclerosis, surface irregularities, erosion and osteophyte. For the CDC/TMD interpretations, the positive predictive of DJD for OA was 67%, and for the presence of degenerative joint changes 88%. The overall diagnostic agreement for DJD was 44.6% with a corresponding K-value of 0.01. Most of the disagreement was due to false-negative interpretations of asymptomatic joints. The results suggest CDC/TMD to be predictive for degenerative joint changes but insufficient for determination of OA. Patients assigned a clinical TMJ-related diagnosis of DJD may need to be supplemented by evidence from MRI to determine the presence or absence of OA.

  10. Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain

    Energy Technology Data Exchange (ETDEWEB)

    Caviness, V.S. Jr. (Massachusetts General Hospital, Boston, MA (United States)); Phil, D.; Filipek, P.A.; Kennedy, D.N.

    1992-05-01

    The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging-based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently avaiable MRI-based methods. Opimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level. (author).

  11. Degenerative suspensory ligament desmitis as a systemic disorder characterized by proteoglycan accumulation

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    Yoon Jung

    2006-04-01

    Full Text Available Abstract Background Degenerative suspensory ligament desmitis (DSLD is a debilitating disorder thought to be limited to suspensory ligaments of Peruvian Pasos, Peruvian Paso crosses, Arabians, American Saddlebreds, American Quarter Horses, Thoroughbreds, and some European breeds. It frequently leads to persistent, incurable lameness and need to euthanize affected horses. The pathogenesis remains unclear, though the disease appears to run in families. Treatment and prevention are empirical and supportive, and not effective in halting the progression of the disease. Presently, the presumptive diagnosis of DSLD is obtained from patient signalment and history, clinical examination, and ultrasonographic examination of clinically affected horses, and is confirmed at post mortem examination. Presently, there are no reliable methods of diagnosing DSLD in asymptomatic horses. The goal of this study was to characterize and define the disorder in terms of tissue involvement at the macroscopic and microscopic levels. Results We examined tissues and organs from 28 affected horses (22 Peruvian Pasos, 6 horses of other breeds and from 8 control horses. Histopathological examination revealed the presence of excessive amounts of proteoglycans in the following tissues removed from DSLD-affected horses: suspensory ligaments, superficial and deep digital flexor tendons, patellar and nuchal ligaments, cardiovascular system, and sclerae. Electron microscopy demonstrated changes in diameters of collagen fibrils in the tendon, and in smooth muscle cells of the media of the aorta compatible with increased cell permeability in DSLD-affected cells. Separation of tendon extracts by gel chromatography revealed the presence of additional proteoglycan(s in extracts from affected, but not control extracts. Conclusion This study demonstrates for the first time that DSLD, a disease process previously thought to be limited to the suspensory ligaments of the distal limbs of

  12. Designing and testing scene enhancement algorithms for patients with retina degenerative disorders

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    Downes Susan M

    2010-06-01

    Full Text Available Abstract Background Retina degenerative disorders represent the primary cause of blindness in UK and in the developed world. In particular, Age Related Macular Degeneration (AMD and Retina Pigmentosa (RP diseases are of interest to this study. We have therefore created new image processing algorithms for enhancing the visual scenes for them. Methods In this paper we present three novel image enhancement techniques aimed at enhancing the remaining visual information for patients suffering from retina dystrophies. Currently, the only effective way to test novel technology for visual enhancement is to undergo testing on large numbers of patients. To test our techniques, we have therefore built a retinal image processing model and compared the results to data from patient testing. In particular we focus on the ability of our image processing techniques to achieve improved face detection and enhanced edge perception. Results Results from our model are compared to actual data obtained from testing the performance of these algorithms on 27 patients with an average visual acuity of 0.63 and an average contrast sensitivity of 1.22. Results show that Tinted Reduced Outlined Nature (TRON and Edge Overlaying algorithms are most beneficial for dynamic scenes such as motion detection. Image Cartoonization was most beneficial for spatial feature detection such as face detection. Patient's stated that they would most like to see Cartoonized images for use in daily life. Conclusions Results obtained from our retinal model and from patients show that there is potential for these image processing techniques to improve visual function amongst the visually impaired community. In addition our methodology using face detection and efficiency of perceived edges in determining potential benefit derived from different image enhancement algorithms could also prove to be useful in quantitatively assessing algorithms in future studies.

  13. Phonological buffer and selective deficits of grammar, with distinct time onsets, in a patient with a focal degenerative disorder.

    Science.gov (United States)

    Kartsounis, Luke D; Crewes, Hilary

    2007-04-01

    We report a patient with a focal degenerative disorder and very circumscribed neuropsychological deficits, the evolution of which we were able to study over a lengthy period. For years, he presented with only a speech production impediment that clinical observations and experimental studies enabled us to identify as a phonological buffer disorder. Subsequently, he developed agrammatism that appeared to be largely due to his inability to produce pronouns and auxiliary verbs. Remarkably, throughout our studies, even when he was virtually rendered mute, his ability to name objects on demand in writing remained intact. We discuss his case from clinical and theoretical perspectives.

  14. Specificity of transcranial sonography in parkinson spectrum disorders in comparison to degenerative cognitive syndromes

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    Laučkaitė Kristina

    2012-03-01

    Full Text Available Abstract Background Hyperechogenicity of the substantia nigra (SN+, detected by transcranial sonography (TCS, was reported as a characteristic finding in Parkinson's disease (PD, with high diagnostic accuracy values, when compared mainly to healthy controls or essential tremor (ET group. However, some data is accumulating that the SN + could be detected in other neurodegenerative and even in non-neurodegenerative disorders too. Our aim was to estimate the diagnostic accuracy of TCS, mainly focusing on the specificity point, when applied to a range of the parkinsonian disorders, and comparing to the degenerative cognitive syndromes. Methods A prospective study was carried out at the Hospital of Lithuanian University of Health Sciences from January until September 2011. Initially, a TCS and clinical examination were performed on 258 patients and 76 controls. The General Electric Voluson 730 Expert ultrasound system was used. There were 12.8% of cases excluded with insufficient temporal bones, and 4.3% excluded with an unclear diagnosis. The studied sample consisted of the groups: PD (n = 71, 33.2%, ET (n = 58, 27.1%, PD and ET (n = 10, 4.7%, atypical parkinsonian syndromes (APS (n = 3, 1.4%, hereditary neurodegenerative parkinsonism (HDP (n = 3, 1.4%, secondary parkinsonism (SP (n = 23, 10.8%, mild cognitive impairment (MCI (n = 33, 15.4%, dementia (n = 13, 6.1%, and control (n = 71. Results There were 80.3% of PD patients at stages 1 & 2 according to Hoehn and Yahr. At the cut-off value of 0.20 cm2 of the SN+, the sensitivity for PD was 94.3% and the specificity - 63.3% (ROC analysis, AUC 0.891, in comparison to the rest of the cohort. At the cut-off value of 0.26 cm2, the sensitivity was 90% and the specificity 82.4%. The estimations for the lowest specificity for PD, in comparison to the latter subgroups (at the cut-off values of 0.20 cm2 and 0.26 cm2, respectively were: 0% and 33.3% to APS, 33.3% and 66.7% to HDP, 34.8% and 69.6% to SP, 55

  15. Altered somatosensory profile according to quantitative sensory testing in patients with degenerative lumbar spine disorders scheduled for surgery.

    Science.gov (United States)

    Lindbäck, Yvonne; Tropp, Hans; Enthoven, Paul; Gerdle, Björn; Abbott, Allan; Öberg, Birgitta

    2017-06-17

    Somatosensory profiling in affected and non-affected body regions can strengthen our insight regarding the underlying pain mechanisms, which can be valuable in treatment decision making and to improve outcomes, in patients with degenerative lumbar spine disorders pre-surgery. The aim was to describe somatosensory profiles in patients with degenerative lumbar spine disorders, to identify the proportion with altered somatosensory profile, and to analyze demographic characteristics, self-reported function, pain, and health pre- and 3 months post-surgery. In this prospective cohort study in a Spine Clinic, 105 patients scheduled for surgery for spinal stenosis, disc herniation, degenerative disc disease, or spondylolisthesis were consecutively recruited. Exclusion criteria were; indication for acute surgery or previous surgery at the same spinal level or severe grade of pathology. Quantitative sensory testing (QST) and self-reported function, pain, and health was measured pre- and 3 months post-surgery. The somatosensory profile included cold detection threshold, warmth detection threshold, cold pain threshold, heat pain threshold and pressure pain threshold in affected and non-affected body regions. On a group level, the patients' somatosensory profiles were within the 95% confidence interval (CI) from normative reference data means. On an individual level, an altered somatosensory profile was defined as having two or more body regions (including a non-affected region) with QST values outside of normal ranges for reference data. The 23 patients (22%) with altered somatosensory profiles, with mostly loss of function, were older (P = 0.031), more often female (P = 0.005), had higher back and leg pain (P = 0.016, 0.020), lower mental health component summary score (SF-36 MCS) (P = 0.004) and larger pain distribution (P = 0.047), compared to others in the cohort. Post-surgery there was a tendency to worse pain, function and health in the group with

  16. What's on Your Mind? Conversation Topics Chosen by People With Degenerative Cognitive-Linguistic Disorders for Communication Boards.

    Science.gov (United States)

    Fried-Oken, Melanie; Daniels, Darlene; Ettinger, Olivia; Mooney, Aimee; Noethe, Glory; Rowland, Charity

    2015-05-01

    Conversational topics chosen by a group of adults with degenerative cognitive-linguistic disorders for personalized communication board development were examined. The patient-generated themes commonly selected are presented to guide treatment planning and communication board development. Communication boards were created for 109 adults as part of a larger research project. One autobiographical topic that each participant would enjoy discussing multiple times was represented on each communication board with 16 pictures and word labels. For this review, topics were collapsed into general themes through a consensus process and examined by gender and age. Sixty unique conversational topics were identified from 109 participants and collapsed into 9 general themes: Hobbies, Family, Travel, Work, Home/Places I've Lived, Sports/Fitness, Religion, Animals, and World War II. Age and gender produced variations in themes chosen, though no significance in rank orders was found across groups. Topics selected by adults with degenerative cognitive-linguistic disorders for communication boards resemble common conversational adult themes and do not center around basic needs or medical issues. Differences in gender and age for topic selection tend to be based on traditional roles. These general themes should be used when creating personalized communication boards for those who benefit from conversational aids.

  17. MicroRNA in central nervous system trauma and degenerative disorders.

    Science.gov (United States)

    Liu, Nai-Kui; Xu, Xiao-Ming

    2011-05-01

    MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level by binding to the 3'-untranslated region of target mRNAs leading to their translational inhibition or sometimes degradation. MiRNAs are predicted to control the activity of at least 20-30% of human protein-coding genes. Recent studies have demonstrated that miRNAs are highly expressed in the central nervous system (CNS) including the brain and spinal cord. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in neurological biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of diverse biological processes such as cell differentiation, growth, proliferation, and apoptosis. Moreover, miRNAs are key modulators of both CNS development and plasticity. Some miRNAs have been implicated in several neurological disorders such as traumatic CNS injuries and neurodegenerative diseases. Recently, several studies suggested the possibility of miRNA involvement in neurodegeneration. Identifying the roles of miRNAs and their target genes and signaling pathways in neurological disorders will be critical for future research. miRNAs may represent a new layer of regulators for neurobiology and a novel class of therapeutic targets for neurological diseases.

  18. [Retinal regeneration with iPS cells ‒ Clinical trials for retinal degenerative disorders].

    Science.gov (United States)

    Sugita, Sunao

    2015-01-01

    Potential for re-programming cells has become widely accepted as a tool for obtaining transplantation materials. There has been great interest in cell-based therapies, including retinal transplants, because there is a reduced risk of immune rejection. Stem cells have the capacity for self-renewal plus the capacity to generate several differentiated cells. They are derived from many sources including human adult-derived induced pluripotent stem (iPS) cells and have found early application in the context of ocular disease. In results, our established iPS-retinal pigment epithelial (RPE) cells are high-quality RPE cells. iPS cells-derived RPE cells clearly showed polygonal morphology (mostly hexagonal) and contained melanin. Moreover, RPE cells derived from iPS cells had many characteristics of mature RPE cells in vivo, but no characteristics of pluripotent stem cells. Recently, we transplanted RPE cell sheets to treat a patient with wet age-related macular degeneration (September, 2014). In addition, we are now conducting experiments to determine whether allogeneic T cells can recognize iPS-RPE cells from HLA-A, B, DRB1 locus homozygote donors. iPS bank might be useful as allografts in retinal disorders, if the recipient T cells cannot respond to allogeneic RPE cells because of match to some of main HLA antigens.

  19. MR Imaging and Radiographic Imaging of Degenerative Spine Disorders and Spine Alignment.

    Science.gov (United States)

    Galbusera, Fabio; Lovi, Alessio; Bassani, Tito; Brayda-Bruno, Marco

    2016-08-01

    Advances in MR imaging technologies, as well as the widening of their availability, boosted their use in the diagnosis of spinal disorders and in the preoperative planning of spine surgeries. However, the most consolidated approach to the assessment of adult patients with spinal disorders is based on the analysis of full standing radiographs (posteroanterior and laterolateral views). In this article, the radiographic spinal and pelvic parameters, which have relevance in the clinical management of adults with spinal disorders, are summarized.

  20. SDF-1/CXCR4 axis induces apoptosis of human degenerative nucleus pulposus cells via the NF-κB pathway

    Science.gov (United States)

    LIU, ZONGCHAO; MA, CHUAN; SHEN, JIELIANG; WANG, DAWU; HAO, JIE; HU, ZHENMING

    2016-01-01

    Intervertebral disc degeneration (IVDD) is a major cause of lower back pain, and increased cell apoptosis is a key characteristic of IVDD. The present study aimed to investigate the effects and mechanism of the stromal cell-derived factor-1 (SDF-1)/C-X-C motif chemokine receptor 4 (CXCR4) axis on apoptosis in human degenerative nucleus pulposus cells (NPCs). The expression levels of SDF-1 and CXCR4 in human intervertebral discs (IVD) were determined using immunohistochemistry and western blot analysis. Apoptosis of primary cultured NPCs was quantified by Annexin V/propidium iodide staining following stimulation with SDF-1 and knockdown of CXCR4 using small interfering RNA (siRNA). The association with the nuclear factor-κB (NF-κB) signaling pathway was investigated using CXCR4-siRNA and NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), treatment. The results demonstrated that SDF-1 and its receptor, CXCR4, were upregulated in degenerative IVD samples compared with normal samples. Stimulation with SDF-1 increased the level of apoptosis in cultured NPCs, and conversely, the apoptosis level was suppressed post-transfection with CXCR4 siRNA compared with SDF-1 stimulation alone. Furthermore, SDF-1 treatment increased the level of phosphorylated NF-κB subunit P65, which was downregulated following CXCR4 siRNA and PDTC treatment. In addition, CXCR4 siRNA and PDTC inhibited the nuclear translocation of P65, which was induced by SDF-1. Taken together, SDF-1-mediated apoptosis was suppressed by NF-κB inhibition using PDTC. In conclusion, the SDF-1/CXCR4 axis promoted cell apoptosis in human degenerative NPCs via the NF-κB pathway, thus suggesting that SDF-1/CXCR signaling may be a therapeutic target for the treatment of degenerative IVD diseases. PMID:27220474

  1. Are degenerative rotator cuff disorders a cause of shoulder pain? Comparison of prevalence of degenerative rotator cuff disease to prevalence of nontraumatic shoulder pain through three systematic and critical reviews.

    Science.gov (United States)

    Vincent, Karl; Leboeuf-Yde, Charlotte; Gagey, Olivier

    2017-05-01

    The role of degeneration is not well understood for rotator cuff pain. If age-related degenerative changes would be the cause of symptoms, degeneration would precede or concur with self-reported pain. We performed 3 systematic literature reviews. Our objectives were to determine the prevalence estimates for rotator cuff partial or complete tears (1) in cadavers and (2) in the general population and (3) to estimate the incidence/prevalence of self-reported nontraumatic shoulder pain in the general population in order to compare their respective age-related profiles. We searched PubMed and ScienceDirect, including 2015, for cadaveric studies and transverse and longitudinal studies of the general population reporting the incidence/prevalence of rotator cuff disorders or nontraumatic shoulder pain, or both, according to age. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results were interpreted visually. We found 6 cadaveric studies, 2 studies from the general population reporting complete tears, and 10 articles on nontraumatic shoulder pain in the general population that met our criteria. The profiles of degeneration vs. pain were very similar in early years. Although degenerative rotators cuff lesions increased gradually after 50 years, the incidence/prevalence of nontraumatic shoulder pain decreased after 65 years. The profile of age-related degenerative rotator cuff disorders fails to correlate systematically with self-reported nontraumatic shoulder pain, particularly in older age; thus, it appears that degeneration should not be considered the primary source of the pain. Physical activity may play an important role in the production of the pain, a theory that warrants further study. Copyright © 2017. Published by Elsevier Inc.

  2. Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality

    Directory of Open Access Journals (Sweden)

    Jakowec Michael W.

    2016-09-01

    Full Text Available Exercise and physical activity are fundamental components of a lifestyle essential in maintaining a healthy brain. This is primarily due to the fact that the adult brain maintains a high degree of plasticity and activity is essential for homeostasis throughout life. Plasticity is not lost even in the context of a neurodegenerative disorder, but could be maladaptive thus promoting disease onset and progression. A major breakthrough in treating brain disorders such as Parkinson’s disease is to drive neuroplasticity in a direction to improve motor and cognitive dysfunction. The purpose of this short review is to present the evidence from our laboratories that supports neuroplasticity as a potential therapeutic target in treating brain disorders. We consider that the enhancement of motor recovery in both animal models of dopamine depletion and in patients with Parkinson’s disease is optimized when cognitive circuits are engaged; in other words, the brain is engaged in a learning modality. Therefore, we propose that to be effective in treating Parkinson’s disease, physical therapy must employ both skill-based exercise (to drive specific circuits and aerobic exercise (to drive the expression of molecules required to strengthen synaptic connections components to select those neuronal circuits, such as the corticostriatal pathway, necessary to restore proper motor and cognitive behaviors. In the wide spectrum of different forms of exercise, learning as the fundamental modality likely links interventions used to treat patients with Parkinson’s disease and may be necessary to drive beneficial neuroplasticity resulting in symptomatic improvement and possible disease modification.

  3. Huntington disease: a single-gene degenerative disorder of the striatum.

    Science.gov (United States)

    Nopoulos, Peggy C

    2016-03-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

  4. [Basic disorders in human communication].

    Science.gov (United States)

    Peñaloza-López, Y; Gutiérrez-Silva, J; Andrade-Illañez, E N; Fierro-Evans, M A; Hernández-López, X

    1989-01-01

    This paper specifies the areas and disorders that concern human communication medicine. The frequency of the diverse disorders is analyzed in relation to age and sex, and the distribution in group ages of several disabling diseases is also discussed.

  5. Incidence and risk factors of adjacent segment disease following posterior decompression and instrumented fusion for degenerative lumbar disorders

    Science.gov (United States)

    Wang, Hui; Ma, Lei; Yang, Dalong; Wang, Tao; Liu, Sen; Yang, Sidong; Ding, Wenyuan

    2017-01-01

    Abstract The purpose of this study was to explore incidence and risk factors of adjacent segment disease (ASD) following posterior decompression and instrumented fusion for degenerative lumbar disorders, and hope to provide references in decision making and surgical planning for both spinal surgeon and surgically treated patients. By retrieving the medical records from January 2011 to December 2013 in our hospital, 237 patients were retrospectively reviewed. According to the occurrence of ASD at follow up, patients were divided into 2 groups: ASD and N-ASD group. To investigate risk values for the occurrence of ASD, 3 categorized factors were analyzed statistically: Patient characteristics: age, sex, body mass index (BMI), bone mineral density (BMD), duration. Surgical variables: surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, intraoperative superior facet joint violation. Radiographic parameters: preoperative lumbar lordosis, preoperative angular motion at adjacent segment, preoperative adjacent segment disc degeneration, preoperative paraspinal muscle degeneration. Postoperative ASD was developed in 15 of 237 patients (6.3%) at final follow up. There was no statistically significant difference between the 2 groups in patient characteristics of age, sex composition, BMD, duration, while the BMI was higher in ASD group than that in N-ASD group. There was no difference in surgical variables of surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, while intraoperative superior facet joint violation was more common in ASD group than that in N-ASD group. There was no difference in radiographic parameters of preoperative lumbar lordosis, preoperative paraspinal muscle degeneration, while preoperative adjacent segment disc degeneration were more severe in ASD group than that in N-ASD group. The Logistic regression analysis revealed that, BMI >25 kg/m2, preoperative disc degeneration, and superior

  6. Incidence and risk factors of adjacent segment disease following posterior decompression and instrumented fusion for degenerative lumbar disorders.

    Science.gov (United States)

    Wang, Hui; Ma, Lei; Yang, Dalong; Wang, Tao; Liu, Sen; Yang, Sidong; Ding, Wenyuan

    2017-02-01

    The purpose of this study was to explore incidence and risk factors of adjacent segment disease (ASD) following posterior decompression and instrumented fusion for degenerative lumbar disorders, and hope to provide references in decision making and surgical planning for both spinal surgeon and surgically treated patients.By retrieving the medical records from January 2011 to December 2013 in our hospital, 237 patients were retrospectively reviewed. According to the occurrence of ASD at follow up, patients were divided into 2 groups: ASD and N-ASD group. To investigate risk values for the occurrence of ASD, 3 categorized factors were analyzed statistically: Patient characteristics: age, sex, body mass index (BMI), bone mineral density (BMD), duration. Surgical variables: surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, intraoperative superior facet joint violation. Radiographic parameters: preoperative lumbar lordosis, preoperative angular motion at adjacent segment, preoperative adjacent segment disc degeneration, preoperative paraspinal muscle degeneration.Postoperative ASD was developed in 15 of 237 patients (6.3%) at final follow up. There was no statistically significant difference between the 2 groups in patient characteristics of age, sex composition, BMD, duration, while the BMI was higher in ASD group than that in N-ASD group. There was no difference in surgical variables of surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, while intraoperative superior facet joint violation was more common in ASD group than that in N-ASD group. There was no difference in radiographic parameters of preoperative lumbar lordosis, preoperative paraspinal muscle degeneration, while preoperative adjacent segment disc degeneration were more severe in ASD group than that in N-ASD group. The Logistic regression analysis revealed that, BMI >25 kg/m, preoperative disc degeneration, and superior facet joint

  7. Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    Science.gov (United States)

    2017-09-14

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  8. Disorder in Complex Human System

    Science.gov (United States)

    Akdeniz, K. Gediz

    2011-11-01

    Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

  9. Degenerative myelopathy in dogs

    Directory of Open Access Journals (Sweden)

    Nikolovski Goran

    2010-05-01

    Full Text Available One of the chronic progressive disorders of the spinal cord in dogs is the degenerative myelopathy (DM. The most predisposed age in dog is 5 to 14 years, while rarely noted in younger, there is no gender predisposition. This disorder most commonly appears in dogs of the German shepherd breed, but it can appear in other breeds too. The main changes about this disease are degeneration of the myelin, especially in the thoracic-lumbar segments of the spinal cord and the dorsal nerve roots. The progression of the disease is slow and can last months to years. Undoubtedly, diagnosis is made by examinations of the CSF and establishing elevated level of protein segments.

  10. Could astrocytes be the primary target of an offending agent causing the primary degenerative diseases of the human central nervous system? A hypothesis.

    Science.gov (United States)

    Sica, Roberto E

    2015-05-01

    Most of the named primary degenerative diseases of the human central nervous system have been attributed to a direct, primary damage of some particular population of neurons. Within the spectrum of these illnesses there are disorders like amyotrophic lateral sclerosis, fronto-temporal dementia, Alzheimer's dementia, Parkinson's disease, Huntington's dementia and cerebellar ataxias affecting exclusively the human species. In the last years it has been shown that non-neural cells, mainly astrocytes, have a crucial role in the starting and development of these diseases. We suggest that the causative agent of these illnesses gets home first within the astrocytes, rather than the neurons, making them sick by modifying the structure of some proteins; from these cells the abnormal process would start a trip to other astrocytes having the same genetic, metabolic, structural and functional profiles that the originally affected astrocytes have, going through the gap junctions which connect that particular population devoted to a particular set of neurons. This appears to be a likely hypothesis because the astrocytes related to a defined population of neurons have their own, private properties and characteristics needed to support one particular set of neurons performing a defined function, making them a different and unique population, a fact which would limit the spreading of the disease to those astrocytes, sparing other astrocyte populations which do not share those characteristics. If this were the mechanism underlying these illnesses, the neurons, which their health depends on those astrocytes, would be deprived of their patronage and would start all the changes that characterizes a programmed cell death, and the clinical manifestations of a defined pathology would consequently appear. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. [Nineteen cases of school-aged children with degenerative or metabolic neurological disorders initially presenting with learning difficulty and/or behavior disturbance].

    Science.gov (United States)

    Honzawa, Shiho; Sugai, Kenji; Akaike, Hiroto; Nakayama, Tojo; Fujikawa, Yoshinao; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki

    2012-07-01

    We reported 19 cases of school-aged children. They were initially judged to have learning difficulty or school maladaptation because of attention deficits, hyperactive behaviors or poor school performance, followed by the diagnosis such as degenerative or metabolic neurological diseases. The patients consisted of 4 cases of adrenoleukodystrophy, 5 cases of dentatorubral-pallidoluysian atrophy, 3 cases of Sanfilippo syndrome, 3 cases of subacute sclerosing panencephalitis, and each one case of juvenile Gaucher disease, juvenile Huntington disease, juvenile metachromatic leukodystrophy and Leigh disease. They had markedly poor school performance, and/or abnormal behaviors, followed by seizures, character disorders or psychomotor regression. The diagnostic clues included brain CT scan and/or MRI, peculiar facial appearance and notable family histories. When the children were indicated to have learning difficulty or maladjustment to school life, we should make deliberate differential diagnoses before concluding that they have a learning disorder and/or attention-deficit/hyperactivity disorder. Instead they should be recommended to visit child neurologists, when they present with any problems as aforesaid.

  12. Peripheral degenerative joint diseases

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2008-03-01

    Full Text Available Osteoarthritis, a degenerative joint disease, is the most commonrheumatic disorder mainly in a geriatric population. Manifestationsare pain, stiffness and functional loss in the affected joint.According to etiology it is classifi ed as primary (or idiopathicand secondary. Some risk factors for disease development aregenetics, race, age, sex, obesity, occupational activities andarticular biomechanics. Pathogenesis is the same for any cause orlocalization, being catabolic alterations, with synthesis, inhibitionand reparing intent of the cartilage matrix. Metalloproteinases andcytokines (IL-1,IL-6,TNF-α actions promote infl ammatory reactionand cartilage degradation. Pain, the most important symptom,does not correlate with radiologic fi ndings. Peripheral osteoarthritisoccurs predominantly in the knee, hip and hand. Diagnosis is basedon clinical features, laboratorial tests and radiological changes.Rheumatological associations’ guidelines for treatment includenon-pharmacologic (education, physiotherapy, assistive devices,and pharmacologic (analgesics, anti-infl ammatory drugs therapyand surgery. Arthroplasty seems to work better than medicines, butshould be used if other treatments have failed.

  13. [Multiple system atrophy and Alzheimer's disease: a case report of a rare association of two neuro-degenerative disorders].

    Science.gov (United States)

    Rusina, R; Bourdain, F; Matej, R

    2007-12-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder typically characterised by cerebellar dysfunction, parkinsonism, pyramidal signs and dysautonomy. Cognitive impairement is usually limited to a moderate subcortical dysexecutive syndrom. We report the case of a 62-year-old woman suffering from MSA who progressively developed severe dementia. Neuropathological examination confirmed the diagnosis of definite MSA and also showed histopathological hallmarks of Alzheimer's disease. This association is extremely rare in the literature. Our observation confirmes that franc dementia in MSA should prompt a search for another associated cause and underlines the usefulness of neuropathological verifications in atypical clinical pictures.

  14. Degenerative Nerve Diseases

    Science.gov (United States)

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  15. Human Genetic Disorders of Axon Guidance

    Science.gov (United States)

    Engle, Elizabeth C.

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID:20300212

  16. Human Genetic Disorders of Axon Guidance

    OpenAIRE

    Engle, Elizabeth C

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Gene...

  17. 'Lumbar Degenerative Kyphosis' Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception.

    Science.gov (United States)

    Lee, Chang-Hyun; Chung, Chun Kee; Jang, Jee-Soo; Kim, Sung-Min; Chin, Dong-Kyu; Lee, Jung-Kil

    2017-03-01

    Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal deformity. Unlike what its name suggests, LDK does not only include sagittal balance disorder of the lumbar spine and kyphosis, but also sagittal balance disorder of the whole spine and little lordosis of the lumbar spine. Moreover, this disease is closely related to the occupation of female farmers and an outdated Asian life style. These reasons necessitate a change in the nomenclature of this disorder to prevent misunderstanding. We suggest the name "primary degenerative sagittal imbalance" (PDSI), which encompasses degenerative sagittal misalignments of unknown origin in the whole spine in older-age patients, and is associated with back muscle wasting. LDK may be regarded as a subgroup of PDSI related to an occupation in agriculture. Conservative treatments such as exercise and physiotherapy are recommended as first-line treatments for patients with PDSI, and surgical treatment is considered only if conservative treatments failed. The measurement of spinopelvic parameters for sagittal balance is important prior to deformity corrective surgery. LDK can be considered a subtype of PDSI that is more likely to occur in female farmers, and hence the use of LDK as a global term for all degenerative sagittal imbalance disorders is better avoided. To avoid confusion, we recommend PDSI as a newer, more accurate diagnostic term instead of LDK.

  18. [Dysexecutive syndromes and degenerative diseases].

    Science.gov (United States)

    Pillon, B; Czernecki, V; Dubois, B

    2004-04-01

    A dysexecutive syndrome is observed not only in frontotemporal lobar degeneration, but also in subcortical degenerative diseases, and even in Alzheimer's disease whose lesions predominate in temporoparietal associative areas. The association between a dysexecutive syndrome and various cerebral localisations may be explained by the fact that cognitive and behavioral organisation recruits anatomofunctional frontostriatal and frontoparietal circuits. Both animal experimentation and human clinical observation argue in favour of a functional continuity and complementarity among these loops. The prefrontal cortex would be particularly needed in new situations, to inhibit old programs of action not adapted to the present context and to elaborate new ones; the basal ganglia would be rather required by the repetition of the situation to progressively transform the new program in routine. If we refer to Shallice model, we can hypothesize that optimal executive functions require the preservation not only of the Supervisory Attentional System, mainly dependent on the prefrontal cortex, but also of the Contention Scheduling, recruiting the basal ganglia, and of the Schemas of Action, represented in parietal and premotor areas. Therefore, the neuropsychological assessment of patients with degenerative diseases contributes to the understanding of the anatomofunctional architecture of executive functions.

  19. Degenerative cerebellar diseases and differential diagnoses; Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W.; Roumia, S.; Dietrich, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-11-15

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [German] Klinisch imponieren Kleinhirnsyndrome durch Ataxie, Dysarthrie, Dysmetrie, Intentionstremor und Augenbewegungsstoerungen. Neben der Anamnese und klinischen Untersuchung ist die Bildgebung v. a. wichtig um andere Erkrankungen wie Hydrozephalus und Multiinfarktdemenz von degenerativen Kleinhirnerkrankungen zu differenzieren. Zu den degenerativen Erkrankungen mit Kleinhirnbeteiligung gehoeren der Morbus Parkinson, die Multisystematrophie sowie weitere Erkrankungen einschliesslich der spinozerebellaeren Ataxien. Neben der MRT sind auch nuklearmedizinische Untersuchungen zur Differenzierung hilfreich. Axiale Fluid-attenuated-inversion-recovery(FLAIR)- und T2-gewichtete Sequenzen koennen mitunter eine Signalsteigerung im Pons als Ausdruck einer Degeneration der pontinen Neuronen und transversalen Bahnen im Brueckenfuss zeigen. Die Bildgebung ist aber v. a. notwendig, um andere Erkrankungen wie Normaldruckhydrozephalus

  20. Modeling human craniofacial disorders in Xenopus.

    Science.gov (United States)

    Dubey, Aditi; Saint-Jeannet, Jean-Pierre

    2017-03-01

    Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease.

  1. The in vitro effects of dexamethasone, insulin and triiodothyronine on degenerative human intervertebral disc cells under normoxic and hypoxic conditions

    Directory of Open Access Journals (Sweden)

    A Bertolo

    2011-02-01

    Full Text Available Degeneration of intervertebral discs (IVD is one of the main causes of back pain and tissue engineering has been proposed as a treatment. Tissue engineering requires the use of highly expensive growth factors, which might, in addition, lack regulatory approval for human use. In an effort to find readily available differentiation factors, we tested three molecules – dexamethasone, triiodothyronine (T3 and insulin – on human IVD cells isolated after surgery, expanded in vitro and transferred into alginate beads. Triplicates containing 40 ng/ml dexamethasone, 10 nM T3 and 10 µg/ml insulin, together with a positive control (10 ng/mL transforming growth factor (TGF-beta 1, were sampled weekly over six weeks and compared to a negative control. Furthermore, we compared the results to cultures with optimized chondrogenic media and under hypoxic condition (2% O2. Glycosaminoglycan (GAG determination by Alcian Blue assay and histological staining showed dexamethasone to be more effective than T3 and insulin, but less than TGF-beta1. DNA quantification showed that only dexamethasone stimulated cell proliferation. qPCR demonstrated that TGF-beta1 and the optimized chondrogenic groups increased the expression of collagen type II, while aggrecan was stimulated in cultures containing dexamethasone. Hypoxia increased GAG accumulation, collagen type II and aggrecan expression, but had no effect on or even lowered cell number. In conclusion, dexamethasone is a valuable and cost-effective molecule for chondrogenic and viability induction of IVD cells under normoxic and hypoxic conditions, while insulin and T3 did not show significant differences.

  2. Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders.

    Science.gov (United States)

    Sims, Natalie A

    2015-10-01

    Mutations in cardiotrophin-like cytokine factor (CLCF1) and the related cytokine to which it binds, cytokine receptor-like factor 1 (CRLF1), are associated with Crisponi/cold induced sweating syndromes, and lead to early neonatal death in mice due to a suckling defect. These cytokines are members of the IL-6 superfamily, and form a range of composite cytokines that signal through gp130 bound either to the ciliary neurotrophic factor receptor (CNTFR) or a complex that involves the IL-27 p28 subunit. This review describes current knowledge of the signalling complexes formed by these cytokines, and explores their described and suggested roles in the neural, haematopoietic, skeletal, renal, immune and respiratory systems during development and adulthood, and in degenerative diseases and cancer.

  3. Labelling and tracking of human mesenchymal stromal cells in preclinical studies and large animal models of degenerative diseases.

    Science.gov (United States)

    Vaegler, Martin; Maerz, Jan K; Amend, Bastian; da Silva, Luis Arenas; Mannheim, Julia G; Fuchs, Kerstin; Will, Susanne; Sievert, Karl D; Stenzl, Arnulf; Hart, Melanie L; Aicher, Wilhelm K

    2014-01-01

    Success of stem cell therapies were reported in different medical disciplines, including haematology, rheumatology, orthopaedic surgery, traumatology, and others. Currently, more than 4000 clinical trials using stem cells have been completed or are underway, among which 378 investigated or are at present investigating mesenchymal stromal cells (MSCs). The majority of clinical trials using stem- or progenitor- cells, including hematopoietic stem cells and MSCs, target the immune system. However, therapies based on MSCs are increasingly implemented to treat symptoms in which failure of the resident stem cells in situ, or malfunction of tissues or structures are not associated with immune cells or inflammation, but instead are associated with mechanical or metabolic stress, ageing, developmental or acquired malformations, and other causes. To proceed further in the development of stem cell therapies as a safe and effective treatment for surgical and other medical specialities, the behaviour of MSCs implanted in preclinical models and their impact on the site of application need to be explored in detail. Depending on the pre-clinical model employed, tracking of labelled stem cells in live animals makes an enormous difference for exploration of the mechanisms and kinetics involved in MSC-mediated tissue regeneration. Here we review (pre-)clinically applicable key methods to label human MSCs for short and long-term observations in small and large animal models.

  4. Falls in degenerative cerebellar ataxias

    NARCIS (Netherlands)

    van de Warrenburg, Bart P C; Steijns, Janneke A G; Munneke, Marten; Kremer, Berry P H; Bloem, Bastiaan R

    2005-01-01

    We retrospectively and prospectively assessed the frequency and characteristics of falls in patients with degenerative cerebellar ataxias. The results show that falls occur very frequently in patients with degenerative cerebellar ataxias and that these falls are serious and often lead to injuries or

  5. [Degenerative adult scoliosis].

    Science.gov (United States)

    García-Ramos, C L; Obil-Chavarría, C A; Zárate-Kalfópulos, B; Rosales-Olivares, L M; Alpizar-Aguirre, A; Reyes-Sánchez, A A

    2015-01-01

    Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance.

  6. Degenerative Suspensory Ligament Desmitis – A New Reality

    Directory of Open Access Journals (Sweden)

    Jaroslava Halper*, Ahrar Khan1 and P. O. Eric Mueller2

    2011-01-01

    Full Text Available Degenerative suspensory ligament desmitis (DSLD is a chronic, debilitating disease occurring primarily in Peruvian Pasos and Peruvian Paso crosses. However, many other breeds are afflicted as well. DSLD is characterized by a slowly progressing bilateral or quadrilateral lameness. Typically, the owner does not recall any trauma or performance related injury. Fetlock effusion, static and dynamic hyperextension and degenerative joint disease are hallmarks on physical examination. Ultrasonography of affected ligaments reveals diffuse loss of echogenicity, and an irregular fiber pattern. Though until recently DSLD was considered a collagen disorder strictly limited to suspensory ligaments (SLs, our data show that it is a systemic disease involving tissues with high content of collagen. We have identified abnormal accumulations of proteoglycans not only in the SLs, but also in the superficial and deep digital flexor tendons, patellar and nuchal ligaments, aorta, coronary arteries and sclerae of DSLD-affected horses. Our most recent data point to the presence of an abnormal form of decorin in these proteoglycan deposits. This decorin also exhibited altered biological activity. Treatment for DSLD-affected horses is empirical and directed at minimizing musculoskeletal pain and providing support for the suspensory apparatus. Restricted exercise, supportive bandages and nonsteroidal anti-inflammatory drugs provide some, but usually only temporary relief. Unfortunately, unrelenting pain, severe lameness and suffering require all too often humane euthanasia.

  7. Degenerative disease of the spine.

    Science.gov (United States)

    Gallucci, Massimo; Limbucci, Nicola; Paonessa, Amalia; Splendiani, Alessandra

    2007-02-01

    Degenerative disease of the spine is a definition that includes a wide spectrum of degenerative abnormalities. Degeneration involves bony structures and the intervertebral disk, although many aspects of spine degeneration are strictly linked because the main common pathogenic factor is identified in chronic overload. During life the spine undergoes continuous changes as a response to physiologic axial load. These age-related changes are similar to pathologic degenerative changes and are a common asymptomatic finding in adults and elderly persons. A mild degree of degenerative changes is paraphysiologic and should be considered pathologic only if abnormalities determine symptoms. Imaging allows complete evaluation of static and dynamic factors related to degenerative disease of the spine and is useful in diagnosing the different aspects of spine degeneration.

  8. SENILE DEGENERATIVE CHANGES IN ADULT LUMBAR SPINE! - A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Garjesh Singh

    2015-11-01

    Full Text Available : BACKGROUND: Low back pain (LBP is a common presenting complaint affecting mostly middle aged and older person and traditionally considered as ageing process, but now-a-days large number of younger people are also affected by this debilitating chronic disorder. The cause of early onset of degenerative spine disease is multifactorial, but genetical predisposition plays very important role. AIMS AND OBJECTIVE: To find out association between genetic predisposition and degenerative spine disease in adult patients and to assess the pattern of MRI findings of various degenerative diseases in lumbo-sacral spine. MATERIAL AND METHOD: The present cross-sectional study had been performed among 100 selected patients in 1yr period, who presented with chief complaint of chronic low back pain. After taking detailed clinical and professional history, MRI of lumbosacral spine had been performed. Total 100 patients were divided in two groups on the basis of genetical predisposition. Prevalence and spectrum of degenerative changes were compared between both groups. RESULTS: Hundred patients of 20 to 35-year age had been selected with mean age of 27yr. Out of 100 patients; 47 were male and 53 were female. The most common degenerative findings were desiccation of disc (95% followed by disc bulge, herniation, spinal canal stenosis, ligamentum flavum hypertrophy, facet joint hypertrophy and modic changes. L4-L5 and L5- S1 were the most commonly involved spinal levels for any degenerative pathology. CONCLUSION: Good association is seen between early onset of degenerative spine disease and genetical predisposition in patients who have history of similar type degenerative spine disease in one or more first degree relatives in comparison to those patients who do not have any genetical predisposition. So it can be concluded that heredity play important role in early onset of degenerative spine disease in adults.

  9. Continuation of medically necessary platelet aggregation inhibitors - acetylsalicylic acid and clopidogrel - during surgery for spinal degenerative disorders: Results in 100 patients

    Directory of Open Access Journals (Sweden)

    Reza Akhavan-Sigari

    2014-01-01

    Full Text Available Background: Patients undergoing spinal surgery while under anticoagulation therapy are at risk of developing bleeding complications, even though lower incidences have been reported for joint arthroplasty surgery. There is a gap in the medical literature examining the incidence of postoperative spinal bleeding in patients who were under anticoagulation medication at the time of surgery. Methods: We prospectively followed a consecutive cohort of 100 patients (58 male, 42 female undergoing spinal surgery. The average patient age was 48.7 years and the minimum follow up time was 12 months. Diagnosis was lumbar spinal stenosis in 20, herniated lumbar discs in 63, degenerative cervical disc disease in 3, and cervical disc herniation in 14 cases. In our study, platelet aggregation inhibitors (clopidogrel and/or acetylsalicylic acid were given for the treatment of cardiovascular and cerebrovascular thrombotic events, to reduce risk of stroke in patients who have had transient ischemia of the brain or acute coronary syndrome, and as secondary prevention of atherosclerotic events (fatal or nonfatal myocardial infarction (MI. A cessation of anticoagulants (acetylsalicylic acid or clopidogrel in our patients in the peri- and postoperative period was contraindicated. Results: Sixty-three patients were on both clopidogrel and acetylsalicylic acid and 37 on acetylsalicylic acid only. None of the patients suffered any postoperative bleeding complication. Three patients suffered postoperative wound dehiscence and one patient had an infection that required reoperation. Conclusion: The question of whether preoperative platelet aggregation inhibitors must be stopped before elective spinal surgery has never been answered in the literature. In our prospective series, we have found no increase in the risk of postoperative spinal bleeding with the use of clopidogrel or acetylsalicylic acid. This finding suggests that spine surgery can be done without stopping

  10. Imaging of degenerative spine disease--the state of the art.

    Science.gov (United States)

    Sasiadek, Marek J; Bladowska, Joanna

    2012-01-01

    The authors review the current state of imaging of degenerative spinal disease (DSD), which is one of the most common disorders in humans. The most important definitions as well as short descriptions of the etiopathology and clinical presentation of DSD are provided first, followed by an overview of conventional and advanced imaging methods that are used in DSD. The authors then discuss in detail the imaging patterns of particular types of degenerative changes. Finally, the current imaging algorithm in DSD is presented. The imaging method of choice is magnetic resonance, including advanced techniques--especially diffusion tensor imaging. Other imaging methods (plain radiography, computed tomography, vascular studies, scintigraphy, positron emission tomography, discography) play a supplementary role ).

  11. Advances in gene technology: Human genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  12. 人松果体组织结构的退行性变化及其意义%Degenerative pathological change of human pineal body and its significance

    Institute of Scientific and Technical Information of China (English)

    申新华; 马超; 李文婷; 王乃利; 鲍双振; 王保芝

    2012-01-01

    Objective:To study the size, amount, distribution of brain sands and other morphology features in the human pineal body. Methods: Micro-and ultra-structure of 43 pineal bodies from human cadaver was observed under a light microscope, scanning-and transmission electron microscope. Results: The human pineal body was mainly composed of two elements of parenchyma and interstitium. The pineal parenchyma consisted of many pinealocytes and a few neurogliocytes. The pineal interstitium was made up of connective tissues through which the blood vessels and nerve fibers went The brain sands usually clustered together and formed large plaques in the central part of the pineal body. The number and size of brain sands varied individually. In the samples from aged people, we observed an increase in the number and size of brain sands together with proliferation of connective tissues in the interstitium. However, the pinealocytes of parenchyma decreased with aging. In addition, granulovacuolar degeneration was also seen in the pinealocytes. Conclusion: These degenerative pathological changes observed in the human pineal body may lead to progressive degradation of its neuroendo-crine function.%目的:观察人松果体的细微和超微结构,探讨松果体内脑砂的形态特点、大小、多少及分布规律.方法:取人尸体的松果体,光镜、扫描和透射电镜观察其结构特征.结果:松果体主要由实质和间质两种成分构成;松果体实质由松果体细胞和神经胶质细胞组成,间质为结缔组织和穿行其中的神经和血管.脑砂多分布于松果体的中央部,常聚集形成较大的斑块.脑砂的大小、多少个体差异较大.变化趋势为随着年龄的增加,松果体内脑砂增多、增大,并伴有间质成分的结缔组织增生;然而,松果体实质成分减少;而且,在大量的松果体细胞内,可观察到颗粒空泡样变性.结论:松果体组织结构出现的退行性变化,可造成松果体神经内分泌功能的进行性减退.

  13. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    David Oehme

    2015-01-01

    Full Text Available Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

  14. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials.

    Science.gov (United States)

    Oehme, David; Goldschlager, Tony; Ghosh, Peter; Rosenfeld, Jeffrey V; Jenkin, Graham

    2015-01-01

    Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

  15. Cross-cultural adaptation of the Neck Disability Index and Copenhagen Neck Functional Disability Scale for patients with neck pain due to degenerative and discopathic disorders. Psychometric properties of the Polish versions

    Directory of Open Access Journals (Sweden)

    Glowacki Maciej

    2011-04-01

    Full Text Available Abstract Background Even though there are several region-specific functional outcome questionnaires measuring neck disorders that have been developed in English-speaking countries, no Polish version has ever been validated. The purpose of our study was to translate, culturally adapt and validate the Neck Disability Index (NDI and Copenhagen Neck Functional Disability Scale (CDS for Polish-speaking patients with neck pain. Methods The translation was carried out according to the International Quality of Life Association (IQOLA Project. Sixty patients were treated due to degenerative and discopathic disorders in the cervical spine filled out the NDI-PL and the CDS-PL. The pain level was evaluated using the Visual Analog Scale. The mean age of the assessed group was 47.1 years (SD 8.9. We used Cronbach's alpha to assess internal consistency. We assessed the test-retest reliability using the Intraclass Correlation Coefficients (ICCs. The Spearman's rank correlation coefficient (rS was used to determine dependency between quantitative characteristics. The Mann-Whitney test was applied to determine dependency between quantitative and qualitative characteristics. Results The Cronbach's alpha values were excellent for the NDI-PL in the test and in the retest (0.84, 0.85, respectively, and for the CDS-PL (0.90 in the test and in the retest. Intraclass Correlation Coefficients were excellent for the CDS-PL and NDI-PL and equalled 0.93 (95% CI from 0.89 to 0.95 and 0.87 (95% CI from 0.80 to 0.92, respectively The concurrent validity was good in the test and in the retest (rs = 0.42 p Conclusions The present versions of the NDI-PL and CDS-PL, the first to be published in Polish, have proven to be reliable and valid for patients with degenerative changes in the cervical spine. The NDI-PL and CDS-PL have excellent internal consistency and test-retest reliability, and good concurrent validity. The adapted questionnaires showed a strong inter-correlation both

  16. Degenerative lumbosacral stenosis in dogs

    NARCIS (Netherlands)

    Suwankong, N.

    2007-01-01

    Degenerative lumbosacral stenosis (DLS) is now recognized as a significant cause of caudal lumbar pain and pelvic limb lameness in dogs. The condition includes lumbosacral intervertebral disc degeneration and protrusion, spondylosis deformans, sclerosis of the vertebral end plates, osteoarthrosis of

  17. Rotary deformity in degenerative spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sung Gwon; Kim, Jeong; Kho, Hyen Sim; Yun, Sung Su; Oh, Jae Hee; Byen, Ju Nam; Kim, Young Chul [Chosun University College of Medicine, Gwangju (Korea, Republic of)

    1994-05-15

    We studied to determine whether the degenerative spondylolisthesis has rotary deformity in addition to forward displacement. We have made analysis of difference of rotary deformity between the 31 study groups of symptomatic degenerative spondylolisthesis and 31 control groups without any symptom, statistically. We also reviewed CT findings in 15 study groups. The mean rotary deformity in study groups was 6.1 degree(the standard deviation is 5.20), and the mean rotary deformity in control groups was 2.52 degree(the standard deviation is 2.16)(p < 0.01). The rotary deformity can be accompanied with degenerative spondylolisthesis. We may consider the rotary deformity as a cause of symptomatic degenerative spondylolisthesis in case that any other cause is not detected.

  18. Skipping Posterior Dynamic Transpedicular Stabilization for Distant Segment Degenerative Disease

    Directory of Open Access Journals (Sweden)

    Bilgehan Solmaz

    2012-01-01

    Full Text Available Objective. To date, there is still no consensus on the treatment of spinal degenerative disease. Current surgical techniques to manage painful spinal disorders are imperfect. In this paper, we aimed to evaluate the prospective results of posterior transpedicular dynamic stabilization, a novel surgical approach that skips the segments that do not produce pain. This technique has been proven biomechanically and radiologically in spinal degenerative diseases. Methods. A prospective study of 18 patients averaging 54.94 years of age with distant spinal segment degenerative disease. Indications consisted of degenerative disc disease (57%, herniated nucleus pulposus (50%, spinal stenosis (14.28%, degenerative spondylolisthesis (14.28%, and foraminal stenosis (7.1%. The Oswestry Low-Back Pain Disability Questionnaire and visual analog scale (VAS for pain were recorded preoperatively and at the third and twelfth postoperative months. Results. Both the Oswestry and VAS scores showed significant improvement postoperatively (P<0.05. We observed complications in one patient who had spinal epidural hematoma. Conclusion. We recommend skipping posterior transpedicular dynamic stabilization for surgical treatment of distant segment spinal degenerative disease.

  19. Reclaiming the humanity in personality disorder.

    Science.gov (United States)

    Wright, Karen; Haigh, Kevin; McKeown, Mick

    2007-08-01

    This paper provides a commentary upon the nursing care of individuals diagnosed with personality disorder and associated education courses. The discussion focuses upon recent policy trends in the UK as a point of departure. This policy discourse is critical of mainstream mental health services in previously operating to exclude such individuals. One of the consequences has been a recent growth in interest in relevant training courses, many of which devote significant attention to staff attitudes regarding this client group. Various previous researchers and commentators have remarked upon the implications for practice of a perceived negative attitude among care staff. We reflect upon our own anecdotal experience of developing and delivering new university-based courses for practitioners working in the field of personality disorder to offer a particular critique of the UK context, in which this policy, training, and practice is framed. Social constructionist theories are drawn on to offer insights into public and practitioner discourse and the possible effects on therapeutic relationships. The available discourse constructs individuals with a diagnosis of personality disorder as essentially different from other people. We argue that staff training and practice development initiatives are likely to be more successful if such discourse is challenged, and attempts are made in therapeutic encounters to recognize shared characteristics and positive attributes as much as perceived difference and negative attributes. We refer to this as a re-engagement with common humanity. Despite the singular national context, the discursive themes explored are not necessarily restricted to the UK.

  20. ‘Lumbar Degenerative Kyphosis’ Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception

    Science.gov (United States)

    Lee, Chang-Hyun; Chung, Chun Kee; Jang, Jee-Soo; Kim, Sung-Min; Chin, Dong-Kyu; Lee, Jung-Kil

    2017-01-01

    Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal deformity. Unlike what its name suggests, LDK does not only include sagittal balance disorder of the lumbar spine and kyphosis, but also sagittal balance disorder of the whole spine and little lordosis of the lumbar spine. Moreover, this disease is closely related to the occupation of female farmers and an outdated Asian life style. These reasons necessitate a change in the nomenclature of this disorder to prevent misunderstanding. We suggest the name “primary degenerative sagittal imbalance” (PDSI), which encompasses degenerative sagittal misalignments of unknown origin in the whole spine in older-age patients, and is associated with back muscle wasting. LDK may be regarded as a subgroup of PDSI related to an occupation in agriculture. Conservative treatments such as exercise and physiotherapy are recommended as first-line treatments for patients with PDSI, and surgical treatment is considered only if conservative treatments failed. The measurement of spinopelvic parameters for sagittal balance is important prior to deformity corrective surgery. LDK can be considered a subtype of PDSI that is more likely to occur in female farmers, and hence the use of LDK as a global term for all degenerative sagittal imbalance disorders is better avoided. To avoid confusion, we recommend PDSI as a newer, more accurate diagnostic term instead of LDK. PMID:28264231

  1. Arthroscopic surgery for degenerative knee

    DEFF Research Database (Denmark)

    Thorlund, J B; Juhl, C B; Roos, E M;

    2015-01-01

    OBJECTIVE: To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease. DESIGN: Systematic review and meta-analysis. MAIN OUTCOME MEASURES: Pain and physical function....... RESULTS: The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small...... included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death. CONCLUSIONS: The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time...

  2. Natural killer cells in human autoimmune disorders

    Science.gov (United States)

    2013-01-01

    Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases. PMID:23856014

  3. Degenerative spinal disease in large felids.

    Science.gov (United States)

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

  4. The degenerative spine: pattern recognition and guidelines to image interpretation.

    Science.gov (United States)

    Parizel, P M; Van Hoyweghen, A J L; Bali, A; Van Goethem, J; Van Den Hauwe, L

    2016-01-01

    Degenerative disease of the spine, in the form of intervertebral disc degeneration and bony growth, causing osteophytes and impinging upon the spinal canal and neural foramina, is the most frequent disorder affecting the spine. In this chapter we first discuss briefly the indications for computed tomography or magnetic resonance imaging in suspected degenerative spine disease. We then describe changes of disc height, signal intensity, and disc contour with aging and repeated microtrauma, as well as the imaging techniques most appropriate to image them. A grading system for lumbar disc changes is provided. Stenosis of the canal and neural foramina is reviewed next, concluding with a description of degenerative changes affecting the vertebral endplates and bone marrow.

  5. Human rights, bioethics, and mental disorder.

    Science.gov (United States)

    Fennell, Phil

    2008-03-01

    This article considers the international human rights instruments which set minimum standards for the content and use of mental health legislation, and the extent to which they represent 'hard law' (binding and enforceable in domestic or international courts) or 'soft law' which is not strictly binding in the same sense but which may provide persuasive authority or may be used in debate to embarrass a Government into compliance. The article considers the extent to which these various instruments impose both 'negative obligations' on states not to interfere with rights such as physical integrity or protection against arbitrary detention and 'positive' obligations on states to take positive steps to uphold the rights of individuals. The article on the case law under the European Convention on Human Rights showing how 'soft law' sources are increasingly used by the Strasbourg Court as aids to construing the scope of Convention rights. The article concludes by suggesting that whilst mentally disordered people may be afforded different treatment in relation to general bioethics instruments on the international plane, they are also entitled to rights under Disability Conventions which enjoin states to take positive steps to promote equal treatment, social inclusion and protection against discrimination and stigma.

  6. Psychological Disorders among Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Ofovwe et al. Psychological Disorders in PLWHA ... Keywords: Psychological disorders, HIV/AIDS, Southern Nigeria. Résumé ... and psychological treatment or for research purposes. ... Phobic Anxiety (Irrational fears and avoidance of objects ...

  7. Adult degenerative and senile degenerative hyperostosis triangularis ilii

    Energy Technology Data Exchange (ETDEWEB)

    Nebel, G.; Hering, L.; Lingg, G.

    1981-10-01

    A randomised study of 2000 patients (1000 males, 1000 females) revealed two forms of the triangular hyperostosis of the ilium in female patients. The hyperostosis triangularis ilii, HTI, is also known as osteitis condensans. One form of HTI concerning women under the age of 50 is called the adult generative HTI, the other beyond the age of 50 senile degenerative HTI. These two forms are not evident in male patients. The 3.05% incidence of HTI in adults appeared to be higher than presumed till now. The sex incidence male/female of 1:1.6 diverges considerably from preceding investigations. Histomorphological studies of two autopsies of cases of senile degenerative HTI revealed no signs of inflammation. Statistical correlations of HTI with other chronic diseases of the pelvis and hip could doubtlessly and generally be established only for osteoarthrosis of the sacro-iliac joints in females beyond the age of 50 and in males as a matter of principle.

  8. Free Software for Disorders of Human Communication

    Directory of Open Access Journals (Sweden)

    William Ricardo Rodríguez Dueñas

    2015-05-01

    Full Text Available Introduction: New technologies are increasingly used by the health sector for its implementation in therapeutic interventions. However, in the case of speech therapists, there are many unknown free software-based tools which could support their daily work. This paper summarizes fourteen free software-based tools that can support interventions in early stimulation, assessment and control of voice and speech, several resources for augmentative and alternative communication and tools that facilitate access to the computer. Materials and methods: The information presented here is the result of a general review of software-based tools designed to treat human communication disorders. Criteria for inclusion and exclusion were established to select tools and these were installed and tested. Results: 22 tools were found and 14 were selected and classified in these categories: Early stimulation and capture attention, acoustic signal processing of voice, speech processing, Augmentative and Alternative Communication and Other; the latter includes tools for access to the computer without the need for advanced computer skills. Discussion: The set of tools discussed in this paper provides free computer-based tools to therapists in order to help their interventions, additionally, promotes the improvement of computer skills so necessary in today’s society of professionals.

  9. Arthroscopic surgery for degenerative knee

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Juhl, C B; Roos, E M

    2015-01-01

    . DATA SOURCES: Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms. ELIGIBILITY CRITERIA FOR SELECTING...... included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death. CONCLUSIONS: The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time...

  10. Untapped Potential of Disordered Proteins in Current Druggable Human Proteome.

    Science.gov (United States)

    Hu, Gang; Wu, Zhonghua; Wang, Kui; Uversky, Vladimir N; Kurgan, Lukasz

    2016-01-01

    Current efforts in design and characterization of drugs often rely on the structure of their protein targets. However, a large fraction of proteins lack unique 3-D structures and exist as highly dynamic structural ensembles. These intrinsically disordered proteins are involved in pathogenesis of various human diseases and are highly abundant in eukaryotes. Based on a comprehensive analysis of the current druggable human proteome covering 12 drug classes and 18 major classes of drug targets we show a significant bias toward high structural coverage and low abundance of intrinsic disorder. We review reasons for this bias including widespread use of the structural information in various stages of drug development and characterization process and difficulty with attaining structures for the intrinsically disordered proteins. We also discuss future of intrinsically disordered proteins as drug targets. Given the overall high disorder content of the human proteome and current bias of the druggable human proteome toward structural proteins, it is inevitable that disordered proteins will have to raise up on the list of prospective drug targets. The protein disorder-assisted drug design can draw from current rational drug design techniques and would also need novel approaches that no longer rely on a unique protein structure.

  11. The human histaminergic system in neuropsychiatric disorders.

    Science.gov (United States)

    Shan, Ling; Bao, Ai-Min; Swaab, Dick F

    2015-03-01

    Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary nucleus, from where they project to many brain areas. The histaminergic system is involved in basic physiological functions, such as the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, cognition, and attention, which are all severely affected in neuropsychiatric disorders. Here, we present recent postmortem findings on the alterations in this system in neuropsychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight the need to validate animal models for these diseases and also for Tourette's syndrome (TS) in relation to alterations in the histaminergic system. Moreover, we discuss the potential for, and concerns over, the use of novel histamine 3 receptor (H3R) antagonists/inverse agonists as treatment for such disorders.

  12. Revertant mosaicism in human genetic disorders

    NARCIS (Netherlands)

    Jonkman, MF

    1999-01-01

    Somatic reversion of inherited mutations is known for many years in plant breeding, however it was recognized only recently in humans. The concept of revertant mosaicism is important in medical genetics. (C) 1999 Wiley-Liss, Inc.

  13. The etiology and molecular genetics of human pigmentation disorders.

    Science.gov (United States)

    Baxter, Laura L; Pavan, William J

    2013-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically, normal human pigmentation encompasses a variety of skin and hair color as well as punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions in different cell types. Thus, unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, arising from a common developmental origin and/or shared genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities are instructive for understanding normal pathways governing development and function of melanocytes. Copyright © 2012 Wiley Periodicals, Inc.

  14. Stereotypic behaviors in degenerative dementias.

    Science.gov (United States)

    Prioni, S; Fetoni, V; Barocco, F; Redaelli, V; Falcone, C; Soliveri, P; Tagliavini, F; Scaglioni, A; Caffarra, P; Concari, L; Gardini, S; Girotti, F

    2012-11-01

    Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

  15. Dynamic stabilization for degenerative spondylolisthesis and lumbar spinal instability.

    Science.gov (United States)

    Ohtonari, Tatsuya; Nishihara, Nobuharu; Suwa, Katsuyasu; Ota, Taisei; Koyama, Tsunemaro

    2014-01-01

    Lumbar interbody fusion is a widely accepted surgical procedure for patients with lumbar degenerative spondylolisthesis and lumbar spinal instability in the active age group. However, in elderly patients, it is often questionable whether it is truly necessary to construct rigid fixation for a short period of time. In recent years, we have been occasionally performing posterior dynamic stabilization in elderly patients with such lumbar disorders. Posterior dynamic stabilization was performed in 12 patients (6 women, 70.9 ± 5.6 years old at the time of operation) with lumbar degenerative spondylolisthesis in whom % slip was less than 20% or instability associated with lumbar disc herniation between March 2011 and March 2013. Movement occurs through the connector linked to the pedicle screw. In practice, 9 pairs of D connector system where the rod moves in the perpendicular direction alone and 8 pairs of Dynamic connector system where the connector linked to the pedicle screw rotates in the sagittal direction were installed. The observation period was 77-479 days, and the mean recovery rate of lumbar Japanese Orthopedic Association (JOA) score was 65.6 ± 20.8%. There was progression of slippage due to slight loosening in a case with lumbar degenerative spondylolisthesis, but this did not lead to exacerbation of the symptoms. Although follow-up was short, there were no symptomatic adjacent vertebral and disc disorders during this period. Posterior dynamic stabilization may diminish the development of adjacent vertebral or disc disorders due to lumbar interbody fusion, especially in elderly patients, and it may be a useful procedure that facilitates decompression and ensures a certain degree of spinal stabilization.

  16. GUIDELINES FOR TREATMENT OF DEGENERATIVE LUMBAR SPONDYLOLISTHESIS

    Directory of Open Access Journals (Sweden)

    CARMEN YOSSALETH BRICEÑO-GONZÁLEZ

    Full Text Available ABSTRACT Objectives: To determine the standard of treatment of degenerative lumbar spondylolisthesis in its different clinical presentations in UMAE Dr. Victorio de la Fuente Narváez. Methods: Six cases found in the literature were presented to 36 experts in spine surgery, along with treatment options, to thereby obtain a standard prescription for the treatment of degenerative lumbar spondylolisthesis. Analytical observational cross-sectional descriptive study. Results: It was found that the treatment of choice in cases of degenerative lumbar spondylolisthesis with axial symptoms is conservative. The surgical treatment of choice for both stable and unstable patients with radiculopathy and/or claudication is decompression + posterolateral graft + transpedicular instrumentation + discectomy (graft. Conclusions: We managed to define the degenerative lumbar spondylolisthesis treatment guidelines in our unit, which can serve as a basis for the development of a clinical practice guide.

  17. Human embryonic stem cells carrying mutations for severe genetic disorders.

    Science.gov (United States)

    Frumkin, Tsvia; Malcov, Mira; Telias, Michael; Gold, Veronica; Schwartz, Tamar; Azem, Foad; Amit, Ami; Yaron, Yuval; Ben-Yosef, Dalit

    2010-04-01

    Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il.

  18. ?Lumbar Degenerative Kyphosis? Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception

    OpenAIRE

    Lee, Chang-Hyun; Chung, Chun Kee; Jang, Jee-Soo; Kim, Sung-Min; Chin, Dong-Kyu; Lee, Jung-Kil

    2017-01-01

    Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal...

  19. An unusual splice defect in the mitofusin 2 gene (MFN2 is associated with degenerative axonopathy in Tyrolean Grey cattle.

    Directory of Open Access Journals (Sweden)

    Cord Drögemüller

    Full Text Available Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2, is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.

  20. Evolutionary Conservation in Genes Underlying Human Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Lisa Michelle Ogawa

    2014-05-01

    Full Text Available Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago and thirty one non-primate mammalian species. Evolutionary parameters, including dN/dS, are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant compared to their small-brained sister species. Evidence of differential selection in primates supports the hypothesis that schizophrenia and autism are a cost of higher brain function. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained.

  1. Low back pain and degenerative disc disease

    Directory of Open Access Journals (Sweden)

    Jandrić Slavica

    2006-01-01

    Full Text Available Introduction. Various clinical conditions can cause low back pain, and in most cases it is of a degenerative origin. Degenerative disc disease is a common condition which affects young to middle-aged men and women equally. Changes in the mechanical properties of the disc lead to degenerative arthritis in the intervertebral joints, osteophytes, and narrowing the intervertebral foramen or the spinal canal. Pathophysiology. Degenerative cascade, described by Kirkaldy-Willis, is the widely accepted pathophysiologic model describing the degenerative process as it affects the lumbar spine in 3 phases. Diagnosis. There are two forms of low back pain secondary to degenerative disc disease: a lumbalgia and b lumbar radiculopathy. Limitation of movement, problems with balance, pain, loss of reflexes in the extremities, muscle weakness, loss of sensation or other signs of neurological damage can be found on physical examination. For accurate diagnosis, it is often necessary to combine clinical examination and sophisticated technology. Treatment. Coservative treatment consists of rest, physical therapy, pharmacological therapy and injection therapy. Physical rehabilitation with active patient participation is a key approach to treatment of patients with discogenic pain. Physical therapy, occupational therapy and kinesitherapy are important for improving muscle strength, endurance, and flexibility. Disc surgery is performed if surgical intervention is required. .

  2. Evolutionary conservation in genes underlying human psychiatric disorders.

    Science.gov (United States)

    Ogawa, Lisa M; Vallender, Eric J

    2014-01-01

    Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of the protein-coding regions of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago) and 34 non-primate mammalian species. Evolutionary parameters, including dN/dS, are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals, and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant) compared to their small-brained sister species. Evidence of differential selection in humans to the exclusion of non-human primates was absent, however elevated dN/dS was detected in catarrhines as a whole, as well as in cetaceans, possibly as part of a more general trend. Although this may suggest that protein changes associated with schizophrenia and autism are not a cost of the higher brain function found in humans, it may also point to insufficiencies in the study of these diseases including incomplete or inaccurate gene association lists and/or a greater role of regulatory changes or copy number variation. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained.

  3. Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002.

    Science.gov (United States)

    2003-02-21

    Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue. CJD has an annual incidence of approximately 1 case per million population in the United States and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD). During 1993-1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

  4. Precocious Degenerative Arthropathy And Bluish Patches On Ears : Ochronosis And Alkaptonuria

    Directory of Open Access Journals (Sweden)

    Mahajan Vikram K

    2004-01-01

    Full Text Available Alkaptonuria is a rare, autosomal recessive disorder of phenylalanin/tyrosine metabolism due to congenital deficiency of the enzyme homogentisic acid oxidase. The diagnosis is clinical and the triad of homogentisic aciduria, ochronosis and precocious degenerative arthritis is characteristic. Its diagnosis in infancy and early therapeutic intervention help delaying its complications. These patients may remain undiagnosed until the darkening of urine soaked diapers is noticed or the early degenerative arthropathy develops. This paper describes two cases of alkaptonuria presenting late in life; one of them had associated hyperthyroidism.

  5. Human imprinting disorders: Principles, practice, problems and progress.

    Science.gov (United States)

    Mackay, Deborah J G; Temple, I Karen

    2017-11-01

    Epigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic 'imprint' of the parent from whom they were inherited. Imprinted genes are (as a general rule) expressed from one parental allele only. Some imprinted genes are critical regulators of growth and development, and thus disruption of their normal monoallelic expression causes congenital imprinting disorders, with clinical features impacting growth, development, behaviour and metabolism. Imprinting disorders as a group have characteristics that challenge diagnosis and management, including clinical and molecular heterogeneity, overlapping clinical features, somatic mosaicism, and multi-locus involvement. New insights into the biology and epigenomics of the early embryo offers new clues about the origin and importance of imprinting disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Common surgical complications in degenerative spinal surgery.

    Science.gov (United States)

    Papadakis, Michael; Aggeliki, Lianou; Papadopoulos, Elias C; Girardi, Federico P

    2013-04-18

    The rapid growth of spine degenerative surgery has led to unrelenting efforts to define and prevent possible complications, the incidence of which is probably higher than that reported and varies according to the region of the spine involved (cervical and thoracolumbar) and the severity of the surgery. Several issues are becoming progressively clearer, such as complication rates in primary versus revision spinal surgery, complications in the elderly, the contribution of minimally invasive surgery to the reduction of complication rate. In this paper the most common surgical complications in degenerative spinal surgery are outlined and discussed.

  7. Radiographical analysis concernig the etiology of degenerative spondylolisthesis of the lumbar spine

    Energy Technology Data Exchange (ETDEWEB)

    Ihara, Koichiro (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1989-12-01

    The purpose of this article is to evaluate radiographically degenerative spondylolisthesis of the lumbar spine, with the main focus on the configuration of posterior elements. A comparative study between 49 cases of degenerative spondylolisthesis and 99 cases of other lumbar disorders was performed, using 13 radiographical parameters. The results clearly indicate the posterior elements of degenerative spondylolisthesis shifted horizontally and sagittally to allow slipping. This was due to the weak bony hook mechanism. Furthermore, almost all facet joints were morphologically classified as sagittal or intermediate type. Another meaningful difference was the alignment of the lumbar spine which showed an increase in both lordosis and lumbosacral angle. On the other hand, the level of Jacoby's line was almost the same in both groups. These characteristic configurations could be the cause of listhesis, although further study should be carried out to elucidate whether they are present at the non-listhetic stage. (author).

  8. D-penicillamine induced degenerative dermopathy

    Directory of Open Access Journals (Sweden)

    Sujay Khandpur

    2015-01-01

    Full Text Available D-penicillamine interferes with elastin and collagen metabolism and produces several cutaneous and multi-systemic side-effects. We present two cases of Wilson′s disease who on long-term penicillamine therapy developed drug-induced degenerative dermopathy manifesting as skin fragility over pressure sites and cutis laxa-like changes.

  9. Degenerative Pathways of Lumbar Motion Segments

    DEFF Research Database (Denmark)

    Jensen, Rikke K.; Kjaer, Per; Jensen, Tue S.

    2016-01-01

    BACKGROUND: Magnetic resonance imaging (MRI) is used to identify spinal pathoanatomy in people with persistent low back pain. However, the clinical relevance of spinal degenerative MRI findings remains uncertain. Although multiple MRI findings are almost always present at the same time, research ...

  10. Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice.

    Science.gov (United States)

    Moriyama, K; Hashimoto, R; Hanai, A; Yoshizaki, N; Yonezawa, S; Otani, H

    1997-01-01

    The bustling mouse (BUS/Idr: bus) is a mutant mouse strain which exhibits deafness, bustling/hyperkinetic behaviour and functional disorders seemingly related to the vestibular system. This phenotype develops in homozygous (bus/bus) mice and has been shown from cross experiments to be genetically induced by a single autosomal recessive gene. We previously detected, with light and electron microscopy, post-natal degeneration of the inner ear sensory cells in homozygotes. In the present study, we examined, by electron microscopy, the development of pathological changes in the sensory epithelia of the macula acustica and crista ampullaris of homozygous mice of various ages, paying special attention to the detailed morphology of the sensory hairlets. The homozygous mice exhibited specific pathological changes: a decrease in the number of hairs; disarrangement of the kinocilium-stereocilia pattern; and, fused and/or very large stereocilia. Homozygotes also frequently exhibited apical cytoplasmic herniation, or bleb of hair cells, as well as a degenerated kinocilium in the sensory epithelium. Heterozygotes showed similar changes, but to a lesser degree and frequency. As for the vestibular organs, similar pathological changes had developed at day, 17 of gestation. These pathological findings and onset suggest that the BUS mouse may be a mutant mouse strain distinct from other reported strains which display similar behaviour, and may be a useful animal model for the study of human degenerative vestibular disorders.

  11. The expression of aquaporin-1 in various degenerative human intervertebral discs and its significance%水通道蛋白1在不同程度退变腰椎间盘中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    林世洲; 杨少华; 张博; 陈微

    2013-01-01

    Objective To observe the changes of the expression of aquaporin -4 ( AQP-1 ) in various degenerative human intervertebral discs , and to investigate its relationship with intervertebral disk degeneration. Methods Thirty intervertebral disc samples were collected from patients with prolapse of lumbar intervertebral disc during operation , including protrusion , extrusion and sequestration type and 10 samples for each type. Ten intervertebral disc samples in control group were collected from patients who had lumbar vertebral fractures. The expression of AQP-1 in lumbar intervertebral disc was detected using immunohistochemistry method. Results The result of hematoxylin and eosin staining showed that the intervertebral disc tissue in control group still maintained a dense lamellar structure, while the intervertebral disc tissue in study group presented fibrotic changes . The expression of AQP-1 in nucleus cells in both groups was significantly higher than that in fibrous ring cells ( P ≤0. 01 ). The expression of AQP-1 in the protrusion specimen, including nucleus cells and fibrous ring cells , in study group was significantly lower than that in control group ( P < 0. 01 ). And the expression of AQP-1 in both extrusion type and sequestration type specimen was significantly lower than that in protrusion type specimen (P < 0. 01 ). Conclusion The expression of AQP-1 decreases along with protrusion , extrusion, and sequestration stages of the intervertebral disc degeneration .%目的 观察水通道蛋白1在退变腰椎间盘组织中的表达变化,研究其与椎间盘退变的关系.方法 实验组取材于经手术治疗腰椎间盘突出症患者椎间盘标本30例,突出型、脱出型、游离型各10例;对照组取材于腰椎损伤致椎体骨折患者切除椎间盘10例.应用免疫组织化学法检测水通道蛋白1在椎间盘组织中的表达.结果 (1)苏木精-伊红染色显示,对照组椎间盘组织仍保持着致密的板层结构,实

  12. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges

    Indian Academy of Sciences (India)

    Zi-Bing Jin; Satoshi Okamoto; Michiko Mandai; Masayo Takahashi

    2009-12-01

    Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

  13. Genomic disorders: A window into human gene and genome evolution

    Science.gov (United States)

    Carvalho, Claudia M. B.; Zhang, Feng; Lupski, James R.

    2010-01-01

    Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events. PMID:20080665

  14. Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

    2005-04-15

    Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

  15. Complement, a target for therapy in inflammatory and degenerative diseases.

    Science.gov (United States)

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

  16. MR imaging of degenerative disc disease

    Energy Technology Data Exchange (ETDEWEB)

    Farshad-Amacker, Nadja A., E-mail: nadja.farshad@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland); Farshad, Mazda [Department of Orthopaedic Surgery, Balgrist University Hospital, Zurich (Switzerland); Winklehner, Anna; Andreisek, Gustav [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland)

    2015-09-15

    Highlights: • This systematic literature review summarizes the current knowledge on MR imaging in degenerative disc disease. • Different classification systems for segmental spine degeneration are summarized. • It outlines the diagnostic limitations of MR imaging. - Abstract: Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided.

  17. [Pharmacotherapy of degenerative joint diseases in dogs].

    Science.gov (United States)

    Klee, S; Ungemach, F R

    1998-02-01

    The pharmacological treatment of degenerative joint diseases is restricted essentially to the alleviation of acute symptoms of activated arthropathies. Suitable compounds are the non-steroidal and steroidal antiinflammatory drugs, which however do not allow long-term therapy due to their overall catabolic effects on cartilage metabolism. Since causally acting drugs are not available, the progressive course of the disease cannot be prevented so far. Natural components of the cartilage's matrix, being recommended as so-called chondroprotective drugs, do not fulfill the expectation of a remission of the degenerative process. Indeed, regarding the necessity of multiple local applications of these drugs, they are not superior to antiinflammatory drugs. Provided careful dosing and surveillance of untoward gastrointestinal effects, non-steroidal antiinflammatory agents still are the drugs of first choice.

  18. Cervical myelopathy due to degenerative spondylolisthesis

    OpenAIRE

    Koakutsu, Tomoaki; Nakajo, Junko; Morozumi, Naoki; Hoshikawa, Takeshi; Ogawa, Shinji; Ishii, Yushin

    2011-01-01

    Objective To investigate clinical-radiological features of cervical myelopathy due to degenerative spondylolisthesis (DSL). Methods A total of 448 patients were operated for cervical myelopathy at Nishitaga National Hospital between 2000 and 2003. Of these patients, DSL at the symptomatic disc level was observed in 22 (4.9%) patients. Clinical features were investigated by medical records, and radiological features were investigated by radiographs. Results Disc levels of DSL were C3/4 in 6 ca...

  19. Surgical Treatment of Adult Degenerative Scoliosis

    OpenAIRE

    Cho, Kyu-Jung; Kim, Young-tae; Shin, Sang-hyun; Suk, Se-Il

    2014-01-01

    The rapid increase of elderly population has resulted in increased prevalence of adult scoliosis. Adult scoliosis is divided into adult idiopathic scoliosis and adult degenerative scoliosis. These two types of scoliosis vary in patient age, curve pattern and clinical symptoms, which necessitate different surgical indications and options. Back pain and deformity are major indications for surgery in adult idiopathic scoliosis, whereas radiating pain to the legs due to foraminal stenosis is what...

  20. Stem cells in human neurodegenerative disorders--time for clinical translation?

    Science.gov (United States)

    Lindvall, Olle; Kokaia, Zaal

    2010-01-01

    Stem cell-based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment.

  1. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2014-01-01

    Full Text Available Glycosaminoglycans (GAGs are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.

  2. Combination of interspinous stabilization system and fusion fixation system to treat degenerative lumbar disorders%棘突间固定系统与融合固定系统联合应用治疗腰椎退变性疾患

    Institute of Scientific and Technical Information of China (English)

    张建伟

    2012-01-01

    [目的]探讨棘突间固定系统与融合固定系统联合应用治疗腰椎退变性疾病的临床疗效.[方法]2007年2月~2009年2月本院收治的90例腰椎退变性疾病患者90例,分为棘突间固定系统与融合固定系统联合应用组和单纯棘突间固定系统应用组,各45例.分别对两组患者术后即时疗效进行评价.术后定期随访(30 ~ 54个月),分别对两组患者不良预后指标进行评估.[结果]两组患者术后即时疗效相比,联合应用组总有效率(93.3%)明显优于单纯应用组(75.6%)(P<0.05).从随访结果分析看,联合应用组不良预后发生率显著低于单纯应用组(P<0.05).[结论]棘突间固定系统与融合固定系统联合应用治疗腰椎退变性疾病较单纯棘突间固定系统应用具有更好的临床治疗效果.%[ Objective] To investigate curative effect of the combination of interspinous stabilization system and fusion fixation system to treat lumbar degenerative disorders. [ Methods] A retrospective analysis was carried out on 90 patients of lumbar degenerative disease from February 2007 to February 2009. In the combination treatment group, 45 patients received a combined therapy of interspinous stabilization system and fusion fixed system. In the control group, 45 patients only received interspinous stabilization system for treatment Patients were followed up for 30 - 54 months. Immediate postoperative efficacy evaluation was performed in both groups, and the prognosis and complication were recorded and analyzed at end of following. [Results] The total immediately effective rate in the combination treatment group was 93. 3% , and significantly higher than that of control group (75. 6% ) (P <0.05) . The incidence rate of complication in the combination treatment group were markedly less than that of control group (P<0. 05) . [Conclusion] The combined use of interspinous stabilization system and fusion fixation system is effective in treatment of

  3. Ranibizumab for the treatment of degenerative ocular conditions

    Directory of Open Access Journals (Sweden)

    Triantafylla M

    2014-06-01

    Full Text Available Magdalini Triantafylla,1 Horace F Massa,2 Doukas Dardabounis,1 Zisis Gatzioufas,2 Vassilios Kozobolis,1 Konstantinos Ioannakis,1 Irfan Perente,1,3 Georgios D Panos1,21Department of Ophthalmology, University General Hospital of Alexandroupolis, School of Medicine, University of Thrace, Alexandroupolis, Greece; 2Department of Ophthalmology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland; 3Beyoglou Eye Research and Teaching Hospital, Istanbul University, Istanbul, TurkeyAbstract: Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions.Keywords: age-related macular degeneration, diabetic macular edema, retinal vein occlusion, anti-VEGF, safety, efficacy, quality of life

  4. Correlative Factors for the Efficacy of Surgical Treatment for Single Segment Degenerative Lumbar Spinal Disorders%影响单节段腰椎退变性疾病手术治疗效果的相关因素分析

    Institute of Scientific and Technical Information of China (English)

    刘进; 刘浩; 李涛; 龚全; 曾建成; 宋跃明

    2016-01-01

    Objective To investigate the correlative factors for the efficacy of surgical treatment for single segment degenerative lumbar spinal disorders.Methods From October 2008 to November 2010,a prospective non-randomized controlled study was carried out on 179 patients who were diagnosed to have L4-s degenerative lumbar spinal disorders and underwent surgical treatment.Ninety-seven patients were included in our study,including 64 males and 33 females,aged between 21 and 86 years old,averaging 49.0.The follow up lasted for an average of 18.9 (12-27) months.The correlative factors including age,sex,body mass index,preoperative psychological state and degree of low back pain,surgical methods,combination with adjacent segment degeneration and recurrence state were analyzed.Single and multiple-factor Logistic regression analysis was used to determine the relationship between independent factors and surgical results of lumbar degenerative disease.Results At the last follow-up,Japanese Orthopaedic Association scores were improved to 22.40±3.18 with an improving rate of (68.5±15.7)% compared with the preoperative condition (7.61±3.09),and the difference was significant (t=-33.031,P < 0.001).Univariate analysis showed that all factors were variables associated with the surgical results excluding sex and age (P < 0.05).Multiple-factor logistic regression analysis showed that the preoperative psychological state,combination with adjacent segment degeneration and surgical methods had important impact on the surgical results (P < 0.05).Conclusions Surgical treatment of lumbar degenerative disease is effective.The preoperative psychological state,combination with adjacent segment degeneration and surgical methods are important factors associated with the surgical results.%目的 探讨影响单节段腰椎退变性疾病手术治疗效果的相关因素.方法 对2008年10月-2010年11月接受手术治疗的179例腰4-5节段退变性疾病患

  5. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  6. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning

    OpenAIRE

    Mauro eMuszkat; Claudia Berlim De Melo; Patricia de Oliveira Lima Muñoz; Tania Kiehl Lucci; Vinicius Frayze David; José de Oliveira Siqueira; Emma eOtta

    2015-01-01

    This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth are...

  7. Cell-Based Therapy for Degenerative Retinal Disease.

    Science.gov (United States)

    Zarbin, Marco

    2016-02-01

    Stem cell-derived retinal pigment epithelium (RPE) and photoreceptors (PRs) have restored vision in preclinical models of human retinal degenerative disease. This review discusses characteristics of stem cell therapy in the eye and the challenges to clinical implementation that are being confronted today. Based on encouraging results from Phase I/II trials, the first Phase II clinical trials of stem cell-derived RPE transplantation are underway. PR transplant experiments have demonstrated restoration of visual function in preclinical models of retinitis pigmentosa and macular degeneration, but also indicate that no single approach is likely to succeed in overcoming PR loss in all cases. A greater understanding of the mechanisms controlling synapse formation as well as the immunoreactivity of transplanted retinal cells is urgently needed.

  8. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    OpenAIRE

    Madeira, Maria H.; Raquel Boia; Santos, Paulo F.; António F. Ambrósio; Santiago, Ana R.

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A bett...

  9. The radioisotope osteogram: Kinetic studies of skeletal disorders in humans

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, N.S.

    1959-10-16

    Radioactive strontium can serve as a tracer to gain information concerning calcium metabolism in human subjects. Gamma-emitting Sr{sup 85} is used rather than the much more hazardous, beta-emitting Sr{sup 89} and Sr{sup 90}. (ca{sup 47} -- the ideal tracer for normal calcium -- is quite expensive and difficult to procure.) Very significant information may be obtained merely by measuring and recording the changes in radioactivity in various body areas during the first hour after intravenous injection of the bone-seeking radioisotope. This is accomplished by placing a lead-shielded gamma-scintillation detector in contact with the skin over the sites of interest and recording the activities on a scaler or ratemeter. The activity versus time curves so obtained are called radioisotope osteograms. Data were presented which indicated that Sr{sup 85} osteograms for patients afflicted with osteoporosis, Paget`s disease, tumor metastases to bone, and possibly multiple myeloma, differ significantly from those obtained from subjects with no skeletal abnormalities. Some interpretations of these deviations were discussed. The value of conducting double-tracer tests (e.g. -- Sr{sup 85} plus radio-iodinated serum albumin) was demonstrated, and correlations with excretion data were made. With further refinements the technique may ultimately become useful for certain diagnostic problems in the clinic and.for evaluating the efficacy of treatment of these disorders.

  10. Canine Degenerative Valve Disease: A Case Report

    Directory of Open Access Journals (Sweden)

    Carmenza Janneth Benavides Melo

    2014-07-01

    Full Text Available Degenerative valvular disease or endocardiosis is the most common cardiovascular pathology in dogs. It is characterized by regurgitation of blood into the atria with decreased cardiac output, leading to volume overload with eccentric hypertrophy and congestive heart failure. This report describes the clinical and autopsy findings of a dog, suggestive of valvular endocardiosis. The patient was admitted to the outpatient Veterinary Clinic “Carlos Martínez Hoyos” at the University of Nariño (Pasto, Colombia. His owner said the dog was sick for two months, with signs of respiratory disease, weight loss, and decay. Clinical examination showed very pale mucous membranes, inspiratory dyspnea, rale, split S2, grade 4 mid-systolic murmur of regurgitation, and abdominal dilatation with sign of positive shock wave. Necropsy evidenced plenty of translucent watery material in the abdominal, chest and pericardium cavity, severely enlarged and rounded heart with thickened atrioventricular valves, moderate reduction in liver size and signs of lobulation, severely diminished and pale kidneys with irregular surface showing the presence of multiple cystic areas in corticomedullary region. Samples were taken from these tissues and fixed in 10% buffered formalin to be processed for histopathological analysis at the Laboratory of Pathology at the University of Nariño, using hematoxylin and eosin stain. This way, degenerative valvular disease was diagnosed.

  11. Human maxillary sinus floor elevation as a model for bone regeneration enabling the application of one-step surgical procedures

    NARCIS (Netherlands)

    Farre-Guasch, E.; Prins, H.J.; Overman, J.R.; ten Bruggenkate, C.M.; Schulten, E.A.J.M.; Helder, M.N.; Klein-Nulend, J.

    2013-01-01

    Bone loss in the oral and maxillofacial region caused by trauma, tumors, congenital disorders, or degenerative diseases is a health care problem worldwide. To restore (reconstruct) these bone defects, human or animal bone grafts or alloplastic (synthetic) materials have been used. However, several d

  12. Human immunodeficiency virus (HIV)-associated polymorphic lymphoproliferative disorders.

    Science.gov (United States)

    Nador, Roland G; Chadburn, Amy; Gundappa, Girija; Cesarman, Ethel; Said, Jonathan W; Knowles, Daniel M

    2003-03-01

    The majority of AIDS-related non-Hodgkin's lymphomas are clinically aggressive monoclonal B-cell Burkitt's lymphomas, large cell lymphomas, or immunoblastic lymphomas. In contrast, the lymphoid proliferations arising in solid organ transplant recipients, collectively referred to as posttransplantation lymphoproliferative disorders (PT-LPDs), represent a clinically and histopathologically heterogeneous group of Epstein-Barr virus (EBV)-driven B-cell proliferations of variable clonal composition. During a retrospective histopathologic review of lymphoid proliferations associated with human immunodeficiency virus (HIV) infection we identified 10 cases that morphologically resemble the polymorphic PT-LPDs. They arose in lymph nodes (five), lungs (two), and the parotid gland, perineum, and skin (one each). They exhibit a diffuse growth pattern and are composed of a polymorphic lymphoid cell population exhibiting a variable degree of plasmacytic differentiation, cytologic atypia, and numbers of atypical immunoblasts. A clonal B-cell population was detected by immunoglobulin heavy and light chain gene rearrangement and/or EBV terminal repeat analysis in 8 of the 10 (80%) cases by Southern blotting. The nongermline hybridizing bands were usually faint, however, suggesting that the clonal B-cell population represented only a subpopulation within the polymorphic lesion. Strong clonal rearrangement bands were present in one case in which there was clear morphologic evidence of transformation to diffuse large cell lymphoma. This case exhibited C-MYC, BCL-6, and p53 gene mutations. One other case exhibited a p53 gene mutation. The remaining eight cases lacked C-MYC, BCL-6, RAS, and p53 gene alterations. Clonal EBV infection was detected in 4 of the 10 (40%) lesions. Like EBV-containing PT-LPDs, all four EBV-positive HIV-associated polymorphic lesions were associated with type A EBV. The Kaposi's sarcoma-associated herpesvirus was detectable in two cases by polymerase chain

  13. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning

    Science.gov (United States)

    Muszkat, Mauro; de Mello, Claudia Berlim; Muñoz, Patricia de Oliveira Lima; Lucci, Tania Kiehl; David, Vinicius Frayze; Siqueira, José de Oliveira; Otta, Emma

    2015-01-01

    This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders. PMID:26557097

  14. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning.

    Science.gov (United States)

    Muszkat, Mauro; de Mello, Claudia Berlim; Muñoz, Patricia de Oliveira Lima; Lucci, Tania Kiehl; David, Vinicius Frayze; Siqueira, José de Oliveira; Otta, Emma

    2015-01-01

    This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders.

  15. Face scanning in autism spectrum disorder (ASD and attention deficit/hyperactivity disorder (ADHD: human versus dog face scanning

    Directory of Open Access Journals (Sweden)

    Mauro eMuszkat

    2015-10-01

    Full Text Available This study used eye-tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD, attention deficit/hyperactivity disorder (ADHD, and typical development (TD. Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders.

  16. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders

    Science.gov (United States)

    Gurwitz, David

    2016-01-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

  17. DMPD: Nod1 and Nod2 in innate immunity and human inflammatory disorders. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031249 Nod1 and Nod2 in innate immunity and human inflammatory disorders. Le Bour...w Nod1 and Nod2 in innate immunity and human inflammatory disorders. PubmedID 18031249 Title Nod1 and Nod2 i...n innate immunity and human inflammatory disorders. Authors Le Bourhis L, Benko S

  18. Computational Biomechanics of Human Red Blood Cells in Hematological Disorders.

    Science.gov (United States)

    Li, Xuejin; Li, He; Chang, Hung-Yu; Lykotrafitis, George; Em Karniadakis, George

    2017-02-01

    We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.

  19. Imaging of genetic and degenerative disorders primarily causing Parkinsonism.

    Science.gov (United States)

    Brooks, David J

    2016-01-01

    In this chapter the structural and functional imaging changes associated with both genetic causes of Parkinson's disease and the sporadic condition are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression are debated. Additionally, the use of imaging for differentiating atypical parkinsonian syndromes from Parkinson's disease is presented.

  20. Limited Life Expectancy, Human Capital and Health Investments: Evidence from Huntington Disease

    OpenAIRE

    Emily Oster; Ira Shoulson; Ray Dorsey, E.

    2012-01-01

    One of the most basic predictions of human capital theory is that life expectancy should impact human capital investment. Limited exogenous variation in life expectancy makes this difficult to test, especially in the contexts most relevant to the macroeconomic applications. We estimate the relationship between life expectancy and human capital investments using genetic variation in life expectancy driven by Huntington disease (HD), an inherited degenerative neurological disorder with large im...

  1. Limited Life Expectancy, Human Capital and Health Investments: Evidence from Huntington Disease

    OpenAIRE

    Emily Oster; Ira Shoulson; Ray Dorsey, E

    2012-01-01

    One of the most basic predictions of human capital theory is that life expectancy should impact human capital investment. Limited exogenous variation in life expectancy makes this difficult to test, especially in the contexts most relevant to the macroeconomic applications. We estimate the relationship between life expectancy and human capital investments using genetic variation in life expectancy driven by Huntington disease (HD), an inherited degenerative neurological disorder with large im...

  2. Degenerative disease of the lumbar spine.

    Science.gov (United States)

    Kovacs, F M; Arana, E

    2016-04-01

    In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures.

  3. [Development and developmental disorders of the human brain. III. Neuronal migration disorders of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Lammens, M.M.Y.; Wesseling, P.; Thijssen, H.O.M.; Renier, W.O.; Gabreëls, F.J.M.

    2001-01-01

    Neuronal migration disorders of the cerebral cortex form a heterogeneous group of abnormalities, characterised by mental retardation, epilepsy and hypotonia. They are prevalent in 1% of the population and in 20-40% of the untreatable forms of epilepsy. Disorders at the start of the migration result

  4. Influence of degenerative changes of intervertebral disc

    Directory of Open Access Journals (Sweden)

    WANG Yi

    2012-04-01

    Full Text Available 【Abstract】Objective: To investigate the material properties of normal and degenerated intervertebral discs (IVDs and examine the effect of degenerative changes on IVD pathology. Methods: A computer-based online search was under-taken to identify English articles about material properties of IVDs published from January 1950 to 2011 in PubMed database. The retrieved keywords included material properties, intervertebral disc and degeneration. Based on the principles of reliability, advancement and efficiency, the obtained data were primarily examined, and the original source was retrieved to read the full-text. Repetitive articles were excluded. The data of material properties of normal and degenerated IVDs were summarized and analyzed by meta-analysis. Results: The data of Young's modulus, Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pres-sure of normal and degenerated IVDs were obtained. Com-pared with normal IVDs, the Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic permeability and intradiscal pressure were higher. Besides, the degeneration-related alterations in IVDs had an influence both on itself and other spinal structures, leading to diseases such as bulging disc, discogenic pain and spinal stenosis. Meanwhile, the heavy mechanical loading and injury indicated important pathways to IVD degeneration. Conclusions: To a certain extent, the degenerative changes of IVD influence its material properties. And the degeneration-related alterations of composition can cause structural failure of IVDs, leading to injuries and diseases. Key words: Intervertebral disc; Mechanical phenomena; Degeneration; Elastic modulus; Permeability; Pathology

  5. Lumbar degenerative kyphosis: radiologic analysis and classifications.

    Science.gov (United States)

    Jang, Jee-Soo; Lee, Sang-Ho; Min, Jun-Hong; Han, Kyoung-Mi

    2007-11-15

    Retrospective study of a consecutive patient series. To review the radiographic classification of patients with sagittal imbalance due to lumbar degenerative kyphosis (LDK) and to determine correlation between thoracic and lumbar curve. Lumbar degenerative kyphosis is one of the common spinal deformities in Asian countries, especially Korea and Japan. However, there have been few studies regarding the classification and treatment of this disease. Seventy-eight patients with LDK were analyzed and classified according to the standing lateral whole spine findings. Total lumbar lordosis (L1-S1), thoracic kyphosis (T5-T12), sacral slope, thoracolumbar angle (T11-L1), and sagittal vertical axis (SVA) were measured on the lateral view of the whole spine. Spinal curve deformities were classified into 2 groups according to the thoracolumbar (T-L) junction angle: flat or lordotic angle (Group 1; N = 53) and kyphotic angle (Group 2; N = 25). In Group 1, significant correlations between the thoracic and lumbar curves (r = 0.772, P sagittal thoracic compensated group. In contrast, In Group 2, no correlation was found between the thoracic and lumbar curves in the decompensated group (r = 0.179, P = 0.391), but we found a significant correlation between lordosis and sacral slope (r = 0.442, P = 0.027). By this result, Group 2 was classified as sagittal thoracic decompensated group. There was significant difference in SVA between 2 groups (P = 0.020). The angle of the thoracolumbar junction is an important parameter in determining whether a sagittal thoracic compensatory mechanism exists in LDK. We assumed that existence of a compensatory mechanism in the proximal spine is central to the determination of the fusion levels in the treatment of LDK.

  6. OPERATIVE TREATMENT FOR DEGENERATIVE LUMBAR SPINAL STENOSIS

    Directory of Open Access Journals (Sweden)

    Samo K. Fokter

    2002-11-01

    Full Text Available Background. Degenerative lumbar spinal stenosis (DLSS is a common cause of low back and leg pain in the elderly. Conservative treatment seldom results in sustained improvement.Methods. Fifty-six patients (33 women, 23 men older than 50 years (mean 67 years, range 51 to 82 years and with no prior low back surgery were treated from 1993 to 1999 for clinical and radiologic evidence of DLSS. The goal of this study was to describe the results of decompressive laminectomy with or without fusion in terms of reoperation, severity of back pain, leg pain and patient satisfaction. Answers to Swiss spinal stenosis questionnaires completed before surgery and one to five years afterwards were evaluated. Seven patients (12.5% with degenerative spondylolisthesis, scoliosis and/or more radical facetectomies received fusion.Results. Of the 56 patients in the original cohort, two were deceased and two had undergone reoperation by follow-up. Forty-eight patients answered questionnaires. Average duration of follow-up was 2.5 years. More than 70 percent of the respondents had no or only mild back or buttock pain at follow-up and more than 60 percent were able to walk more than 500 m. Added fusion reduced the incidence of low back pain and pain frequency, and increased walking distance (ANOVA.Conclusions. Eighty-one percent of patients were satisfied with the results of surgery and 87.5% would choose to have the operation again if they had the choice. Decompressive laminectomy for DLSS yields best results if instrumented fusion is included in the procedure.

  7. Neutral versus Emotional Human Stimuli Processing in Children with Pervasive Developmental Disorders not Otherwise Specified

    Science.gov (United States)

    Vannetzel, Leonard; Chaby, Laurence; Cautru, Fabienne; Cohen, David; Plaza, Monique

    2011-01-01

    Pervasive developmental disorder not otherwise specified (PDD-NOS) represents up to two-thirds of autism spectrum disorders; however, it is usually described in terms of the symptoms not shared by autism. The study explores processing of neutral and emotional human stimuli (by auditory, visual and multimodal channels) in children with PDD-NOS (n =…

  8. Animal Models of Psychiatric Disorders That Reflect Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Jun Nomura

    2012-01-01

    Full Text Available The development of genetic technologies has led to the identification of several copy number variations (CNVs in the human genome. Genome rearrangements affect dosage-sensitive gene expression in normal brain development. There is strong evidence associating human psychiatric disorders, especially autism spectrum disorders (ASDs and schizophrenia to genetic risk factors and accumulated CNV risk loci. Deletions in 1q21, 3q29, 15q13, 17p12, and 22q11, as well as duplications in 16p11, 16p13, and 15q11-13 have been reported as recurrent CNVs in ASD and/or schizophrenia. Chromosome engineering can be a useful technology to reflect human diseases in animal models, especially CNV-based psychiatric disorders. This system, based on the Cre/loxP strategy, uses large chromosome rearrangement such as deletion, duplication, inversion, and translocation. Although it is hard to reflect human pathophysiology in animal models, some aspects of molecular pathways, brain anatomy, cognitive, and behavioral phenotypes can be addressed. Some groups have created animal models of psychiatric disorders, ASD, and schizophrenia, which are based on human CNV. These mouse models display some brain anatomical and behavioral abnormalities, providing insight into human neuropsychiatric disorders that will contribute to novel drug screening for these devastating disorders.

  9. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease

    OpenAIRE

    Yu, Ivarosa Bing-Ye; Huang, Hui-Pi

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York ...

  10. Global warming and neurodegenerative disorders: speculations on their linkage.

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  11. Non degenerative disease in MRI cervical spine of symptomatic patients

    Directory of Open Access Journals (Sweden)

    Dan B Karki

    2016-01-01

    Full Text Available Background & Objectives: The most common etiology of neck pain is degenerative disc disease, however non-degenerative disease can be important cause of neck pain. This study aims to study the non-degenerative findings in cervical MRI in symptomatic patients with neck and radicular pain.Materials & Methods: The study was a institutional record based retrospective study performed for the duration of 3 years. MRI performed for patients with neck pain and/ or radiculopathy were reviewed. Patients with post operative findings were excluded from the study. Statistical analysis was done using SPSS 21.0.Results: A total of 721 MRI were performed for neck pain and radiculopathy, among which 91 (12.13% cases had non-degenerative changes. Most common non degenerative change was traumatic lesions followed by neoplastic lesions and syrinx. Traumatic lesions were more common in males as compared to females. Infection was more common in females as compared to males. C5 and C6 vertebrae were most common vertebra involved in trauma and infection. Some cases like signal change in spinal cord, and syrinx were also noted in our study.Conclusion: Non degenerative cause of neck pain were less common but important cause of neck pain. Traumatic lesions were the most common cause of non degenerative neck pain.Journal of College of Medical Sciences-Nepal, Vol.11(4 2015: 20-23

  12. X-ray diagnosis of post-traumatic degenerative-dystrophic lesions of the vertebrae

    Energy Technology Data Exchange (ETDEWEB)

    Novikov, V.P. (Omskij Meditsinskij Inst. (USSR))

    Immediate and long-term consequences of the spinal injury have been studied in 221 patients aged 13 to 70 years, applying clinical and radiological methods. Various degenerative-dystrophic alterations have been frequently found at the level of the damaged spinal segment and included cartilaginous knots and discal hernia and fibrosis, local spondylosis and spondylarthrosis, osteochondrosis, calcification of the disk and ligamentous apparatus. These pathologic changes infrequently cause patients' complaints and neurological disturbances. The degenerative-dystrophic processes in the spine, following an acute injury manifest no specific features, except for some peculiarities of the traumatic cartilaginous knot (greater size and depth, partial hanging of the obturating plate over the knot bed). The type and gravity of the fracture, the degree of static-dynamic disorders of the vertebral column and, to some extent, the patient's age most significantly determine the development of the degenerative-dystrophic processes in the damaged spinal segment. Post-traumatic clinicofunctional examination of the spine has been proved important.

  13. Human Sexual Desire Disorder: Do We Have a Problem?

    Science.gov (United States)

    McNab, Warren L.; Henry, Jean

    2006-01-01

    Hypoactive Sexual Desire Disorder (HSDD), loss of sexual desire for sexual activity, is one of the most common sexual dysfunctions of men and women in the United States. This article presents an overview of this specific sexual dysfunction including incidence, possible causes, treatment options, and the role of the health educator in addressing…

  14. Chronic degenerative diseases in elderly: physiotherapeutic data

    Directory of Open Access Journals (Sweden)

    Lais Keylla Felipe

    2011-09-01

    Full Text Available Objective: To assess the most frequent chronic diseases in the elderly population of a private clinic of Physiotherapy. Methods: We assessed medical records of clients who received treatment at a Physiotherapy clinic in the period 2005 to 2008, looking for chronic diseases as diagnosis and/or related to them. Of these, we selected those which contained birth date and/or aged sixty-five years or above. An instrument like a check list, developed by the researchers, identified: quantity, gender, medical diagnosis and comorbidities. For quantification of variables we applied simple percentage calculation. Results: In the study period, there were four hundred fifty-eight records, of which forty-nine corresponded to the survey’s inclusion criteria. The majority 59.2% (n=29 referred to the year 2008; 26.6% (n=13 being males and 73.4% (n=36 females. The most commonly found diagnosis comprised osteoarthritis 57.1% (n=28, fracture and/or history of fractures 24.4% (n=12 and other diagnosis 48.9% (n=24. Associated chronic diseases included diabetes mellitus 18.3% (n=9 and systemic hypertension 57.1% (n=23. Conclusion: Chronic degenerative diseases in elderly have received increasing attention from health professionals; osteoarthritis being the most common diagnosis in this study, followed by fracture and/or history of fractures. The comorbidities represented a greater negative impact in the quality of life of elderly.

  15. Computed tomography in lumbar degenerative disease

    Energy Technology Data Exchange (ETDEWEB)

    Isu, Toyohiko; Miyasaka, Kazuo; Abe, Satoru; Takei, Hidetoshi; Kaneda, Kiyoshi (Hokkaido Univ., Sapporo (Japan). School of Medicine)

    1984-02-01

    We reported the 18 patients which underwent surgical exploration and reviewed these CT findings. Method All CT scans were obtained on Somatom II, high resolution CT scanner, with the patient in the supine position. A lateral localizer image (Topogram) was used to select the appropriate intervertebral disk space. The slice thickness was 4 mm. Results 1) CT findings in lumbar degenerative diseases include bony canal stenosis (central canal stenosis, narrowed lateral recess), soft tissue abnormalities (herniated nucleus pulposus, bulging annulus, hypertrophy and/or ossification of ligamentum flavum, no delineation of nerve root in lateral recess), and spinal instability (spondylolisthesis, vacuum phenomenon). 2) The above three factors contribute to narrowing of spinal canal. 3) No delineation of nerve root or soft tissue replacement of epidural fat in lateral recess suggests that the nerve root may be compressed by some factors. 4) Herniated nucleus pulposus may cause nerve root compression with or without canal stenosis. Conclusion This study revealed that the CT findings correlated closely with the surgical findings and the site of nerve root compression could be determined.

  16. Emotion Recognition in Animated Compared to Human Stimuli in Adolescents with Autism Spectrum Disorder

    Science.gov (United States)

    Brosnan, Mark; Johnson, Hilary; Grawmeyer, Beate; Chapman, Emma; Benton, Laura

    2015-01-01

    There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon…

  17. Evolutionary conservation in genes underlying human psychiatric disorders

    OpenAIRE

    Lisa Michelle Ogawa; Eric Joseph Vallender

    2014-01-01

    Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of the protein-coding regions of genes associated...

  18. Deciphering the cause of evolutionary variance within intrinsically disordered regions in human proteins.

    Science.gov (United States)

    Banerjee, Sanghita; Chakraborty, Sandip; De, Rajat K

    2017-02-01

    Why the intrinsically disordered regions evolve within human proteome has became an interesting question for a decade. Till date, it remains an unsolved yet an intriguing issue to investigate why some of the disordered regions evolve rapidly while the rest are highly conserved across mammalian species. Identifying the key biological factors, responsible for the variation in the conservation rate of different disordered regions within the human proteome, may revisit the above issue. We emphasized that among the other biological features (multifunctionality, gene essentiality, protein connectivity, number of unique domains, gene expression level and expression breadth) considered in our study, the number of unique protein domains acts as a strong determinant that negatively influences the conservation of disordered regions. In this context, we justified that proteins having a fewer types of domains preferably need to conserve their disordered regions to enhance their structural flexibility which in turn will facilitate their molecular interactions. In contrast, the selection pressure acting on the stretches of disordered regions is not so strong in the case of multi-domains proteins. Therefore, we reasoned that the presence of conserved disordered stretches may compensate the functions of multiple domains within a single domain protein. Interestingly, we noticed that the influence of the unique domain number and expression level acts differently on the evolution of disordered regions from that of well-structured ones.

  19. Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults.

    Science.gov (United States)

    Gale, Shawn D; Brown, Bruce L; Berrett, Andrew; Erickson, Lance D; Hedges, Dawson W

    2014-08-01

    Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

  20. Imaging of lumbar degenerative disk disease: history and current state

    Energy Technology Data Exchange (ETDEWEB)

    Emch, Todd M. [Cleveland Clinic, Division of Neuroradiology, Imaging Institute, Neuroradiology L-10, Cleveland, OH (United States); Modic, Michael T. [Cleveland Clinic, Division of Neuroradiology, Imaging Institute, Neurological Institute T-13, Cleveland, OH (United States)

    2011-09-15

    One of the most common indications for performing magnetic resonance (MR) imaging of the lumbar spine is the symptom complex thought to originate as a result of degenerative disk disease. MR imaging, which has emerged as perhaps the modality of choice for imaging degenerative disk disease, can readily demonstrate disk pathology, degenerative endplate changes, facet and ligamentous hypertrophic changes, and the sequelae of instability. Its role in terms of predicting natural history of low back pain, identifying causality, or offering prognostic information is unclear. As available modalities for imaging the spine have progressed from radiography, myelography, and computed tomography to MR imaging, there have also been advances in spine surgery for degenerative disk disease. These advances are described in a temporal context for historical purposes with a focus on MR imaging's history and current state. (orig.)

  1. Degenerative Changes in the Spine: Is This Arthritis?

    Science.gov (United States)

    ... in my spine. Does this mean I have arthritis? Answers from April Chang-Miller, M.D. Yes. ... spine. Osteoarthritis is the most common form of arthritis. Doctors may also refer to it as degenerative ...

  2. Vacuum facet phenomenon: a computed tomographic sign of degenerative spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Lefkowitz, D.M.; Quencer, D.M.

    1982-08-01

    A vacuum facet phenomenon, seen on computed tomography as a lens-shaped lucency within a lumbar facet joint, was observed as a consequence of degenerative spondylolisthesis. The significance of this finding is discussed.

  3. Peritalar destabilisation syndrome (adult flatfoot with degenerative glenopathy).

    Science.gov (United States)

    Pisani, Giacomo

    2010-12-01

    In cases of adult acquired flatfoot associated with peritalar destabilisation, special reference is made to the plantar calcaneo-navicular (spring) ligament's degenerative disease (degenerative glenopathy) and to the presence of the accessory navicular bone as a possible pathogenic cause. Peritalar destabilization syndrome is proposed for the articular (subtalar and talo-navicular joints) or tendinosis (tibialis posterior tendon) separately or in association with degenerative glenopathy of the coxa pedis. In degenerative glenopathy surgical reconstruction of the glenoid also makes use of a posterior tibial split to create a new tibial-navicular ligament. The concept of pronatory syndrome deemed as the root the pathological subtalar pronation, which is an entirely secondary factor in peritalar destabilisation, must be questioned. We must keep in mind that subtalar pronation and supination are respectively subsequent to opening and closing of the coxa pedis (talo-calcaneo-navicular joint) kinetic chain.

  4. Functional outcome of surgical management of degenerative lumbar canal stenosis

    Directory of Open Access Journals (Sweden)

    Rajendra Nath

    2012-01-01

    Conclusion: Operative treatment in patients of degenerative lumbar canal stenosis yields excellent results as observed on the basis of JOA scoring system. No patient got recurrence of symptoms of nerve compression.

  5. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Maria H. Madeira

    2015-01-01

    Full Text Available Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

  6. Development of modulators against degenerative aging using radiation fusion technology

    Energy Technology Data Exchange (ETDEWEB)

    Jo, S. K.; Park, H. R.; Jang, B. S.; Roh, C. H.; Eom, H. S.; Choi, N. H.; Seol, M. A.; Kim, S. H.; Choi, H. M.; Park, M. K.; Shin, H. J.; Ryu, D. K.; Oh, W. J.; Kim, S. H; Yee, S. T.

    2012-04-15

    1. Objectives Establishment of modelling of degenerative aging using radiation technology Development of aging modulators using radiation degenerative aging model 2. Project results Establishment of the modeling of degenerative aging using radiation technology - The systematic study on the comparison of radiation-induced degeneration and natural aging process in animals and cells confirmed the biological similarity between these two degeneration models - The effective biomarkers were selected for the modelling of degenerative aging using radiation (10 biomarkers for immune/hematopoiesis, 1 for oxidative stress, 6 for molecular signaling, 3 for lipid metabolism) - The optimal irradiation condition was established for the modelling of degerative aging (total 5Gy with fractionation by over 10 times, lapse of over 4 months) - The molecular mechanisms of radiation-induced degeneration were studied including chronic inflammation (lung), inflammation-related lipid metabolism disturbance, mitochondria biogenesis and dynamics - The radiation degenerative model was evaluated with previously known natural substances (resveratrol, EGCG, etc) Development of aging modulators using radiation degenerative aging model - After the screening of about 800 natural herb extracts, 5 effective substances were selected for aging modulation. - 3 candidate compositions were selected from 20 compositions made from effective substances by in vitro evaluation (WAH2, WAH6, WAH7) - 1 composition (WAH6) was selected as the best aging modulator by in vivo evaluation in radiation-induced aging models and degenerative disease models. 3. Expected benefits and plan of application The modelling of degenerative aging using radiation can facilitate the aging research by providing the useful cell/animal models for aging research A large economic benefits are expected by the commercialization of developed aging modulators (over 10 billion KW in 2015.

  7. Minimally invasive transforaminal lumbar interbody fusion or posterior lumbar interbody fusion in treatment of lumbar degenerative disorder disease%椎间盘镜辅助X-Tube下椎体间融合术治疗退变性腰椎间盘疾病

    Institute of Scientific and Technical Information of China (English)

    马维虎; 刘观燚; 徐荣明; 孙韶华; 赵刘军; 胡勇; 蒋伟宇; 顾永杰

    2011-01-01

    目的 探讨椎间盘镜辅助X-Tube下腰椎后路椎体间融合术(posterior lumbar interbody fusion,PLIF)和经椎间孔腰椎椎体间融合术(transforaminal lumbar interbody fusion,TLIF)治疗退变性椎间盘疾病的临床疗效.方法 2007年11月至2008年4月,采用椎间盘镜辅助X-Tube下TLIF和PLIF 治疗退变性椎间盘疾病32例:PLIF 13例,TLIF 19例.单节段腰椎间盘突出症伴相应节段腰椎不稳定21例,腰椎滑脱症11例(Ⅰ度6例,Ⅱ度5例).病变节段:L3-4 2例,L4-5 18例,L5S1 12例.年龄38~72岁,平均51.2岁;男19例,女13例.术后进行定期随访和影像学检查,并进行Oswestry功能障碍指数评定以评价术后康复情况.结果 手术时间90~180 min,平均120 min;手术出血量100~400 ml,平均190ml.切口均为甲级愈合,未见切口及椎管、椎间隙感染、内固定失败等并发症发生.所以患者均获随访,随访时间13~41个月,平均21个月.Oswestry功能障碍指数由术前40.1%±4.1%下降到术后3个月的9.5%±3.7%.疗效评价:优19例,良10例,可3例;优良率为90.6%.骨融合均取得成功.结论 椎间盘镜辅助X-Tube下TLIF和PLIF治疗退变性椎间盘疾病具有切口小,创伤小,术后恢复快等优点.%Objective To evaluate the clinical effects of transforaminal lumbar interbody fusion (TLIF) or posterior lumbar interbody fusion(PLIF) using microendoscopic discectomy under X-Tube system in treatment of lumbar degenerative disc diseases.Methods From December 2007 to April 2008,32 patients with low back disorders were treated by microendoscopic discectomy TLIF or PLIF under X-Tube system,including 19 cases in TLIF and 13 in PLIF.Etiologies including lumbar disc herniation combined with segmental instability in 21 cases,and spondylolisthesis in 11 cases.All patients were under regular postoperative follow-up and radiological examination.The clinical functional outcomes were evaluated according to Oswestry disability questionnaire.Results The

  8. Etiology, pathophysiology and conservative management of degenerative joint disease

    Directory of Open Access Journals (Sweden)

    Jandrić Slavica

    2002-01-01

    Full Text Available Etiology of degenerative joint diseases Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors inflammation and other risk factors contribute to development of osteoarthrosis. Pathophysiology of degenerative joint diseases Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. Treatment of degenerative joint diseases Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy.

  9. HUMAN NATURE, DIRTY HANDS AND SOCIAL DISORDER: A ...

    African Journals Online (AJOL)

    Dr Ike

    problems and various forms of immorality. Every society desires ..... 2(c) Human Nature and Machiavellian Challenge. Politics, in the .... salary (enforcing the laws against tax evasion with threats of .... shares something of the others concerns.

  10. Minireview: Human Obesity—Lessons from Monogenic Disorders

    National Research Council Canada - National Science Library

    O’Rahilly, Stephen; Farooqi, I. Sadaf; Yeo, Giles S. H; Challis, Benjamin G

    2003-01-01

    .... However, in the last 6 yr, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually...

  11. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    Science.gov (United States)

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system:

  12. Healthcare professionals and the practice of the human rights of individuals with mental disorders

    Directory of Open Access Journals (Sweden)

    Carla Aparecida Arena Ventura

    2013-12-01

    Full Text Available This qualitative study aimed at describing the perception that healthcare professionals of a Psychosocial Care Center (CAPS, as per its acronym in Portuguese make of the human rights of individuals with mental health disorders and the means used to make rights effective in health care. Data were collected in 2010 by semi-structured interviews with seven professionals, and submitted to content analysis. It was observed that subjects have different perceptions regarding the human rights of individuals with mental health disorders, centered on freedom, protection of life, living in society and being a participative citizen. Despite the political advancements, gaps still hinder making the rights of people with mental disorders effective, which could be supplied by an engagement of the family, society, and government. Healthcare professionals have played an important role as of regarding rights, helping to raise awareness of patients and their families, aiming at their social reinsertion. Descriptors: Human Rights; Right to Health; Mentally Ill Persons; Mental Health.

  13. Complex posttraumatic stress disorder and survivors of human rights violations.

    Science.gov (United States)

    McDonnell, Matthew; Robjant, Katy; Katona, Cornelius

    2013-01-01

    This article reviews recent findings on Complex Posttraumatic Stress Disorder (CPTSD) and proposes future research which would help to establish the nature of CPTSD in relation to Posttraumatic Stress Disorder (PTSD). Research on survivors of torture and war has found that CPTSD can occur when there is no history of childhood abuse. fMRI studies appear to highlight differences in neural activity in individuals exhibiting primary dissociation compared with individuals exhibiting secondary dissociation. Research has begun to show that, when symptoms of secondary dissociation are appropriately managed, exposure-based therapies are an effective treatment for individuals with CPTSD. Much research on CPTSD has emphasized its developmental basis and the disruptive effects of trauma in childhood and adolescence on subsequent emotional development. However, some studies on survivors of torture in adult life identify similar symptom patterns, despite there being no history of childhood trauma. It is argued that comparative research is required between victims of developmental trauma (such as childhood sexual abuse) and victims who experienced prolonged interpersonal trauma in adulthood (such as torture), as this could be useful in establishing the cause of CPTSD and in delineating clinically and therapeutically meaningful subtypes. It is also proposed that a focus on underlying neurobiological processes would help in developing and refining CPTSD as a construct and informing treatment.

  14. Minireview: human obesity-lessons from monogenic disorders.

    Science.gov (United States)

    O'Rahilly, Stephen; Farooqi, I Sadaf; Yeo, Giles S H; Challis, Benjamin G

    2003-09-01

    Genetic influences on the determination of human fat mass are profound and powerful, a statement that does not conflict with the obvious influence of environmental factors that drive recent changes in the prevalence of obesity. The assertion of the importance of genetic factors has, until recently, largely been based on twin and adoption studies. However, in the last 6 yr, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually associated with disruption of normal appetite control mechanisms. Progress in the identification of more common, subtler genetic variants that influence fat mass in larger numbers of people has been slower, but discernible. Human genetics will continue to make an invaluable contribution to the study of human obesity by identifying critical molecular components of the human energy balance regulatory systems, pointing the way toward more targeted and effective therapies and assisting the prediction of individual responses to environmental manipulations.

  15. Defining the inherent stability of degenerative spondylolisthesis: a systematic review.

    Science.gov (United States)

    Simmonds, Andrea M; Rampersaud, Y Raja; Dvorak, Marcel F; Dea, Nicolas; Melnyk, Angela D; Fisher, Charles G

    2015-08-01

    OBJECT A range of surgical options exists for the treatment of degenerative lumbar spondylolisthesis (DLS). The chosen technique inherently depends on the stability of the DLS. Despite a substantial body of literature dedicated to the outcome analysis of numerous DLS procedures, no consensus has been reached on defining or classifying the disorder with respect to stability or the role that instability should play in a treatment algorithm. The purpose of this study was to define grades of stability and to develop a guide for deciding on the optimal approach in surgically managing patients with DLS. METHODS The authors conducted a qualitative systematic review of clinical or biomechanical analyses evaluating the stability of and surgical outcomes for DLS for the period from 1990 to 2013. Research focused on nondegenerative forms of spondylolisthesis or spinal stenosis without associated DLS was excluded. The primary extracted results were clinical and radiographic parameters indicative of DLS instability. RESULTS The following preoperative parameters are predictors of stability in DLS: restabilization signs (disc height loss, osteophyte formation, vertebral endplate sclerosis, and ligament ossification), no disc angle change or less than 3 mm of translation on dynamic radiographs, and the absence of low-back pain. The validity and magnitude of each parameter's contribution can only be determined through appropriately powered prospective evaluation in the future. Identifying these parameters has allowed for the creation of a preliminary DLS instability classification (DSIC) scheme based on the preoperative assessment of DLS stability. CONCLUSIONS Spinal stability is an important factor to consider in the evaluation and treatment of patients with DLS. Qualitative assessment of the best available evidence revealed clinical and radiographic parameters for the creation of the DSIC, a decision aid to help surgeons develop a method of preoperative evaluation to better

  16. Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.

    Science.gov (United States)

    Izumi, Aiko; Iijima, Yoshimi; Noguchi, Hiroko; Numakawa, Tadahiro; Okada, Takeya; Hori, Hiroaki; Kato, Tadafumi; Tatsumi, Masahiko; Kosuga, Asako; Kamijima, Kunitoshi; Asada, Takashi; Arima, Kunimasa; Saitoh, Osamu; Shiosaka, Sadao; Kunugi, Hiroshi

    2008-12-01

    Human neuropsin (NP) (hNP) has been implicated in the progressive change of cognitive abilities during primate evolution. The hNP gene maps to chromosome 19q13, a region reportedly linked to schizophrenia and bipolar disorder. Therefore, hNP is a functional and positional candidate gene for association with schizophrenia, mood disorders, and cognitive ability. Polymorphism screening was performed for the entire hNP gene. The core promoter region was determined and whether or not transcriptional activity alters in an allele-dependent manner was examined by using the dual-luciferase system. Allelic and genotypic distributions of five single-nucleotide polymorphisms (SNPs) were compared between patients with schizophrenia (n=439), major depression (n=409), bipolar disorder (n=207), and controls (n=727). A possible association of the hNP genotype with memory index (assessed with Wechsler Memory Scale, revised, WMS-R) and intelligence quotient (IQ assessed with Wechsler Adult Intelligence Scale, revised; WAIS-R) was examined in healthy controls (n=166). A total of 28 SNPs, including nine novel SNPs, were identified. No significant effects on transcriptional activity were observed for SNPs in the promoter region. A significant allelic association was found between several SNPs and bipolar disorder (for SNP23 at the 3' regulatory region; odds ratio 1.48, 95% confidential interval 1.16-1.88, P=0.0015). However, such an association was not detected for schizophrenia or depression. Significant differences were observed between SNP23 and attention/concentration sub-scale score of WMS-R (P=0.016) and verbal IQ (P<0.001). Genetic variation of the hNP gene may contribute to molecular mechanisms of bipolar disorder and some aspects of memory and intelligence.

  17. What's new in using platelet research? To unravel thrombopathies and other human disorders.

    Science.gov (United States)

    Freson, Kathleen; Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Geet, Chris Van

    2007-12-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines such as neurology, nephrology, endocrinology and metabolic diseases. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet research and disorders with a broader clinical phenotype. Classical thrombopathies involve disorders of platelet adhesion such as Glanzmann thrombastenia and Bernard-Soulier syndrome, defective G protein signalling diseases with impaired phospholipase C activation, and abnormal platelet granule secretion disorders such as gray platelet disorder and delta-storage pool disease. Other clinical symptoms besides a bleeding tendency have been described in MYH9-related disorders and Duchenne muscular dystrophy due to adhesion defects, and also in disorders of impaired Gs signalling, in Hermansky Pudlack disease and Chediak Higashi disease with abnormal secretion. Finally, platelet research can also be used to unravel novel mechanisms involved in many neurological disorders such as depression and autism with only a subclinical platelet defect.

  18. What’s new in using platelet research? To unravel thrombopathies and other human disorders

    Science.gov (United States)

    Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Geet, Chris Van

    2007-01-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines such as neurology, nephrology, endocrinology and metabolic diseases. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet research and disorders with a broader clinical phenotype. Classical thrombopathies involve disorders of platelet adhesion such as Glanzmann thrombastenia and Bernard-Soulier syndrome, defective G protein signalling diseases with impaired phospholipase C activation, and abnormal platelet granule secretion disorders such as gray platelet disorder and delta-storage pool disease. Other clinical symptoms besides a bleeding tendency have been described in MYH9-related disorders and Duchenne muscular dystrophy due to adhesion defects, and also in disorders of impaired Gs signalling, in Hermansky Pudlack disease and Chediak Higashi disease with abnormal secretion. Finally, platelet research can also be used to unravel novel mechanisms involved in many neurological disorders such as depression and autism with only a subclinical platelet defect. PMID:17619901

  19. Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla Woznica; Ehrenreich, Hannelore; Christensen, Ellen M

    2014-01-01

    OBJECTIVE: Available drug treatments for bipolar disorder fail to reverse patients' cognitive deficits. Erythropoietin has neurotrophic actions and aids neurocognitive function. The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar......; secondary outcomes were sustained attention and facial expression recognition; and tertiary outcomes were attention, executive function, subjective cognitive function, and mood. Analysis was by intention to treat, using repeated-measures analysis of covariance adjusted for stratification variables and mood...... in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple...

  20. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates.

    Science.gov (United States)

    Careaga, Milo; Murai, Takeshi; Bauman, Melissa D

    2017-03-01

    A subset of women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental or neuropsychiatric disorder. Although epidemiology studies have primarily focused on the association between maternal infection and an increased risk of offspring schizophrenia, mounting evidence indicates that maternal infection may also increase the risk of autism spectrum disorder. A number of factors, including genetic susceptibility, the intensity and timing of the infection, and exposure to additional aversive postnatal events, may influence the extent to which maternal infection alters fetal brain development and which disease phenotype (autism spectrum disorder, schizophrenia, other neurodevelopmental disorders) is expressed. Preclinical animal models provide a test bed to systematically evaluate the effects of maternal infection on fetal brain development, determine the relevance to human central nervous system disorders, and to evaluate novel preventive and therapeutic strategies. Maternal immune activation models in mice, rats, and nonhuman primates suggest that the maternal immune response is the critical link between exposure to infection during pregnancy and subsequent changes in brain and behavioral development of offspring. However, differences in the type, severity, and timing of prenatal immune challenge paired with inconsistencies in behavioral phenotyping approaches have hindered the translation of preclinical results to human studies. Here we highlight the promises and limitations of the maternal immune activation model as a preclinical tool to study prenatal risk factors for autism spectrum disorder, and suggest specific changes to improve reproducibility and maximize translational potential.

  1. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  2. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    Science.gov (United States)

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery.

  3. A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

    Science.gov (United States)

    Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

    2007-01-01

    Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

  4. Clinical and radiological outcome of conservative vs. surgical treatment of atraumatic degenerative rotator cuff rupture : design of a randomized controlled trial

    NARCIS (Netherlands)

    Heerspink, Frederik O. Lambers; Hoogeslag, Roy A. G.; Diercks, Ron L.; van Eerden, Pepijn J. M.; van den Akker-Scheek, Inge; van Raay, Jos J. A. M.

    2011-01-01

    Background: Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice. Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present. However, degenerative ruptures of the rotator cuff can also be observed in asymptomatic

  5. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2014-01-01

    Full Text Available Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders. Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment. Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death. The profibrotic cytokine transforming growth factor beta (TGFβ is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues. This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis. Elevated NADPH oxidase 4 (NOX4-derived hydrogen peroxide (H2O2 supported by concomitant decreases in nitric oxide (NO signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation. Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation. Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders.

  6. Transplantation of Fetal Stem Cells: a New Horizon for Treat¬ment of Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Farideh RAZI

    2015-10-01

    Full Text Available Background: The purpose of the current study was to present an overview of different types of stem-cells and their application for treatment different degenerative disorders with specific focus on ongoing clinical trials. Methods: For the purpose of the current narrative review article, a comprehensive search was carried out on the existing literature in Google Scholar, PubMed and Scopus using the keywords: stem-cell (fetal and mesenchymal, regenerative. Relevant articles published from 1957 to 2013 are extracted and presented. Results: During the past decades, different types of stem-cells (including adult and fetal have been used for treatment of a wide range of immunologic (Severe Combined Immunodeficiency, Di George syndrome, neurologic (Parkinson’s disease, Huntington Chorea, Cerebral Palsy, musculoskeletal (ALS, and cardiovascular diseases (heart failure and cardiomyopathies as well as chronic and acute ulcers, and diabetes. Conclusion: The results of our study demonstrated that during the past decades, stem-cell technology has been applied for treatment of a wide range of degenerative disorders with considerable success. The current ongoing clinical trials clearly demonstrate a great potential and a promising future for the technology in terms of offering curative treatment for a wide range of hitherto-incurable diseases. Keywords: Stem cell, Transplantation, Treatment, Review Article 

  7. Investigation of signs of attachment disorders in sheltered children using human figure drawing

    OpenAIRE

    Renata Hottum Melani

    2010-01-01

    This research aimed to investigate signs of Attachment Disorders in sheltered children using the Human Figure Drawing. 25 children (15 males and 10 female), aged 4 to 12 years living in a sheltered home in São Paulo metropolitan area were assessed. The instrument used for assessment was the Human Figure Drawing (HFD), following Koppitz‟s 30 emotional indicators. Results showed that 48% of the assessed children present shyness, withdrawal and lack of aggression, as well as poor social in...

  8. Healthcare professionals and the practice of the human rights of individuals with mental disorders

    OpenAIRE

    Carla Aparecida Arena Ventura; Viviana Carolina Oyan de Moraes; Márjore Serena Jorge

    2013-01-01

    This qualitative study aimed at describing the perception that healthcare professionals of a Psychosocial Care Center (CAPS, as per its acronym in Portuguese) make of the human rights of individuals with mental health disorders and the means used to make rights effective in health care. Data were collected in 2010 by semi-structured interviews with seven professionals, and submitted to content analysis. It was observed that subjects have different perceptions regarding the human rights of ind...

  9. CT findings of isthmic spondylolisthesis and degenerative spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Suk Kyeong; Cho, Seong II; Chung, Gyung Ho; Lee, Sang Yong; Han, Young Min; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul [Chonbuk National Univ. College of Medicine, Chonju (Korea, Republic of)

    1996-01-01

    CT evaluate the finding useful for differential diagnosis and associated abnormalities of isthmic spondylolisthesis and degenerative spondylolisthesis on CT. We reviewed retrospectively the CT images of 164 patients who were diagnosed spondylolisthesis. One hundred twelve patients had isthmic spondylolisthesis and 52 patients had degenerative spondylolisthesis. Isthmic spondylolisthesis most frequently occurred at L5. The degree of anterior displacement was grade I and II. The defect had a horizontal plane, an irregular surface, a sclerotic margin, and protruding hypertrophic bony spur in the spinal canal. The most frequently associated structural abnormality was a herniated nucleus pulposus at the upper level of the defect. Degenerative spondylolisthesis most frequently occurred at L4-5 and were grade I. The degenerative facet joint had a vertical plane, a hypertrophic bony spur, and a vacuum facet phenomenon. We frequently detected a pseudobulging disk. The most frequently associated structural abnormality was a herniated nucleus pulposus at the level of the displacement. In spondylolisthesis, the findings in CT were valuable for differential diagnosis of isthmic and degenerative types and the detection of associated symptomatic abnormalities.

  10. Constructing and identifying a lentiviral vector of RNA interference targeting matrix metalloproteinases-3 gene in human degenerative nucleus pulposus cells%人基质金属蛋白酶3基因RNA慢病毒载体构建及在人退变髓核细胞中的鉴定

    Institute of Scientific and Technical Information of China (English)

    曹进; 傅培荣; 房晶; 杨建坤; 位华卫; 李思源; 高峰; 西永明

    2016-01-01

    BACKGROUND: Inhibiting the degradation of extracellular matrix in the intervertebral disc can delay the degenerative process of intervertebral disc. Matrix metalloproteinases-3 (MMP3) is considered as a key enzyme for degradation of extracelular matrix components such as type II collagen and aggrecan. OBJECTIVE:To construct the short hairpin RNA lentiviral vector targeting human MMP3 gene and to detect its efficiency of gene silence by infecting human degenerative nucleus pulposus cells. METHODS:According to the human MMP3 mRNA (NM_002422.4) sequence, four groups of the short hairpin RNA gene sequences targeting MMP3 were designed, synthesized and annealed to form double stranded DNA fragments, which were connected with the LV3 vectors digested by BamHI andEcoRI enzymes, and then transfected into the competent cels. The positive clones were identified by PCR, and analyzed by sequencing. The packaging and titer of lentivirus were determined after transfecting 293T cells. Human degenerative nucleus pulposus cels were infected with lentivirus vector, and the transfection efficiency of each group was observed under inverted fluorescence microscope. The interfering efficiency was detected by real time-PCR and western blot at 72 and 96 hours. RESULTS AND CONCLUSION:The ds-oligo DNA was successfully inserted into the lentiviral vector as confirmed by electrophoresis and sequence analysis. The recombinant lentivirus was harvested from 293T cels with a viral titer of 1-5 ×108 TU/mL. RNA interference targeting the GCC AGG CTT TCC CAA GCA AAT sequences with the highest interfering efficiency in MMP3 gene at 72 and 96 hours resulted in suppression of MMP3 mRNA expression by 98% and 72%, respectively; and at 96 hours, the interfering efficiency of protein expression was 57.2%. The recombinant lentivirus vector containing RNA interference targeting MMP3 gene is successfuly constructed, which lays a foundation for further studies on the MMP3 function and gene therapy.%背景:

  11. Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research.

    Science.gov (United States)

    Dymond, Simon; Dunsmoor, Joseph E; Vervliet, Bram; Roche, Bryan; Hermans, Dirk

    2015-09-01

    Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

  12. 白藜芦醇干预对已退变椎间盘终板软骨细胞SIRT1表达的影响%Duration-and concentration-dependent induction of SIRT1 on human degenerative endplate chondrocytes by Resveratrol

    Institute of Scientific and Technical Information of China (English)

    钟小明; 胡侦明; 沈皆亮; 甘强; 郝杰

    2013-01-01

    目的 探讨不同浓度及不同时间的白藜芦醇干预对退变椎间盘终板软骨细胞沉默信息调节因子2相关酶1(SIRT1)表达的影响.方法 老年患者的终板软骨细胞培养、传代,P2代细胞随机分组,分别用不同浓度及不同作用时间的白藜芦醇干预,终止培养后检测SIRT1蛋白及mRNA表达水平.结果 与空白对照组相比较,DMSO组SIRT1蛋白及mRNA表达无显著差异(P>0.05);白藜芦醇干预的浓度在12.5 μmol/L、作用24 h,以及浓度在50 μmol/L、作用12h以上时能够显著促进已退变椎间盘终板软骨细胞表达SIRT1蛋白及mRNA(P <0.05).结论 白藜芦醇干预可促进退变椎间盘终板软骨细胞表达SIRT1蛋白及mRNA,且该作用呈现浓度、时间依赖关系;0.1% DMSO对细胞表达SIRT1蛋白无抑制作用.%Objective To explore the effect of different concentrations and time of Resveratrol intervention on the expression of SIRT1 in human degenerative endplate chondrocytes. Methods Degenerative disc endplate chondrocytes ( DEC) were harvested from elder patient with lumbar disc hernia, and then cultured. Passage 2 DEC were stimulated by Resveratrol of different concentrations and duration re spectively , and then expression levels of SIRT1 protein and mRNA were detected by the end of stimulation. Results Compared with the ex pression levels of SIRT1 and of SIRT1 mRNA in control group, there was no significant difference in DMSO group (P>0. 05). Resveratrol of 12. 5 μmol/L and 24 hours, Resveratrol of 50 μmol/L and 12 hours could stimulate the expressions of SIRT1 protein and mRNA (P < 0. 05). Conclusions Resveratrol intervention can significantly stimulate the expressions of SIRT1 protein and mRNA in human DEC in a concentration- and time-dependent manner. 0. 1 % DMSO has no inhibiting effect of SIRT1 protein expression.

  13. Degenerative lumbar spondylolisthesis: an epidemiological perspective: the Copenhagen Osteoarthritis Study

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Sonne-Holm, Stig; Rovsing, Hans;

    2007-01-01

    STUDY DESIGN: A cross-sectional epidemiological survey of 4151 participants of the Copenhagen Osteoarthritis Study. OBJECTIVE: To identify prevalences and individual risk factors for degenerative lumbar spondylolisthesis. SUMMARY OF BACKGROUND DATA: The Copenhagen Osteoarthritis Study has...... registered health parameters since 1976. In 1993, standardized, lateral radiographs of the lumbar spine were recorded. There were 1533 men and 2618 women. METHODS: Statistical correlations were made between degenerative spondylolisthesis, and physical, occupational, and general epidemiological data. RESULTS......: A total of 254 cases of lumbar slip were found (males 2.7%, females 8.4%). In females, no significant relationship between age at menopause or childbirths and the presence of degenerative spondylolisthesis were found. In women, relationships between body mass index (BMI) in 1976 and L4 olisthesis (P = 0...

  14. Neuromuscular exercise as treatment of degenerative knee disease

    DEFF Research Database (Denmark)

    Ageberg, Eva; Roos, Ewa M.

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional instabil......Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional...... instability associated with the degenerative knee disease than traditionally used training methods.SUMMARY FOR TABLE OF CONTENTS PAGECurrent data suggests that the effect from neuromuscular exercise on pain and function is comparable to the effects seen from other forms of exercise....

  15. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study

    Science.gov (United States)

    2013-01-01

    Background Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. Methods A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2–12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women’s pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. Results 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Conclusions Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and

  16. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study.

    Science.gov (United States)

    Abas, Melanie; Ostrovschi, Nicolae V; Prince, Martin; Gorceag, Viorel I; Trigub, Carolina; Oram, Siân

    2013-08-03

    Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2-12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women's pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and maintaining factors. Care plans for survivors of

  17. Using skin to assess iron accumulation in human metabolic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Guinote, I. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. 10, 2685-953 Sacavem (Portugal); Fleming, R. [Imunohaemotherapy Department, Hospital de St. Maria, Lisbon (Portugal); Silva, R. [Dermatology Department, Hospital de St. Maria, Lisbon (Portugal); Filipe, P. [Dermatology Department, Hospital de St. Maria, Lisbon (Portugal); Silva, J.N. [Dermatology Department, Hospital de St. Maria, Lisbon (Portugal); Verissimo, A. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. 10, 2685-953 Sacavem (Portugal); Napoleao, P. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisbon (Portugal); Alves, L.C. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisbon (Portugal); Pinheiro, T. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. 10, 2685-953 Sacavem (Portugal) and Centro de Fisica Nuclear, Universidade de Lisbon (Portugal)]. E-mail: murmur@itn.pt

    2006-08-15

    The distribution of Fe in skin was assessed to monitor body Fe status in human hereditary hemochromatosis. The paper reports on data from nine patients with hemochromatosis that were studied along the therapeutic programme. Systemic evaluation of Fe metabolism was carried out by measuring with PIXE technique the Fe concentration in plasma and blood cells, and by determining with biochemical methods the indicators of Fe transport in serum (ferritin and transferrin). The Fe distribution and concentration in skin was assessed by nuclear microscopy and Fe deposits in liver estimated through nuclear magnetic resonance. Elevated Fe concentrations in skin were related to increased plasma Fe (p < 0.004), serum ferritin content (p < 0.01) and Fe deposits in liver (p < 0.004). The relationship of Fe deposits in organs and metabolism markers may help to better understand Fe pools mobilisation and to establish the quality of skin as a marker for the disease progression and therapy efficacy.

  18. Using skin to assess iron accumulation in human metabolic disorders

    Science.gov (United States)

    Guinote, I.; Fleming, R.; Silva, R.; Filipe, P.; Silva, J. N.; Veríssimo, A.; Napoleão, P.; Alves, L. C.; Pinheiro, T.

    2006-08-01

    The distribution of Fe in skin was assessed to monitor body Fe status in human hereditary hemochromatosis. The paper reports on data from nine patients with hemochromatosis that were studied along the therapeutic programme. Systemic evaluation of Fe metabolism was carried out by measuring with PIXE technique the Fe concentration in plasma and blood cells, and by determining with biochemical methods the indicators of Fe transport in serum (ferritin and transferrin). The Fe distribution and concentration in skin was assessed by nuclear microscopy and Fe deposits in liver estimated through nuclear magnetic resonance. Elevated Fe concentrations in skin were related to increased plasma Fe (p serum ferritin content (p < 0.01) and Fe deposits in liver (p < 0.004). The relationship of Fe deposits in organs and metabolism markers may help to better understand Fe pools mobilisation and to establish the quality of skin as a marker for the disease progression and therapy efficacy.

  19. Apoptotic pathways in degenerative disk lesions in the wrist.

    Science.gov (United States)

    Unglaub, Frank; Thomas, Susanne B; Kroeber, Markus W; Dragu, Adrian; Fellenberg, Jörg; Wolf, Maya B; Horch, Raymund E

    2009-12-01

    Degenerative articular disk perforations of the triangular fibrocartilage (TFC) of the wrist could result from chronic loading of the ulnocarpal joint. Apoptosis played a crucial role in fibrocartilage cell loss, and the purpose of this study was to clarify which apoptotic pathway was involved in the development of degenerative disk lesions. We also investigated whether ulna length played an etiologic role in the occurrence of fibrocartilage cell loss. Included in the study were 17 patients with degenerative articular disk tears of the TFC (Palmer type 2C). After arthroscopic debridement of the TFC, histologic sections were examined to assess the presence of apoptosis. Apoptosis was determined by use of caspase 3, caspase 8, and caspase 9 immunohistochemistry. Furthermore, Fas ligand and BID (BH3 interacting domain death) agonist were applied for immunohistochemical analysis. Cells positive for caspase 3, caspase 8, caspase 9, Fas ligand, and BID were found in all specimens. The number of cells positive for caspase 3 and BID was significantly increased in specimens from patients with an ulna-positive variance. In contrast, for cells positive for caspase 8, caspase 9, and Fas ligand, no significant difference was found between specimens from patients with an ulna-positive variance and those from patients with an ulna-neutral/ulna-negative variance. The extrinsic and intrinsic apoptotic pathways are involved in the development of degenerative disk lesions. Fibrocartilage cell loss occurs mainly through the intrinsic apoptotic pathway. The accumulation of apoptotic cells is not significantly different between the 3 zones of the TFC. It could be verified that ulna length is correlated with fibrocartilage cell loss. Ulnar shortening is a valuable treatment option for degenerative TFC lesions. Knowledge of the specific apoptotic pathway that is causing degenerative disk lesions is critical in selecting the appropriate and most beneficial therapeutic treatment to halt

  20. Destructive discovertebral degenerative disease of the lumbar spine.

    Science.gov (United States)

    Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

    2012-09-01

    The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

  1. From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

    Science.gov (United States)

    VanElzakker, Michael B; Dahlgren, M Kathryn; Davis, F Caroline; Dubois, Stacey; Shin, Lisa M

    2014-09-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.

  2. From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and in anxiety disorders

    Science.gov (United States)

    VanElzakker, Michael B.; Dahlgren, M. Kathryn; Davis, F. Caroline; Dubois, Stacey; Shin, Lisa M.

    2014-01-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. PMID:24321650

  3. Both dog and human faces are explored abnormally by young children with autism spectrum disorders.

    Science.gov (United States)

    Guillon, Quentin; Hadjikhani, Nouchine; Baduel, Sophie; Kruck, Jeanne; Arnaud, Mado; Rogé, Bernadette

    2014-10-22

    When looking at faces, typical individuals tend to have a right hemispheric bias manifested by a tendency to look first toward the left visual hemifield. Here, we tested for the presence of this bias in young children with autism spectrum disorders (ASD) for both human and dog faces. We show that children with ASD do not show a left visual hemifield (right hemispheric) bias for human faces. In addition, we show that this effect extends to faces of dogs, suggesting that the absence of bias is not specific to human faces, but applies to all faces with the first-order configuration, pointing to an anomaly at an early stage of visual analysis of faces. The lack of right hemispheric dominance for face processing may reflect a more general disorder of cerebral specialization of social functions in ASD.

  4. Role of Vitamin D in human Diseases and Disorders – An Overview

    Directory of Open Access Journals (Sweden)

    Priyanshee Gohil

    2014-06-01

    Full Text Available Vitamin D is a fat soluble vitamin and generated in human skin by ultraviolet (UV light. Today, vitamin D is considered to be a steroidal hormone and plays a central role in bone mineralization and calcium homeostasis. The active form of the vitamin D is 1, 25-dihydroxyvitamin D [1, 25-dihydroxycholecalciferol (DHCC] which mediatesproliferation, differentiation and various functions at the cellular level through Vitamin D receptors (VDR.Therefore, compromised vitamin D status is likely to be involved in progression or pathogenesis of various disorders. This assumption is consistent with findings from epidemiological studies that a compromised vitamin D status in humans increases the risk of autoimmune diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus (SLE, multiple sclerosis and type I diabetes mellitus. However, diseases like cancer, cardiovascular disorders and bone disorders are yet not focused. Thus the role of vitamin D in pathogenesis of various diseases is complex and controversial. This review briefly summarizes the role of vitamin D in development and progression of different human disorders.

  5. Axon guidance pathways served as common targets for human speech/language evolution and related disorders.

    Science.gov (United States)

    Lei, Huimeng; Yan, Zhangming; Sun, Xiaohong; Zhang, Yue; Wang, Jianhong; Ma, Caihong; Xu, Qunyuan; Wang, Rui; Jarvis, Erich D; Sun, Zhirong

    2017-07-07

    Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Helga Rodrigues

    Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

  7. Evaluation of the correlation between disc displacements and degenerative bone changes of the temporomandibular joint by means of magnetic resonance images.

    Science.gov (United States)

    Dias, Isabela Maddalena; Coelho, Patrícia Rocha; Picorelli Assis, Neuza Maria Souza; Pereira Leite, Fabiola Pessôa; Devito, Karina Lopes

    2012-09-01

    The aim was to evaluate the correlation between disc displacements and degenerative bone changes in magnetic resonance images (MRI) of 112 patients of both genders, with signs and symptoms of temporomandibular disorder. For this purpose, a calibrated examiner evaluated 224 MRI by assigning scores for the displacement of the disc and degenerative bone changes. Disc displacement was found in 58.42% of the temporomandibular joints (TMJs) evaluated. Anterior displacement of the disc with reduction was the most common, occurring in 67.18% cases of joints with disc displacement. Degenerative bone changes were observed in 53.94% of the TMJs analysed. There was significant correlation between disc displacement with reduction and condylar flattening, disc displacement without reduction and condylar flattening, disc displacement without reduction, and associated degenerative bone changes (flattening and erosion, flattening, osteophyte and erosion; flattening and osteophytes, erosion and sclerosis, flattening and sclerosis, flattening, osteophytes and sclerosis). The correlation between advanced cases of disc displacement and the occurrence of degenerative bone changes emphasises the importance of MRI for an accurate diagnosis and development of an appropriate treatment plan and in cases in which clinical examination is not sufficient for these purposes.

  8. Overlap of food addiction and substance use disorders definitions: analysis of animal and human studies.

    Science.gov (United States)

    Hone-Blanchet, Antoine; Fecteau, Shirley

    2014-10-01

    Food has both homeostatic and hedonic components, which makes it a potent natural reward. Food related reward could therefore promote an escalation of intake and trigger symptoms associated to withdrawal, suggesting a behavioral parallel with substance abuse. Animal and human theoretical models of food reward and addiction have emerged, raising further interrogations on the validity of a bond between Substance Use Disorders, as clinically categorized in the DSM 5, and food reward. These models propose that highly palatable food items, rich in sugar and/or fat, are overly stimulating to the brain's reward pathways. Moreover, studies have also investigated the possibility of causal link between food reward and the contemporary obesity epidemic, with obesity being potentiated and maintained due to this overwhelming food reward. Although natural rewards are a hot topic in the definition and categorization of Substance Use Disorders, proofs of concept and definite evidence are still inconclusive. This review focuses on available results from experimental studies in animal and human models exploring the concept of food addiction, in an effort to determine if it depicts a specific phenotype and if there is truly a neurobiological similarity between food addiction and Substance Use Disorders. It describes results from sugar, fat and sweet-fat bingeing in rodent models, and behavioral and neurobiological assessments in different human populations. Although pieces of behavioral and neurobiological evidence supporting a food addiction phenotype in animals and humans are interesting, it seems premature to conclude on its validity.

  9. MRI of degenerative cysts of the lumbar spine

    Energy Technology Data Exchange (ETDEWEB)

    Khalatbari, K. [Department of MRI, Iran Gamma Knife Centre, Iran University of Medial Sciences-Kamrani Charity Foundation, Tehran (Iran, Islamic Republic of)], E-mail: khalatbarik@yahoo.com; Ansari, H. [Department of Orthopaedics, Rassoul Akram University Hospital, Tehran (Iran, Islamic Republic of)

    2008-03-15

    Degenerative cysts of the lumbar spine encompass a heterogeneous group of cystic lesions that are presumed to share a common aetiology. Some of these cysts may be incidental findings, whereas others may produce acute or chronic symptoms. These cysts have been categorized using various combinations of topographic and pathological characteristics and by their attachment to or communication with a specific spinal structure.

  10. Effects of interspinous spacers on lumbar degenerative disease.

    Science.gov (United States)

    Zhou, Dong; Nong, Lu-Ming; DU, Rui; Gao, Gong-Ming; Jiang, Yu-Qing; Xu, Nan-Wei

    2013-03-01

    The present study aimed to evaluate the early effects of interspinous spacers on lumbar degenerative disease. The clinical outcomes of 23 patients with lumbar degenerative disease, treated using interspinous spacer implantation alone or combined with posterior lumbar fusion, were retrospectively studied and assessed with a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Pre-operative and post-operative interspinous distance, disc space height, foraminal width and height and segmental lordosis were determined. The early effects and complications associated with the interspinous spacers were recorded. The surgical procedures performed with the in-space treatment were easy and minimally invasive. The VAS scores and ODI were improved post-operatively compared with pre-operatively. Significant changes in the interspinous distance, disc space height, foraminal width and height and segmental lordosis were noted. In-space treatment for degenerative lumbar disease is easy and safe, with good early effects. The in-space system provides an alternative treatment for lumbar degenerative disease.

  11. Degenerative lumbar spondylolisthesis: an epidemiological perspective: the Copenhagen Osteoarthritis Study

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Sonne-Holm, Stig; Rovsing, Hans

    2007-01-01

    : A total of 254 cases of lumbar slip were found (males 2.7%, females 8.4%). In females, no significant relationship between age at menopause or childbirths and the presence of degenerative spondylolisthesis were found. In women, relationships between body mass index (BMI) in 1976 and L4 olisthesis (P = 0...

  12. Degenerative spondylolisthesis is associated with low spinal bone density

    DEFF Research Database (Denmark)

    Andersen, Thomas; Christensen, Finn B; Langdahl, Bente Lomholt

    2013-01-01

    Spinal stenosis and degenerative spondylolisthesis share many symptoms and the same treatment, but their causes remain unclear. Bone mineral density has been suggested to play a role. The aim of this study was to investigate differences in spinal bone density between spinal stenosis and degenerat...

  13. 78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Science.gov (United States)

    2013-10-31

    ... AFFAIRS Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune... (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis...-Degenerative Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and...

  14. [Sagittal balance of the spine and degenerative spondylolisthesis].

    Science.gov (United States)

    Morel, E; Ilharreborde, B; Lenoir, T; Hoffmann, E; Vialle, R; Rillardon, L; Guigui, P

    2005-11-01

    Several reports have examined the pathophysiology of degenerative spondylolisthesis. Very little work has however been devoted to the influence of spinal balance in the sagittal plane in its pathogenesis. The purpose of this work was to present a descriptive analysis of pelvic and spinal sagittal balance in a cohort of seventy patients treated for degenerative spondylolisthesis and to compare findings with those established in a population of 250 volunteers. The goal was to deduct pathophysiological hypotheses and identify therapeutic implications. Seventy patients were included in this study. The following variables were noted: pelvic incidence and version, sacral slope, lumbar lordosis, thoracic kyphosis, T9 sagittal tilt and S1-S2 angle. These variables were measured on digitalized lateral views of the spine using a dedicated software (SpineView). Univariate analysis of the values obtained was performed to identify the variable distributions. Multivariate analysis was applied to study the relationships between these variables and to better define perturbations of spinal balance in the anteroposterior plane. The findings were compared with those obtained in a control population. One of the essential characteristics of the cohort of patients with degenerative spondylolisthesis was the presence of an exaggerated pelvic incidence (62.6 degrees versus 54.7 degrees in the control population). The most significant determinants of T9 sagittal tilt (which reflects sagittal balance) were: pelvic version, pelvic incidence, lumbar lordosis, and L4-S1 local lordosis. One-third of our patients presented posterior tilt due to exaggerated thoracic kyphosis. The high pelvic incidence, via hyperlordosis and increased pelvic version, could be one of the factors favoring degenerative disease of the spinal unit. This work enabled us to better describe sagittal balance in patients with degenerative spondylolisthesis and to propose hypotheses concerning the underlying mechanism of

  15. MR imaging of degenerative lumbar disc disease emphasizing on signal intensity changes in vertebral body

    Energy Technology Data Exchange (ETDEWEB)

    Toyoda, Keiko; Ida, Masahiro; Murakami, Yoshitaka; Harada, Junta; Tada, Shimpei (Jikei Univ., Tokyo (Japan). School of Medicine)

    1992-12-01

    Magnetic resonance imaging was performed in 400 patients with degenerative disc disease. Signal changes and their sites in the vertebral body were classified and referred to narrowing of the intervertebral disc space. MR findings were compared with those of plain roentgenograms of the lumbar spine. Signal changes in the vertebral body were noted in 83 cases (102 vertebral bodies). Low-intensity abnormality on both T1- and T2-weighted images (WI) was the most common finding, and was most frequently seen at the end plate and/or the angle. These changes were correlated with narrowing of the disc space and osteosclerosis on the plain roentgenogram of the lumbar spine. Signal changes occasionally occurred in the inner region of the vertebral body, and these lesions tended to show a high-intensity abnormality on T1-WI. We conclude that signal changes in degenerative disc disease are not specific, but are sometimes difficult to distinguish from the signal changes in other conditions such as spinal tumor or bone marrow disorder. (author).

  16. Functional genomics of human brain development and implications for autism spectrum disorders.

    Science.gov (United States)

    Ziats, M N; Grosvenor, L P; Rennert, O M

    2015-10-27

    Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic-epigenetic-environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics-non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.

  17. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  18. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    Directory of Open Access Journals (Sweden)

    Ubadah Sabbagh

    2016-01-01

    Full Text Available The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES. A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  19. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder.

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans.

  20. Current Applications of Chromatographic Methods in the Study of Human Body Fluids for Diagnosing Disorders.

    Science.gov (United States)

    Jóźwik, Jagoda; Kałużna-Czaplińska, Joanna

    2016-01-01

    Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders.

  1. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders

    OpenAIRE

    Bouazoune, Karim; Kingston, Robert Edward

    2012-01-01

    Mutations in the CHD7 gene cause human developmental disorders including CHARGE syndrome. Genetic studies in model organisms have further established CHD7 as a central regulator of vertebrate development. Functional analysis of the CHD7 protein has been hampered by its large size. We used a dual-tag system to purify intact recombinant CHD7 protein and found that it is an ATP-dependent nucleosome remodeling factor. Biochemical analyses indicate that CHD7 has characteristics distinct from SWI/S...

  2. What’s new in using platelet research? To unravel thrombopathies and other human disorders

    OpenAIRE

    Freson, Kathleen; Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Van Geet, Chris

    2007-01-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines suc...

  3. To grow or not to grow: hair morphogenesis and human genetic hair disorders.

    Science.gov (United States)

    Duverger, Olivier; Morasso, Maria I

    2014-01-01

    Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. Published by Elsevier Ltd.

  4. Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

    Science.gov (United States)

    Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

    2015-01-01

    Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

  5. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders

    Science.gov (United States)

    Persson, Mia E.; Wright, Dominic; Roth, Lina S. V.; Batakis, Petros; Jensen, Per

    2016-01-01

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog’s human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders. PMID:27685260

  6. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders.

    Science.gov (United States)

    Persson, Mia E; Wright, Dominic; Roth, Lina S V; Batakis, Petros; Jensen, Per

    2016-09-29

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog's human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders.

  7. Inflammation and the degenerative diseases of aging.

    Science.gov (United States)

    McGeer, Patrick L; McGeer, Edith G

    2004-12-01

    Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson-dementia complex of Guam, all of the tauopathies, and age-related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two-edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte-directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue-based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti-inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti-inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken

  8. Prevalence and clinical signs of degenerative temporomandibular joint changes validated by magnetic resonance imaging in a non-patient group.

    Science.gov (United States)

    Bernhardt, Olaf; Biffar, Reiner; Kocher, Thomas; Meyer, Georg

    2007-01-01

    The aim of this study is to investigate associations between degenerative bony changes of the temporomandibular joint (TMJ) evaluated by magnetic resonance imaging (MRI) and signs and symptoms of temporomandibular disorders (TMD) in a non-patient group. A total of 307 subjects (140 males and 167 females) were selected from the cross-sectional epidemiological study "Study of Health in Pomerania" (SHIP) for this evaluation. A clinical functional examination of the masticatory muscles and the TMJs was performed as well as an MRI examination of the TMJs. Another 77 subjects (25%) exhibited degenerative changes of one or both TMJs in the MRI. Clinical analysis revealed pain on palpation of the masticatory muscles in 113 subjects. Some 39 subjects had pain during palpation of the TMJs. There were significant associations between the MRI confirmed diagnosis of osteoarthrosis and some clinical signs (joint noises, joint palpation pain, reduced mouth opening) and symptoms (reported pain in the jaw and masticatory muscles) of TMD as well as further MRI diagnoses (disc displacement with and without reduction, fibrosis of the posterior ligament). Although there were some associations, clinical examination alone is not sufficient for diagnosing degenerative joint diseases. MRI is a necessary diagnostic adjunct for estimating the prevalence of TMD subgroups in non-patient populations.

  9. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.

    Science.gov (United States)

    Shekhawat, Prem; Bennett, Michael J; Sadovsky, Yoel; Nelson, D Michael; Rakheja, Dinesh; Strauss, Arnold W

    2003-06-01

    The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.

  10. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

    Science.gov (United States)

    Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

    2014-08-01

    Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P brain disorders had lesions that were significantly more likely to be located in hubs (P human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  12. [Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders].

    Science.gov (United States)

    Podzamczer Palter, Daniel; Muñoz-Moreno, José A; Alcolea Rodríguez, Daniel; Alonso Villaverde, Carlos; Antela López, Antonio; Blanch Andreu, Jordi; Casado Osorio, José Luis; Galindo Puerto, M José; Garolera i Freixa, Maite; Locutura Rupérez, Jaime; Lleó Bisa, Albert; Prats París, Anna; Pérez-Valero, Ignacio; Portilla Sogorb, Joaquín; Rovira Cañellas, Alex; Téllez Molina, M Jesús; Tiraboschi, Juan Manuel; Vergara Moragues, Esperanza; Arribas López, José Ramón; Goenaga Sánchez, Miguel Ángel; de León-Naranjo, Fernando Lozano; Martínez Chamorro, Esteban; Polo Rodríguez, Rosa; Muñoz-Moreno, José A; Podzamczer, Daniel

    2014-01-01

    To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy.

    Science.gov (United States)

    Shroff, Geeta; Dhanda Titus, Jyoti; Shroff, Rhea

    2017-01-01

    The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson's disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders. Following this, we will discuss the development of a unique hESC line, how it differs from the other available hESC lines and its use in the treatment of neurological disorders. hESCs were isolated from mixture of neuronal and non-neuronal progenitor cells in their pre progenitor state in a Good Laboratory Practices, Good Tissue Practices and Good Manufacturing Practices compliant laboratory. Blastomere cells have served as a source to derive the hESCs and the xeno-free culture was demonstrated to be more safe and effective in clinical therapeutic application of hESCs. All the patients showed a remarkable improvement in their conditions and no serious adverse events were reported. This study concluded that hESC lines could be scalable and used in the treatment of various neurological disorders such as SCI, CP, and PD.

  14. DEGENERATIVE AORTIC STENOSIS: PATHOGENESIS AND NEW PRINCIPLES OF TREATMENT

    Directory of Open Access Journals (Sweden)

    O. V. Andropova

    2006-01-01

    Full Text Available Aim. To reveal of markers of inflammation and progression of calcification in patients with degenerative aortic stenosis (DAS. Material and methods. A single-stage study was done in 85 patients with degenerative calcification of aortic valve (42 patients with DAS and 43 patients without DAS. The techniques for assessing the severity of aortic valve calcification included ultrasonic diagnostics and multislice spiral computed tomography. Markers of inflammation and lipid profile were investigated.    Results. Higher blood levels of total holesterol and holesterol of low density lipoprotein were revealed in patients with DAS in comparison with patients without DAS. They also had higher levels of inflammation markers: C-reactive protein and interleukin-6. There were significant correlations between DAS severity, lipid metabolism disturbances and inflammation markers. Conclusion. Atherogenesis and inflammation may have pathogenic influence on progression of aortic valve calcification and DAS development by lipid infiltration and endothelium cells damage.

  15. Predictive factors of hyaluronic acid injections short-term effectiveness for TMJ degenerative joint disease.

    Science.gov (United States)

    Guarda-Nardini, L; Ferronato, G; Favero, L; Manfredini, D

    2011-05-01

    This study attempted to identify baseline predictors of positive outcome of arthrocenteses plus hyaluronic acid injections in degenerative temporomandibular joint disease (TMJ DJD). Ninety (n=90) consecutive patients with Research Diagnostic Criteria for Temporomandibular Disorders TMJ osteoarthritis (RDC/TMD 1.0 Axis I Group IIIb) underwent a cycle of five arthrocenteses with injections of 1mL hyaluronic acid and were followed up for 3months. Eight potential predictors of positive treatment outcome (sex, age, pain duration, baseline pain at chewing, presence of uni- or bilateral arthritis, presence of other concurrent RDC/TMD diagnoses, type of intervention and tolerability of treatment) were included in a logistic regression model to identify baseline predictors of treatment effectiveness. At follow-up, 85·6% of patients improved with respect to baseline VAS values, and 64·4% had a 50% or more decrease (positive outcomes). Correlation with positive outcomes existed only for unilateral osteoarthritis, and the logistic regression identified the side of arthritis (unilateral/bilateral) as the only predictor of positive treatment outcome (P=0·032). The achievement of any treatment improvement was predicted by high baseline pain levels (P=0·016). The regression models explained only 7·7-15% of the variance in the outcome variable. The attempts to find predictors of positive treatment outcome with HA injections for TMJ degenerative joint disease have been successful only in part. The search for other outcome predictors is likely to benefit from the assessment of psychosocial features associated with TMJ disorders.

  16. Structural Disorder in the Complex of Human Pregnane X Receptor and the Macrolide Antibiotic Rifampicin

    Energy Technology Data Exchange (ETDEWEB)

    Chrencik, Jill E.; Orans, Jillian; Moore, Linda B.; Xue, Yu; Peng, Li; Collins, Jon L.; Wisely, G. Bruce; Lambert, Millard H.; Kliewer, Steven A.; Redinbo, Matthew R. (U. of Texas-SMED); (UNC)

    2010-07-13

    The human nuclear xenobiotic receptor, pregnane X receptor (PXR), detects a variety of structurally distinct endogenous and xenobiotic compounds and controls expression of genes central to drug and cholesterol metabolism. The macrolide antibiotic rifampicin, a front-line treatment for tuberculosis, is an established PXR agonist and, at 823 Da, is one of the largest known ligands for the receptor. We present the 2.8 {angstrom} crystal structure of the ligand-binding domain of human PXR in complex with rifampicin. We also use structural and mutagenesis data to examine the origins of the directed promiscuity exhibited by the PXRs across species. Three structurally flexible loops adjacent to the ligand-binding pocket of PXR are disordered in this crystal structure, including the 200-210 region that is part of a sequence insert novel to the promiscuous PXRs relative to other members of the nuclear receptor superfamily. The 4-methyl-1-piperazinyl ring of rifampicin, which would lie adjacent to the disordered protein regions, is also disordered and not observed in the structure. Taken together, our results indicate that one wall of the PXR ligand-binding cavity can remain flexible even when the receptor is in complex with an activating ligand. These observations highlight the key role that structural flexibility plays in PXR's promiscuous response to xenobiotics.

  17. Comparing ESC and iPSC—Based Models for Human Genetic Disorders

    Directory of Open Access Journals (Sweden)

    Tomer Halevy

    2014-10-01

    Full Text Available Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs from patients’ somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn’t be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.

  18. Genome engineering of isogenic human ES cells to model autism disorders.

    Science.gov (United States)

    Martinez, Refugio A; Stein, Jason L; Krostag, Anne-Rachel F; Nelson, Angelique M; Marken, John S; Menon, Vilas; May, Ryan C; Yao, Zizhen; Kaykas, Ajamete; Geschwind, Daniel H; Grimley, Joshua S

    2015-05-26

    Isogenic pluripotent stem cells are critical tools for studying human neurological diseases by allowing one to study the effects of a mutation in a fixed genetic background. Of particular interest are the spectrum of autism disorders, some of which are monogenic such as Timothy syndrome (TS); others are multigenic such as the microdeletion and microduplication syndromes of the 16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell (hESC) lines for modeling these two disorders using locus-specific endonucleases to increase the efficiency of homology-directed repair (HDR). We developed a system to: (1) computationally identify unique transcription activator-like effector nuclease (TALEN) binding sites in the genome using a new software program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in an amplification-based HDR assay that is more sensitive than the typical non-homologous end joining assay. We applied these methods to identify, construct, and test TALENs that were used with HDR donors in hESCs to generate an isogenic TS cell line in a scarless manner and to model the 16p11.2 copy number disorder without modifying genomic loci with high sequence similarity.

  19. Adjacent segment disease in degenerative pathologies with posterior instrumentation

    OpenAIRE

    Ana Guadalupe Ramírez Olvera; Manuel Villarreal Arroyo; Luis Mario Hinojosa Martínez; Enrique Méndez Pérez; Luis Romeo Ramos Hinojosa

    2015-01-01

    OBJECTIVE: To establish the real incidence of adjacent segment disease after fusion, and to identify the levels and predisposing factors for the pathology, as well as the functional results. METHODS: a retrospective case series study with level of evidence IIB, in a sample of 179 patients diagnosed with stenosis of the lumbar spine, spondylolisthesis and degenerative scoliosis, submitted to surgery in the period 2005 to December 2013, with posterior instrumentation and posterolateral fusion, ...

  20. Sagittal Balance Correction in Lateral Interbody Fusion for Degenerative Scoliosis

    Science.gov (United States)

    Gallizzi, Michael A.; Sheets, Charles; Smith, Benjamin T.; Isaacs, Robert E.; Eure, Megan; Brown, Christopher R.

    2016-01-01

    Background Sagittal balance restoration has been shown to be an important determinant of outcomes in corrective surgery for degenerative scoliosis. Lateral interbody fusion (LIF) is a less-invasive technique which permits the placement of a high lordosis interbody cage without risks associated with traditional anterior or transforaminal interbody techniques. Studies have shown improvement in lumbar lordosis following LIF, but only one other study has assessed sagittal balance in this population. The objective of this study is to evaluate the ability of LIF to restore sagittal balance in degenerative lumbar scoliosis. Methods Thirty-five patients who underwent LIF for degenerative thoracolumbar scoliosis from July 2013 to March 2014 by a single surgeon were included. Outcome measures included sagittal balance, lumbar lordosis, Cobb Angle, and segmental lordosis. Measures were evaluated pre-operative, immediately post-operatively, and at their last clinical follow-up. Repeated measures ANOVAs were used to assess the differences between pre-operative, first postoperative, and a follow-up visit. Results The average sagittal balance correction was not significantly different: 1.06cm from 5.79cm to 4.74cm forward. The average Cobb angle correction was 14.1 degrees from 21.6 to 5.5 degrees. The average change in global lumbar lordosis was found to be significantly different: 6.3 degrees from 28.9 to 35.2 degrees. Conclusions This study demonstrates that LIF reliably restores lordosis, but does not significantly improve sagittal balance. Despite this, patients had reliable improvement in pain and functionality suggesting that sagittal balance correction may not be as critical in scoliosis correction as previous studies have indicated. Clinical Relevance LIF does not significantly change sagittal balance; however, clinical improvement does not seem to be contingent upon sagittal balance correction in the degenerative scoliosis population. The DUHS IRB has determined this

  1. MR imaging of the spine: trauma and degenerative disease

    Energy Technology Data Exchange (ETDEWEB)

    Wilmink, J.T. [Department of Radiology, University Hospital Maastricht (Netherlands)

    1999-09-01

    The purpose of this paper is to discuss the capabilities and drawbacks of MR imaging in patients with trauma to the spine and degenerative spinal conditions. In spinal trauma MR imaging is secondary to plain X-ray films and CT because of the greater availability and ease of performance of these techniques and their superior capability for detecting vertebral fractures. Magnetic resonance imaging is useful for detecting ligamentous ruptures and intraspinal mass lesions such as hematoma, and for assessing the state of the spinal cord and prognosis of a cord injury. In degenerative spinal disease the necessity is emphasized of critically evaluating the clinical relevance of any abnormal feature detected, as findings of degenerative pathology are common in individuals without symptoms. Magnetic resonance myelography permits rapid and accurate assessment of the state of the lumbar nerve roots (compressed or not). In the cervical region the quality of the myelographic picture is often degraded in patients with a narrow spinal canal. (orig.) With 10 figs., 14 refs.

  2. NONOPERATIVE VERSUS OPERATIVE TREATMENT OF PATIENTS WITH DEGENERATIVE SPONDYLOLISTHESIS

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    Jose Alfredo Corredor

    2016-03-01

    Full Text Available ABSTRACT Objective: To evaluate clinical and functional results of patients with lumbar degenerative spondylolisthesis treated with operatively or nonoperatively. Methods: Patients with degenerative spondylolisthesis treated either nonoperatively or operatively from 2004 to 2014 were selected from databases and a cross-sectional evaluation was performed. Outcome measures included back and leg visual analogue scales (VAS, Fischgrund criteria, Short Form-36 (SF-36 function score, and the modified Oswestry Disability Index (ODI. Results: 43 patients were evaluated: 20 with nonoperative treatment and 23 with operative treatment. Baseline characteristics were similar without significant differences between groups. Mean follow-up time was 43 months (range 10 - 72 for the nonoperative group and 36 months (range 6-80 for the operative group. Significant statistical difference in favor of operative group were found in back VAS (mean 4 versus 8, p = 0.000, leg VAS (mean 3 versus 6, p = 0.0015, SF-36 function score (mean 77 versus 35, p = 0.000, and ODI (mean 17 versus 46, p = 0.000. On the basis of the Fischgrund criteria, only 10 % of patients reported excellent or good health post nonoperative treatment versus 83% for those treated operatively (p = 0.000. Conclusion: In this cross-sectional study, we observed that symptomatic patients with degenerative spondylolisthesis who underwent operative treatment have superior clinical and functional scores compared to those that underwent nonoperative treatment.

  3. Adjacent segment disease in degenerative pathologies with posterior instrumentation

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    Ana Guadalupe Ramírez Olvera

    2015-03-01

    Full Text Available OBJECTIVE: To establish the real incidence of adjacent segment disease after fusion, and to identify the levels and predisposing factors for the pathology, as well as the functional results. METHODS: a retrospective case series study with level of evidence IIB, in a sample of 179 patients diagnosed with stenosis of the lumbar spine, spondylolisthesis and degenerative scoliosis, submitted to surgery in the period 2005 to December 2013, with posterior instrumentation and posterolateral fusion, with follow-up from 2007 until May 2014, in which the symptomology and radiographic findings were evaluated, to establish the diagnosis and treatment. RESULTS: the study included 179 patients diagnosed with stenosis of the lumbar spine (n=116, isthmic and degenerative spondylolisthesis (n=50 and degenerative scoliosis (n=13; during the study, 20 cases of adjacent level segment were identified, 80% of which were treated surgically with extension of the instrumentation, while 20% were treated conservatively with NSAIDs and therapeutic blocks. CONCLUSION: An incidence of 11% was found, with an average of 3.25 years in diagnosis and treatment, a prevalence of females and diagnosis of stenosis of the lumbar canal on posterior instrumentation, a predominance of levels L4-L5; 80% were treated with extension of the instrumentation. The complications were persistent radiculopathy, infection of the surgical wound, and one death due to causes not related to the lumbar pathology.

  4. High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization

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    Celina A. Reis Paula

    2017-01-01

    Full Text Available Autism spectrum disorder (ASD is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD.

  5. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

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    Kasey N Davis

    Full Text Available Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA, the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC. No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517 in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

  6. [Drinking water hardness and chronic degenerative diseases. I. Analysis of epidemiological research].

    Science.gov (United States)

    Nardi, G; Donato, F; Monarca, S; Gelatti, U

    2003-01-01

    For many years a causal relation between drinking water hardness and cardiovascular or other chronic degenerative diseases in humans has been hypothesized. In order to evaluate the association between the concentration of minerals (calcium and magnesium) responsible for the hardness of drinking water and human health, a review of all the articles published on the subject from 1980 up to today has been carried out. The retrieved articles have been divided into 4 categories: geographic correlation studies, cross-sectional studies, case-control and cohort studies, and clinical trials. The methods for the selection of the articles and the extraction and analysis of the data are detailed in this paper. Epidemiological studies have been reviewed critically, and some conclusions have been drawn taking into account the research in basic sciences and experimental studies. However, a formal meta-analysis has not been performed, due to the heterogeneity of measures of effect among the different studies.

  7. A dual comparative approach: integrating lines of evidence from human evolutionary neuroanatomy and neurodevelopmental disorders.

    Science.gov (United States)

    Hanson, Kari L; Hrvoj-Mihic, Branka; Semendeferi, Katerina

    2014-01-01

    The evolution of the human brain has been marked by a nearly 3-fold increase in size since our divergence from the last common ancestor shared with chimpanzees and bonobos. Despite increased interest in comparative neuroanatomy and phylogenetic methods, relatively little is known regarding the effects that this enlargement has had on its internal organization, and how certain areas of the brain have differentially expanded over evolutionary time. Analyses of the microstructure of several regions of the human cortex and subcortical structures have demonstrated subtle changes at the cellular and molecular level, suggesting that the human brain is more than simply a 'scaled-up' primate brain. Ongoing research in comparative neuroanatomy has much to offer regarding our understanding of human brain evolution. Through analysis of the neuroanatomical phenotype at the level of reorganization in cytoarchitecture and cellular morphology, new data continue to highlight changes in cell density and organization associated with volumetric changes in discrete regions. An understanding of the functional significance of variation in neural circuitry can further be approached through studies of atypical human development. Many neurodevelopmental disorders cause disruption in systems associated with uniquely human features of cognition, including language and social cognition. Understanding the genetic and developmental mechanisms that underlie variation in the human cognitive phenotype can help to clarify the functional significance of interspecific variation. By uniting approaches from comparative neuroanatomy and neuropathology, insights can be gained that clarify trends in human evolution. Here, we explore these lines of evidence and their significance for understanding functional variation between species as well as within neuropathological variation in the human brain.

  8. Video Analysis of Human Gait and Posture to Determine Neurological Disorders

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    Ivan Lee

    2008-08-01

    Full Text Available This paper investigates the application of digital image processing techniques to the detection of neurological disorder. Visual information extracted from the postures and movements of a human gait cycle can be used by an experienced neurologist to determine the mental health of the person. However, the current visual assessment of diagnosing neurological disorder is based very much on subjective observation, and hence the accuracy of diagnosis heavily relies on experience. Other diagnostic techniques employed involve the use of imaging systems which can only be operated under highly constructed environment. A prototype has been developed in this work that is able to capture the subject's gait on video in a relatively simple setup, and from which to process the selected frames of the gait in a computer. Based on the static visual features such as swing distances and joint angles of human limbs, the system identifies patients with Parkinsonism from the test subjects. To our knowledge, it is the first time swing distances are utilized and identified as an effective means for characterizing human gait. The experimental results have shown a promising potential in medical application to assist the clinicians in diagnosing Parkinsonism.

  9. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    Energy Technology Data Exchange (ETDEWEB)

    Ponnusamy, Rajesh [Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal); Lebedev, Andrey A. [Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); Pahlow, Steffen [University of Hamburg, Ohnhorststrasse 18, 22609 Hamburg (Germany); Lohkamp, Bernhard, E-mail: bernhard.lohkamp@ki.se [Karolinska Institutet, Tomtebodavägen 6, 4tr, 17177 Stockholm (Sweden); Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal)

    2014-06-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

  10. Animal models for human contiguous gene syndromes and other genomic disorders

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    Katherina Walz

    2004-01-01

    Full Text Available Genomic disorders refer to a group of syndromes caused by DNA rearrangements, such as deletions and duplications, which result in an alteration of normal gene dosage. The chromosomal rearrangements are usually relatively small and often difficult to detect cytogenetically. In a subset of such conditions the rearrangements comprise multiple unrelated contiguous genes that are physically linked and thus have been referred to as contiguous gene syndromes (CGS. In general, each syndrome presents a complex clinical phenotype that has been attributed generally to dosage sensitive gene(s present in the responsible chromosomal interval. A common mechanism for CGS resulting from interstitial deletion/duplication has recently been elucidated. The DNA rearrangements result from nonallelic homologous recombination (NAHR utilizing flanking low-copy repeats (LCRs as recombination substrates. The resulting rearrangements often involve the same genomic region, a common deletion or duplication, making it difficult to assign a specific phenotype or endophenotype to a single responsible gene. The human and mouse genome sequencing projects, in conjunction with the ability to engineer mouse chromosome rearrangements, have enabled the production of mouse models for CGS and genomic disorders. In this review we present an overview of different techniques utilized to generate mouse models for selected genomic disorders. These models foment novel insights into the specific genes that convey the phenotype by dosage and/or position effects and provide opportunities to explore therapeutic options.

  11. Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

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    Mamchaoui Kamel

    2011-11-01

    Full Text Available Abstract Background Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies. Methods Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders. Results The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both in vitro and in vivo after transplantation into regenerating muscle of immunodeficient mice. Conclusions Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess in vivo the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.

  12. 退行性脊柱侧凸的最新研究进展%Latest research progress of degenerative scoliosis

    Institute of Scientific and Technical Information of China (English)

    邱浩; 初同伟

    2014-01-01

    Objective To review and summarize the latest progress of the natural history, pathophysiological changes, diagnostic classiifcation and treatment methods of degenerative scoliosis, and to explore a more effective therapeutic scheme. Methods The domestic and foreign literatures related to degenerative scoliosis were reviewed and summarized. All the research hotspots were analyzed and the differences were compared. Results Degenerative scoliosis was prevalent among the elderly people, which was believed to develop as a result of asymmetric degeneration of intervertebral discs and facet joints. Severe pain in the back and lower extremities and intermittent claudication made such patients to ask for medical assistance. At present, there were a lot of controversies on the selection of treatment methods and curative effects, because of a paucity of universally accepted classification to guide the treatment. Conclusions The incidence of degenerative scoliosis is rising year by year. As a result, the life quality of patients are severely affected by the pain and functional disorders. More and more patients begin to seek surgical treatment. In spite of a high rate of surgical complications, the curative effects are not lessened.

  13. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders.

    Science.gov (United States)

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M; Weinberger, Daniel R; Kleinman, Joel E; Law, Amanda J

    2017-03-01

    Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I-IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. NRG3 isoform classes I-IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Mapping the temporal expression of genes

  14. Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

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    Y Song; J Willer; P Scherer; J Panzer; A Kugath; E Skordalakes; R Gregg; G Willer; R Balice-Gordon

    2011-12-31

    Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.

  15. The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders

    Science.gov (United States)

    Cattaneo, A; Cattane, N; Begni, V; Pariante, C M; Riva, M A

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels. PMID:27874848

  16. Gene identification using exon amplification on human chromosome 18q21: implications for bipolar disorder.

    Science.gov (United States)

    Chen, H; Huo, Y; Patel, S; Zhu, X; Swift-Scanlan, T; Reeves, R H; DePaulo, R; Ross, C A; McInnis, M G

    2000-09-01

    We previously reported linkage between bipolar disorder and a region on human chromosome (HC) 18q21. To identify genes in this region, exon trapping was performed on cosmids isolated from an HC18-specific cosmid library (LL18NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridization probes. A total of 285 unique sequences (exons) were obtained from 850 sequenced clones. Homology searching of the databases using NCBI's BLAST algorithms revealed that 31 exons have identity to known genes and/or ESTs, seven are identical to regions of finished genomic sequences in the 18q21 region, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility region for further study in bipolar disorder or other diseases that map to this region.

  17. Analysis of trace element in intervertebral disc by Atomic Absorption Spectrometry techniques in degenerative disc disease in the Polish population

    Directory of Open Access Journals (Sweden)

    Andrzej Nowakowski

    2015-05-01

    Full Text Available Objective. Although trace elements are regarded crucial and their content has been determined in number of tissue there are only few papers addressing this problem in intervertebral disc in humans. Most of the trace elements are important substrates of enzymes influencing metabolism and senescence process. Others are markers of environmental pollution. Therefore the aim of the research was to analyzed of the trace element content in the intervertebral disc, which may be a vital argument recognizing the background of degenerative changes to be the effect of the environment or metabolic factors. Materials and methods. Material consist of 18 intervertebral disc from 15 patients, acquired in surgical procedure of due to the degenerative disease with Atomic Absorption Spectrometry content of Al, Cd, Co, Pb, Cu, Ni, Mo, Mg, Zn was evaluated. Results. Only 4 of the trace elements were detected in all samples. The correlation analysis showed significant positive age correlation with Al and negative in case of Co. Among elements significant positive correlation was observed between Al/Pb, Co/Mo, Al/Mg, Al/Zn Pb/Zn and Mg/Zn. Negative correlation was observed in Al/Co, Cd/Mg, Co/Mg, Mo/Mg, Co/Zn and Mo/Zn. Conclusions. This study is the first to our knowledge that profiles the elements in intervertebral disc in patients with degenerative changes. We have confirmed significant differences between the trace element contents in intervertebral disc and other tissue. It can be ground for further investigation.

  18. Extracellular matrix synthesis and ultrastructural changes of degenerative disc cells transfected by Ad/CMV-hTGF-β1

    Institute of Scientific and Technical Information of China (English)

    谭延斌; 胡有谷; 谭江威

    2003-01-01

    Objective To determine whether the synthesis of proteoglycan, collagen and associated ultrastructure are related to the adenovirus-mediated gene transferred to adult degenerative cells.Methods Adenovirus/cytomegalovirus human transforming growth fector-β1 (Ad/CMV-hTGF-β1) was used to transfect degenerative cells. Antonopulos method, Miamine method and transmission electrion microscopy were conducted to study the synthesis of proteoglycan, collagen, and ultrastructure, respectively. Cell cultures were established from the nucleus pulpous and annulus fibrosus tissues, which were taken from surgery.Results Nucleus pulpous and annulus fibrosus cells were efficiently transduced by the adenoviral vector carrying hTGF-β1 gene. The synthesis of proteoglycan and collagen increased compared with the control group (P<0.05). The metabolism of cells was slightly improved. No significant toxic effects were found.Conclusions Expression of hTGF-β1 gene is efficient to accelerates proteoglycan synthesis and thus accelerates the improvement of collagen. The function and structure of degenerative cells are improved. Ad/CMV-hTGF-β1 may be suitable for treating disc degeneration.

  19. Keratin Gene Mutations in Disorders of Human Skin and its Appendages

    Science.gov (United States)

    Chamcheu, Jean Christopher; Siddiqui, Imtiaz A.; Syed, Deeba N.; Adhami, Vaqar M.; Liovic, Mirjana; Mukhtar, Hasan

    2011-01-01

    Keratins, the major structural protein of all epithelia, are a diverse group of cytoskeletal scaffolding proteins that form intermediate filament networks, providing structural support to keratinocytes that maintain the integrity of the skin. Expression of keratin genes is usually regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Amongst the 54 known functional keratin genes in humans, about 21 different genes including hair and hair follicle-specific keratins have been associated with diverse hereditary disorders. The exact phenotype of each disease mostly reflects the spatial level of expression and types of the mutated keratin genes, the positions of the mutations as well as their consequences at sub-cellular levels. The identification of specific mutations in keratin disorders is the basis of our understanding that lead to reclassification, improved diagnosis with prognostic implications, prenatal testing and genetic counseling in severe cutaneous keratin genodermatoses. A disturbance in cutaneous keratins as a result of mutation(s) in the gene(s) that encode keratin intermediate filaments (KIF) causes keratinocytes and cutaneous tissue fragility, accounting for a large number of genetic disorders in human skin and its appendages. These diseases are characterized by a loss of structural integrity in keratinocytes expressing mutated keratins in vivo, often manifested as keratinocytes fragility (cytolysis), intra-epidermal blistering, hyperkeratosis, and keratin filament aggregation in severely affected tissues. Examples include epidermolysis bullosa simplex (EBS), keratinopathic ichthyosis (KPI), pachyonychia congenital (PC), monilethrix, steatocystoma multiplex and ichthyosis bullosa of Siemens (IBS). These keratins also have been identified to have roles in cell growth, apoptosis, tissue polarity, wound healing and tissue remodeling. PMID:21176769

  20. Degenerative spondylolisthesis: contemporary review of the role of interbody fusion.

    Science.gov (United States)

    Baker, Joseph F; Errico, Thomas J; Kim, Yong; Razi, Afshin

    2017-02-01

    Degenerative spondylolisthesis is a common presentation, yet the best surgical treatment continues to be a matter of debate. Interbody fusion is one of a number of options, but its exact role remains ill defined. The aim of this study was to provide a contemporary review of the literature to help determine the role, if any, of interbody fusion in the surgical treatment of degenerative spondylolisthesis. A systematic review of the literature since 2005 was performed. Details on study size, patient age, surgical treatments, levels of slip, patient reported outcome measures, radiographic outcomes, complications and selected utility measures were recorded. Studies that compared a cohort treated with interbody fusion and at least one other surgical intervention for comparison were included for review. Only studies examining the effect in degenerative spondylolisthesis were included. Two authors independently reviewed the manuscripts and extracted key data. Thirteen studies were included in the final analysis. A total of 565 underwent interbody fusion and 761 underwent other procedures including decompression alone, interspinous stabilisation and posterolateral fusion with or without instrumentation. Most studies were graded Level III evidence. Heterogeneous reporting of outcomes prevented formal statistical analysis. However, in general, studies reviewed concluded no significant clinical or radiographic difference in outcome between interbody fusion and other treatments. Two small studies suggested interbody fusion is a better option in cases of definite instability. Interbody fusion only provided outcomes as good as instrumented posterolateral fusion. However, most studies were Level III, and hence, we remain limited in defining the exact role of interbody fusion-cases with clear instability appear to be most appropriate. Future work should use agreed-upon common outcome measures and definitions.

  1. Development of Modulators Against Degenerative Aging Using Radiation Fusion Technology

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U.; Park, H. R.

    2010-04-15

    In this study, we selected final 20 biomarkers for the degenerative aging to develop radiation aging modeling, and validated a few of selected markers to utilize them in the screening of aging modulators. To select the biomarkers of the degenerative aging, 4 categories of aging-related markers (immune/hematopoiesis, oxidative damage, signaling molecule, lipid metabolism) were comparatively analyzed in irradiated and normally aged biosystems (cell lines or mice). In result, most of the biomarkers showed similar changes by irradiation and normal aging. Regarding the immune/hematopoiesis, the decline of immune cell functions (lymphocyte, NK cell) and Th1/Th2 imbalance, and decreased antigen-presenting of dendritic cells were observed and 10 biomarkers were selected in this category. mtDNA deletion was selected for the oxidative damage marker, 6 biomarkers including p21 and p-FOXO3a for signaling molecule biomarkers, and 3 biomarkers including the adipose tissue weight were selected for lipid metabolism. In addition, the various radiation application conditions by single/factionated irradiation and the periods after the irradiation were investigated for the optimal induction of changes of biomarker, which revealed that total 5Gy of 10 or more fractionated irradiations and 4 months or greather period were observed to be optimal. To found the basis for the screening of natural aging modulators, some selected aging biomarkers were validated by their inhibition by well-known natural agents (EGCG, HemoHIM, etc) in aged cell or mouse model. Additionally, by evaluating the reductive efficacy of 5 natural agents on the degeneration of skin and reproductive organs induced by radiation and chemicals (cyclophosphamide, etc), we established the base for the screening of degenerative diseases by various factors

  2. Visuo-proprioceptive interactions in degenerative cervical spine diseases requiring surgery.

    Science.gov (United States)

    Freppel, S; Bisdorff, A; Colnat-Coulbois, S; Ceyte, H; Cian, C; Gauchard, G; Auque, J; Perrin, P

    2013-01-01

    Cervical proprioception plays a key role in postural control, but its specific contribution is controversial. Postural impairment was shown in whiplash injuries without demonstrating the sole involvement of the cervical spine. The consequences of degenerative cervical spine diseases are underreported in posture-related scientific literature in spite of their high prevalence. No report has focused on the two different mechanisms underlying cervicobrachial pain: herniated discs and spondylosis. This study aimed to evaluate postural control of two groups of patients with degenerative cervical spine diseases with or without optokinetic stimulation before and after surgical treatment. Seventeen patients with radiculopathy were recruited and divided into two groups according to the spondylotic or discal origin of the nerve compression. All patients and a control population of 31 healthy individuals underwent a static posturographic test with 12 recordings; the first four recordings with the head in 0° position: eyes closed, eyes open without optokinetic stimulation, with clockwise and counter clockwise optokinetic stimulations. These four sensorial situations were repeated with the head rotated 30° to the left and to the right. Patients repeated these 12 recordings 6weeks postoperatively. None of the patients reported vertigo or balance disorders before or after surgery. Prior to surgery, in the eyes closed condition, the herniated disc group was more stable than the spondylosis group. After surgery, the contribution of visual input to postural control in a dynamic visual environment was reduced in both cervical spine diseases whereas in a stable visual environment visual contribution was reduced only in the spondylosis group. The relative importance of visual and proprioceptive inputs to postural control varies according to the type of pathology and surgery tends to reduce visual contribution mostly in the spondylosis group.

  3. Prolonged upright posture induces degenerative changes in intervertebral discs in rat lumbar spine.

    Science.gov (United States)

    Liang, Qian-Qian; Zhou, Quan; Zhang, Min; Hou, Wei; Cui, Xue-Jun; Li, Chen-Guang; Li, Tian-Fang; Shi, Qi; Wang, Yong-Jun

    2008-09-01

    Both forelimbs of rats were amputated, and these rats were kept in the custom-made cages that kept the rats in prolonged upright posture. Pathologic changes were observed in the lumbar spine at different time points after the surgery. To investigate the effect of upright posture on intervertebral discs of rat lumbar spine. Previous studies have shown that increased axial forces on the spine can decrease the height of the intervertebral disc, but there are no data to indicate whether or not long-term and repeated assumption of the upright posture could result in degenerative changes. The forelimbs of 30 rats were amputated when they were 1-month old. These rats were kept in the custom-made cages and were forced to stand upright on their hind-limbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were killed at 5, 7, and 9 months after the surgery, and the intervertebral discs samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples was used for real-time PCR of type II collagen (Col2alpha1), type X collagen (Col10alpha1), matrix metalloproteinase-13 (MMP-13), aggrecan, and disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). RESULTS.: Histologic analysis showed degenerative changes of the intervertebral discs after surgery such as disordered collagen structure of endplate cartilage, fragmentation of annulus fibrosus, and decreased height of disc. Immunostaining revealed decreased protein level of type II collagen and increased protein expression of type X collagen. Real-time PCR showed upregulated expression of MMP 13, ADAMTS-5, and Col10alpha1 mRNA and downregulated mRNA expression of Col2alpha1 and aggrecan. Long-term and repeated assumption of the upright stance accelerates disc degeneration in rats.

  4. How Relevant Are Imaging Findings in Animal Models of Movement Disorders to Human Disease?

    Science.gov (United States)

    Bannon, Darryl; Landau, Anne M; Doudet, Doris J

    2015-08-01

    The combination of novel imaging techniques with the use of small animal models of disease is often used in attempt to understand disease mechanisms, design potential clinical biomarkers and therapeutic interventions, and develop novel methods with translatability to human clinical conditions. However, it is clear that most animal models are deficient when compared to the complexity of human diseases: they cannot sufficiently replicate all the features of multisystem disorders. Furthermore, some practical differences may affect the use or interpretation of animal imaging to model human conditions such as the use of anesthesia, various species differences, and limitations of methodological tools. Nevertheless, imaging animal models allows us to dissect, in interpretable bits, the effects of one system upon another, the consequences of variable neuronal losses or overactive systems, the results of experimental treatments, and we can develop and validate new methods. In this review, we focus on imaging modalities that are easily used in both human subjects and animal models such as positron emission and magnetic resonance imaging and discuss aging and Parkinson's disease as prototypical examples of preclinical imaging studies.

  5. TRACTION-EXTENDED THERAPY OF PATIENTS WITH LUMBAR DEGENERATIVE DISEASE

    OpenAIRE

    V. A. Zhirnov; D. P. Krest'yanov; A. K. Vasil'kin

    2013-01-01

    Based on the survey of 148 patients with an lumbar degenerative disease, there have been studied immediate and medium-term results of the comprehensive conservative treatment of the patients with and without application of traction exposure on the spine. It was found out that the traction of the spine leads to a quicker and more durable relief of symptoms in comparison with the control groups where traction therapy wasn't carried out. Application of the traction-extended therapy in three plan...

  6. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases

    Science.gov (United States)

    Orsini, Marco; Nascimento, Osvaldo J.M.; Matta, Andre P.C.; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S.; Filho, Pedro F. Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-01-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome – among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson’s disease, Alzheimer’s disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  7. Plantar fasciitis: a degenerative process (fasciosis) without inflammation.

    Science.gov (United States)

    Lemont, Harvey; Ammirati, Krista M; Usen, Nsima

    2003-01-01

    The authors review histologic findings from 50 cases of heel spur surgery for chronic plantar fasciitis. Findings include myxoid degeneration with fragmentation and degeneration of the plantar fascia and bone marrow vascular ectasia. Histologic findings are presented to support the thesis that "plantar fasciitis" is a degenerative fasciosis without inflammation, not a fasciitis. These findings suggest that treatment regimens such as serial corticosteroid injections into the plantar fascia should be reevaluated in the absence of inflammation and in light of their potential to induce plantar fascial rupture.

  8. Location and Initiation of Degenerative Rotator Cuff Tears

    Science.gov (United States)

    Kim, H. Mike; Dahiya, Nirvikar; Teefey, Sharlene A.; Middleton, William D.; Stobbs, Georgia; Steger-May, Karen; Yamaguchi, Ken; Keener, Jay D.

    2010-01-01

    Background: It has been theorized that degenerative rotator cuff tears most commonly involve the supraspinatus tendon, initiating at the anterior portion of the supraspinatus insertion and propagating posteriorly. The purposes of this study were to determine the most common location of degenerative rotator cuff tears and to examine tear location patterns associated with various tear sizes. Methods: Ultrasonograms of 360 shoulders with either a full-thickness rotator cuff tear (272) or a partial-thickness rotator cuff tear (eighty-eight) were obtained to measure the width and length of the tear and the distance from the biceps tendon to the anterior margin of the tear. Tears were grouped on the basis of their size (anteroposterior width) and extent (partial or full-thickness). Each tear was represented numerically as a column of consecutive numbers representing the tear width and distance posterior to the biceps tendon. All tears were pooled to graphically represent the width and location of the tears within groups. Frequency histograms of the pooled data were generated, and the mode was determined for each histogram representing various tear groups. Results: The mean age (and standard deviation) of the 233 subjects (360 shoulders) was 64.7 ± 10.2 years. The mean width and length of the tears were 16.3 ± 12.1 mm and 17.0 ± 13.0 mm, respectively. The mean distance from the biceps tendon to the anterior tear margin was 7.8 ± 5.7 mm (range, 0 to 26 mm). Histograms of the various tear groups invariably showed the location of 15 to 16 mm posterior to the biceps tendon to be the most commonly torn location within the posterior cuff tendons. The histograms of small tears (a width of infraspinatus. The patterns of tear location across multiple tear sizes suggest that degenerative cuff tears may initiate in a region 13 to 17 mm posterior to the biceps tendon. Clinical Relevance: The findings of this study speak to the specific location of the most common type of rotator

  9. Relationships between disk displacement, joint effusion, and degenerative changes of the TMJ in TMD patients based on MRI findings.

    Science.gov (United States)

    Roh, Hee-Seok; Kim, Wook; Kim, Young-Ku; Lee, Jeong-Yun

    2012-04-01

    This study was performed to investigate the relationships between disk displacement, joint effusion, and degenerative changes in patients with temporomandibular disorders using MRI. Randomly selected MRIs of 508 temporomandibular joints of 254 patients (92 males and 162 females, mean age was 30.5±12.0 years) were reviewed retrospectively. Seventy-eight percent (198 out of 254) of the patients complained of joint pain. Compared with joints with a normal disk position, the joints with anterior disk displacement with reduction showed a 2.01 odds ratio (Pdegenerative changes and a 2.85 odds ratio (Pdegenerative changes and a 4.61 odds ratio (Pdegenerative changes and joint effusions increase with displacement of the disk position in patients with temporomandibular disorders. Although all disk displacement situations do not progress to painful joints and/or degenerative joint diseases, the possibility of an increased risk of progression by a breakdown in the balance between a patient's adaptive capacity and functional loading of the TMJ should be assessed in each and every patient through comprehensive evaluation of various contributing factors.

  10. Characterization of Intercostal Muscle Pathology in Canine Degenerative Myelopathy: A Disease Model for Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Bujnak, Alyssa C.; Katz, Martin L.

    2014-01-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions accompanied by atrophic changes in the descending spinal cord tracts , and some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure due to severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and an alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  11. Dynamic of Grassland Biomass in Different Degenerative Stages

    Institute of Scientific and Technical Information of China (English)

    YAN Yan; LIU Shuzhen; ZHOU Wei

    2006-01-01

    The dynamics of plant community and above- and belowground biomass of the different degenerative stages was researched of Kobresia humlis meadows of Nakchu prefecture in Tibet Autonomous Region. The results indicated that the aggravation of the degree of deterioration of alpine meadow is, the lower the vegetation coverage, percentage of excellent forage, and biodiversity are. The total aboveground biomass is highest in the lightly degraded stages while it is lowest in the extremely degraded stages. With the aggravation of degradation, the aboveground biomass of forbs increases while that of Cyperaceae decreases. We found that the belowground biomass was mostly distributed in the 0-10 cm soil depth in the alpine meadow with a "T"-shape distribution feature, and with the acceleration of deterioration, the numbers of roots becomes less and less. Meanwhile, the above- and belowground biomass of the different degraded communities was significantly correlated(r=0.963). There is an obvious positive correlation with the above- and belowground biomass in different degenerative stages, and their ratio increased with the aggravation of degradation.

  12. Long term results of radiotherapy of degenerative joint diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lindner, H.; Freislederer, R.

    1982-04-01

    At the Radiologic Department of the Staedt. Krankenhaus Passau, 473 patients with degenerative diseases in the big joints and the spine were irradiated with the caesium unit between 1971 and 1979. Among these patients, 249 could be followed up during a prolonged period (1/2 to 9 years, i.e. 4.2 years on an average). According to the categories of v. Pannewitz, 11% were pain-free at this moment, 21% showed an essential improvement, 29% showed an improvement, and 39% were not influenced by the treatment. 13.5% showed recurrent pains; these were mentioned as 'not influenced' in the statistical analysis. It is proved that the relief of pain does not depend on the age of the patients, but on the anamnesis period, the results of the X-ray examiantion, and the degree of the restriction of mobility. Due to the delay of irradiation, a preliminary treatment mostly produces a less favorable radiotherapeutic result. Compared with other therapeutic methods, the long term results of radiotherapy of degenerative joint diseases are generally favorable. This conclusion is also confirmed by the results of patients checked up more than five years after the treatment.

  13. Flexible Stabilisation of the Degenerative Lumbar Spine Using PEEK Rods

    Directory of Open Access Journals (Sweden)

    Jacques Benezech

    2016-01-01

    Full Text Available Posterior lumbar interbody fusion using cages, titanium rods, and pedicle screws is considered today as the gold standard of surgical treatment of lumbar degenerative disease and has produced satisfying long-term fusion rates. However this rigid material could change the physiological distribution of load at the instrumental and adjacent segments, a main cause of implant failure and adjacent segment disease, responsible for a high rate of further surgery in the following years. More recently, semirigid instrumentation systems using rods made of polyetheretherketone (PEEK have been introduced. This clinical study of 21 patients focuses on the clinical and radiological outcomes of patients with lumbar degenerative disease treated with Initial VEOS PEEK®-Optima system (Innov’Spine, France composed of rods made from PEEK-OPTIMA® polymer (Invibio Biomaterial Solutions, UK without arthrodesis. With an average follow-up of 2 years and half, the chances of reoperation were significantly reduced (4.8%, quality of life was improved (ODI = 16%, and the adjacent disc was preserved in more than 70% of cases. Based on these results, combined with the biomechanical and clinical data already published, PEEK rods systems can be considered as a safe and effective alternative solution to rigid ones.

  14. Raptor Acupuncture for Treating Chronic Degenerative Joint Disease

    Directory of Open Access Journals (Sweden)

    Keum Hwa Choi

    2016-12-01

    Full Text Available A permanently captive 21-year-old male bald eagle was diagnosed with chronic degenerative joint disease in the right stifle with severe lameness (Grade 5 based on radiography. Clinical signs included decreased movement, vocalization, non weight-bearing on the affected limb, inappetence, depression, and pododermatitis on the left foot (bumblefoot, Grade 3. The eagle was treated with anti-inflammatory or analgesic drugs including carprofen and celecoxib. As there was no observed clinical improvement with any of the treatments, acupuncture treatment was provided. The eagle was treated with dry needle acupuncture once per week for 2 months and biweekly for another 2 months. The Traditional Eastern Medicine diagnosis of this eagle was Bony Bi syndrome. The selected acupuncture points were ST 36, LI 4, BL 40, BL 60, GB 34, and Ba Feng (Table 3. The lameness score improved from Grade 5 to Grade 1 after 4 months of acupuncture treatment. The observed pododermatitis improved from Grade 3 to Grade 0. Symptoms including inappetence and vocalizations were significantly reduced over the 4 month period. There was no significant improvement in the radiographic signs. In conclusion, acupuncture may be a potential medical option for permanently captive raptors having musculoskeletal conditions, such as degenerative joint disease.

  15. Raptor Acupuncture for Treating Chronic Degenerative Joint Disease.

    Science.gov (United States)

    Choi, Keum Hwa; Buhl, Gail; Ponder, Julia

    2016-12-01

    A permanently captive 21-year-old male bald eagle was diagnosed with chronic degenerative joint disease in the right stifle with severe lameness (Grade 5) based on radiography. Clinical signs included decreased movement, vocalization, non weight-bearing on the affected limb, inappetence, depression, and pododermatitis on the left foot (bumblefoot, Grade 3). The eagle was treated with anti-inflammatory or analgesic drugs including carprofen and celecoxib. As there was no observed clinical improvement with any of the treatments, acupuncture treatment was provided. The eagle was treated with dry needle acupuncture once per week for 2 months and biweekly for another 2 months. The Traditional Eastern Medicine diagnosis of this eagle was Bony Bi syndrome. The selected acupuncture points were ST 36, LI 4, BL 40, BL 60, GB 34, and Ba Feng (Table 3). The lameness score improved from Grade 5 to Grade 1 after 4 months of acupuncture treatment. The observed pododermatitis improved from Grade 3 to Grade 0. Symptoms including inappetence and vocalizations were significantly reduced over the 4 month period. There was no significant improvement in the radiographic signs. In conclusion, acupuncture may be a potential medical option for permanently captive raptors having musculoskeletal conditions, such as degenerative joint disease. Copyright © 2016. Published by Elsevier B.V.

  16. PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Lindsey A. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States); Allis, C. David [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: alliscd@rockefeller.edu; Wang, Gang G. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: gwang@rockefeller.edu

    2008-12-01

    Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies

  17. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Science.gov (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  18. Order-disorder transitions govern kinetic cooperativity and allostery of monomeric human glucokinase.

    Directory of Open Access Journals (Sweden)

    Mioara Larion

    Full Text Available Glucokinase (GCK catalyzes the rate-limiting step of glucose catabolism in the pancreas, where it functions as the body's principal glucose sensor. GCK dysfunction leads to several potentially fatal diseases including maturity-onset diabetes of the young type II (MODY-II and persistent hypoglycemic hyperinsulinemia of infancy (PHHI. GCK maintains glucose homeostasis by displaying a sigmoidal kinetic response to increasing blood glucose levels. This positive cooperativity is unique because the enzyme functions exclusively as a monomer and possesses only a single glucose binding site. Despite nearly a half century of research, the mechanistic basis for GCK's homotropic allostery remains unresolved. Here we explain GCK cooperativity in terms of large-scale, glucose-mediated disorder-order transitions using 17 isotopically labeled isoleucine methyl groups and three tryptophan side chains as sensitive nuclear magnetic resonance (NMR probes. We find that the small domain of unliganded GCK is intrinsically disordered and samples a broad conformational ensemble. We also demonstrate that small-molecule diabetes therapeutic agents and hyperinsulinemia-associated GCK mutations share a strikingly similar activation mechanism, characterized by a population shift toward a more narrow, well-ordered ensemble resembling the glucose-bound conformation. Our results support a model in which GCK generates its cooperative kinetic response at low glucose concentrations by using a millisecond disorder-order cycle of the small domain as a "time-delay loop," which is bypassed at high glucose concentrations, providing a unique mechanism to allosterically regulate the activity of human GCK under physiological conditions.

  19. Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

    2015-03-01

    ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

  20. Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders

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    Shuji Mizumoto

    2017-03-01

    Full Text Available The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.

  1. Human imprinting anomalies in fetal and childhood growth disorders: clinical implications and molecular mechanisms.

    Science.gov (United States)

    Azzi, Salah; Brioude, Fréderic; Le Bouc, Yves; Netchine, Irène

    2014-01-01

    Genomic imprinting is among the most important epigenetic mechanisms whereby expression of a subset of genes is restricted to a single parental allele. Loss of imprinting (LOI) through hypo or hyper methylation is involved in various human syndromes. These LOI occur early during development and usually impair growth. Some imprinting syndromes are the consequences of genetic anomalies, such as uniparental disomies (UPD) or copy number variations (deletion or duplications) involving the imprinted domains; others are due to LOI at the imprinting control regions (ICR) regulating each domain. Imprinting disorders are phenotypically heterogeneous, although some share various common clinical features such that diagnosis may be difficult. Multilocus imprinting defects associated with several syndromes have been increasingly reported in recent years, although there are no obvious clinical differences between monolocus and multilocus LOI patients. Subsequently, some rare mutations of transacting factors have been identified in patients with multilocus imprinting defects but they do not explain the majority of the cases; this therefore implies that other factors are involved. By contrast, no mutation of a transacting factor has yet been identified in monolocus LOI. The effect of the environment on the regulation of imprinting is clearly illustrated by studies of assisted reproductive technology (ART). The regulation of imprinting is complex and involves a huge range of genetic and environmental factors; the identification of these factors will undoubtedly help to elucidate the regulation of imprinting and contribute to the understanding of imprinting disorders. This would be beneficial for diagnostics, clinical follow up and the development of treatment guidelines.

  2. Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders.

    Science.gov (United States)

    Hattori, Yuka; Mukaide, Takahiro; Jiang, Li; Kotani, Tomomi; Tsuda, Hiroyuki; Mano, Yukio; Sumigama, Seiji; Hirayama, Tasuku; Nagasawa, Hideko; Kikkawa, Fumitaka; Toyokuni, Shinya

    2015-01-01

    Amniotic fluid contains numerous biomolecules derived from fetus and mother, thus providing precious information on pregnancy. Here, we evaluated oxidative stress of human amniotic fluid and measured the concentration of catalytic Fe(II). Amniotic fluid samples were collected with consent from a total of 89 subjects in Nagoya University Hospital, under necessary medical interventions: normal pregnancy at term, normal pregnancy at the 2nd trimester, preterm delivery with maternal disorders but without fetal disorders, congenital diaphragmatic hernia, fetal growth restriction, pregnancy-induced hypertension, gestational diabetes mellitus, Down syndrome and trisomy 18. Catalytic Fe(II) and oxidative stress markers (8-hydroxy-2'-deoxyguanosine, 8-OHdG; dityrosine) were determined with RhoNox-1 and specific antibodies, respectively, using plate assays. Levels of 8-OHdG and dityrosine were higher in the 3rd trimester compared with the 2nd trimester in normal subjects, and the abnormal groups generally showed lower levels than the controls, thus suggesting that they represent fetal metabolic activities. In contrast, catalytic Fe(II) was higher in the 2nd trimester than the 3rd trimester in the normal subjects, and overall the abnormal groups showed higher levels than the controls, suggesting that high catalytic Fe(II) at late gestation reflects fetal pathologic alterations. Notably, products of H2O2 and catalytic Fe(II) remained almost constant in amniotic fluid.

  3. Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2010-07-01

    The rapidly emerging science of epigenetics and epigenomic medicine promises to reveal novel insights into the susceptibility to and the onset and progression of epileptic disorders. Epigenetic regulatory mechanisms are now implicated in orchestrating aspects of neural development (e.g., cell fate specification and maturation), homeostasis and stress responses (e.g., immediate early gene transcription), and neural network function (e.g., excitation-inhibition coupling and activity-dependent plasticity). These same neurobiological processes are responsible for determining the heterogeneous features of complex epileptic disease states. Thus, we highlight recent evidence that is beginning to elucidate the specific roles played by epigenetic mechanisms, including DNA methylation, histone code modifications and chromatin remodeling, noncoding RNAs and RNA editing, in human epilepsy syndromes and in the process of epileptogenesis. The highly integrated layers of the epigenome are responsible for the cell type specific and exquisitely environmentally responsive deployment of genes and functional gene networks that underlie the molecular pathophysiology of epilepsy and its associated comorbidities, including but not limited to neurotransmitter receptors (e.g., GluR2, GLRA2, and GLRA3), growth factors (e.g., BDNF), extracellular matrix proteins (e.g., RELN), and diverse transcriptional regulators (e.g., CREB, c-fos, and c-jun). These important observations suggest that future epigenetic studies are necessary to better understand, classify, prevent, and treat epileptic disorders.

  4. Hormonal and Metabolic Disorders of Human Immunodeficiency Virus Infection and Substance Abuse

    Directory of Open Access Journals (Sweden)

    Jag H. Khalsa

    2006-01-01

    Full Text Available There are an estimated 200 million users of an illicit drug in the world today. In addition, an estimated 40 million people are infected with the human immunodeficiency virus (HIV and an estimated 180 million people are infected with the hepatitis C virus (HCV. Both the use of an illicit drug and the co-occurrence of infections are associated with a multitude of medical and health consequences including hormonal and metabolic disorders. Thus, the National Institute on Drug Abuse (NIDA, a part of the National Institutes of Health (NIH hosted a workshop on hormonal and metabolic disorders of HIV among substance abusers. A number of clinicians and scientists participated and discussed a wide range of issues concerning hormones, nutrition and metabolic complications in HIV and substance abuse. Their observations and the recommendations they made for future research are presented in these proceedings. The readers are encouraged to contact the NIH staff (JK, FV for technical guidance and programmatic priorities on the subject and directly contact the individual authors for collaborations.

  5. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders.

    Science.gov (United States)

    Bouazoune, Karim; Kingston, Robert E

    2012-11-20

    Mutations in the CHD7 gene cause human developmental disorders including CHARGE syndrome. Genetic studies in model organisms have further established CHD7 as a central regulator of vertebrate development. Functional analysis of the CHD7 protein has been hampered by its large size. We used a dual-tag system to purify intact recombinant CHD7 protein and found that it is an ATP-dependent nucleosome remodeling factor. Biochemical analyses indicate that CHD7 has characteristics distinct from SWI/SNF- and ISWI-type remodelers. Further investigations show that CHD7 patient mutations have consequences that range from subtle to complete inactivation of remodeling activity, and that mutations leading to protein truncations upstream of amino acid 1899 of CHD7 are likely to cause a hypomorphic phenotype for remodeling. We propose that nucleosome remodeling is a key function for CHD7 during developmental processes and provide a molecular basis for predicting the impact of disease mutations on that function.

  6. Involvement of the modifier gene of a human Mendelian disorder in a negative selection process.

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    Isabelle Jéru

    Full Text Available BACKGROUND: Identification of modifier genes and characterization of their effects represent major challenges in human genetics. SAA1 is one of the few modifiers identified in humans: this gene influences the risk of renal amyloidosis (RA in patients with familial Mediterranean fever (FMF, a Mendelian autoinflammatory disorder associated with mutations in MEFV. Indeed, the SAA1 alpha homozygous genotype and the p.Met694Val homozygous genotype at the MEFV locus are two main risk factors for RA. METHODOLOGY/PRINCIPAL FINDINGS: HERE, WE INVESTIGATED ARMENIAN FMF PATIENTS AND CONTROLS FROM TWO NEIGHBORING COUNTRIES: Armenia, where RA is frequent (24%, and Karabakh, where RA is rare (2.5%. Sequencing of MEFV revealed similar frequencies of p.Met694Val homozygotes in the two groups of patients. However, a major deficit of SAA1 alpha homozygotes was found among Karabakhian patients (4% as compared to Armenian patients (24% (p = 5.10(-5. Most importantly, we observed deviations from Hardy-Weinberg equilibrium (HWE in the two groups of patients, and unexpectedly, in opposite directions, whereas, in the two control populations, genotype distributions at this locus were similar and complied with (HWE. CONCLUSIONS/SIGNIFICANCE: The excess of SAA1alpha homozygotes among Armenian patients could be explained by the recruitment of patients with severe phenotypes. In contrast, a population-based study revealed that the deficit of alpha/alpha among Karabakhian patients would result from a negative selection against carriers of this genotype. This study, which provides new insights into the role of SAA1 in the pathophysiology of FMF, represents the first example of deviations from HWE and selection involving the modifier gene of a Mendelian disorder.

  7. Evolving towards a human-cell based and multiscale approach to drug discovery for CNS disorders

    Directory of Open Access Journals (Sweden)

    Eric eSchadt

    2014-12-01

    Full Text Available A disruptive approach to therapeutic discovery and development is required in order to significantly improve the success rate of drug discovery for central nervous system (CNS disorders. In this review, we first assess the key factors contributing to the frequent clinical failures for novel drugs. Second, we discuss cancer translational research paradigms that addressed key issues in drug discovery and development and have resulted in delivering drugs with significantly improved outcomes for patients. Finally, we discuss two emerging technologies that could improve the success rate of CNS therapies: human induced pluripotent stem cell (hiPSC-based studies and multiscale biology models. Coincident with advances in cellular technologies that enable the generation of hiPSCs directly from patient blood or skin cells, together with methods to differentiate these hiPSC lines into specific neural cell types relevant to neurological disease, it is also now possible to combine data from large-scale forward genetics and post-mortem global epigenetic and expression studies in order to generate novel predictive models. The application of systems biology approaches to account for the multiscale nature of different data types, from genetic to molecular and cellular to clinical, can lead to new insights into human diseases that are emergent properties of biological networks, not the result of changes to single genes. Such studies have demonstrated the heterogeneity in etiological pathways and the need for studies on model systems that are patient-derived and thereby recapitulate neurological disease pathways with higher fidelity. In the context of two common and presumably representative neurological diseases, the neurodegenerative disease Alzheimer’s Disease (AD, and the psychiatric disorder schizophrenia (SZ, we propose the need for, and exemplify the impact of, a multiscale biology approach that can integrate panomic, clinical, imaging, and literature

  8. Value of different MR techniques in diagnosis of degenerative disorders of the hyaline cartilage - in vitro study on 50 joint specimens of the knee with 1.5 T; Vergleich von verschiedenen MRT-Techniken in der Diagnose von degenerativen Knorpelerkrankungen - in-vitro-Studie an 50 Gelenkpraeparaten des Knies bei 1,5 T

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, G. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Heinrichs, C. [Klinikum der Univ. Giessen (Germany). Inst. fuer Pathologie; Juergensen, I. [Klinikum der Univ. Giessen (Germany). Orthopaedische Klinik; Rominger, M. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Scheiter, A. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Rau, W.S. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie

    1997-05-01

    Verbindung mit T{sub 1}-gew. SE und T{sub 2}-gew. FLASH-2D, die STIR, FISP-3 D, FLASH-3 D mit Fettsuppression und die MR-Arthrographie. Fuer jede Sequenz wurden subjektive Qualitaetskriterien, Signal-Rausch-Verhaeltnisse von Knorpel und Gelenkfluessigkeit und Nachweisraten fuer Knorpellaesionen bestimmt. Als Referenz zur MRT dienten pathologische und arthroskopische Untersuchungen, die an 186 der 300 Knorpelflaechen degenerative Veraenderungen Grad 1-4 nachwiesen. Ergebnisse: Die Defektstadien Grad 3 und 4 (65 Laesionen) waren mit den klassischen SE-Sequenzen in 67-94% nachweisbar. Die Volumentechniken (FISP-3 D und FLASH-3 D), Sequenzen mit 512er Matrix, der MTC (mit FLASH-2 D) und die MR-Arthrographie fuehrten zu einer Verbesserung der Sensitivitaet auf 82-100%. Oberflaechliche Defekte Grad 2 (65 Laesionen) hatten Nachweisraten von 3-38%, in der MR-Arthrographie betrug sie 45%. Die rein strukturellen Knorpelveraenderungen Grad 1 (56 Faelle) wurden in ca. 10% diagnostiziert. Schlussfolgerung: Die Diagnostik von Knorpelerkrankungen laesst sich gegenueber den klassischen SE-Sequenzen mit grosser Bildmatrix, verbessertem Knorpelkontrast und Volumentechnik verwenden. (orig.)

  9. Attention Deficit Disorder--A New Age Yuppie Disorder or an Age Old Human Characteristic Essential for Our Survival?

    Science.gov (United States)

    Orgill, Anna A.

    This brief paper suggests that Attention Deficit Disorder (ADD) may result from a specific "novelty seeking" gene which has been associated over the history of man's evolution with a biological advantage in situations where energy, risk taking, and creativity are essentials. It reviews research on the genetics of ADD which suggest that novelty…

  10. Reasons for rarity of Th17 cells in inflammatory sites of human disorders.

    Science.gov (United States)

    Annunziato, Francesco; Santarlasci, Veronica; Maggi, Laura; Cosmi, Lorenzo; Liotta, Francesco; Romagnani, Sergio

    2013-11-15

    T helper 17 (Th17) cells have been reported to be responsible for several chronic inflammatory diseases. However, a peculiar feature of human Th17 cells is that they are very rare in the inflammatory sites in comparison with Th1 cells. The first reason for this rarity is the existence of some self-regulatory mechanisms that limit their expansion. The limited expansion of human Th17 cells is related to the retinoic acid orphan (ROR)C-dependent up-regulation of the interleukin (IL)-4 induced gene 1 (IL4I1), which encodes for a l-phenylalanine oxidase, that has been shown to down-regulate CD3ζ expression in T cells. This results in abnormalities of the molecular pathway which is responsible for the impairment of IL-2 production and therefore for the lack of cell proliferation in response to T-cell receptor (TCR) signalling. IL4I1 up-regulation also associates with the increased expression of Tob1, a member of the Tob/BTG anti-proliferative protein family, which is involved in cell cycle arrest. A second reason for the rarity of human Th17 cells in the inflammatory sites is their rapid shifting into the Th1 phenotype, which is mainly related to the activity of IL-12 and TNF-α. We have named these Th17-derived Th1 cells as non-classic because they differ from classic Th1 cells for the expression of molecules specific for Th17 cells, such as RORC, CD161, CCR6, IL4I1, and IL-17 receptor E. This distinction may be important for defining the respective pathogenic role of Th17, non-classic Th1 and classic Th1 cells in many human inflammatory disorders.

  11. LUMBOSACRAL TRANSITIONAL ANATOMY TYPES AND DISC DEGENERATIVE CHANGES

    Directory of Open Access Journals (Sweden)

    Chabukovska Radulovska Jasminka

    2014-07-01

    Full Text Available Background and purpose: The relationship between presence of lumbo sacral transitional vertebra (LSTV and disc degenerative changes is unclear. The aim of the study was to examine the relation between different types of LSTV and disc degenerative changes at the transitional and the adjacent cephalad segment. Material and methods: Sixty-three patients (mean age 51.48 ± 13.51 out of 200 adults with low back pain who performed MRI examination of the lumbo sacral spine, classified as positive for LSTV, were included in the study. Annular tears, disc degeneration according to Phirmann classification and disc herniations were evaluated and graded at transitional and adjacent cephalad level. Results: The severity of disc degeneration at the transitional level and the adjacent level correlated with the types of LSTV. Severe disc degenerative changes were most frequent in articulated connection LSTV types and incombined LSTV type at the transitional level and in osseus connection LSTV types at the adjacent cephalad level. These changes were more frequent in unilateral articulated connection LSTV subtype (64% vs 54%; and in unilateral osseus connection LSTV subtype (25% vs no patients at transitional level, and in bilateral osseus connection LSTV subtype (100% vs 50% at the level above. High prevalence of disc herniations was observed in articulated connection LSTV types as well as in unilateral osseus connection LSTV subtype at transitional and the adjacent cephalad level. At the transitional level higher prevalence of disc herniations was characteristic for unilateral articulated connection LSTV sub type (46%vs 41% and for unilateral osseus connection LSTV subtype (50% vs no patients. At the adjacent level higher prevalence of disc herniations was observed in bilateral articulated connection LSTV subtype (38% vs 27% and in bilateral osseus connection LSTV subtype (50% vs 25%. Conclusions: The compact osseus connection (osseus bridging vs articular

  12. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, D. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Izzotti, A. [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy); Bonica, P.; Pera, P. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Pulliero, A., E-mail: alessandra.pulliero@unige.it [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy)

    2009-07-10

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  13. 退变性脊柱侧凸发病机制%Pathogenesis of degenerative scoliosis

    Institute of Scientific and Technical Information of China (English)

    吴炜; 王洪立; 马晓生; 姜建元

    2015-01-01

    Degenerative scoliosis is one of the main causes of low back pain and cosmetic deformity among the elderly. And it is more prevalent nowadays. Although the etiology is unclear, it is thought to be associated with osteoporosis, asymmetric degeneration, abnormal expression of gene, age, gender, etc. Better understanding the pathogenesis will be useful in the management of degenerative scoliosis.

  14. Disordering of human telomeric G-quadruplex with novel antiproliferative anthrathiophenedione.

    Directory of Open Access Journals (Sweden)

    Dmitry Kaluzhny

    Full Text Available Linear heteroareneanthracenediones have been shown to interfere with DNA functions, thereby causing death of human tumor cells and their drug resistant counterparts. Here we report the interaction of our novel antiproliferative agent 4,11-bis[(2-{[acetimido]amino}ethylamino]anthra[2,3-b]thiophene-5,10-dione with telomeric DNA structures studied by isothermal titration calorimetry, circular dichroism and UV absorption spectroscopy. New compound demonstrated a high affinity (K(ass∼10⁶ M⁻¹ for human telomeric antiparallel quadruplex d(TTAGGG₄ and duplex d(TTAGGG₄∶d(CCCTAA₄. Importantly, a ∼100-fold higher affinity was determined for the ligand binding to an unordered oligonucleotide d(TTAGGG TTAGAG TTAGGG TTAGGG unable to form quadruplex structures. Moreover, in the presence of Na+ the compound caused dramatic conformational perturbation of the telomeric G-quadruplex, namely, almost complete disordering of G-quartets. Disorganization of a portion of G-quartets in the presence of K+ was also detected. Molecular dynamics simulations were performed to illustrate how the binding of one molecule of the ligand might disrupt the G-quartet adjacent to the diagonal loop of telomeric G-quadruplex. Our results provide evidence for a non-trivial mode of alteration of G-quadruplex structure by tentative antiproliferative drugs.

  15. The difficult relationship between occlusal interferences and temporomandibular disorder - insights from animal and human experimental studies.

    Science.gov (United States)

    Xie, Q; Li, X; Xu, X

    2013-04-01

    The aetiology of temporomandibular disorder (TMD) is multifactorial, and numerous studies have addressed that occlusion may be of great importance. However, whether occlusion plays a crucial role in the pathogenesis of TMD remains controversial. Study designs utilising animal models have been used to study the effects of artificial occlusal alterations. Experimental traumatic occlusion affects blood flow in the temporomandibular joint and results in changes in the condylar cartilage, and artificial occlusal interference induces masticatory muscle nociceptive responses that are associated with peripheral sensitisation and lead to central sensitisation, which maintains masticatory muscle hyperalgesia. The possibility that occlusal interference results in TMD has been investigated in humans using a double-blind randomised design. Subjects without a history of TMD show fairly good adaptation to interferences. In contrast, subjects with a history of TMD develop a significant increase in clinical signs and self-report stronger symptoms (occlusal discomfort and chewing difficulties) in response to interferences. Meanwhile, psychological factors appear meaningful for symptomatic responses to artificial interferences in subjects with a history of TMD. Thus, individual differences in vulnerability to occlusal interferences do exist. Although there are advantages and disadvantages to using human and animal occlusal interference models, these approaches are indispensable for discovering the role of occlusion in TMD pathogenesis.

  16. Kinematic Measures during a Clinical Diagnostic Technique for Human Neck Disorder: Inter- and Intraexaminer Comparisons

    Directory of Open Access Journals (Sweden)

    Joseph Vorro

    2013-01-01

    Full Text Available Diagnoses of human musculoskeletal dysfunction of the cervical spine are indicated by palpable clues of a patient’s structural compliance/noncompliance as this body segment responds to diagnostic motion demands applied by a clinician. This process includes assessments of motion range, motion performance, and changes in tissue responses. However, biomechanical quantification of these diagnostic actions and their reproducible components is lacking. As a result, this study sought to use objective kinematic measures to capture aspects of the diagnostic process to compare inter- and intraexaminer motion behaviors when performing a specific clinical diagnostic protocol. Pain-free volunteers and a group determined to be symptomatic based on a psychometric pain score were examined by two clinicians while three-dimensional kinematic data were collected. Intraexaminer diagnostic motion ranges of cervical lateral flexion and secondary rotations were consistent for each examiner and for each subject group. However, interexaminer comparisons for motion range, secondary rotations, and average velocities yielded consistently larger measures for one examiner for both subject groups (P<0.05. This research demonstrates that fundamental aspects of the clinical diagnostic process for human neck disorders can be identified and measured using kinematic parameters. Further, these objective data have the potential to be linked to clinical decision making.

  17. Cartilage cell proliferation in degenerative TFCC wrist lesions.

    Science.gov (United States)

    Unglaub, Frank; Thomas, Susanne B; Wolf, Maya B; Dragu, Adrian; Kroeber, Markus W; Mittlmeier, Thomas; Horch, Raymund E

    2010-08-01

    The central zone of the triangular fibrocartilage complex (TFCC) of the wrist is thought to be avascular and is generally considered to lack any healing potential. The purpose of this study was to investigate, if cartilage cells of degenerative disc lesions possess any healing or proliferation potential and whether ulna length plays a significant role in the proliferation process. Cells positive for proliferating cell nuclear antigen (PCNA) were found in all specimens. Specimens of patients with ulna positive variance showed a decreased number of PCNA positive cells than specimens of patients with either negative or neutral ulna variance. We found that cartilage cells of Palmer type 2C lesions undergo mitotic cell division, thus exhibiting proliferation capability. It could not be shown that ulnar length is significantly correlated with the number of PCNA positive cells.

  18. Degenerative spine disease : pathologic findings in 985 surgical specimens.

    Science.gov (United States)

    Pytel, Peter; Wollmann, Robert L; Fessler, Richard G; Krausz, Thomas N; Montag, Anthony G

    2006-02-01

    A number of pathologic changes have been reported in spinal surgery specimens. The frequency of many of these is not well defined. We retrospectively reviewed the histologic features of 985 extradural spinal surgery specimens. Of the cases, 1.6% were identified clinically as synovial cysts. In addition, synovial tissue was seen in another 5.3% of cases, often embedded within disk material. Neovascularization of disk tissue was present in 8.1% of cases, chondrocyte clusters in 18.3%, and calcium pyrophosphate crystals in 2.8%, predominantly within disk material. With the exception of crystal deposits, all of these changes were significantly more common in the lumbar spine. A better understanding of cell-based degenerative changes will become essential with increasing research into cell-based therapies for spinal disk disease. We report data on the frequency of different pathologic changes and describe synovial metaplasia as a reactive change not previously reported.

  19. Vitamin K, osteoporosis and degenerative diseases of ageing.

    Science.gov (United States)

    Vermeer, Cees; Theuwissen, Elke

    2011-03-01

    The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.

  20. Nuclear microscopy in medical research. Investigations into degenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Makjanic, J.; Thong, P.; Watt, F. [National University of Singapore (Singapore). Dept. of Physics

    1997-03-01

    The high energy (1-4MeV) focused ion beam (nuclear microbeam) has found uses in many scientific disciplines through a wide variety of ion beam based techniques. Of the many techniques available, the powerful combination of Particle Induced X-Ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS), and Scanning Transmission Ion Microscopy (STIM) is proving to be extremely useful, particularly in the characterisation and elemental analysis of thin specimens. In this paper we briefly review these ion beam techniques, as well as the hardware required for their application. Finally, we describe the application of the PIXE, RBS and STIM techniques in conjunction with a scanning focused 2MeV proton microbeam (nuclear microscopy). The examples chosen to illustrate the potential of nuclear microscopy are recent investigations into the degenerative diseases atherosclerosis (coronary heart disease), Parkinson`s disease and Alzheimer`s disease. (author)

  1. TRACTION-EXTENDED THERAPY OF PATIENTS WITH LUMBAR DEGENERATIVE DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Zhirnov

    2013-01-01

    Full Text Available Based on the survey of 148 patients with an lumbar degenerative disease, there have been studied immediate and medium-term results of the comprehensive conservative treatment of the patients with and without application of traction exposure on the spine. It was found out that the traction of the spine leads to a quicker and more durable relief of symptoms in comparison with the control groups where traction therapy wasn't carried out. Application of the traction-extended therapy in three planes with a usage of robotized set for dry skeletal traction of a new generation KinetracKNX-7000 is proved to increase the effectiveness of treatment for the patients with stated pathology, fasten regress of the pain syndrome and clinical symptomatology, lead to more durable and lasting remission of the desease, in comparison with the patients that had traction of the spine in one plane only during the treatment.

  2. Osteoporosis and the Management of Spinal Degenerative Disease

    Directory of Open Access Journals (Sweden)

    Felix Tome-Bermejo

    2017-09-01

    Full Text Available Osteoporosis has become a major medical problem as the aged population of the world rapidly grows. Osteoporosispredisposes patients to fracture, progressive spinal deformities, and stenosis, and is subject to be a major concernbefore performing spine surgery, especially with bone fusions and instrumentation. Osteoporosis has often beenconsidered a contraindication for spinal surgery, while in some instances patients have undergone limited and inadequateprocedures in order to avoid concomitant instrumentation. As the population ages and the expectations of older patientsincrease, the demand for surgical treatment in older patients with osteoporosis and spinal degenerative diseasesbecomes progressively more important. Nowadays, advances in surgical and anesthetic technology make it possible tooperate successfully on elderly patients who no longer accept disabling physical conditions. This article discusses thebiomechanics of the osteoporotic spine, the diagnosis and management of osteoporotic patients with spinal conditions,as well as the novel treatments, recommendations, surgical indications, strategies and instrumentation in patients withosteoporosis who need spine operations.

  3. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders.

    Science.gov (United States)

    Drenth, Joost P H; Waxman, Stephen G

    2007-12-01

    The voltage-gated sodium-channel type IX alpha subunit, known as Na(v)1.7 and encoded by the gene SCN9A, is located in peripheral neurons and plays an important role in action potential production in these cells. Recent genetic studies have identified Na(v)1.7 dysfunction in three different human pain disorders. Gain-of-function missense mutations in Na(v)1.7 have been shown to cause primary erythermalgia and paroxysmal extreme pain disorder, while nonsense mutations in Na(v)1.7 result in loss of Na(v)1.7 function and a condition known as channelopathy-associated insensitivity to pain, a rare disorder in which affected individuals are unable to feel physical pain. This review highlights these recent developments and discusses the critical role of Na(v)1.7 in pain sensation in humans.

  4. Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

    Science.gov (United States)

    Nagy, K; Marschalkó, Márta; Kemény, B; Horváth, A

    2005-01-01

    The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

  5. Shoulder activity level and progression of degenerative cuff disease.

    Science.gov (United States)

    Keener, Jay D; Skelley, Nathan W; Stobbs-Cucchi, Georgia; Steger-May, Karen; Chamberlain, Aaron M; Aleem, Alex W; Brophy, Robert H

    2017-09-01

    This study prospectively examined the relationship of direct and indirect measures of shoulder activity with the risks of tear progression and pain development in subjects with an asymptomatic degenerative rotator cuff tear. A cohort of asymptomatic degenerative rotator cuff tears was prospectively monitored annually, documenting tear size progression with ultrasound imaging and potential shoulder pain development. Shoulder activity level, self-reported occupational and physical demand level, and hand dominance were compared with risks of tear enlargement and future pain development. The study monitored 346 individuals with a mean age of 62.1 years for a median duration of 4.1 years (interquartile range [IQR], 2.4-7.9 years). Tear enlargement was seen in 177 shoulders (51.2%), and pain developed in 161 shoulders (46.5%) over time. Tear presence in the dominant shoulder was associated with a greater risk of tear enlargement (hazard ratio, 1.40; P = .03) and pain development (hazard ratio, 1.63; P = .002). Shoulder activity level (P = .37) and occupational demand level (P = .62) were not predictive of tear enlargement. Occupational demand categories of manual labor (P = .047) and "in between" (P = .045) had greater risks of pain development than sedentary demands. The median shoulder activity score for shoulders that became painful was lower than for shoulders that remained asymptomatic (10.0 [IQR, 7.0-13.0] vs. 11.0 [IQR, 8.0-14.0], P = .02). Tear enlargement and pain development in asymptomatic tears are more common with involvement of the dominant shoulder. Shoulder activity level is not related to tear progression risks. Pain development is associated with a lower shoulder activity level even though patients with higher occupational demands are more likely to develop pain. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  6. Posatirelin for the treatment of degenerative and vascular dementia: results of explanatory and pragmatic efficacy analyses.

    Science.gov (United States)

    Gasbarrini, G; Stefanini, G; Addolorato, G; Foschi, F; Ricci, C; Bertolotti, P; Voltolini, G; Bonavita, E; Bertoncelli, R; Renzi, G; Bianchini, G; Bonaiuto, S; Giannandrea, E; Cavassini, G; Mazzini, V; Chioma, V; Marzara, G; D'Addetta, G; Totaro, G; Dalmonte, E; Tassini, D; Giungi, F; De Nitto, C; Di Fazio, G; Tessitore, A; Guadagnino, M; Tessitore, E; Spina, P; Luppi, M; Bignamini, A; Peracino, L; Fiorentino, M; Beun-Garbe, D; Poli, A; Ambrosoli, L; Girardello, R

    1998-01-01

    In order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

  7. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys

    NARCIS (Netherlands)

    Bromet, E J; Atwoli, L; Kawakami, N; Navarro-Mateu, F; Piotrowski, P; King, A J; Aguilar-Gaxiola, S; Alonso, J; Bunting, B; Demyttenaere, K; Florescu, S; de Girolamo, G; Gluzman, S; Haro, J M; de Jonge, P; Karam, E G; Lee, S; Kovess-Masfety, V; Medina-Mora, M E; Mneimneh, Z; Pennell, B-E; Posada-Villa, J; Salmerón, D; Takeshima, T; Kessler, R C

    2016-01-01

    BACKGROUND: Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few

  8. Non-opioid nociceptive activity of human dynorphin mutants that cause neurodegenerative disorder spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Watanabe, Hiroyuki; Mizoguchi, Hirokazu; Verbeek, Dineke S.; Kuzmin, Alexander; Nyberg, Fred; Krishtal, Oleg; Sakurada, Shinobu; Bakalkin, Georgy

    2012-01-01

    We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23). Three mutations substitute Leu(5), Arg(6), and Arg(9) to Ser (L5S), Trp (R6W) and Cys (R9C) in dynorphin A(1-17) (Dyn A), a peptide with both

  9. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys

    NARCIS (Netherlands)

    Bromet, E J; Atwoli, L; Kawakami, N; Navarro-Mateu, F; Piotrowski, P; King, A J; Aguilar-Gaxiola, S; Alonso, J; Bunting, B; Demyttenaere, K; Florescu, S; de Girolamo, G; Gluzman, S; Haro, J M; de Jonge, P; Karam, E G; Lee, S; Kovess-Masfety, V; Medina-Mora, M E; Mneimneh, Z; Pennell, B-E; Posada-Villa, J; Salmerón, D; Takeshima, T; Kessler, R C

    Background. Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few

  10. Non-opioid nociceptive activity of human dynorphin mutants that cause neurodegenerative disorder spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Watanabe, Hiroyuki; Mizoguchi, Hirokazu; Verbeek, Dineke S.; Kuzmin, Alexander; Nyberg, Fred; Krishtal, Oleg; Sakurada, Shinobu; Bakalkin, Georgy

    2012-01-01

    We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23). Three mutations substitute Leu(5), Arg(6), and Arg(9) to Ser (L5S), Trp (R6W) and Cys (R9C) in dynorphin A(1-17) (Dyn A), a peptide with both

  11. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys

    NARCIS (Netherlands)

    Bromet, E. J.; Atwoli, L.; Kawakami, N.; Navarro-Mateu, F.; Piotrowski, P.; King, A. J.; Aguilar-Gaxiola, S.; Alonso, J.; Bunting, B.; Demyttenaere, K.; Florescu, S.; de Girolamo, G.; Gluzman, S.; Haro, J. M.; de Jonge, P.; Karam, E. G.; Lee, S.; Kovess-Masfety, V.; Medina-Mora, M. E.; Mneimneh, Z.; Pennell, B. -E.; Posada-Villa, J.; Salmeron, D.; Takeshima, T.; Kessler, R. C.

    2017-01-01

    Background. Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few

  12. Impairments in Monkey and Human Face Recognition in 2-Year-Old Toddlers with Autism Spectrum Disorder and Developmental Delay

    Science.gov (United States)

    Chawarska, Katarzyna; Volkmar, Fred

    2007-01-01

    Face recognition impairments are well documented in older children with Autism Spectrum Disorders (ASD); however, the developmental course of the deficit is not clear. This study investigates the progressive specialization of face recognition skills in children with and without ASD. Experiment 1 examines human and monkey face recognition in…

  13. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Perron, H; Hamdani, N; Faucard, R; Lajnef, M; Jamain, S; Daban-Huard, C; Sarrazin, S; LeGuen, E; Houenou, J; Delavest, M; Moins-Teisserenc, H; Moins-Teiserenc, H; Bengoufa, D; Yolken, R; Madeira, A; Garcia-Montojo, M; Gehin, N; Burgelin, I; Ollagnier, G; Bernard, C; Dumaine, A; Henrion, A; Gombert, A; Le Dudal, K; Charron, D; Krishnamoorthy, R; Tamouza, R; Leboyer, M

    2012-12-04

    Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of

  14. An official American thoracic society workshop report: comparative pathobiology of fibrosing lung disorders in humans and domestic animals.

    Science.gov (United States)

    Roman, Jesse; Brown, Kevin K; Olson, Amy; Corcoran, Brendan M; Williams, Kurt J

    2013-12-01

    The clinical outcome of idiopathic pulmonary fibrosis (IPF) is poor, with a 50% survival rate at 3 years. Furthermore, current treatments provide little amelioration of symptoms. Despite significant advances in understanding the clinical features and pathobiology of IPF, further advances have been hampered by a lack of suitable animal models of the disease. Interestingly, spontaneously occurring disorders with a similarity to IPF have been recognized in the dog, cat, horse, and donkey. These disorders share clinical and pathologic features with human IPF and are emerging diseases of veterinary importance. To improve awareness about these disorders in domestic animals and stimulate interactions between disciplines, and to facilitate the elucidation of mechanisms of fibrosing lung disorders using a comparative natural-occurrence disease model approach. A 1-day meeting joined physicians, veterinarians, pathologists, researchers, and advocacy experts to discuss information available in this area. A review of the literature was conducted, and an executive committee discussed the findings and prepared a summary statement during subsequent meetings. Clinical, diagnostic, and treatment opportunities were identified, and common areas of interest where collaborative efforts could accelerate discovery regarding etiological factors, methods for early detection, determinants of disease progression, and novel therapies were defined. Comparing fibrosing lung disorders in humans and domestic animals will allow for a better understanding of the similarities and differences among species and may offer novel insights into the underlying mechanisms of spontaneously occurring fibrotic lung diseases.

  15. Keratin gene mutations in disorders of human skin and its appendages.

    Science.gov (United States)

    Chamcheu, Jean Christopher; Siddiqui, Imtiaz A; Syed, Deeba N; Adhami, Vaqar M; Liovic, Mirjana; Mukhtar, Hasan

    2011-04-15

    Keratins, the major structural protein of all epithelia are a diverse group of cytoskeletal scaffolding proteins that form intermediate filament networks, providing structural support to keratinocytes that maintain the integrity of the skin. Expression of keratin genes is usually regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Amongst the 54 known functional keratin genes in humans, about 22 different genes including, the cornea, hair and hair follicle-specific keratins have been implicated in a wide range of hereditary diseases. The exact phenotype of each disease usually reflects the spatial expression level and the types of mutated keratin genes, the location of the mutations and their consequences at sub-cellular levels as well as other epigenetic and/or environmental factors. The identification of specific pathogenic mutations in keratin disorders formed the basis of our understanding that led to re-classification, improved diagnosis with prognostic implications, prenatal testing and genetic counseling in severe keratin genodermatoses. Molecular defects in cutaneous keratin genes encoding for keratin intermediate filaments (KIFs) causes keratinocytes and tissue-specific fragility, accounting for a large number of genetic disorders in human skin and its appendages. These diseases are characterized by keratinocytes fragility (cytolysis), intra-epidermal blistering, hyperkeratosis, and keratin filament aggregation in severely affected tissues. Examples include epidermolysis bullosa simplex (EBS; K5, K14), keratinopathic ichthyosis (KPI; K1, K2, K10) i.e. epidermolytic ichthyosis (EI; K1, K10) and ichthyosis bullosa of Siemens (IBS; K2), pachyonychia congenita (PC; K6a, K6b, K16, K17), epidermolytic palmo-plantar keratoderma (EPPK; K9, (K1)), monilethrix (K81, K83, K86), ectodermal dysplasia (ED; K85) and steatocystoma multiplex. These keratins also have been identified to have roles in apoptosis, cell proliferation

  16. Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases.

    Science.gov (United States)

    Loperfido, Mariana; Steele-Stallard, Heather B; Tedesco, Francesco Saverio; VandenDriessche, Thierry

    2015-01-01

    Human pluripotent stem cells represent a unique source for cell-based therapies and regenerative medicine. The intrinsic features of these cells such as their easy accessibility and their capacity to be expanded indefinitely overcome some limitations of conventional adult stem cells. Furthermore, the possibility to derive patient-specific induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization. Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials for skeletal muscle disorders.

  17. Citicoline, use in cognitive decline: vascular and degenerative.

    Science.gov (United States)

    García-Cobos, Rocío; Frank-García, Ana; Gutiérrez-Fernández, María; Díez-Tejedor, Exuperio

    2010-12-15

    CDP-choline has been widespread used in humans for decades as a treatment for many types of cognitive impairment. Despite this, its mechanism of action still remains unclear, but several experimental models in acute cerebral ischaemia suggest that it could have a brain repair action. Due to the lack of significant adverse effects and its high tolerability, there has been a growing interest for this molecule in recent years. In this article, a review of the most significant published clinical trials in cognitive decline has been made. A few Citicoline trials have studied its effects at medium and long-term on vascular cognitive impairment and Alzheimer's disease. Results show that Citicoline seems to have beneficial impact on several cognitive domains, but the methodological heterogeneity of the these studies makes it difficult to draw conclusions about these effects. New trials with a greater number of patients, uniform diagnostic criteria for inclusion and standardized neuropsychological assessment are needed to evidence with much more consistency Citicoline efficacy upon cognitive disorders. The use of new neuroimaging procedures in current trials could be of great interest.

  18. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

    Science.gov (United States)

    Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi

    2017-01-01

    Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. PMID:28053046

  19. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders

    OpenAIRE

    Drenth, J.P.H.; Waxman, S G

    2007-01-01

    The voltage-gated sodium-channel type IX alpha subunit, known as Na(v)1.7 and encoded by the gene SCN9A, is located in peripheral neurons and plays an important role in action potential production in these cells. Recent genetic studies have identified Na(v)1.7 dysfunction in three different human pain disorders. Gain-of-function missense mutations in Na(v)1.7 have been shown to cause primary erythermalgia and paroxysmal extreme pain disorder, while nonsense mutations in Na(v)1.7 result in los...

  20. Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes.

    Science.gov (United States)

    Hwang, Min Ho; Kim, Kyoung Soo; Yoo, Chang Min; Shin, Jae Hee; Nam, Hyo Geun; Jeong, Jin Su; Kim, Joo Han; Lee, Kwang Ho; Choi, Hyuk

    2016-05-01

    Destruction of extracellular matrix (ECM) leads to degeneration of the intervertebral disk (IVD), which is a major contributor to many spine disorders. IVD degeneration is induced by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), which are secreted by immune cells, including macrophages and neutrophils. The cytokines modulate ECM-modifying enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human annulus fibrosus (AF) cells. The resulting imbalance in catabolic and anabolic enzymes can cause generalized back, neck, and low back pain (LBP). Photobiomodulation (PBM) is known to regulate inflammatory responses and wound healing. The aim of this study was to mimic the degenerative IVD microenvironment, and to investigate the effect of a variety of PBM conditions (wavelength: 635, 525, and 470 nm; energy density: 16, 32, and 64 J/cm(2)) on the production of ECM-modifying-enzymes by AF cells under degenerative conditions induced by macrophage-conditioned medium (MCM), which contains pro-inflammatory cytokines such as TNF-α and IL-β secreted by macrophage during the development of intervertebral disk inflammation. We showed that the MCM-stimulated AF cells express imbalanced ratios of TIMPs (TIMP-1 and TIMP-2) and MMPs (MMP-1 and MMP-3). PBM selectively modulated the production of ECM-modifying enzymes in AF cells. These results suggest that PBM can be a therapeutic tool for degenerative IVD disorders.

  1. Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders.

    Science.gov (United States)

    Brugmann, S A; Powder, K E; Young, N M; Goodnough, L H; Hahn, S M; James, A W; Helms, J A; Lovett, M

    2010-03-01

    Mammals and birds have common embryological facial structures, and appear to employ the same molecular genetic developmental toolkit. We utilized natural variation found in bird beaks to investigate what genes drive vertebrate facial morphogenesis. We employed cross-species microarrays to describe the molecular genetic signatures, developmental signaling pathways and the spectrum of transcription factor (TF) gene expression changes that differ between cranial neural crest cells in the developing beaks of ducks, quails and chickens. Surprisingly, we observed that the neural crest cells established a species-specific TF gene expression profile that predates morphological differences between the species. A total of 232 genes were differentially expressed between the three species. Twenty-two of these genes, including Fgfr2, Jagged2, Msx2, Satb2 and Tgfb3, have been previously implicated in a variety of mammalian craniofacial defects. Seventy-two of the differentially expressed genes overlap with un-cloned loci for human craniofacial disorders, suggesting that our data will provide a valuable candidate gene resource for human craniofacial genetics. The most dramatic changes between species were in the Wnt signaling pathway, including a 20-fold up-regulation of Dkk2, Fzd1 and Wnt1 in the duck compared with the other two species. We functionally validated these changes by demonstrating that spatial domains of Wnt activity differ in avian beaks, and that Wnt signals regulate Bmp pathway activity and promote regional growth in facial prominences. This study is the first of its kind, extending on previous work in Darwin's finches and provides the first large-scale insights into cross-species facial morphogenesis.

  2. Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, J.L.; Kaplan, P.A.; Dussault, R.G.; Anderson, M.W. [Dept. of Radiology, Univ. of Virginia Health System, Charlottesville, VA (United States)

    2000-12-01

    Objective. Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease.Design. Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease.Results. Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease.Conclusions. Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment. (orig.)

  3. Property of Regenerating Serotonin Fibers in the Hippocampus of Human Migration Disorders Model

    Science.gov (United States)

    Ueda, Shuichi; Ehara, Ayuka; Ohmomo, Hideki

    Individual mood and mental conditions exert a great influence on one's own kansei. Abnormality or dysfunction of the 5-HT neuron system in the developing and/or adult brain is closely associated with their conditions. Thus, the 5-HT neuron system may play an important role in the neuronal mechanisms underlying kansei. Interestingly, previous studies have shown that heterotopic clusters in the hippocampus (hippocampal heterotopia), deriving from neocortical neurons, after prenatally treated with methylazoxymethanol acetate in rat (MAM rat), exhibit abundant 5-HT innervation. After neonatal intracisternal 5, 7-dihydroxytryptamine (DHT) injection, these 5-HT fibers degenerate and disappear throughout the forebrain, and then regenerating 5-HT fibers densely innervate in the hippocampal heterotopia. The 5-HT fiber system in the hippocampal heterotopia of MAM rat provides useful experimental models for study the plasticity of human migration disorder. In the present study, to evaluate the properties of regenerating 5-HT fibers in the hippocampal heterotopia of MAM rats, we examined the origin of these projections by combined retrograde transport and immunohistochemical methods. Prenatal exposure to MAM resulted in the formation of hippocampal heterotopia in the dorsal hippocampus. Regenerating 5-HT fibers formed a dense innervation within the hippocampal heterotopia after neonatal DHT injection. These projections appeared to arise mainly from 5-HT neurons in the median raphe nucleus, with a small portion from 5-HT neurons in the dorsal raphe nucleus. These findings suggest a specific profile of regenerating 5-HT fibers, providing the new insights for serotonergic plasticity.

  4. Neuropathologic confirmation of definitional criteria for human immunodeficiency virus-associated neurocognitive disorders.

    Science.gov (United States)

    Cherner, Mariana; Cysique, Lucette; Heaton, Robert K; Marcotte, Thomas D; Ellis, Ronald J; Masliah, Eliezer; Grant, Igor

    2007-01-01

    Research findings have suggested a need for modifications to the original nomenclature for human immunodeficiency virus (HIV)-associated neurocognitive disorders issued in 1991 by the American Academy of Neurology (AAN). The HIV Neurobehavioral Research Center (HNRC) proposed a diagnostic scheme that departs from the AAN 1991 criteria primarily in the inclusion of an asymptomatic neurocognitive impairment (ANI) category that relies on cognitive disturbances as a necessary criterion for diagnosis, without requiring declines in daily functioning, motor, or other behavioral abnormalities. In order to test the predictive validity of these two nomenclatures, the authors compared the correspondence between antemortem neurocognitive diagnoses resulting from AAN and HNRC criteria to a neuropathological diagnosis of HIV encephalitis (HIVE) made at autopsy. Agreement between the two sets of definitional criteria was 79% regarding the classification of cases as either neurocognitively normal or impaired, and 54% with regard to specific neurocognitive diagnoses. When pathological evidence of HIVE was considered as the external indicator of HIV-related brain involvement, 64% of cases were correctly classified by AAN criteria, compared to 72% by HNRC criteria. HNRC criteria had better positive predictive power (95% versus 88%), sensitivity (67% versus 56%), and specificity (92% versus 83%). Three cases with HIVE and were correctly identified by HNRC criteria for ANI but called normal by AAN criteria, supporting inclusion of an asymptomatic neurocognitive condition. The modifications to the AAN 1991 criteria proposed by the HNRC and others in the field have served as a point of departure for a recently revised consensus nomenclature.

  5. Structural Basis for a Human Glycosylation Disorder Caused by Mutation of the COG4 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, B.; Smith, R; Ungar, D; Nakamura, A; Jeffrey, P; Lupashin, V; Hughson, F

    2009-01-01

    The proper glycosylation of proteins trafficking through the Golgi apparatus depends upon the conserved oligomeric Golgi (COG) complex. Defects in COG can cause fatal congenital disorders of glycosylation (CDGs) in humans. The recent discovery of a form of CDG, caused in part by a COG4 missense mutation changing Arg 729 to Trp, prompted us to determine the 1.9 A crystal structure of a Cog4 C-terminal fragment. Arg 729 is found to occupy a key position at the center of a salt bridge network, thereby stabilizing Cog4's small C-terminal domain. Studies in HeLa cells reveal that this C-terminal domain, while not needed for the incorporation of Cog4 into COG complexes, is essential for the proper glycosylation of cell surface proteins. We also find that Cog4 bears a strong structural resemblance to exocyst and Dsl1p complex subunits. These complexes and others have been proposed to function by mediating the initial tethering between transport vesicles and their membrane targets; the emerging structural similarities provide strong evidence of a common evolutionary origin and may reflect shared mechanisms of action.

  6. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders

    Science.gov (United States)

    Barnig, Cindy; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

    2015-01-01

    Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach–in a limited number of patients and controls—to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology. PMID:26524763

  7. Total knee replacement for posttraumatic degenerative arthritis of the knee

    Institute of Scientific and Technical Information of China (English)

    WU Li-dong; XIONG Yan; YAN Shi-gui; YANG Quan-sen

    2005-01-01

    Objective: To evaluate the results of total knee arthroplasty (TKA) in patients with posttraumatic degenerative arthritis due to a previous fracture around the knee. Methods: We analyzed the results of 15 TKAs, performed from 1997 to 2003, in 15 patients with post-traumatic degenerative arthritis due to a previous fracture around knee. There were 3 women and 12 men with an average age of 58 years (range, 31-76 years). The time from fracture to arthroplasty averaged 8.2 years (range, 2-27 years). Internal fixation had previously been performed in 8 patients resulting in retained hardware. At the time of arthroplasty a femoral fracture malunion was present in two knees. Lateral retinacular release (4 knees), extensor mechanism realignment (1 knee) or medial collateral ligament reconstruction (1 knee) were needed at the time of arthroplasty. Results: Follow-up averaged 35 months (range, 12-73 months). No patient was lost for follow-up. According to the Knee Society Score scale, the mean preoperative knee score was 37 (range, 10-70) and functional score was 41 (range, 0-60). They were improved significantly to a mean of 84 (range, 10-100) and 76 (range, 20-100) points, respectively at the latest follow-up. The mean knee arc of motion were improved from 84° preoperation to 94° at the latest follow-up. Postoperative manipulation under anesthesia for poor motion was carried out in 4 knees. No knee had aseptic loosening that required subsequent revision. Two knees developed superficial infection and were treated with debridement. It subsequently recovered with the retention of components. Conclusions: Significant improvement in function and relief of pain has been achieved in patients with previous fractures undergoing subsequent TKA. However, this procedure is technically demanding and patients are at increased risk for restricted motion and need more care following TKA. This study suggests that the outcome of TKA may be improved further by making special efforts to

  8. Degenerative Changes of the Spine of Pilots of the RNLAF

    Science.gov (United States)

    2000-08-01

    loads. Therefore, acute in-flight arthrosis deformans was found in the cervical neck injury is a common complaint among pilots spine. Further...views of the spine taken in standing 7-3 Table 2 Classification of disorders Disorder Levels General: Osteo- arthrosis / Spondylosis / Arthrosis ...significant relationship between II found Arthrosis Deformans. Agreement exists these disorders and high +G, forces was not between both radiologists on levels

  9. [Complex outpatient care to patients with osteoarthrosis and degenerative-dystrophic diseases of juxtaarticular soft tissues].

    Science.gov (United States)

    Saks, L A

    2014-04-01

    The aim of the article is an evaluation of effectiveness of the complex outpatient care to patients with osteoarthrosis and degenerative-dystrophic diseases ofjuxtaarticular soft tissues. Recent researches showed that the key factors of the pathogenesis of diseases were degenerative-dystrophic and inflammatory changes in the synovio-entheseal complex ofparaarticular muscles' tendon. 411 patients with osteoarthrosis of 531 synovial joints and degenerative-dystrophic diseases of periarticular soft tissues underwent sequential corticosteroid therapy combined with hyaluronic acid injections. In 84% of cases positive results were observed.

  10. Progressive cerebellar degenerative changes in the severe mental retardation syndrome caused by duplication of MECP2 and adjacent loci on Xq28.

    LENUS (Irish Health Repository)

    Reardon, William

    2010-08-01

    Localised duplications, involving the MECP2 locus, at Xq28 have been associated with a syndrome comprising X-linked mental retardation, hypotonia and recurrent infections in males. We now present neuroradiological evidence that progressive cerebellar degenerative changes may also be a consistent feature of this syndrome, emerging in the second decade of life. We report seven affected males, from three different families who, in addition to the previously described clinical findings, have a reduction in the volume of the white matter and mild dilatation of the lateral ventricles. Three of the older patients show a consistent cerebellar degenerative phenotype. Furthermore, we describe the first female affected with the disorder. The female was mildly affected and shows X-inactivation in the ratio of 70:30, demonstrating that X-inactivation cannot be exclusively relied upon to spare the female carriers from symptoms. In conclusion, there is a radiological phenotype associated with Xq28 duplication which clearly demonstrates progressive degenerative cerebellar disease as part of the syndrome.

  11. Vertebral degenerative disc disease severity evaluation using random forest classification

    Science.gov (United States)

    Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.

    2014-03-01

    Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.

  12. Environmental Radon Gas and Degenerative Conditions An Overview

    Energy Technology Data Exchange (ETDEWEB)

    Groves-Kirkby, C.J. [Medical Physics Department, Northampton General Hospital, Northampton NN1 5BD (United Kingdom)]|[School of Health, University of Northampton, Northampton NN2 7AL (United Kingdom); Denman, A.R. [Medical Physics Department, Northampton General Hospital, Northampton NN1 5BD (United Kingdom); Woolridge, A.C. [School of Health, University of Northampton, Northampton NN2 7AL (United Kingdom)]|[School of Applied Sciences, University of Northampton, Northampton NN2 7AL (United Kingdom); Phillips, P.S. [School of Applied Sciences, University of Northampton, Northampton NN2 7AL (United Kingdom); Phillips, C. [School of Health, University of Northampton, Northampton NN2 7AL (United Kingdom)

    2006-07-01

    Radon, a naturally occurring radioactive gas, has variable distribution in the environment as a decay product of uranium occurring in a wide range of rocks, soils and building materials. Although radon dissipates rapidly in outdoor air, it concentrates in the built environment, and inhalation of {sup 222}Rn and its progeny {sup 218}Po and {sup 214}Po is believed to provide the majority of the radioactive dose to the respiratory system. While the connection between radon and lung cancer has long been recognised and investigated, recent studies have highlighted potential links between radon and other conditions, among them Multiple Sclerosis, Alzheimer and Parkinson Diseases, and Paget Disease of Bone. A strong case exists for clarifying the relationship between radon and these other conditions, not least since radon remediation to reduce lung cancer may conceivably have additional benefits hitherto unrecognized. The present status of the postulated links between environmental radon gas and degenerative conditions is reviewed, and recommendations for further research into levering current anti-radon campaigns are made. (authors)

  13. Degenerative Achilles tendon disease; Assessment by magnetic resonance and ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Neuhold, A.; Stiskal, M. (Rudolfinerhaus, Vienna (Austria). Department of Diagnostic Imaging); Kainberger, F.; Schwaighofer, B. (Vienna Univ. (Austria). 2. Medizinische Klinik)

    As Magnetic Resonance (MR) imaging and Ultrasound (US) allow the evaluation of soft-tissue structures not previously possible with other imaging techniques, a clinical study has been undertaken to determine the value of these 2 modalities in the detection of lesions in the Achilles tendon (AT), other than acute total rupture. Seven healthy subjects and 28 symptomatic patients with Achillodynia and/or signs of thickening of the AT were investigated with MR and US; all results were compared with the clinical features. Surgical findings were available in 14 patients. Patients were divided into 3 groups; those with tendon thickening, incomplete and complete ruptures. Thickening of the AT was easily detected with both methods. MR was superior in the detection of incomplete tendon rupture and in the evaluation of various stages of chronic degenerative changes. It is concluded that only if US remains unclear, an additional MR study should be performed and together with the clinical diagnosis indication for surgery can be made more efficient. (author). 24 refs.; 4 figs.

  14. Human pluripotent stem cell models of autism spectrum disorder: emerging frontiers, opportunities, and challenges towards neuronal networks in a dish

    OpenAIRE

    Aigner, Stefan; Heckel, Tobias; Zhang, Jitao D.; Andreae, Laura C.; Jagasia, Ravi

    2013-01-01

    Autism spectrum disorder (ASD) is characterized by deficits in language development and social cognition and the manifestation of repetitive and restrictive behaviors. Despite recent major advances, our understanding of the pathophysiological mechanisms leading to ASD is limited. Although most ASD cases have unknown genetic underpinnings, animal and human cellular models of several rare, genetically defined syndromic forms of ASD have provided evidence for shared pathophysiological mechanisms...

  15. Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease.

    Science.gov (United States)

    Marei, Hany E S; Lashen, Samah; Farag, Amany; Althani, Asmaa; Afifi, Nahla; A, Abd-Elmaksoud; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-07-01

    Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25 ± 2.88%), neuron-like (52.63 ± 4.16%), and astrocyte -like (22.36 ± 1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease. © 2014 Wiley Periodicals, Inc.

  16. Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies.

    Science.gov (United States)

    Nestor, Michael W; Phillips, Andre W; Artimovich, Elena; Nestor, Jonathan E; Hussman, John P; Blatt, Gene J

    2016-05-01

    Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models. Recent progress has implicated numerous autism-risk genes but efforts to gain a better understanding of the underlying biological mechanisms have seen slow progress. This is in part due to lack of appropriate models for complete molecular and pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has reinvigorated efforts to establish more complete model systems that more reliably identify molecular pathways and predict effective drug targets and candidates in ASD. iPSCs are particularly appealing because they can be derived from human patients and controls for research purposes and provide a technology for the development of a personalized treatment regimen for ASD patients. The pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell types and phenotypically screened across many patients. This quality is already being exploited in protocols to generate 2-dimensional (2-D) and three-dimensional (3-D) models of neurons and developing brain structures. iPSC models make powerful platforms that can be interrogated using electrophysiology, gene expression studies, and other cell-based quantitative assays. iPSC technology has limitations but when combined with other model systems has great potential for helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513-535. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  17. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    Science.gov (United States)

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life.

  18. Metallomics studies of human blood serum from treated bipolar disorder patients.

    Science.gov (United States)

    Sussulini, Alessandra; Kratzin, Hartmut; Jahn, Olaf; Banzato, Claudio E Muller; Arruda, Marco A Zezzi; Becker, Johanna Sabine

    2010-07-01

    In the present work, metallomics studies using biomolecular (matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry, MALDI-TOF MS/MS) and elemental mass spectrometry (laser ablation inductively coupled plasma mass spectrometry, LA-ICPMS) of human blood serum samples from bipolar disorder (BD) patients compared to controls were performed. The serum samples from three different groups: control (n = 25), BD patients treated with Li (n = 15), and BD patients not treated with Li (n = 10), were pooled according to their groups and separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Then, in order to determine the metals bound to the protein spots and search for differences among the studied groups, the 2-D gels were analyzed by LA-ICPMS in three distinct modes: bioimaging of metals in gel sections, line scan through the protein spots, and microlocal analysis of selected protein spots. MALDI-TOF MS/MS characterized 32 serum proteins, and they were associated with the metals previously detected. When comparing control and treated BD patient groups, a differentiation in terms of metals bound to proteins was possible to observe. The main metals bound to proteins found in all groups were Na, Mg, Zn, Ca, and Fe. Mn was only detected in the control group; Co was only observed in the control and BD patients treated with Li group. K and Ti were only found in the BD patient groups, and P was only observed in control and BD patients not treated with Li drugs. This exploratory work shows that the association of LA-ICPMS with MALDI-TOF MS/MS is a powerful strategy in metallomics studies applied to determine differences in metal-containing proteins, being able to play an important role on the discovery of potential markers for BD and its treatment with Li in serum samples.

  19. Short term outcome of posterior dynamic stabilization system in degenerative lumbar diseases

    Directory of Open Access Journals (Sweden)

    Mingyuan Yang

    2014-01-01

    Conclusion: Dynamic stabilization system treating lumbar degenerative disease showed clinical benefits with motion preservation of the operated segments, but does not have the significant advantage on motion preservation at adjacent segments, to avoid the degeneration of adjacent intervertebral disk.

  20. Management of degenerative rotator cuff tears: a review and treatment strategy

    Science.gov (United States)

    2012-01-01

    The aim of this review was to present an over view of degenerative rotator cuff tears and a suggested management protocol based upon current evidence. Degenerative rotator cuff tears are common and are a major cause of pain and shoulder dysfunction. The management of these tears is controversial, as to whether they should be managed non-operatively or operatively. In addition when operative intervention is undertaken, there is question as to what technique of repair should be used. This review describes the epidemiology and natural history of degenerative rotator cuff tears. The management options, and the evidence to support these, are reviewed. We also present our preferred management protocol and method, if applicable, for surgical fixation of degenerative rotator cuff tears. PMID:23241147

  1. Echocardiographic Follow-up of Robotic Mitral Valve Repair for Mitral Regurgitation due to Degenerative Disease

    Directory of Open Access Journals (Sweden)

    Yao Wang

    2016-01-01

    Conclusion: Robotic MV repair for MR due to degenerative disease is associated with a low rate of recurrent MR, and a significant improvement in MR grade, LAD, and LVEDD, but a significant decrease in LVEF at echocardiographic follow-up.

  2. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Science.gov (United States)

    2013-06-17

    ... AFFAIRS Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune... Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric... inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis Disability...

  3. When dialogue fails. Music therapy with elderly with neurological degenerative diseases

    DEFF Research Database (Denmark)

    Wigram, Anthony Lewis

    2004-01-01

    When dialogue fails. Music therapy with elderly with neurological degenerative diseases. In persons suffering from neurological degenerative diseases we often see the following symptoms: difficulties in remembering, concentrating, perceiving input, and controlling and timing movements. Normal every...... interaction with others means that psychosocial needs are not met, and this leads to secondary symptoms of the neurological degeneration. Secondary symptoms might be expressed as repetitive behaviour, catastrophic reactions and situationally inappropriate behaviour. In a music therapeutical setting...

  4. Comparison of the diagnostic accuracy of CBCT and conventional CT in detecting degenerative osseous changes of the TMJ: A systematic review

    Directory of Open Access Journals (Sweden)

    Ranjeni Rajamani Veerappan

    2015-01-01

    Full Text Available Temporomandibular joint (TMJ disorders are a group of conditions that cause pain and dysfunction in the jaw joint and muscles that control jaw movement. According to the Research Diagnostic Criteria (RDC/TMD, temporomandibular disorders (TMDs may be classified into three different groups: a myofacial pain dysfunction syndrome (MPDS, b internal derangement, and c arthritis. Complicated anatomy of the TMJ was the reason for developing standardized radiographic techniques to diagnose TMDs. The introduction of computed tomography (CT in the diagnosis of TMJ disorders enabled much better delineation of anatomical structures of the joint due to lack of tissue superposition. Cone beam CT (CBCT is the latest imaging modality for craniofacial deformities, with a lesser radiation exposure and cheaper cost when compared to CT. A systematic literature search was done to identify articles describing degenerative osseous changes of the TMJ using CBCT and conventional CT. Electronic search of scientific papers was carried out in PubMed (MeSH, ScienceDirect, and Cochrane databases using specific keywords. In this systematic review, all the selected articles demonstrate the role of CBCT and CT in diagnosing the degenerative osseous changes of the TMJ. The studies included in the review suggested that CT has been the method of choice to assess the TMJ dynamics and contours of the cortical bone.

  5. Frying process in the relation fat/degenerative diseases.

    Directory of Open Access Journals (Sweden)

    Varela, G.

    1998-08-01

    Full Text Available Among the various components of the diet, fat receives very dose attention because of its relationship to several chronic degenerative diseases (CDD. Currently most of the available information on these relationships is derived from epidemiologic or experimental studies in which lipid intake is calculated using food composition tables. In most of these tables the quoted lipid content is that of raw food, whereas most foods are usually consumed only after being subjected to several culinary processes. Often there is no indication of the type of fat used in food processing in general or in frying in particular. But as it known, in the course of these processes the lipid content undergoes important qualitative and quantitative changes and not keeping them in mind may be the underlying cause of the difficulties an the confounding results in studies trying to establish the relationship between lipid intake an health. In the Mediterranean diet, about 50% of total dietary fat is derived not from the food itself but from the cooking fat, of which only a small fraction is eaten raw (as dressings and the greatest proportion is used in thermal culinary processes, mainly deep-frying. The scientific study of the process whereby fat penetrates into fried foods has shown the benefits of this cooking method. If the process is correctly carried out, the amount of fat ingested with fried foodstuffs is not greater than when other procedures involving fat are used (for example, sautening, stewing or canning in oil. Very schematically deep-frying is a technique that replaces a fraction of the water content of food by cooking fat. Consecuently, the fat composition of the fried lean foods will be the same as that cooking fat. The process is more complex with fatty foods, and there are not great changes in the total quantity of fat in the fried food before and after frying. However, there are notable quality changes and these depend on the concentration gradients

  6. Nerve fiber staining investigations in traumatic and degenerative disc lesions of the wrist.

    Science.gov (United States)

    Unglaub, Frank; Wolf, Maya B; Dragu, Adrian; Schwarz, Stephan; Kroeber, Markus W; Horch, Raymund E

    2011-05-01

    Traumatic and degenerative disc lesions cause ulnar-sided wrist pain. To date, anatomical investigations of cadaver triangular fibrocartilage discs examining the innervation of the triangular fibrocartilage complex have found no evidence of nerve fibers in the healthy disc. In this study, we immunohistologically investigated biopsies from patients with either central traumatic or degenerative disc lesions, to determine the existence of nerve fibers. We hypothesized that an ingrowth of nerve fibers causes ulnar-sided wrist pain associated with traumatic and degenerative disc lesions. We included 32 patients with a traumatic Palmer 1A lesion and 17 patients with a degenerative Palmer 2C lesion in the study. We obtained a biopsy of each patient and stained the specimen with protein gene product 9.5 for nerve fiber detection. There were no nerve fibers in either traumatic or degenerative disc lesions. In addition, the marginal areas of the biopsies showed no evidence of nerve fibers. Traumatic and degenerative disc lesions show no ingrowth of nerve fibers. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  7. Degenerative changes of the sacroiliac auricular joint surface-validation of influential factors.

    Science.gov (United States)

    Nishi, Keita; Saiki, Kazunobu; Imamura, Takeshi; Okamoto, Keishi; Wakebe, Tetsuaki; Ogami, Keiko; Hasegawa, Takashi; Moriuchi, Takefumi; Sakamoto, Junya; Manabe, Yoshitaka; Tsurumoto, Toshiyuki

    2016-06-24

    The purpose of this study was to clarify the relevance of degenerative changes in the sacroiliac joint (SIJ) and the joints in the lower limb and lumbar spine using age estimation methods. We also examined the shape of the auricular surface to determine the effect of degenerative changes on each joint. A total of 200 iliac auricular surfaces from 100 Japanese male skeletons were examined macroscopically in accordance with conventional methods of age estimation. From the obtained estimated age, we calculated the deflection values, which represented the degree of degenerative changes of the joints. For comparison, we used osteophyte score data of the hip, knee, and zygapophyseal joints in lumbar spines from previous studies which had used the same bone specimens. As a quantitative indicator of auricular surface morphology, we defined the constriction ratio (CR) of the auricular surface and compared the CR values obtained with various measured values. Degenerative changes in the SIJ were positively correlated with those in both the hip joint and zygapophyseal joint, but a correlation with knee joints was found only on the left side. In skeletons from individuals aged ≥60 years as time of death, the CR was significantly different between the group with high scores and those with low scores in both the hip and sacroiliac joints. It has been suggested that degenerative changes in SIJs interact with those in the hip joint and zygapophyseal joint. In addition, the shape of the auricular surface may also be a relevant factor for degenerative changes in these joints.

  8. Scaphocapitolunate arthrodesis and radial styloidectomy for posttraumatic degenerative wrist disease.

    Science.gov (United States)

    Klausmeyer, Melissa A; Fernandez, Diego L; Caloia, Martin

    2012-08-01

    Long-standing scaphoid nonunion, scaphoid malunion, and chronic scapholunate dissociation result in malalignment of the carpal bones, progressive carpal collapse, instability, and osteoarthritis of the wrist. The most commonly used procedures to treat scaphoid nonunion advanced collapse (SNAC) and scapholunate advanced collapse (SLAC) wrists are the four-corner fusion (4CF) and the proximal row carpectomy (PRC). The purpose of this study was to evaluate the clinical outcome of a different treatment modality: radial styloidectomy and scaphocapitolunate (SCL) arthrodesis. This treatment option is chosen in an effort to maintain the joint contact surface and load transmission across the radiocarpal joint. We conducted a retrospective review of 20 patients (average age 62 years, range: 27 to 75 years) treated from 1994 to 2010. Seven patients were treated for SNAC, 12 patients for SLAC wrists, and 1 for degenerative joint disease following a transscapho-transcapitate perilunar dislocation. Sixteen patients had Herbert screw fixation, and four had Spider plate fixation. All patients had autologous bone graft used for the arthrodesis. The mean follow-up was 4.6 years (range: 2 to 9.6 years). Patients were evaluated clinically and radiographically. Nineteen of 20 arthrodeses healed on an average of 9.6 weeks. One patient was reoperated 8 months after the initial operation with salvage of the SCL arthrodesis with a spider plate with an adequate result. The mean active flexion-extension arc was 70 degrees and the radioulnar deviation arc was 23 degrees. Pain decreased in all patients, 13 of whom were pain free postoperatively. The average postoperative disabilities of arm, shoulder, and hand score was 24. Radiographically, neither radiolunate nor radioscaphoid arthritis was noted on follow-up. SCL arthrodesis with radial styloidectomy resulted in an adequate residual range of motion and pain relief. This method preserves the normal ulnar sided joints of the carpus and

  9. Degenerative effects in rat eyes after experimental ocular hypertension

    Directory of Open Access Journals (Sweden)

    G. Scarsella

    2012-10-01

    Full Text Available This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs, by means of fluorescein isothiocyanate-coniugated dextran (FITC, the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

  10. Management of degenerative cervical myelopathy – An update

    Directory of Open Access Journals (Sweden)

    ANDREI F. JOAQUIM

    Full Text Available SUMMARY Introduction Degenerative cervical myelopathy (DCM is the most common cause of spinal cord dysfunction in adult patients. Patients generally present with a slow, progressive neurological decline or a stepwise deterioration pattern. In this paper, we discuss the most important factors involved in the management of DCM, including a discussion about the surgical approaches. Method The authors performed an extensive review of the peer-reviewed literature addressing the aforementioned objectives. Results Although the diagnosis is clinical, magnetic resonance imaging (MRI is the study of choice to confirm stenosis and also to exclude the differential diagnosis. The severity the clinical symptoms of DCM are evaluated by different scales, but the modified Japanese Orthopedic Association (mJOA and the Nürick scale are probably the most commonly used. Spontaneous clinical improvement is rare and surgery is the main treatment form in an attempt to prevent further neurological deterioration and, potentially, to provide some improvement in symptoms and function. Anterior, posterior or combined cervical approaches are used to decompress the spinal cord, with adjunctive fusion being commonly performed. The choice of one approach over the other depends on patient characteristics (such as number of involved levels, site of compression, cervical alignment, previous surgeries, bone quality, presence of instability, among others as well as surgeon preference and experience. Conclusion Spine surgeons must understand the advantages and disadvantages of all surgical techniques to choose the best procedure for their patients. Further comparative studies are necessary to establish the superiority of one approach over the other when multiple options are available.

  11. Replacement of Homologous Mouse DNA Sequence With Pathogenic 6-Base Human CREB1 Promoter Sequence Creates Murine Model of Major Depressive Disorder

    OpenAIRE

    Zubenko, George S.; Hughes, Hugh B.

    2011-01-01

    Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Families with Recurrent, Early-Onset MDD (RE-MDD), a severe, familial form of MDD, have provided an important resource for identifying and characterizing genetic variants that confer susceptibility to MDD and related disorders. Previous studies identified a rare, highly penetrant A(-115)G transition within the human CREB1 promoter that reduced promoter activity in vitro and was associated with depressive disorders in ...

  12. Toward psychiatry as a 'human' science of mind. The case of depressive disorders in DSM-5.

    Science.gov (United States)

    Castiglioni, Marco; Laudisa, Federico

    2014-01-01

    The aim of this paper is to argue that a strictly reductionist approach to psychiatry represents a theoretical and clinical obstacle to a fruitful synthesis between neurobiological and sociocultural aspects of the sciences of mind. We examine the theoretical and practical motivations underlying this approach, by analyzing the case of depressive disorders, as defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), and the related removal of the "bereavement exclusion clause." We first explore the claim that DSM is atheoretical, observing that, far from being atheoretical, DSM adopts an implicit, biologically inspired view of the mind; we show that such a view leads to a sort of circularity in the definition of depressive disorders, in which psychopharmacology seems to play a key role. We then turn to further problems deriving from this position, analyzing the issue of placebo effects in the treatment of depressive disorders and the philosophical question of normative preconditions for psychopathological diagnosis. Finally, we address the issue of subjectivity, which, together with the related aspect of the subject's relational context, appears to be crucial to any scientific theorizing about mental disorders, despite DSM's attempt to exclude it. Our defense of a non-reductionist view of mental disorders, however, does not imply that we endorse any sort of metaphysical dualism, or anti-diagnostic or anti-psychiatric positions. On the contrary, we argue that the adoption of a reductionist position actually undermines the theoretical and clinical accuracy in explaining depressive disorders.

  13. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease.

    Science.gov (United States)

    Yu, Ivarosa Bing-Ye; Huang, Hui-Pi

    2016-01-01

    In humans, heart failure (HF) and renal insufficiency (RI) have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD) was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA) class IV HF (33.3%), followed by classes III (15.2%) and II (0%; p 1.6 mg/dL (both p dogs had a shorter median survival [13 months; 95% confidence interval (CI): 0.7-19.1] than nonanemic dogs (28 months; 95% CI: 15.3-40.7; p 1.7 (HR: 2.7, 95% CI: 1.7-4.2; p = 0.001), and presence of anemia (HR: 1.43, 95% CI: 1.1-1.9; p = 0.004) emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD.

  14. Prevalence and Prognosis of Anemia in Dogs with Degenerative Mitral Valve Disease

    Directory of Open Access Journals (Sweden)

    Ivarosa Bing-Ye Yu

    2016-01-01

    Full Text Available In humans, heart failure (HF and renal insufficiency (RI have negative reciprocal effects, and anemia can exacerbate their progression. In this retrospective study, the prevalence and prognostic significance of anemia in 114 dogs with degenerative mitral valve disease (DMVD was investigated. Pretreatment clinical parameters, prevalence of anemia and azotemia, and survival time were analyzed in relation to HF severity. The prevalence of anemia was highest in dogs with the modified New York Heart Association (NYHA class IV HF (33.3%, followed by classes III (15.2% and II (0%; p 1.6 mg/dL (both p 1.7 (HR: 2.7, 95% CI: 1.7–4.2; p = 0.001, and presence of anemia (HR: 1.43, 95% CI: 1.1–1.9; p = 0.004 emerged as predictors of mortality. A cardiorenal-anemia syndrome-like triangle was observed and anemia was a prognostic factor for survival in dogs with DMVD.

  15. Therapeutic potential of human adipose-derived stem cells in neurological disorders.

    Science.gov (United States)

    Chang, Keun-A; Lee, Jun-Ho; Suh, Yoo-Hun

    2014-01-01

    Stem cell therapy has been noted as a novel strategy to various diseases including neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and Huntington's disease that have no effective treatment available to date. The adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency with the ability to differentiate into various types of cells and immuno-modulatory property. These biological features make ASCs a promising source for regenerative cell therapy in neurological disorders. Here we discuss the recent progress of regenerative therapies in various neurological disorders utilizing ASCs.

  16. Clinical Aspects of Temporomandibular Disorders

    OpenAIRE

    2000-01-01

    Temporomandibular disorders are common problems in populations presenting signs and symptoms of muscle and joint pain on palpation, limitations in mandibular motion, joint sounds, pain and locking on mandibular function as well as dental, periodontal, occlusal and psychosocial variables. Problems that involve the temporomandibular joint and related structures include myofacial pain-dysfunction, various internal disarrangements of the joint space and degenerative joint diseases. T...

  17. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clincal Trial

    NARCIS (Netherlands)

    Schrantee, A.; Tamminga, H.G.H.; Bouziane, C.; Bottelier, M.A.; Bron, E.E.; Mutsaerts, H.J.M.M.; Zwinderman, A.H.; Groote, I.R.; Rombouts, S.A.R.B.; Lindauer, R.J.L.; Klein, S.; Niessen, W.J.; Opmeer, B.C.; Boer, F.; Lucassen, P.J.; Andersen, S.L.; Geurts, H.M.; Reneman, L.

    2016-01-01

    Importance: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. Objectives: To determine whether th

  18. Systematic large-scale study of the inheritance mode of Mendelian disorders provides new insight into human diseasome.

    Science.gov (United States)

    Hao, Dapeng; Wang, Guangyu; Yin, Zuojing; Li, Chuanxing; Cui, Yan; Zhou, Meng

    2014-11-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity.

  19. Cross-species genetics converge to TLL2 for mouse avoidance behavior and human bipolar disorder

    NARCIS (Netherlands)

    de Mooij-van Malsen, J G; van Lith, H A; Laarakker, M C; Brandys, M K; Oppelaar, H; Collier, D A; Olivier, B; Breen, G; Kas, M J

    2013-01-01

    Interspecies genetic analysis of neurobehavioral traits is critical for identifying neurobiological mechanisms underlying psychiatric disorders, and for developing models for translational research. Recently, after screening a chromosome substitution strain panel in an automated home cage environmen

  20. Vitreitis and movement disorder associated with neurosyphilis and human immunodeficiency virus (HIV) infection: case report

    OpenAIRE

    2008-01-01

    In this report, we describe an unusual patient with a choreiform movement disorder, misdiagnosed as Huntington disease, who later developed dense vitreitis leading to the identification of Treponema pallidum as the underlying pathogen of both abnormalities.

  1. [Review of 1,172 clinical cases with human communication disorders].

    Science.gov (United States)

    de Díaz, M R; de Pustilnik, N F; Tortolero, Y

    1976-01-01

    The study comprised 1,172 clinical cases that were classified according to sex, age and speech disorders. A review is made on the most common alterations that they present, the selective treatment in each type and their rehabilitation.

  2. A Bayesian analysis of the chromosome architecture of human disorders by integrating reductionist data

    OpenAIRE

    Emmert-Streib, Frank; de Matos Simoes, Ricardo; Tripathi, Shailesh; Glazko, Galina V.; Dehmer, Matthias

    2012-01-01

    In this paper, we present a Bayesian approach to estimate a chromosome and a disorder network from the Online Mendelian Inheritance in Man (OMIM) database. In contrast to other approaches, we obtain statistic rather than deterministic networks enabling a parametric control in the uncertainty of the underlying disorder-disease gene associations contained in the OMIM, on which the networks are based. From a structural investigation of the chromosome network, we identify three chromosome subgrou...

  3. From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and in anxiety disorders

    OpenAIRE

    VanElzakker, Michael B; Dahlgren, M. Kathryn; Davis, F. Caroline; Dubois, Stacey; Shin, Lisa M

    2013-01-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this ...

  4. Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants.

    Science.gov (United States)

    Perkins, Andrew; Xu, Xiangmin; Higgs, Douglas R; Patrinos, George P; Arnaud, Lionel; Bieker, James J; Philipsen, Sjaak

    2016-04-14

    Until recently our approach to analyzing human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, in thalassemia, the globin loci are analyzed. Sequencing has become increasingly accessible, and thus a larger panel of genes can be analyzed and whole exome and/or whole genome sequencing can be used when no variants are found in the candidate genes. By using such approaches in patients with unexplained anemias, we have discovered that a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1, a master regulator of erythropoiesis, which were previously considered to be extremely rare causes of human genetic disease.

  5. Structural basis for triplet repeat disorders

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1999-01-01

    Motivation: Over a dozen major degenerative disorders, including myotonic distrophy, Huntington's disease and fragile X syndrome result from unstable expansions of particular trinucleotides. Remarkably, only some of all the possible triplets, namely CAG/CTG, CGG/CCG and GAA/TTC, have been associa......, which we predict to have very high flexibility, may play a role in the pathogenesis of the neurodegenerative disorder multiple system atrophy (MSA)....

  6. An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials.

    Science.gov (United States)

    Bowers, Mallory E; Ressler, Kerry J

    2015-09-01

    Posttraumatic stress disorder manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Preclinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory that have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for posttraumatic stress disorder that have been developed via a bench to bedside translational model.

  7. TRANSFORAMINAL L U MBAR INTERBODY FUSION IN LOW GRADE COMBINED LYTIC AND DEGENERATIVE SPONDYLOLIDTHESIS : FUNCTIONAL OUTCOME OF 21 CASES

    Directory of Open Access Journals (Sweden)

    Suresh

    2015-10-01

    Full Text Available BACKGROUND: Spondylolisthesis is a heterogenous disorder characterised by subluxation of a vertebral body in sagittal plane occuring frequently at l4 - 5 and l5 - S1commonest being isthmic and degenerative variety. While majority are asymptomatic, a subset do produce pain with neurology. Complete decompression of roots is essential, as is the need for solid stabi lization. Several fusion techniques were reported in literature like PLF, TLIF, PLF, ALIF On theoretical grounds, TLIF has been suggested to be safe and result in an improved outcome compared to other techniques. Data to support this view, are lacking. M ETHODS: A total of 21 patients (age range, 27 - 62 years with adult isthmic and degenerative spondylolisthesis were operated. There were 8 males and 13 females with mean age of 46.8 pre - op and 2 - year follow - up, pain (VAS and functional disability were quan tified by Oswestry Disability Index (ODI.Radiological union assessed with xrays by Brantigen and Steffee criteria. The global outcome was excellent in 90%.and 92% fusion. 2 patients presented motor deficit which did not recover. RESULTS: The follow - up was for 2 years. The mean VAS score for low back pain improved from 7.0 preoperatively to 2.1, as did the mean VAS score for leg pain from 6.7 to 1.4 and the mean ODI from 59.5% to 11.3%. CONCLUSION: TLIF does affect the 2 - year outcome of surgical treatment of spondylolisthesis with decreased back pain and ODI’s, with advantages of minimal thecal retraction, restored segmental lordosis and preserved posterior tension band.

  8. Shining light on the head: Photobiomodulation for brain disorders

    Directory of Open Access Journals (Sweden)

    Michael R. Hamblin

    2016-12-01

    Full Text Available Photobiomodulation (PBM describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia, degenerative diseases (dementia, Alzheimer's and Parkinson's, and psychiatric disorders (depression, anxiety, post traumatic stress disorder. There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM application, near-infrared (NIR light is often applied to the forehead because of the better penetration (no hair, longer wavelength. Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED arrays has allowed the development of light emitting helmets or “brain caps”. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.

  9. Evidence for serotonin function as a neurochemical difference between fear and anxiety disorders in humans?

    Science.gov (United States)

    Corchs, Felipe; Nutt, David J; Hince, Dana A; Davies, Simon J C; Bernik, Marcio; Hood, Sean D

    2015-10-01

    The relationships between serotonin and fear and anxiety disorders have been much studied yet many important questions remain, despite selective serotonin reuptake inhibitors having been the primary treatments for these disorders for some time. In order to explore this issue we performed a pooled analysis of six of our studies in remitted patients with a fear/anxiety disorder who were exposed to syndrome-specific aversive stimulation under acute tryptophan depletion. We based our analysis on the hypothesis that the inconsistencies observed in the studies could be predicted by Deakin and Graeff's theory about the dual role of serotonin in responses to threats, whereby serotonin is critical to prevent fear (panic) but not anxiety. In accordance with this view, our results give support to a dissociation of the disorders traditionally grouped under fear and anxiety-related disorders in terms of different roles of serotonin in modulation of responses to aversive stimulation. Implications for future studies and psychiatric nosology are discussed. © The Author(s) 2015.

  10. Immune responses to viable and degenerative metacestodes of Taenia solium in naturally infected swine.

    Science.gov (United States)

    Singh, Aloukick K; Prasad, Kashi N; Prasad, Amit; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2013-12-01

    Neurocysticercosis, caused by the larvae of the pork tapeworm Taenia solium, is the most common helminth infection of the CNS in humans worldwide. There is no existing animal model of neurocysticercosis that resembles human infection. To overcome this limitation, swine (the natural intermediate host of the parasite) may be a suitable model. The immune response associated with different stages of the parasite larva (metacestode) has not yet been explored. Therefore, we investigated the immune response to various stages of the metacestode (cyst) in the brain and muscles of naturally infected swine. Swine with neurocysticercosis (n = 10) and healthy controls (n = 10), as confirmed by magnetic resonance imaging, were included in this study. The animals were sacrificed, and the tissues containing viable or degenerative metacestods in the brain and infected muscles were collected and subjected to reverse transcriptase-PCR and ELISA to determine the expression of different cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4 IL-6, IL-8 and IL-10). Higher expression of IL-10 was found to be associated with viable cysts. Degenerating cysts displayed significantly increased levels of IFN-γ, TNF-α, IL-1β, IL-2, IL-6 and IL-8, whereas calcified cysts had elevated levels of IL-4, IL-10, TNF-α and IL-6. The present study indicated a strong regulatory (IL-10) and Th1 cytokine response in viable and degenerating cysts, respectively, whereas calcified cysts had a mixed anti-inflammatory (IL-4), regulatory (IL-10) and pro-inflammatory (TNF-α and IL-6) response. Thus, Th1 and Th2 immune response operate in the vicinity of metacestodes and the type of immune response may be responsible for disease severity.

  11. Hyper-reactive human ventral tegmental area and aberrant mesocorticolimbic connectivity in overgeneralization of fear in generalized anxiety disorder.

    Science.gov (United States)

    Cha, Jiook; Carlson, Joshua M; Dedora, Daniel J; Greenberg, Tsafrir; Proudfit, Greg H; Mujica-Parodi, Lilianne R

    2014-04-23

    The ventral tegmental area (VTA) has been primarily implicated in reward-motivated behavior. Recently, aberrant dopaminergic VTA signaling has also been implicated in anxiety-like behaviors in animal models. These findings, however, have yet to be extended to anxiety in humans. Here we hypothesized that clinical anxiety is linked to dysfunction of the mesocorticolimbic circuit during threat processing in humans; specifically, excessive or dysregulated activity of the mesocorticolimbic aversion circuit may be etiologically related to errors in distinguishing cues of threat versus safety, also known as "overgeneralization of fear." To test this, we recruited 32 females with generalized anxiety disorder and 25 age-matched healthy control females. We measured brain activity using fMRI while participants underwent a fear generalization task consisting of pseudo-randomly presented rectangles with systematically varying widths. A mid-sized rectangle served as a conditioned stimulus (CS; 50% electric shock probability) and rectangles with widths of CS ±20%, ±40%, and ±60% served as generalization stimuli (GS; never paired with electric shock). Healthy controls showed VTA reactivity proportional to the cue's perceptual similarity to CS (threat). In contrast, patients with generalized anxiety disorder showed heightened and less discriminating VTA reactivity to GS, a feature that was positively correlated with trait anxiety, as well as increased mesocortical and decreased mesohippocampal coupling. Our results suggest that the human VTA and the mesocorticolimbic system play a crucial role in threat processing, and that abnormalities in this system are implicated in maladaptive threat processing in clinical anxiety.

  12. LONG-TERM OUTCOMES OF RETINAL DEGENERATIVE DISORDER TREATMENT WITH PEPTIDE BIOREGULATORS

    Directory of Open Access Journals (Sweden)

    M. I. Razumovskiy

    2015-01-01

    Full Text Available Aim. To analyze long-term outcomes and efficacy of retinal degeneration treatment with Retinalamin.Patients and methods. Group I included 20 patients (40 eyes with pigmentary retinal dystrophy (15 patients, 30 eyes and retinal abiotrophy (5 patients, 10 eyes who received treatment with Retinalamin for 5‑7 years. Group II included 11 patients (22 eyes with pigmentary retinal dystrophy (9 patients, 18 eyes and retinal abiotrophy (2 patients, 4 eyes who received treatment with Retinalamin for 23‑25 years. Group III (controls included 15 patients (30 eyes with pigmentary retinal dystrophy (11 patients, 22 eyes and retinal abiotrophy (4 patients, 8 eyes who received traditional treatment (vasodilators, angioprotectors, antisclerotic agents, vitamins for 25 years. Standard ophthalmological examination, i.e., visual acuity measurement, visual field test, refractometry, biomicroscopy, ophthalmoscopy, was performed.Results. First course of treatment with Retinalamin improved vision in 58.1 % of retinal degeneration patients. Visual fields improved in 64.5 % of cases. Repeated treatment courses (1‑2 times a year for 23‑25 years preserved residual vision in 55.6 % of patients and object vision in 11.1 % of cases. In retinal abiotrophy patients, residual vision preserved in 100 % of cases.Conclusions. In retinal degenerations, Retinalamin improves vision and visual fields and decreases total area of absolute scotomas even after the first treatment course as well as preserves vision in prolonged use. 

  13. A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

    Science.gov (United States)

    Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

    2016-11-01

    Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease.

  14. Experience of human rights violations and subsequent mental disorders - a study following the war in the Balkans.

    Science.gov (United States)

    Priebe, Stefan; Bogic, Marija; Ashcroft, Richard; Franciskovic, Tanja; Galeazzi, Gian Maria; Kucukalic, Abdulah; Lecic-Tosevski, Dusica; Morina, Nexhmedin; Popovski, Mihajlo; Roughton, Michael; Schützwohl, Matthias; Ajdukovic, Dean

    2010-12-01

    War experiences are associated with substantially increased rates of mental disorders, particularly Post-Traumatic Stress Disorder (PTSD) and Major Depression (MD). There is limited evidence on what type of war experiences have particularly strong associations with subsequent mental disorders. Our objective was to investigate the association of violations of human rights, as indicated in the 4th Geneva Convention, and other stressful war experiences with rates of PTSD and MD and symptom levels of intrusion, avoidance and hyperarousal. In 2005/6, human rights violations and other war experiences, PTSD, post-traumatic stress symptoms and MD were assessed in war affected community samples in five Balkan countries (Bosnia-Herzegovina, Croatia, Kosovo, Macedonia, and Serbia) and refugees in three Western European countries (Germany, Italy, United Kingdom). The main outcome measures were the MINI International Neuropsychiatric Interview and the Impact of Event Scale-Revised. In total 3313 participants in the Balkans and 854 refugees were assessed. Participants reported on average 2.3 rights violations and 2.3 other stressful war experiences. 22.8% of the participants were diagnosed with current PTSD and also 22.8% had MD. Most war experiences significantly increased the risk for both PTSD and MD. When the number of rights violations and other stressful experiences were considered in one model, both were significantly associated with higher risks for PTSD and were significantly associated with higher levels of intrusion, avoidance and hyperarousal. However, only the number of violations, and not of other stressful experiences, significantly increased the risk for MD. We conclude that different types of war experiences are associated with increased prevalence rates of PTSD and MD more than 5 years later. As compared to other stressful experiences, the experience of human rights violations similarly increases the risk of PTSD, but appears more important for MD. Copyright

  15. Active Reward Processing during Human Sleep: Insights from Sleep-Related Eating Disorder.

    Science.gov (United States)

    Perogamvros, Lampros; Baud, Patrick; Hasler, Roland; Cloninger, Claude Robert; Schwartz, Sophie; Perrig, Stephen

    2012-01-01

    In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED), a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography, a dream diary and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  16. Active reward processing during human sleep: insights from sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Lampros ePerogamvros

    2012-11-01

    Full Text Available In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED, a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity on reward-related questionnaires. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  17. Disorders of the lower cranial nerves

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2015-01-01

    Full Text Available Lesions of the lower cranial nerves (LCN are due to numerous causes, which need to be differentiated to optimize management and outcome. This review aims at summarizing and discussing diseases affecting LCN. Review of publications dealing with disorders of the LCN in humans. Affection of multiple LCN is much more frequent than the affection of a single LCN. LCN may be affected solely or together with more proximal cranial nerves, with central nervous system disease, or with nonneurological disorders. LCN lesions have to be suspected if there are typical symptoms or signs attributable to a LCN. Causes of LCN lesions can be classified as genetic, vascular, traumatic, iatrogenic, infectious, immunologic, metabolic, nutritional, degenerative, or neoplastic. Treatment of LCN lesions depends on the underlying cause. An effective treatment is available in the majority of the cases, but a prerequisite for complete recovery is the prompt and correct diagnosis. LCN lesions need to be considered in case of disturbed speech, swallowing, coughing, deglutition, sensory functions, taste, or autonomic functions, neuralgic pain, dysphagia, head, pharyngeal, or neck pain, cardiac or gastrointestinal compromise, or weakness of the trapezius, sternocleidomastoid, or the tongue muscles. To correctly assess manifestations of LCN lesions, precise knowledge of the anatomy and physiology of the area is required.

  18. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Directory of Open Access Journals (Sweden)

    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  19. Minimal Access Spinal Technologies (Mast Fusion Procedures For The Treatment Of The Degenerative Lumbar Spine (A Part Of Multicentral Prospective Study

    Directory of Open Access Journals (Sweden)

    Khoshab A.H.

    2014-05-01

    Full Text Available A prospective multicentral observational study of minimally invasive fusion to treat degenerative lumbar disorders, and to report outcomes of one or two level minimally invasive posterior lumbar interbody fusion (MLIF for degenerative lumbar disorders in a multi-center 1-year prospective study. We prospectively studied a group of 32 patients, mostly female 24 ( 75% female , and 8 males ( 25%. They underwent minimally invasive transforaminal lumbar interbody fusion (mTLIF, 21 of them monosegmental and 11 bisegmental. Patients demographics, intraoperative data and complications were recorded. Time to first ambulation, time to study-defined recovery, surgical duration, blood loss, fluoroscopy time and adverse events were recorded. Visual analogue scale (VAS of back and legs pain, Oswestry disability index (ODI and health-related questionnaire (EQ-5D were assessed preoperatively and at defined time points through 12 months postoperatively. Mean surgical duration, blood loss and intraoperative fluoroscopy time were 125 vs.175 minutes, 150 vs. 170 ml, and 105 vs. 145 seconds in one- and twolevel segments, respectively. Mean preoperative VAS back (6.5 and VAS leg (7.9 scores dropped significantly (p<0.0001 to 3.5 (2.6 and 2.1 (2.0 at discharge (6 weeks. At the end, this is the largest prospective multi-center observational study of MLIF to date, following routine local standard of practice and, MLIF demonstrated favourable clinical results with early and sustained improvement in patient reported outcomes and low major perioperative morbidity.

  20. Three Different Methods in Deformity Correction of Degenerative Flat Back: A Single Surgeon's Experience with 64 Consecutive Cases

    OpenAIRE

    Kim, Ki-Tack; Lee, Sang-Hun; Lee, Jung-Hee; Kang, Kyung-Jung; Lee, Jung-Suk; Son, Eun-Seok

    2015-01-01

    Study Design Retrospective study. Purpose To evaluate the radiological and clinical results of three different methods in the deformity correction of a degenerative flat back. Overview of Literature There are no comparative studies about different procedures in the treatment of degenerative flat back. Methods Sixty-four patients who consecutively underwent corrective surgery for degenerative flat back were reviewed. The operations were performed by three different methods: posterior-only (gro...

  1. Intervertebral disc degeneration and bone density in degenerative lumbar scoliosis: a comparative study between patients with degenerative lumbar scoliosis and patients with lumbar stenosis

    Institute of Scientific and Technical Information of China (English)

    DING Wen-yuan; YANG Da-long; CAO Lai-zhen; SUN Ya-peng; ZHANG Wei; XU Jia-xin; ZHANG Ying-ze; SHEN Yong

    2011-01-01

    Background Degenerative lumbar scoliosis is common in older patients.Decreased bone density and the degeneration of intervertebral discs are considered to be correlated with degenerative lumbar scoliosis.A means of quantifying the relative signal intensity for degenerative disc disease has not been previously discussed.The purpose of this study was to compare bone mineral density and intervertebral disc degeneration between degenerative lumbar scoliosis and lumbar spinal stenosis patients in a nine-year retrospective study.Methods From January 2001 to August 2010,96 patients with degenerative lumbar scoliosis were retrospectively enrolled and 96 patients with lumbar spinal stenosis were selected as controls.Cobb angle,height of the apical disc and the contiguous disc superiorly and inferiorly on convex and concave sides,the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly were measured in the scoliosis group.The height of L2/L3,L3/L4,L4/L5 discs and the height of L2/L4 vertebral body was measured in the control group.The grade of intervertebral disc degeneration was evaluated using T2WI sagittal images in both groups.The bone density of lumbar vertebrae was measured with dual-energy X-ray.Results In scoliosis group,the intervertebral disc height on the convex side was greater than the height on the concave side (P <0.001 ).The vertebral body height on the convex side was greater than the height on the concave side (P=0.016).There was a significant difference between the scoliosis group and the control group (P=0.003),and between T-value and the rate of osteoporosis between the two groups (both P <0.001).Results were verified using multiple linear regression analysis.Conclusions Degenerative lumbar scoliosis is accompanied by height asymmetry between the intervertebral disc and vertebral body regarding the convex and concave surfaces.There is a positive correlation between the angle of scoliosis and

  2. Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies

    Science.gov (United States)

    Brondino, Natascia; Fusar-Poli, Laura; Panisi, Cristina; Damiani, Stefano; Barale, Francesco; Politi, Pierluigi

    2016-01-01

    Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic…

  3. A human phenome-interactome network of protein complexes implicated in genetic disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Karlberg, Erik, Olof, Linnart; Størling, Zenia, Marian

    2007-01-01

    the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type...

  4. Dissecting spatio-temporal protein networks driving human heart development and related disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Mølgård, Kjeld; Greenway, Steven

    2010-01-01

    Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ devel...

  5. Sagittal spinopelvic parameters in 2-level lumbar degenerative spondylolisthesis

    Science.gov (United States)

    Wang, Tao; Wang, Hui; Liu, Huan; Ma, Lei; Liu, Feng-Yu; Ding, Wen-Yuan

    2016-01-01

    Abstract The purpose of our study is to evaluate sagittal parameters in 2-level lumbar degenerative spondylolisthesis (DS) (TLDS). A total of 15 patients with TLDS, 40 patients with single-level DS (SLDS), and 30 normal volunteers as control were included in our study. All subjects performed on full spine X-ray. Two categorized data were analyzed: patient characteristics—age, sex, body mass index, radiographic parameters-pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), sacral slope (SS), PI–LL, Cobb between the fifth thoracic vertebral and 12th thoracic vertebral (T5–T12), sagittal vertical axis (SVA) Cobb angle of spondylolisthesis level (CSL), ratio of PT to SS (PT/SS), CSL/LL, variation trend of SS over PI, and LL over PI. The PI (73.1° vs 52.9°), SS (50.8° vs 32.2°), LL (53.1° vs 46.9°), SVA (66.1 vs 22.0 mm), PI–LL (20.0° vs 6.0°), and CSL (23.6° vs 20.0°) in TLDS were significantly larger than these in SLDS. The PI (73.1° vs 40.6°), PT (22.3° vs 17.1°), SS (50.8° vs 23.5°), LL (53.1° vs 32.5°), PI–LL (20.0° vs 8.1°), and SVA (66.1 vs 17.0 mm) in TLDS were significantly larger than those in the normal group (NG). The PI (52.9° vs 40.6°), PT (21.0° vs 17.1°), SS (32.2° vs 23.5°), LL (46.9° vs 32.5°), and SVA (22.0 vs 17.0 mm) in SLDS were significantly higher than those in NG. However, PT/SS (44.0%), LL over PI (y = 0.39x + 24.25), SS over PI (y = 10.79 + 0.55x) were lower in TLDS than these in SLDS (63.8%, y = 0.41x + 25, y = 0.65x − 2.09, respectively), and the similar tend between SLDS and NG (74.0%, y = 0.49x + 13.09, y = 0.67x − 3.9, respectively). Our results showed that 2-level lumbar DS, which was caused by multiple-factors, has a severe sagittal imbalance, but single-level has not any. When we plan for surgical selection for 2-level lumbar DS, global sagittal balance must be considered. PMID:27977581

  6. Radiographic distinction of degenerative slippage (spondylolisthesis and retrolisthesis) from traumatic slippage of the cervical spine

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.; Woodring, J.H.; Rogers, L.F.; Kim, K.S.

    1986-08-01

    In a review of 42 cases of degenerative arthritis of the cervical spine and 22 cases of cervical spine trauma with an observed anterior slip-page (spondylolisthesis) or posterior slippage (retrolisthesis) of the vertebral bodies of 2 mm or more, characteristic features were observed which allowed distinction between degenerative and traumatic slippage of the cervical spine. In degenerative slippage the shape of the articular facets and width of the facet joint space may remain normal; however, in most cases the articular facets become 'ground-down' with narrowing of the facet joint space and the articular facets themselves becoming thinned or ribbon-like. In traumatic slippage the articular facets will either be normally shaped or fractured and the facet joint space will be abnormally widened. Plain radiographs will usually allow this distinction to be made; however, in difficult cases polytomography may be required.

  7. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    Science.gov (United States)

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion.

  8. Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques

    Science.gov (United States)

    Ibrahim, Michael; Rao, Christopher; Athanasiou, Thanos

    2012-01-01

    The surgical repair of degenerative mitral valve disease involves a number of technical points of importance. The use of artificial chordae for the repair of degenerative disease has increased as a part of the move from mitral valve replacement to repair of the mitral valve. The use of artificial chordae provides an alternative to the techniques pioneered by Carpentier (including the quadrangular resection, transfer of native chordae and papillary muscle shortening/plasty), which can be more technically difficult. Despite a growth in their uptake and the indications for their use, a number of challenges remain for the use of artificial chordae in mitral valve repair, particularly in the determination of the correct length to ensure optimal leaflet coaptation. Here, we analyse over 40 techniques described for artificial chordae mitral valve repair in the setting of degenerative disease. PMID:22962321

  9. When dialogue fails. Music therapy with elderly with neurological degenerative diseases

    DEFF Research Database (Denmark)

    Wigram, Anthony Lewis

    2004-01-01

    traces in the brain. Using the same “hello-song” in the beginning of a session - session after session - gives stability. Stability is constancy and familiarity of cues over time (Roberts & Algase 1988), and even people with severe memory deficits are capable of creating new memory traces and of learning......When dialogue fails. Music therapy with elderly with neurological degenerative diseases. In persons suffering from neurological degenerative diseases we often see the following symptoms: difficulties in remembering, concentrating, perceiving input, and controlling and timing movements. Normal every...... degenerative disease like e.g. dementia are often socially isolated because of their failing abilities to communicate. Even if they live in a facility and are surrounded by care staff and peer residents, they might experience the environment as chaotic and the people as non-comprehensible. A missing meaningful...

  10. Association of Pre-Pregnancy Body Mass Index, Pregnancy-Related Weight Changes, and Parity With the Risk of Developing Degenerative Musculoskeletal Conditions

    DEFF Research Database (Denmark)

    Bliddal, Mette; Pottegård, Anton; Kirkegaard, Helene;

    2016-01-01

    Objective To examine how pre-pregnancy body mass index (BMI), parity, and pregnancy-related weight changes are associated with long-term risk of degenerative musculoskeletal conditions. Methods A total of 79,687 mothers with singleton births from the Danish National Birth Cohort were included....... Information on height and weight prior to pregnancy and 6 months postpartum as well as gestational weight gain (GWG) was obtained from telephone interviews, while parity was derived from the Danish Medical Birth Registry. Diagnoses of musculoskeletal conditions, including osteoarthritis, disc disorders, low...... back pain, and soft tissue disorders, were obtained from the Danish National Patient Registry. Hazard ratios (HRs) were estimated using a Cox proportional hazards regression model. Results The cumulative incidence of musculoskeletal conditions during a median follow-up of 12.4 years was 19.7%. The risk...

  11. Lumbar degenerative spinal deformity: Surgical options of PLIF, TLIF and MI-TLIF

    Directory of Open Access Journals (Sweden)

    Hey Hwee Weng

    2010-01-01

    Full Text Available Degenerative disease of the lumbar spine is common in ageing populations. It causes disturbing back pain, radicular symptoms and lowers the quality of life. We will focus our discussion on the surgical options of posterior lumbar interbody fusion (PLIF and transforaminal lumbar interbody fusion (TLIF and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF for lumbar degenerative spinal deformities, which include symptomatic spondylolisthesis and degenerative scoliosis. Through a description of each procedure, we hope to illustrate the potential benefits of TLIF over PLIF. In a retrospective study of 53 ALIF/PLIF patients and 111 TLIF patients we found reduced risk of vessel and nerve injury in TLIF patients due to less exposure of these structures, shortened operative time and reduced intra-operative bleeding. These advantages could be translated to shortened hospital stay, faster recovery period and earlier return to work. The disadvantages of TLIF such as incomplete intervertebral disc and vertebral end-plate removal and potential occult injury to exiting nerve root when under experienced hands are rare. Hence TLIF remains the mainstay of treatment in degenerative deformities of the lumbar spine. However, TLIF being a unilateral transforaminal approach, is unable to decompress the opposite nerve root. This may require contralateral laminotomy, which is a fairly simple procedure.The use of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF to treat degenerative lumbar spinal deformity is still in its early stages. Although the initial results appear promising, it remains a difficult operative procedure to master with a steep learning curve. In a recent study comparing 29 MI-TLIF patients and 29 open TLIF, MI-TLIF was associated with longer operative time, less blood loss, shorter hospital stay, with no difference in SF-36 scores at six months and two years. Whether it can replace traditional TLIF as the surgery of

  12. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys

    Science.gov (United States)

    Bromet, E. J.; Atwoli, L.; Kawakami, N.; Navarro-Mateu, F.; Piotrowski, P.; King, A. J.; Aguilar-Gaxiola, S.; Alonso, J.; Bunting, B.; Demyttenaere, K.; Florescu, S.; de Girolamo, G.; Gluzman, S.; Haro, J. M.; de Jonge, P.; Karam, E. G.; Lee, S.; Kovess-Masfety, V.; Medina-Mora, M. E.; Mneimneh, Z.; Pennell, B.-E.; Posada-Villa, J.; Salmerón, D.; Takeshima, T.; Kessler, R. C.

    2017-01-01

    Background Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20–40% range in disaster-focused studies but considerably lower (3–5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. Method Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). Results Disaster-related PTSD prevalence was 0.0–3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. Conclusion Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions. PMID:27573281

  13. Activator-induced dynamic disorder and molecular memory in human two-pore domain hTREK1 K channel.

    Science.gov (United States)

    Nayak, Tapan Kumar; Dana, Saswati; Raha, Soumyendu; Sikdar, Sujit K

    2011-04-01

    Ion channels are fundamental molecules in the nervous system that catalyze the flux of ions across the cell membrane. Ion channel flux activity is comparable to the catalytic activity of enzyme molecules. Saturating concentrations of substrate induce "dynamic disorder" in the kinetic rate processes of single-enzyme molecules and consequently, develop correlative "memory" of the previous history of activities. Similarly, binding of ions as substrate alone or in presence of agonists affects the catalytic turnover of single-ion channels. Here, we investigated the possible existence of dynamic disorder and molecular memory in the single human-TREK1-channel due to binding of substrate/agonist using the excised inside-out patch-clamp technique. Our results suggest that the single-hTREK1-channel behaves as a typical Michaelis-Menten enzyme molecule with a high-affinity binding site for K(+) ion as substrate. But, in contrast to enzyme, dynamic disorder in single-hTREK1-channel was not induced by substrate K(+) binding, but required allosteric modification of the channel molecule by the agonist, trichloroethanol. In addition, interaction of trichloroethanol with hTREK1 induced strong correlation in the waiting time and flux intensity, exemplified by distinct mode-switching between high and low flux activities. This suggested the induction of molecular memory in the channel molecule by the agonist, which persisted for several decades in time. Our mathematical modeling studies identified the kinetic rate processes associated with dynamic disorder. It further revealed the presence of multiple populations of distinct conformations that contributed to the "heterogeneity" and consequently, to the molecular memory phenomenon that we observed. The online version of this article (doi:10.1007/s12154-010-0053-3) contains supplementary material, which is available to authorized users.

  14. Sexual Risk Behaviors Constructed in Iranian Women's Life with Substance Use Disorders: A New Implication of Human Ecological Theory.

    Science.gov (United States)

    Jamshidimanesh, Mansoureh; Mousavi, Seyed Abbas; Merghati-Khoei, Effat; Emamian, Mohammad Hassan; Keramat, Afsaneh

    2016-07-01

    Drug abuse is one of the important variables influencing protective sexual behavior. The objective of this study was to explore how risky sexual behaviors develop in drug abusing women using human ecological theory. In this study, we used a descriptive exploratory approach. The participants were 32 drug abusing women from two of the selected drop-in centers (DICs) in south Tehran, Iran, where we could have access to a vast number of female drug users. Data was collected using semi-structured face-to-face interviews. Qualitative content analysis was used to analyze the data using Graneheim and Lundman procedure. Risky sexual behavior in drug use disorders in women was found in four themes with thirteen emerged; sexual untaught at micro-system with two subthemes "unsafe home" and "drop out of school", Perception of differences at meso-system with three subthemes "lack of link between family and school", "doing manly behavior" and "low awareness of health puberty than peers", inappropriate marriages at exo-system with three subthemes "stigma", "fear of losing love relationship" and "self-devotion", marginalization at macro-system with four subthemes "barrier access to rights", "selling sex as a tool of security", "lack of belief as a sex worker" and "mistrust and doubt partner" using implication of human ecological theory. Findings suggest that strategies supporting the discovery of risky sexual behaviors in drug use disorders in women are important in order to provide counseling and education to form their decisions toward safety sex.

  15. Mesenchymal Stem Cell Secretome: A Potential Tool for the Prevention of Muscle Degenerative Changes Associated With Chronic Rotator Cuff Tears.

    Science.gov (United States)

    Sevivas, Nuno; Teixeira, Fábio Gabriel; Portugal, Raquel; Araújo, Luís; Carriço, Luís Filipe; Ferreira, Nuno; Vieira da Silva, Manuel; Espregueira-Mendes, João; Anjo, Sandra; Manadas, Bruno; Sousa, Nuno; Salgado, António J

    2016-08-08

    Massive rotator cuff tears (MRCTs) are usually chronic lesions with pronounced degenerative changes, where advanced fatty degeneration and atrophy can make the tear irreparable. Human mesenchymal stem cells (hMSCs) secrete a range of growth factors and vesicular systems, known as secretome, that mediates regenerative processes in tissues undergoing degeneration. To study the effect of hMSC secretome on muscular degenerative changes and shoulder function on a rat MRCT model. Controlled laboratory study. A bilateral 2-tendon (supraspinatus and infraspinatus) section was performed to create an MRCT in a rat model. Forty-four Wistar-Han rats were randomly assigned to 6 groups: control group (sham surgery), lesion control group (MRCT), and 4 treated-lesion groups according to the site and periodicity of hMSC secretome injection: single local injection, multiple local injections, single systemic injection, and multiple systemic injections. Forelimb function was analyzed with the staircase test. Atrophy and fatty degeneration of the muscle were evaluated at 8 and 16 weeks after injury. A proteomic analysis was conducted to identify the molecules present in the hMSC secretome that can be associated with muscular degeneration prevention. When untreated for 8 weeks, the MRCT rats exhibited a significantly higher fat content (0.73% ± 0.19%) compared with rats treated with a single local injection (0.21% ± 0.04%; P muscle atrophy, 8 weeks after injury, only the single local injection group (0.0993% ± 0.0036%) presented a significantly higher muscle mass than that of the untreated MRCT group (0.0794% ± 0.0047%; P muscle regeneration, namely, pigment epithelium-derived factor and follistatin. The study data suggest that hMSC secretome effectively decreases the fatty degeneration and atrophy of the rotator cuff muscles. We describe a new approach for decreasing the characteristic muscle degeneration associated with chronic rotator cuff tears. This strategy is particularly

  16. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2...... ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions...... of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we...

  17. MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If

    OpenAIRE

    Schenk, Barbara; Imbach, Timo; Frank, Christian G.; Grubenmann, Claudia E.; Raymond, Gerald V.; Hurvitz, Haggit; Raas-Rotschild, Annick; Luder, Anthony S.; Berger, Eric G.; Matthijs, Gert; Hennet, Thierry; Aebi, Markus; Jaeken, Jaak

    2003-01-01

    Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients’ fibroblasts accumulated incomplete lipid-linked...

  18. Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis

    OpenAIRE

    2010-01-01

    The rapidly emerging science of epigenetics and epigenomic medicine promises to reveal novel insights into the susceptibility to and the onset and progression of epileptic disorders. Epigenetic regulatory mechanisms are now implicated in orchestrating aspects of neural development (e.g., cell fate specification and maturation), homeostasis and stress responses (e.g., immediate early gene transcription), and neural network function (e.g., excitation-inhibition coupling and activity-dependent p...

  19. [Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

    Science.gov (United States)

    Polo Rodríguez, Rosa; Galindo Puerto, María José; Dueñas, Carlos; Gómez Candela, Carmen; Estrada, Vicente; Villar, Noemí G P; Locutura, Jaime; Mariño, Ana; Pascua, Javier; Palacios, Rosario; von Wichmman, Miguel Ángel; Álvarez, Julia; Asensi, Victor; Lopez Aldeguer, José; Lozano, Fernando; Negredo, Eugenia; Ortega, Enrique; Pedrol, Enric; Gutiérrez, Félix; Sanz Sanz, Jesús; Martínez Chamorro, Esteban

    2015-01-01

    This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    Science.gov (United States)

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  1. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders.

    Science.gov (United States)

    Ye, Zhaohui; Zhan, Huichun; Mali, Prashant; Dowey, Sarah; Williams, Donna M; Jang, Yoon-Young; Dang, Chi V; Spivak, Jerry L; Moliterno, Alison R; Cheng, Linzhao

    2009-12-24

    Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.

  2. Effect of posterior subsidence on cervical alignment after anterior cervical corpectomy and reconstruction using titanium mesh cages in degenerative cervical disease.

    Science.gov (United States)

    Jang, Jae-Won; Lee, Jung-Kil; Lee, Jung-Heon; Hur, Hyuk; Kim, Tae-Wan; Kim, Soo-Han

    2014-10-01

    Subsidence after anterior cervical reconstruction using a titanium mesh cage (TMC) has been a matter of debate. The authors investigated and analyzed subsidence and its effect on clinical and radiologic parameters after cervical reconstruction using a TMC for degenerative cervical disease. Thirty consecutive patients with degenerative cervical spine disorders underwent anterior cervical corpectomy followed by reconstruction with TMC. Twenty-four patients underwent a single-level corpectomy, and six patients underwent a two-level corpectomy. Clinical outcomes were assessed using a Visual Analogue Scale (VAS), the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). Fusion status, anterior and posterior subsidence of the TMC, segmental angle (SA) and cervical sagittal angle (CSA) were assessed by lateral and flexion-extension radiographs of the neck. The mean follow-up period was 27.6 months (range, 24 to 49 months). The VAS, NDI and JOA scores were all significantly improved at the last follow-up. No instances of radiolucency or motion-related pseudoarthrosis were detected on radiographic analysis, yielding a fusion rate of 100%. Subsidence occurred in 28 of 30 patients (93.3%). The average anterior subsidence of the cage was 1.4 ± 0.9 mm, and the average posterior subsidence was 2.9 ± 1.2 mm. The SA and CSA at the final follow-up were significantly increased toward a lordotic angle. Anterior cervical reconstruction using TMC and plating in patients with cervical degenerative disease provides good clinical and radiologic outcomes. Cage subsidence occurred frequently, especially at the posterior part of the cage. Despite the prominent posterior subsidence of the TMC, SA and CSA were improved on final follow-up radiographs, suggesting that posterior subsidence may contribute to cervical lordosis.

  3. Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model.

    Directory of Open Access Journals (Sweden)

    Geoffroy Nourissat

    Full Text Available BACKGROUND: The enthesis, which attaches the tendon to the bone, naturally disappears with aging, thus limiting joint mobility. Surgery is frequently needed but the clinical outcome is often poor due to the decreased natural healing capacity of the elderly. This study explored the benefits of a treatment based on injecting chondrocyte and mesenchymal stem cells (MSC in a new rat model of degenerative enthesis repair. METHODOLOGY: The Achilles' tendon was cut and the enthesis destroyed. The damage was repaired by classical surgery without cell injection (group G1, n = 52 and with chondrocyte (group G2, n = 51 or MSC injection (group G3, n = 39. The healing rate was determined macroscopically 15, 30 and 45 days later. The production and organization of a new enthesis was assessed by histological scoring of collagen II immunostaining, glycoaminoglycan production and the presence of columnar chondrocytes. The biomechanical load required to rupture the bone-tendon junction was determined. PRINCIPAL FINDINGS: The spontaneous healing rate in the G1 control group was 40%, close to those observed in humans. Cell injection significantly improved healing (69%, p = 0.0028 for G2 and p = 0.006 for G3 and the load-to-failure after 45 days (p<0.05 over controls. A new enthesis was clearly produced in cell-injected G2 and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an organized enthesis with columnar chondrocytes as in a native enthesis 45 days after surgery. CONCLUSIONS: Cell therapy is an efficient procedure for reconstructing degenerative entheses. MSC treatment produced better organ regeneration than chondrocyte treatment. The morphological and biomechanical properties were similar to those of a native enthesis.

  4. Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Ramesh Menon

    Full Text Available BACKGROUND: Genome-wide association studies (gwas are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz. CONCLUSIONS/SIGNIFICANCE: The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.

  5. Human sex-determination and disorders of sex-development (DSD).

    Science.gov (United States)

    Bashamboo, Anu; McElreavey, Ken

    2015-09-01

    Several new genes and pathways have been identified in recent years associated with human errors of sex-determination or DSD. SOX family gene mutations, as well as mutations involving GATA4, FOG2 and genes involved in MAP kinase signaling have been associated with virilization in 46,XX individuals or with 46,XY gonadal dysgenesis. Furthermore, mutations involving another key gene in sex-determination, NR5A1, are now known to be an important cause spermatogenic failure in the male and ovarian insufficiency in the female. These new findings offer insights into human sex-determination and highlight important differences between the human and mouse model. This review will critically examine the evidence linking gene mutations, especially MAP3K1, to non-syndromic forms of human 46,XY gonadal dysgenesis or XX testicular/ovotesticular.

  6. Echocardiographic and clinical outcomes of central versus noncentral percutaneous edge-to-edge repair of degenerative mitral regurgitation

    DEFF Research Database (Denmark)

    Estévez-Loureiro, Rodrigo; Franzen, Olaf; Winter, Reidar;

    2013-01-01

    This study aimed to assess the clinical and echocardiographic results of MitraClip implantation in noncentral degenerative mitral regurgitation (dMR) compared with central dMR.......This study aimed to assess the clinical and echocardiographic results of MitraClip implantation in noncentral degenerative mitral regurgitation (dMR) compared with central dMR....

  7. Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

    Directory of Open Access Journals (Sweden)

    Jinyoung Won

    2017-06-01

    Full Text Available Fragile X syndrome (FXS is the most common monogenic form of autism spectrum disorder (ASD. FXS with ASD results from the loss of fragile X mental retardation (fmr gene products, including fragile X mental retardation protein (FMRP, which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

  8. Pathophysiology of movement disorders due to gravity transitions: the channelopathy linkage in human balance and locomotion.

    Science.gov (United States)

    Rizzo-Sierra, Carlos V; Leon-Sarmiento, Fidias E

    2011-07-01

    Despite theoretical and experimental efforts to understand the space adaptation syndrome (SAS), which is responsible for spatial disorientation that severely affects physical and cognitive performance in astronauts, most of its pathophysiology is still unknown. As a consequence, countermeasures for SAS are not completely effective. Accordingly, in addition to the sensory-motor conflict theories, we propose that microgravity would affect the potassium channels of inner ear hair cells that would result in a temporal channelopathy as the most likely molecular origin for SAS, as well as being responsible for perpetuating movement disorders in gravity transition environments including those to be experienced by people visiting or living on the earth, moon, mars and beyond.

  9. Computer-aided diagnosis of knee-joint disorders via vibroarthrographic signal analysis: a review.

    Science.gov (United States)

    Wu, Yunfeng; Krishnan, Sridhar; Rangayyan, Rangaraj M

    2010-01-01

    The knee is the lower-extremity joint that supports nearly the entire weight of the human body. It is susceptible to osteoarthritis and other knee-joint disorders caused by degeneration or loss of articular cartilage. The detection of a knee-joint abnormality at an early stage is important, because it helps increase therapeutic options that may slow down the degenerative process. Imaging-based arthrographic modalities can provide anatomical images of the joint cartilage surfaces, but fail to demonstrate the functional integrity of the cartilage. Knee-joint auscultation, by means of recording the vibroarthrographic (VAG) signal during bending motion of a knee, could be used to develop a noninvasive diagnostic tool. Computer-aided analysis of VAG signals could provide quantitative indices for screening of degenerative conditions of the cartilage surface and staging of osteoarthritis. In addition, the diagnosis of knee-joint pathology by means of VAG signal analysis may reduce the number of semi-invasive diagnostic arthroscopic examinations. This article reviews studies related to VAG signal analysis, first summarizing the pilot studies that demonstrated the diagnostic potential of knee-joint auscultation for the detection of degenerative diseases, and then describing the details of recent progress in analysis of VAG signals using temporal analysis, frequency-domain analysis, time-frequency analysis, and statistical modeling. The decision-making methods used in the related studies are summarized, followed by a comparison of the diagnostic performance achieved by different pattern classifiers. The final section is a perspective on the future and further development of VAG signal analysis.

  10. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

    Directory of Open Access Journals (Sweden)

    Sinha K K

    1999-01-01

    Full Text Available Twenty-four cases of sporadic olivo-ponto-cerebellar atrophy (OPCA of adult onset were studied over a period of two years. Results suggest that this disorder has its usual onset in the 5th and 6th decade of life with a male: female ratio of 2:1. It manifests clinically with gait ataxia in all, dysarthria, other cerebellar signs and autonomic involvement in vast majority. There were features of basal ganglia involvement in some. No known identifiable environmental cause was found and genetically they are quite distinct from the known autosomal dominant spinocerebellar ataxias though sporadic occurrence in recessive inheritance or a de novo mutation could not be ruled out completely, but it is unlikely.

  11. Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy

    NARCIS (Netherlands)

    M. de Mos (Marieke)

    2009-01-01

    textabstractTendon injuries are common in human athletes [1-4]. Furthermore, such injuries are also prevalent in the ageing sedentary population [5-7]. In recent decades, the incidence of tendon injuries has risen due to both an increase in an elderly population and a rise in participation in recrea

  12. Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy

    NARCIS (Netherlands)

    M. de Mos (Marieke)

    2009-01-01

    textabstractTendon injuries are common in human athletes [1-4]. Furthermore, such injuries are also prevalent in the ageing sedentary population [5-7]. In recent decades, the incidence of tendon injuries has risen due to both an increase in an elderly population and a rise in participation in recrea

  13. Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy

    NARCIS (Netherlands)

    M. de Mos (Marieke)

    2009-01-01

    textabstractTendon injuries are common in human athletes [1-4]. Furthermore, such injuries are also prevalent in the ageing sedentary population [5-7]. In recent decades, the incidence of tendon injuries has risen due to both an increase in an elderly population and a rise in participation

  14. Clinical and molecular analysis of human reproductive disorders in Brazilian patients

    Directory of Open Access Journals (Sweden)

    A.C. Latronico

    2004-01-01

    Full Text Available Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

  15. Is risk of degenerative musculoskeletal conditions associated with pre-pregnancy body mass index and parity?

    DEFF Research Database (Denmark)

    Bliddal, Mette; Pottegård, Anton; Kirkegaard, Helene

    Background Obesity among women may influence the risk of degenerative musculoskeletal conditions (MSCs) and contribute to poor quality of life. Parity, which constitutes a sudden natural increase in weight as well it affects long-term body mass index (BMI), may put strain on the musculoskeletal s...

  16. The role of stem cell therapies in degenerative lumbar spine disease: a review.

    Science.gov (United States)

    Oehme, David; Goldschlager, Tony; Rosenfeld, Jeffrey V; Ghosh, Peter; Jenkin, Graham

    2015-07-01

    Degenerative conditions of the lumbar spine are extremely common. Ninety percent of people over the age of 60 years have degenerative change on imaging; however, only a small minority of people will require spine surgery (Hicks et al. Spine (Phila Pa 1976) 34(12):1301-1306, 2009). This minority, however, constitutes a core element of spinal surgery practice. Whilst the patient outcomes from spinal surgeries have improved in recent years, some patients will remain with pain and disability despite technically successful surgery. Advances in regenerative medicine and stem cell therapies, particularly the use of mesenchymal stem cells and allogeneic mesenchymal precursor cells, have led to numerous clinical trials utilising these cell-based therapies to treat degenerative spinal conditions. Through cartilage formation and disc regeneration, fusion enhancement or via modification of pain pathways, stem cells are well suited to enhance spinal surgery practice. This review will focus on the outcomes of lumbar spinal procedures and the role of stem cells in the treatment of degenerative lumbar conditions to enhance clinical practice. The current status of clinical trials utilising stem cell therapies will be discussed, providing clinicians with an overview of the various cell-based treatments likely to be available to patients in the near future.

  17. Clinical outcome of stand-alone ALIF compared to posterior instrumentation for degenerative disc disease

    DEFF Research Database (Denmark)

    Udby, Peter M.; Bech-Azeddine, Rachid

    2015-01-01

    low back pain resulting from degenerative disc disease. ALIF surgery has previously been linked with certain high risk complications and unfavorable long term fusion results. Newer studies suggest that stand-alone ALIF can possibly be advantageous compared to other types of posterior instrumented...

  18. Teaching Early Braille Literacy Skills within a Stimulus Equivalence Paradigm to Children with Degenerative Visual Impairments

    Science.gov (United States)

    Toussaint, Karen A.; Tiger, Jeffrey H.

    2010-01-01

    Despite the need for braille literacy, there has been little attempt to systematically evaluate braille-instruction programs. The current study evaluated an instructive procedure for teaching early braille-reading skills with 4 school-aged children with degenerative visual impairments. Following a series of pretests, braille instruction involved…

  19. Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Md. Asiful Islam

    2016-01-01

    Full Text Available Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA, diabetes mellitus (DM, and cardiovascular disease (CVD. Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

  20. No publication bias in industry funded clinical trials of degenerative diseases of the spine.

    Science.gov (United States)

    Son, Colin; Tavakoli, Samon; Bartanusz, Viktor

    2016-03-01

    Industry sponsorship of clinical research of degenerative diseases of the spine has been associated with excessive positive published results as compared to research carried out without industry funding. We sought the rates of publication of clinical trials of degenerative diseases of the spine based on funding source as a possible explanation for this phenomenon. We reviewed all clinical trials registered at clinicaltrials.gov relating to degenerative diseases of the spine as categorized under six medical subject heading terms (spinal stenosis, spondylolisthesis, spondylolysis, spondylosis, failed back surgery syndrome, intervertebral disc degeneration) and with statuses of completed or terminated. These collected studies were categorized as having, or not having, industry funding. Published results for these studies were then sought within the clinicaltrials.gov database itself, PubMed and Google Scholar. One hundred sixty-one clinical trials met these criteria. One hundred nineteen of these trials had industry funding and 42 did not. Of those with industry funding, 45 (37.8%) had identifiable results. Of those without industry funding, 17 (40.5%) had identifiable results. There was no difference in the rates of publication of results from clinical trials of degenerative diseases of the spine no matter the funding source.

  1. Comparing surgical repair with conservative treatment for degenerative rotator cuff tears : a randomized controlled trial

    NARCIS (Netherlands)

    Lambers Heerspink, Okke; van Raay, Jos J. A. M.; Koorevaar, Rinco C. T.; van Eerden, Pepijn J. M.; Westerbeek, Robin E.; van 't Riet, Esther; van den Akker-Scheek, Inge; Diercks, Ronald L.

    2015-01-01

    Background: Good clinical results have been reported for both surgical and conservative treatment of rotator cuff tears. The primary aim of this randomized controlled trial was to compare functional and radiologic improvement after surgical and conservative treatment of degenerative rotator cuff tea

  2. Temporomandibular degenerative joint disease. Part I. Anatomy, pathophysiology, and clinical description.

    Science.gov (United States)

    Kreutziger, K L; Mahan, P E

    1975-08-01

    The anatomy and function of the temporomandibular joint (TMJ) are described in the detail needed to evaluate and treat temporomandibular degenerative joint disease (TDJD). Innervation of the joint and the mechanism of arthralgia are described and related to TDJD. The clinical course of TDJD, radiographic evaluation of it, histopathologic description, and etiology are presented.

  3. Physiotherapy in degenerative cerebellar ataxias: utilisation, patient satisfaction, and professional expertise

    NARCIS (Netherlands)

    Fonteyn, E.M.R.; Keus, S.H.J.; Verstappen, C.C.P.; Warrenburg, B.P.C. van de

    2013-01-01

    Physiotherapy plays an important role in the management of patients with degenerative cerebellar ataxias. However, our insight in the quantity and quality of physiotherapy prescription in this group of patients is incomplete. The purposes of this study were to investigate the utilization of physioth

  4. Intraosseouss degenerative cyst of the axis approached via transcervical extrapharyngeal avenue

    Directory of Open Access Journals (Sweden)

    Gustavo Rassier Isolan

    2012-01-01

    Full Text Available Intraosseous degenerative cysts (IDC of the cervical spine are rare. IDC within C2 have been reported in three articles only. We report a patient with neck pain due to a IDC within C2. We discuss the differential diagnosis of these lesions and the surgical approaches to reach this complex anatomical region.

  5. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Directory of Open Access Journals (Sweden)

    Matthis Synofzik

    2014-01-01

    Full Text Available The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”. The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability. Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease.

  6. Comparing surgical repair with conservative treatment for degenerative rotator cuff tears : a randomized controlled trial

    NARCIS (Netherlands)

    Lambers Heerspink, Okke; van Raay, Jos J. A. M.; Koorevaar, Rinco C. T.; van Eerden, Pepijn J. M.; Westerbeek, Robin E.; van 't Riet, Esther; van den Akker-Scheek, Inge; Diercks, Ronald L.

    Background: Good clinical results have been reported for both surgical and conservative treatment of rotator cuff tears. The primary aim of this randomized controlled trial was to compare functional and radiologic improvement after surgical and conservative treatment of degenerative rotator cuff

  7. A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome

    Directory of Open Access Journals (Sweden)

    Sonal eGoswami

    2012-06-01

    Full Text Available Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situation known to precipitate PTSD in humans. This study aimed to assess whether the hippocampus-associated deficits observed in the human syndrome are reproduced in this rodent model. Prior to predatory threat, different groups of rats were each tested on one of three object recognition memory tasks that varied in the types of contextual clues (i.e. that require the hippocampus or not the rats could use to identify novel items. After task completion, the rats were subjected to predatory threat and, one week later, tested on the elevated plus maze. Based on their exploratory behavior in the plus maze, rats were then classified as resilient or PTSD-like and their performance on the pre-threat object recognition tasks compared. The performance of PTSD-like rats was inferior to that of resilient rats but only when subjects relied on an allocentric frame of reference to identify novel items, a process thought to be critically dependent on the hippocampus. Therefore, these results suggest that even prior to trauma, PTSD-like rats show a deficit in hippocampal-dependent functions, as reported in twin studies of human PTSD.

  8. Interest towards human, animal and object in children with autism spectrum disorders: an ethological approach at home.

    Science.gov (United States)

    Grandgeorge, Marine; Bourreau, Yannig; Alavi, Zarrin; Lemonnier, Eric; Tordjman, Sylvie; Deleau, Michel; Hausberger, Martine

    2015-01-01

    Autistic spectrum disorders (ASD) are characterised by attention deficits in communication and social interactions and a lack of interest in people. Data are mostly based on clinical situations. However, recent studies have shown a more mixed situation where children with ASD (ASD children) displayed interest towards humans, in both experimental and natural settings. The aim of this study was to assess the interest of ASD children in a natural standardised home setting. Here, we hypothesised that ASD children would display more interest towards animate stimuli-human and pet-when in the child's home than in the lab experimental setting. We used an ethological approach involving observations, a methodological alternative to lab static techniques, to investigate the behaviour of ninety 6- to 12-year-old ASD and typical development (TD) children. Our results were consistent with those of the literature revealing that the ASD children displayed interest towards animate stimuli as did children with TD children. Interestingly, while the ASD children showed higher interest towards humans, e.g. their parent, than the TD children did, they showed less interest towards pet compared to the TD children. Our results suggested that animals are not inherently easy to decode for ASD children, in contrast with previous experiences where a pet was regarded as a more attractive partner, easier to be understood. At last, the ASD children changed more frequently their focus point than the TD children did. These differences may be explained by the reduced attention skills in ASD or the study's context. To conclude, larger exploratory studies in natural settings conducted beyond ordinary human to human interactions are crucial for better understanding of the underlying mechanisms involved in social interactions in ASD.

  9. Early-life risk factors for panic and separation anxiety disorder: insights and outstanding questions arising from human and animal studies of CO2 sensitivity.

    Science.gov (United States)

    Battaglia, Marco; Ogliari, Anna; D'Amato, Francesca; Kinkead, Richard

    2014-10-01

    Genetically informative studies showed that genetic and environmental risk factors act and interact to influence liability to (a) panic disorder, (b) its childhood precursor separation anxiety disorder, and (c) heightened sensitivity to CO2, an endophenotype common to both disorders. Childhood adversities including parental loss influence both panic disorder and CO2 hypersensitivity. However, childhood parental loss and separation anxiety disorder are weakly correlated in humans, suggesting the presence of alternative pathways of risk. The transferability of tests that assess CO2 sensitivity - an interspecific quantitative trait common to all mammals - to the animal laboratory setting allowed for environmentally controlled studies of early parental separation. Animal findings paralleled those of human studies, in that different forms of early maternal separation in mice and rats evoked heightened CO2 sensitivity; in mice, this could be explained by gene-by-environment interactional mechanisms. While several questions and issues (including obvious divergences between humans and rodents) remain open, parallel investigations by contemporary molecular genetic tools of (1) human longitudinal cohorts and (2) animals in controlled laboratory settings, can help elucidate the mechanisms beyond these phenomena.

  10. Lumbar spine degenerative disease : effect on bone mineral density measurements in the lumbar spine and femoral neck

    Energy Technology Data Exchange (ETDEWEB)

    Juhng, Seon Kwan [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of); Koplyay, Peter; Jeffrey Carr, J.; Lenchik, Leon [Wake Forest Univ. School of Medicine, Winston-salem (United States)

    2001-04-01

    To determine the effect of degenerative disease of the lumbar spine on bone mineral density in the lumbar spine and femoral neck. We reviewed radiographs and dual energy x-ray absorptiometry scans of the lumbar spine and hip in 305 Caucasian women with suspected osteoporosis. One hundred and eight-six patient remained after excluding women less than 40 years of age (n=18) and those with hip osteoarthritis, scoliosis, lumbar spine fractures, lumbar spinal instrumentation, hip arthroplasty, metabolic bone disease other than osteoporosis, or medications known to influence bone metabolism (n=101). On the basis of lumbar spine radiographs, those with absent/mild degenerative disease were assigned to the control group and those with moderate/severe degenerative disease to the degenerative group. Spine radiographs were evaluated for degenerative disease by two radiologists working independently; discrepant evaluations were resolved by consensus. Lumbar spine and femoral neck bone mineral density was compared between the two groups. Forty-five (24%) of 186 women were assigned to the degenerative group and 141 (76%) to the control group. IN the degenerative group, mean bone mineral density measured 1.075g/cm? in the spine and 0.788g/cm{sup 2} in the femoral neck, while for controls the corresponding figures were 0.989g/cm{sup 2} and 0.765g/cm{sup 2}. Adjusted for age, weight and height by means of analysis of variance, degenerative disease of the lumbar spine was a significant predictor of increased bone mineral density in the spine (p=0.0001) and femoral neck (p=0.0287). Our results indicate a positive relationship between degenerative disease of the lumbar spine and bone mineral density in the lumbar spine and femoral neck, and suggest that degenerative disease in that region, which leads to an intrinsic increase in bone mineral density in the femoral neck, may be a good negative predictor of osteoporotic hip fractures.

  11. Disorders related to sexuality and gender identity in the ICD-11: revising the ICD-10 classification based on current scientific evidence, best clinical practices, and human rights considerations.

    Science.gov (United States)

    Reed, Geoffrey M; Drescher, Jack; Krueger, Richard B; Atalla, Elham; Cochran, Susan D; First, Michael B; Cohen-Kettenis, Peggy T; Arango-de Montis, Iván; Parish, Sharon J; Cottler, Sara; Briken, Peer; Saxena, Shekhar

    2016-10-01

    In the World Health Organization's forthcoming eleventh revision of the International Classification of Diseases and Related Health Problems (ICD-11), substantial changes have been proposed to the ICD-10 classification of mental and behavioural disorders related to sexuality and gender identity. These concern the following ICD-10 disorder groupings: F52 Sexual dysfunctions, not caused by organic disorder or disease; F64 Gender identity disorders; F65 Disorders of sexual preference; and F66 Psychological and behavioural disorders associated with sexual development and orientation. Changes have been proposed based on advances in research and clinical practice, and major shifts in social attitudes and in relevant policies, laws, and human rights standards. This paper describes the main recommended changes, the rationale and evidence considered, and important differences from the DSM-5. An integrated classification of sexual dysfunctions has been proposed for a new chapter on Conditions Related to Sexual Health, overcoming the mind/body separation that is inherent in ICD-10. Gender identity disorders in ICD-10 have been reconceptualized as Gender incongruence, and also proposed to be moved to the new chapter on sexual health. The proposed classification of Paraphilic disorders distinguishes between conditions that are relevant to public health and clinical psychopathology and those that merely reflect private behaviour. ICD-10 categories related to sexual orientation have been recommended for deletion from the ICD-11.

  12. Disorders related to sexuality and gender identity in the ICD‐11: revising the ICD‐10 classification based on current scientific evidence, best clinical practices, and human rights considerations

    Science.gov (United States)

    Reed, Geoffrey M.; Drescher, Jack; Krueger, Richard B.; Atalla, Elham; Cochran, Susan D.; First, Michael B.; Cohen‐Kettenis, Peggy T.; Arango‐de Montis, Iván; Parish, Sharon J.; Cottler, Sara; Briken, Peer; Saxena, Shekhar

    2016-01-01

    In the World Health Organization's forthcoming eleventh revision of the International Classification of Diseases and Related Health Problems (ICD‐11), substantial changes have been proposed to the ICD‐10 classification of mental and behavioural disorders related to sexuality and gender identity. These concern the following ICD‐10 disorder groupings: F52 Sexual dysfunctions, not caused by organic disorder or disease; F64 Gender identity disorders; F65 Disorders of sexual preference; and F66 Psychological and behavioural disorders associated with sexual development and orientation. Changes have been proposed based on advances in research and clinical practice, and major shifts in social attitudes and in relevant policies, laws, and human rights standards. This paper describes the main recommended changes, the rationale and evidence considered, and important differences from the DSM‐5. An integrated classification of sexual dysfunctions has been proposed for a new chapter on Conditions Related to Sexual Health, overcoming the mind/body separation that is inherent in ICD‐10. Gender identity disorders in ICD‐10 have been reconceptualized as Gender incongruence, and also proposed to be moved to the new chapter on sexual health. The proposed classification of Paraphilic disorders distinguishes between conditions that are relevant to public health and clinical psychopathology and those that merely reflect private behaviour. ICD‐10 categories related to sexual orientation have been recommended for deletion from the ICD‐11. PMID:27717275

  13. Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Masato; Wynn, R. Max; Chuang, Jacinta L.; Tso, Shih-Chia; Machius, Mischa; Li, Jun; Chuang, David T. (UTSMC)

    2009-09-11

    We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-{alpha} (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-{alpha} prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-{alpha}, which nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.

  14. Diagnostical and statistical manual of mental disorders- fifth edition- dsm-5, statistics and human sciences: inflections on normalization and standartization

    Directory of Open Access Journals (Sweden)

    Tito Sena

    2014-12-01

    Full Text Available http://dx.doi.org/10.5007/1807-1384.2014v11n2p96The edition of the Diagnostical and Statistical Manual of Mental Disorders – Fifth Edition- DSM-5 in 2013 remains on the controversy about psychiatric diagnoses. The field of psychiatry, historically at odds with psychology and psychoanalysis (as the form evaluation and therapeutic, continues to sustain a classificatory (taxonomic quadrate practice, based on characteristics and diagnostic criteria of disturbances or verified disorders, mostly empirically. The use of statistical tools in the human sciences is questionable, and what is intended in this article is to point the guise of quantitative criteria in qualitative criteria and, by extension, the common discursive practice of confusing descriptions with appreciations, the latter with evaluative and normative judgments. A circle is closed: the frequencies (statistics define the normalities (axiological and these are sustained in frequencies. In this context, the elaborations of Canguilhem, Ewald, Foucault and Goffman were essential to the articulation of critical theoretical arguments.

  15. [Drinking water hardness and chronic degenerative diseases. II. Cardiovascular diseases].

    Science.gov (United States)

    Monarca, S; Zerbini, I; Simonati, C; Gelatti, U

    2003-01-01

    Since the 1950s a causal relation between water hardness and cardiovascular diseases (CVD) in humans has been hypothesized. In order to evaluate the influence of calcium and magnesium, the minerals responsible for the hardness of drinking water, on human health, a review of all the articles published on the subject from 1980 up to today has been carried out. Many but not all geographic correlation studies showed an inverse association between water hardness and mortality for CVD. Most case-control and one cohort studies showed an inverse relation, statistically significant, between mortality from CVD and water levels of magnesium, but not calcium. Consumption of water containing high concentrations of magnesium seems to reduce of about 30-35% the mortality for CVD, but not the incidence. This inverse association is supported by clinical and experimental findings and is biologically plausible and in line with Hill's criteria for a cause-effect relationship.

  16. Complications and outcomes of surgery for degenerative lumbar deformity in elderly patients

    Directory of Open Access Journals (Sweden)

    Kim HJ

    2013-12-01

    Full Text Available Hyo Jong Kim, Kyu Yeol Lee, Lih WangDepartment of Orthopaedic Surgery, College of Medicine, Dong-A University, Busan, KoreaBackground: The purpose of this study was to analyze the complications, clinical outcomes, and any correlative risk factors associated with degenerative lumbar deformity surgery in elderly patients.Methods: We reviewed 78 patients who underwent posterior decompression and posterolateral fusion requiring a minimum three-level fusion for degenerative lumbar deformity associated with spinal stenosis between May 2001 and May 2006, with at least a one-year follow-up period. We assessed and compared the postoperative complications and clinical outcomes for patients aged 65 years and over (group A and patients aged 50–64 years (group B. Risk factors that could influence complications and clinical outcome were evaluated and statistically analyzed.Results: The postoperative complication rate was not significantly different between the two age groups (53% in group A and 40% in group B; however, group A had a significantly higher frequency of minor complications than group B, especially for urinary retention and postoperative delirium. A statistical relationship between diabetes mellitus and deep wound infection, one of the major complications of degenerative lumbar deformity surgery, was observed in both group A and group B. Male sex was a risk factor for urinary retention and long operative time, and abundant blood loss was a significant risk factor for postoperative delirium in group A.Conclusion: There were no significant differences in results for degenerative lumbar deformity surgery between patients older and younger than 65 years. However, diabetes mellitus showed a significant correlation with deep wound infection, which is one of the major complications of degenerative lumbar deformity surgery, and with urinary retention and postoperative delirium, which occurred frequently in patients aged older than 65 years

  17. Outcomes and Complications of Diabetes Mellitus on Patients Undergoing Degenerative Lumbar Spine Surgery

    Science.gov (United States)

    Guzman, Javier Z.; Iatridis, James C.; Skovrlj, Branko; Cutler, Holt; Hecht, Andrew C.; Qureshi, Sheeraz A.; Cho, Samuel K.

    2014-01-01

    Study Design Retrospective database analysis. Objective To assess the effect glycemic control has on perioperative morbidity and mortality in patients undergoing elective degenerative lumbar spine surgery. Summary of background data Diabetes Mellitus (DM) is a prevalent disease of glucose dysregulation that has been demonstrated to increase morbidity and mortality following spine surgery. However, there is limited understanding of whether glycemic control influences surgical outcomes in DM patients undergoing lumbar spine procedures for degenerative conditions. Methods The Nationwide Inpatient Sample was analyzed from 2002 to 2011. Hospitalizations were isolated based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for lumbar spine surgery and diagnoses codes for degenerative conditions of the lumbar spine. Patients were then classified into three cohorts: controlled diabetics, uncontrolled diabetics and non-diabetics. Patient demographic data, acute complications and hospitalization outcomes were determined for each cohort. Results A total of 403,629 (15.7%) controlled diabetics and 19,421(0.75%) uncontrolled diabetics underwent degenerative lumbar spine surgery from 2002-2011. Relative to non-diabetics, uncontrolled diabetics had significantly increased odds of cardiac complications, deep venous thrombosis and post-operative shock; additionally, uncontrolled diabetics also had an increased mean length of stay (approximately 2.5 days), greater costs (1.3-fold) and a greater risk of inpatient mortality (odds ratio=2.6, 95% confidence interval=1.5-4.8, p degenerative lumbar spine surgery leads to increased risk of acute complications and poor outcomes. Patients with uncontrolled DM, or poor glucose control, may benefit from improving glycemic control prior to surgery. PMID:24983935

  18. Congenital Cervical Fusion as a Risk Factor for Development of Degenerative Cervical Myelopathy.

    Science.gov (United States)

    Nouri, Aria; Martin, Allan R; Lange, Stefan F; Kotter, Mark R N; Mikulis, David J; Fehlings, Michael G

    2017-04-01

    Congenital fusion of cervical vertebrae, including Klippel-Feil syndrome (KFS), is a suspected risk factor for development of degenerative cervical myelopathy (DCM). We aimed to establish prevalence and degenerative patterns of congenital cervical fusion (CCF) among a global cohort of patients with DCM. Data from 3 prospective DCM studies were merged, including clinical data for 813 patients and imaging for 592 patients. CCF was diagnosed by presence of fused cervical vertebrae without signs of degenerative fusion. A wasp-waist sign was used to define a KFS subgroup. Characteristics of patients with CCF and the KFS subgroup were compared with the remainder of patients with DCM. Twenty-three patients with CCF (14 KFS) were identified, indicating a prevalence of 3.9% (2.4% KFS). Patients with CCF were older (P = 0.02), had more operated levels (P = 0.01), had higher rates of ossified posterior longitudinal ligament (P = 0.02), and demonstrated worse degenerative changes at C3-4, including spinal cord compression (P = 0.002) and T2 weighted image T2WI signal hyperintensity (P = 0.04). Levels adjacent to fusions showed a trend toward increased spinal cord compression (P = 0.09), with fusions at C3-4 or above showing cord compression below in 9 of 10 patients, fusions at C5-6 or below having cord compression above in 8 of 8 patients, and fusions at C4-5 showed cord compression above and below in 2 of 2 patients. The prevalence of CCF and KFS is higher in DCM than for the general population, suggesting that these patients are predisposed to DCM development. Patients with CCF also have an altered pattern of degenerative changes, seemingly related to adjacent segment degeneration that preferentially affects midcervical levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Diffusion tensor imaging differentiates vascular parkinsonism from parkinsonian syndromes of degenerative origin in elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Deverdun, Jérémy [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Laboratoire Charles Coulomb, CNRS UMR 5221 - Université Montpellier II, Montpellier (France); I2FH, Institut d’Imagerie Fonctionnelle Humaine, Hôpital Gui de Chauliac, CHRU de, Montpellier (France); Menjot de Champfleur, Sophie [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Clinique du Parc, Castelnau-le-Lez (France); Cabello-Aguilar, Simon [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); I2FH, Institut d’Imagerie Fonctionnelle Humaine, Hôpital Gui de Chauliac, CHRU de, Montpellier (France); Maury, Florence [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Molino, François [Laboratoire Charles Coulomb, CNRS UMR 5221 - Université Montpellier II, Montpellier (France); Institut de Génomique Fonctionnelle, UMR 5203 - INSERM U661 - Université Montpellier II - Université, Montpellier I (France); Charif, Mahmoud [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Leboucq, Nicolas [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Ayrignac, Xavier; Labauge, Pierre [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); and others

    2014-11-15

    Background and Purpose: The etiologic diagnosis of parkinsonian syndromes is of particular importance when considering syndromes of vascular or degenerative origin. The purpose of this study is to find differences in the white-matter architecture between those two groups in elderly patients. Materials and Methods: Thirty-five patients were prospectively included (multiple-system atrophy, n = 5; Parkinson's disease, n = 15; progressive supranuclear palsy, n = 9; vascular parkinsonism, n = 6), with a mean age of 76 years. Patients with multiple-system atrophy, progressive supranuclear palsy and Parkinson's disease were grouped as having parkinsonian syndromes of degenerative origin. Brain MRIs included diffusion tensor imaging. Fractional anisotropy and mean-diffusivity maps were spatially normalized, and group analyses between parkinsonian syndromes of degenerative origin and vascular parkinsonism were performed using a voxel-based approach. Results: Statistical parametric-mapping analysis of diffusion tensor imaging data showed decreased fractional anisotropy value in internal capsules bilaterally in patients with vascular parkinsonism compared to parkinsonian syndromes of degenerative origin (p = 0.001) and showed a lower mean diffusivity in the white matter of the left superior parietal lobule (p = 0.01). Fractional anisotropy values were found decreased in the middle cerebellar peduncles in multiple-system atrophy compared to Parkinson's disease and progressive supranuclear palsy. The mean diffusivity was increased in those regions for these subgroups. Conclusion: Clinically defined vascular parkinsonism was associated with decreased fractional anisotropy in the deep white matter (internal capsules) compared to parkinsonian syndromes of degenerative origin. These findings are consistent with previously published neuropathological data.

  20. Human testicular insulin-like factor 3: in relation to development, reproductive hormones and andrological disorders

    DEFF Research Database (Denmark)

    Bay, K; Andersson, A-M

    2011-01-01

    the endocrine regulation of this process. INSL3 is, along with testosterone, a major secretory product of testicular Leydig cells. In addition to its crucial function in testicular descent, INSL3 is suggested to play a paracrine role in germ cell survival and an endocrine role in bone metabolism. INSL3......, steroidogenic effects of LH, which for example is an important factor in the regulation of testosterone. Clinically, serum INSL3 levels can turn out to be a usable tool to monitor basal Leydig cell function in patients with various disorders affecting Leydig cell function. According to animal studies, foetal...... INSL3 production is, directly or indirectly, sensitive to oestrogenic or anti-androgenic compounds. This provides important insight into the mechanism by which maternal exposure to endocrine disrupters can result in cryptorchidism in the next generation. Conclusively, INSL3 is an interesting testicular...

  1. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    Science.gov (United States)

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  2. Vitamin A derivatives as treatment options for retinal degenerative diseases.

    Science.gov (United States)

    Perusek, Lindsay; Maeda, Tadao

    2013-07-12

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

  3. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Tadao Maeda

    2013-07-01

    Full Text Available The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT and retinal pigment epithelium-specific 65-kDa protein (RPE65 known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA and retinitis pigmentosa (RP. Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

  4. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten;

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  5. [Development and the developmental disorders of human brain. I. Early development of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Wesseling, P.; Lammens, M.M.Y.; Renier, W.O.; Mullaart, R.A.; Thijssen, H.O.M.

    2001-01-01

    The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early

  6. Leveraging Small Aquarium Fishes to Advance Understanding of Environmentally Influenced Human Disorders and Diseases

    Science.gov (United States)

    Small aquarium fishes provide a model organism that recapitulates the development, physiology and specific disease processes present in humans without the many limitations of rodent-based models currently in use. Fish models offer advantages in cost, rapid life-cycles, and extern...

  7. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

    Science.gov (United States)

    Miller, Walter L; Auchus, Richard J

    2011-02-01

    Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.

  8. Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND.

    Directory of Open Access Journals (Sweden)

    Venkata Subba Rao Atluri

    Full Text Available HIV-associated neurocognitive disorders (HAND is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B, which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold down-regulated and 5 genes were significantly (≥3 fold up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1 was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of

  9. Human protein C: new preparations. Effective replacement therapy for some clotting disorders.

    Science.gov (United States)

    2003-02-01

    (1) Depending on its severity, congenital protein C deficiency can cause a variety of problems, such as increasing the frequency of venous thrombosis in high risk situations; recurrent venous thrombosis; skin necrosis at the start of treatment with a vitamin K antagonist; and severe thrombotic events in neonates. For many years the only available replacement treatment consisted of fresh frozen plasma which, among other adverse effects, carries a risk of hypervolemia. (2) Two human protein C concentrates prepared from donated blood have been given marketing authorisation in Europe for intravenous replacement therapy (Ceprotin from Baxter, and Protexel from LFB). (3) Their clinical files contain only retrospective case series (22 children with severe deficiency treated with Ceprotin; and 10 patients of various ages and with different degrees of severity treated with Protexel). The two preparations have not been compared with each other. (4) In patients with severe protein C deficiency, including neonates, replacement therapy with human protein C is effective, especially for treating cutaneous thrombosis and preventing thrombosis in high risk situations. (5) In patients with moderate deficiency, a short-course of human protein C prophylaxis reduces the frequency of thrombosis in high risk situations. (6) In long-term prophylaxis, human protein C replacement therapy, added to ongoing (but inadequately effective) vitamin K antagonist therapy, seems to reduce the risk of recurrent venous thrombosis even though it has some constraints. (7) The adverse effects of the two preparations are poorly documented. Allergic reactions and bleeding have been reported. Human protein C is a blood product, and therefore carries a risk of infection. (8) Ceprotin offers a small advantage, being available in two dose strengths: for a given dose the volume injected is halved. (9) In practice, Ceprotin and Protexel are the reference drugs for replacement therapy of constitutional protein C

  10. [Factors facilitating development of degenerative aortic valvular stenosis].

    Science.gov (United States)

    Andropova, O V; Polubentseva, E I; Anokhin, V N

    2005-01-01

    The aim of the study was to determine factors of risk and progress of aortal valvular calcinosis (AVC) and aortic ostium stenosis (AOS). The subjects were 85 patients with AVC (42--with aortic valvular stenosis (AVS), and 43--without AOS). The study, which included analysis of the lipid and mineral metabolism, and immunological tests, shows that potential factors of AVC are: age (p dislipidemia (high serum level of total cholesterol, cholesterol of low density lipoproteins, and apoB, atherogenic shift of apoB/apoA-1 ratio, low level of cholesterol of high density lipoproteins (CHDLP)), disbalance between intecellular matrix synthesis and destruction (high concentration of alkaline phosphatase and its bone fraction, and accelerated deoxypyridinoline excretion), inflammation (high concentration of C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6)). The factors of AOS were: age (p dislipidemia (high levels of cholesterol of low density and very low density lipoproteins, low concentrations of CHDLP, and apoA-1), degradation of extracellular matrix, and inflammation (high concentrations of CRP, fibrinogen, IL-6, and IL-8). Thus, atherogenic dislipidemia and mineral dysmetabolism disorder facilitate AVC. The revealed immune status changes imply the role of inflammation in the development and progress of AVS.

  11. Magnetic resonance imaging-based interpretation of degenerative changes in the lower lumbar segments and therapeutic consequences

    Institute of Scientific and Technical Information of China (English)

    Adel; Maataoui; Thomas; J; Vogl; M; Fawad; Khan

    2015-01-01

    Intervertebral disc degeneration and facet joint osteoarthritis of the lumbar spine are, among others, wellknown as a cause of low back and lower extremity pain. Together with their secondary disorders they set a big burden on health care systems and economics worldwide. Despite modern imaging modalities, such as magnetic resonance imaging, for a large proportion of patients with low back pain(LBP) it remains difficult to provide a specific diagnosis. The fact that nearly all the lumbar structures are possible sources of LBP, may serve as a possible explanation. Furthermore, our clinical experience confirms, that imaging alone is not a sufficient approach explaining LBP. Here, the Oswestry Disability Index, as the most commonly used measure to quantify disability for LBP, may serve as an easy-toapply questionnaire to evaluate the patient’s ability to cope with everyday life. For therapeutic purposes, among the different options, the lumbar facet joint intraarticular injection of corticosteroids in combination with an anaesthetic solution is one of the most frequently performed interventional procedures. Although widely used the clinical benefit of intra-articular steroid injections remains controversial. Therefore, prior to therapy, standardized diagnostic algorithms for an accurate assessment, classification and correlation of degenerative changes of the lumbar spine are needed.

  12. Contralateral interlaminar approach for intraforaminal lumbar degenerative disease with special emphasis on L5-S1 level: A technical note

    Science.gov (United States)

    Zekaj, Edvin; Menghetti, Claudia; Saleh, Christian; Isidori, Alessandra; Bona, Alberto R.; Aimar, Enrico; Servello, Domenico

    2016-01-01

    Background: Intraforaminal disc herniations at the L5-S1 level are extremely surgically challenging lesions. Intracanal approaches frequently require partial or total facetectomy, which may lead to instability. Solely extraforaminal approaches may offer limited visualization of the more medial superiorly exiting and inferiorly exiting nerve roots; this approach is also more complicated at L5-S1 due to the often large L5 transverse process and the iliac wing. Methods: Nine patients with intraforaminal L5-S1 disc herniations, foraminal stenosis, or synovial cysts underwent contralateral interlaminar approaches for lesion resection. Preoperative and postoperative visual analog scale scores were evaluated, and complications were reviewed. Results: All 9 patients demonstrated immediate postoperative clinical improvement. None of the patients exhibited complications and none developed instability or neuropathic disorders. Conclusions: Although the number of cases in our sample was very small (9 in total), the contralateral interlaminar approach appeared to effectively address multiple degenerative L5-S1 foraminal pathologies. Large studies are needed to further evaluate the pros and cons of this approach. PMID:27713854

  13. Hypertensive disorders of pregnancy are an evolutionary adaptation to mitigate the reproductive consequences of the human physique.

    Science.gov (United States)

    Ayuk, Paul T-Y

    2006-01-01

    The aetiology of hypertensive disorders of pregnancy remains unknown, despite over 30 years of research. The prevalence and natural history of these disorders and the lack of progress in identifying a cause calls for a radical new approach. It is hypothesised that these disorders arise as a consequence of abnormal maternal regulatory mechanisms. The evolution of the physical characteristics unique to humans (bi-pedal gait and a large brain) resulted in a narrow pelvis and a large head. Such a physique is not conducive to viviparity and caused difficult, prolonged and obstructed labour with post-partum haemorrhage--the commonest causes of maternal mortality in the absence of modern medical care. In such circumstances, up to 6.5% of pregnant women will die as a direct consequence of pregnancy, mainly as a result of obstructed labour and haemorrhage. The death toll would have been much higher over millions of years of evolution. These conditions exerted significant adaptive and evolutionary pressure on our species. The adaptations necessary to mitigate the reproductive consequences of the human physique include activation of the coagulation system to reduce post-partum haemorrhage, increased blood pressure to peak after delivery and maintain cerebral perfusion in the face of post-partum blood loss and restriction of fetal growth to prevent obstructed labour. These adaptations must be regulated to guarantee their occurrence but limit their extent to prevent disease. Evidence for blood pressure regulation during pregnancy and a proposed mechanism to achieve this are presented. Regulation requires a redundant feto-placental signal and a single tightly controlled regulator. To guarantee that blood pressure rises, the feto-placental signal is predicted to be conveyed by several different molecules and to be produced in excess in all pregnancies. Normality is then maintained by a single tightly controlled regulator. This model predicts that the feto-placental factors that

  14. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    Science.gov (United States)

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  15. Human obesity as a heritable disorder of the central control of energy balance.

    Science.gov (United States)

    O'Rahilly, S; Farooqi, I S

    2008-12-01

    In the spirit of celebration associated with the 20th anniversary of the Pennington Biomedical Research Center, we have seized the opportunity of taking a highly personal and not at all comprehensive 'whistle-stop tour' of a large body of evidence that, we feel, supports the following conclusions: (1) that body fat stores are regulated by biological control processes in humans as they are in lower animals; (2) that there are major inherited influences on the efficiency whereby such control processes operate in humans; (3) that the precise nature of those genetic and biological influences and how they interact with environmental factors are beginning to be understood; (4) that most of the genes discovered thus far have their principal impact on hunger, satiety and food intake; (5) that while there is understandable resistance to the notion that genes can influence a human behavior such as the habitual ingestion of food, the implications of these discoveries are essentially benign. Indeed, we hope that they may eventually lead to improved treatment for patients and, in addition, help to inculcate a more enlightened attitude to the obese with a reduction in their experience of social and economic discrimination.

  16. Degenerative dementia: nosological aspects and results of single photon emission computed tomography; Les demences degeneratives: aspects nosologiques et resultats de la tomographie d'emission monophotonique

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, B.; Habert, M.O. [Hopital Pitie-Salpetriere, 75 - Paris (France)

    1999-12-01

    Ten years ago, the diagnosis discussion of a dementia case for the old patient was limited to two pathologies: the Alzheimer illness and the Pick illness. During these last years, the frame of these primary degenerative dementia has fallen into pieces. The different diseases and the results got with single photon emission computed tomography are discussed. for example: fronto-temporal dementia, primary progressive aphasia, progressive apraxia, visio-spatial dysfunction, dementia at Lewy's bodies, or cortico-basal degeneration. (N.C.)

  17. MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If

    Science.gov (United States)

    Schenk, Barbara; Imbach, Timo; Frank, Christian G.; Grubenmann, Claudia E.; Raymond, Gerald V.; Hurvitz, Haggit; Raas-Rotschild, Annick; Luder, Anthony S.; Jaeken, Jaak; Berger, Eric G.; Matthijs, Gert; Hennet, Thierry; Aebi, Markus

    2001-01-01

    Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients’ fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If. PMID:11733564

  18. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  19. Thalassemia: Impact of consanguineous marriages on most prevalent monogenic disorders of humans

    Directory of Open Access Journals (Sweden)

    Umar Saeed

    2016-10-01

    Full Text Available Thalassaemia is an inherited autosomal recessive disorder closely associated with consanguineous marriages. A literature search was conducted with an aim to investigate thalassemia and consanguineous marriages. Articles were searched from Google Scholar and Pubmed information regarding thalassemia associated complications, epidemiology of thalassemia and association between consanguineous marriages and thalassemia, which was subjected to contemplation. Thalassemia carrier rate varies differently in different regions of the world. In Indian subcontinent and China, Central Asia, South Europe (also known as North Mediterranean and Arab Region, the thalassemia carrier rates were approximately 1%–40%, 4%–10%, 1%–19% and 3%, respectively. In Pakistan, the annual number of infants born with beta thalassemia is the highest as compared to other countries from Eastern Mediterranean Region. Although the management and control of thalassemia is a difficult task, it can easily be achieved via the assistance of prenatal diagnosis and prevention programs. Consanguineous marriages should be avoided to further limit the future burden of thalassaemia disease.

  20. The theoretical underpinnings of affective temperaments: implications for evolutionary foundations of bipolar disorder and human nature.

    Science.gov (United States)

    Akiskal, Kareen K; Akiskal, Hagop S

    2005-03-01

    We sketch out putative evolutionary roles for affective temperaments within the theoretical framework of mood disorders conceptualized as extremes in an oligogenic model of inheritance, whereby the constituent traits in their dilute phenotypes confer adaptive advantages to individuals and/or their social group. Depressive traits, among other functions, would subserve sensitivity to the suffering of other members of the species, overlapping with those of the generalized anxious temperament, thereby enhancing the survival of not only kin but also other conspecifics. The pursuit of romantic opportunities in cyclothymia suggests that it may have evolved as a mechanism in reproductive success; cyclothymics' creative bent in poetry, music, painting, cooking or fashion design (among men, in particular) also appears useful for sexual seduction. Hyperthymic traits would lend distinct advantages in leadership, exploration, territoriality and mating. These are just some of the possibilities of the rich and complex temperamental traits subserving bipolarity within an evolutionary framework. We test selected aspects of these hypotheses with the use of correlations between the constituent traits of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS) and correlations between the TEMPS and the Temperament and Character Inventory (TCI). Such data support the counterbalancing protective influence of harm avoidance on the risk-taking behavior of cyclothymic individuals, in both men and women. Finally, we outline a hypothesis on the evolutionary function of anxious-depressive traits for women.

  1. Trichothiodystrophy, a human DNA repair disorder with heterogeneity in the cellular response to ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, A.R.; Arlett, C.F.; Broughton, B.C.; Harcourt, S.A.; Steingrimsdottir, H.; Stefanini, M.; Malcolm, A.; Taylor, R.; Natarajan, A.T.; Green, S.

    1988-11-01

    Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD.

  2. Music Therapy and Eating Disorders- A Single Case Study about the Sound of Human Needs

    Directory of Open Access Journals (Sweden)

    Susanne Bauer

    2010-07-01

    Full Text Available In this article, I reflect on a music therapy intervention realized many years ago, with a young woman who had the diagnosis of Bulimia Nervosa. The concepts to which I will refer are the concept of resource orientated psychotherapy and the Bernese concept of need adapted -and motivational attunement (Grawe, 1998; Grawe and Grawe-Gerber, 1999; Stucki and Grawe, 2007. I re-viewed one of my cases, Ms. H., following some of the ideas developed by the authors.  I discovered various moments of interest, which made me think in terms of a Need Adapted Music Therapy process. Therefore, in the presentation of the case, besides talking about the patient’s eating disorder I want to point out her basic needs and how she demanded for them to be met symbolically during shared improvisational moments with the music therapist. And even if the therapist did not have the mentioned concepts in her mind at the time, it seems as if patient and therapist met quite often in this kind of “silent space of needs”.

  3. Molecular evolution of the human SRPX2 gene that causes brain disorders of the Rolandic and Sylvian speech areas

    Directory of Open Access Journals (Sweden)

    Levasseur Anthony

    2007-10-01

    Full Text Available Abstract Background The X-linked SRPX2 gene encodes a Sushi Repeat-containing Protein of unknown function and is mutated in two disorders of the Rolandic/Sylvian speech areas. Since it is linked to defects in the functioning and the development of brain areas for speech production, SRPX2 may thus have participated in the adaptive organization of such brain regions. To address this issue, we have examined the recent molecular evolution of the SRPX2 gene. Results The complete coding region was sequenced in 24 human X chromosomes from worldwide populations and in six representative nonhuman primate species. One single, fixed amino acid change (R75K has been specifically incorporated in human SRPX2 since the human-chimpanzee split. The R75K substitution occurred in the first sushi domain of SRPX2, only three amino acid residues away from a previously reported disease-causing mutation (Y72S. Three-dimensional structural modeling of the first sushi domain revealed that Y72 and K75 are both situated in the hypervariable loop that is usually implicated in protein-protein interactions. The side-chain of residue 75 is exposed, and is located within an unusual and SRPX-specific protruding extension to the hypervariable loop. The analysis of non-synonymous/synonymous substitution rate (Ka/Ks ratio in primates was performed in order to test for positive selection during recent evolution. Using the branch models, the Ka/Ks ratio for the human branch was significantly different (p = 0.027 from that of the other branches. In contrast, the branch-site tests did not reach significance. Genetic analysis was also performed by sequencing 9,908 kilobases (kb of intronic SRPX2 sequences. Despite low nucleotide diversity, neither the HKA (Hudson-Kreitman-Aguadé test nor the Tajima's D test reached significance. Conclusion The R75K human-specific variation occurred in an important functional loop of the first sushi domain of SRPX2, indicating that this evolutionary

  4. Characterization of native human thrombopoietin in the blood of normal individuals and of patients with haematologic disorders.

    Science.gov (United States)

    Matsumoto, A; Tahara, T; Morita, H; Usuki, K; Ohashi, H; Kokubo-Watarai, A; Takahashi, K; Shimizu, E; Tsunakawa, H; Ogami, K; Miyazaki, H; Urabe, A; Kato, T

    1999-07-01

    Thrombopoietin (TPO) isolated from thrombocytopenic plasma of various animal species has previously been shown to comprise only truncated forms of the molecule, presumably generated by proteolysis. Native TPO has now been partially purified from normal human plasma by immunoaffinity chromatography and was confirmed to be biologically active. Gel filtration in the presence of SDS revealed that TPO eluted in two peaks: a major peak corresponding to the elution position of fully glycosylated recombinant human TPO (rhTPO) consisting of 332 amino acid residues, and a minor peak corresponding to a smaller molecular size. Immunoblot analysis also revealed that most plasma-derived TPO migrated at the same position as fully glycosylated rhTPO, corresponding to a molecular size of approximately 80 to 100 kDa. Furthermore, the size distribution of circulating TPO in patients with various haematologic disorders did not differ markedly from that of plasma-derived TPO from healthy individuals. These results indicate that the truncation of circulating TPO is not related to disease pathophysiology, and that the predominant form of TPO in blood is a biologically active approximately 80- to 100-kDa species. The size distribution of TPO extracted from normal platelets was similar to that of TPO in plasma; the proportion of truncated TPO was decreased by prior incubation of platelets with hirudin. indicating that the endogenous truncated TPO, at least in platelet extract, was generated by thrombin-mediated cleavage.

  5. Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design.

    Science.gov (United States)

    Shafqat, Naeem; Turnbull, Andrew; Zschocke, Johannes; Oppermann, Udo; Yue, Wyatt W

    2010-05-14

    3-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl CoA. It is ubiquitous across the phylogenetic tree and is broadly classified into three classes. The prokaryotic isoform is essential in Gram-positive bacteria for isoprenoid synthesis via the mevalonate pathway. The eukaryotic cytosolic isoform also participates in the mevalonate pathway but its end product is cholesterol. Mammals also contain a mitochondrial isoform; its deficiency results in an inherited disorder of ketone body formation. Here, we report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes. Our data represent the first structures solved for human HMGCS and the mitochondrial isoform, allowing for the first time structural comparison among the three isoforms. This serves as a starting point for the development of isoform-specific inhibitors that have potential cholesterol-reducing and antibiotic applications. In addition, missense mutations that cause mitochondrial HMGCS deficiency have been mapped onto the hHMGCS2 structure to rationalize the structural basis for the disease pathology.

  6. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Watson Karli K

    2012-07-01

    Full Text Available Abstract The autism spectrum disorders (ASDs arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  7. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders.

    Science.gov (United States)

    Watson, Karli K; Platt, Michael L

    2012-07-30

    The autism spectrum disorders (ASDs) arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs) provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  8. Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference

    OpenAIRE

    Nair, Pratibha; Bizzari, Sami; Rajah, Nirmal; Assaf, Nada; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

    2016-01-01

    The 6th Pan Arab Human Genetics Conference (PAHGC), “Genetics of Multifactorial Disorders” was organized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in Dubai, United Arab Emirates from 21 to 23 January, 2016. The PAHGCs are held biennially to provide a common platform to bring together regional and international geneticists to share their knowledge and to discuss common issues. Over 800 delegates attended the first 2 days of the conference and these came from various medic...

  9. Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

    NARCIS (Netherlands)

    Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

    2007-01-01

    The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between th

  10. [Stimulation of degenerative changes in the intervertebral disc through axial compression. Radiologic, histologic and biomechanical research in an animal model].

    Science.gov (United States)

    Unglaub, F; Lorenz, H; Nerlich, A; Richter, W; Kroeber, M W

    2003-01-01

    Degeneration of the intervertebral disc is a common disease in the adults, especially at advanced age. A causal therapy is not known, but the progress in new therapeutic strategies, for example in tissue engineering, shows new possibilities. The goal of our study was to develop a new animal model that stimulates a load induced degeneration of the disc. We used the New Zealand rabbit, because morphology is similar to the human intervertebral disc. The degeneration was induced by axial compression of the disc L4 - L5 with an external fixateur. After different loading intervals, the animals were sacrified and the discs examined by radiology, histology, apoptosis and biomechanical testing. Radiography showed a significant decrease of the disc thickness in all loaded groups. Morphologically the intervertebral discs of loaded rabbits showed degenerative changes which were comparable to those in humans. A significantly increased number of dead cells in the annulus occurred after 14 and 28 days loading compared to the controls. The bending stress measured as the load to failure was not significantly different between the unloaded discs and the 28 days loaded discs. The results show that our animal modell can create degeneration. Four weeks compression leads to significant degeneration. Degeneration of the discs persisted in animals that were allowed a recovery time of 28 days after 28 days of loading.

  11. Astrocyte differentiation of human pluripotent stem cells: new tools for neurological disorder research

    Directory of Open Access Journals (Sweden)

    Abinaya Chandrasekaran

    2016-09-01

    Full Text Available Astrocytes have a central role in brain development and function, and so have gained increasing attention over the past two decades. Consequently, our knowledge about their origin, differentiation and function has increased significantly, with new research showing that astrocytes cultured alone or co-cultured with neurons have the potential to improve our understanding of various central nervous system (CNS diseases, such as Amyotrophic lateral sclerosis, Alzheimer’s disease or Alexander disease. The generation of astrocytes derived from pluripotent stem cells (PSCs opens up a new area for studying neurologic diseases in vitro; these models could be exploited to identify and validate potential drugs by detecting adverse effects in the early stages of drug development. However, as it is now known that a range of astrocyte populations exist in the brain, it will be important in vitro to develop standardized protocols for the in vitro generation of astrocyte subsets with defined maturity status and phenotypic properties. This will then open new possibilities for co-cultures with neurons and the generation of neural organoids for research purposes. The aim of this review article is to compare and summarize the currently available protocols and their strategies to generate human astrocytes from PSCs. Furthermore, we discuss the potential role of human-induced PSCs derived astrocytes in disease modeling.

  12. Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

    Directory of Open Access Journals (Sweden)

    Takeshi Nishino

    2012-11-01

    Full Text Available Xanthine oxidoreductase (XOR catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD+ or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.

  13. Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

    Science.gov (United States)

    Vyas, S; Javoy-Agid, F; Herrero, M T; Strada, O; Boissiere, F; Hibner, U; Agid, Y

    1997-07-01

    The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

  14. Repeated assessment of exploration and novelty seeking in the human behavioral pattern monitor in bipolar disorder patients and healthy individuals.

    Directory of Open Access Journals (Sweden)

    Arpi Minassian

    Full Text Available BACKGROUND: Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM, a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD. METHODOLOGY AND PRINCIPAL FINDINGS: Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions. CONCLUSIONS/SIGNIFICANCE: Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design

  15. Differential expression of follistatin and FLRG in human breast proliferative disorders

    Directory of Open Access Journals (Sweden)

    Amaral Vania F

    2009-09-01

    Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

  16. Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders

    DEFF Research Database (Denmark)

    Brickman, J M; Clements, M; Tyrell, R

    2001-01-01

    resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline...... defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1...... mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis...

  17. Disorders of innate immunity in human ageing and effects of nutraceutical administration.

    Science.gov (United States)

    Magrone, Thea; Jirillo, Emilio

    2014-01-01

    Immune decline with ageing accounts for the increased risk of infections, inflammatory chronic disease, autoimmunity and cancer in humans. Both innate and adaptive immune functions are compromised in aged people and, therefore, attempts to correct these dysfunctions represent a major goal of modern medicine. In this review, special emphasis will be placed on the aged innate immunity with special reference to polymorphonuclear cell, monocyte/ macrophage, dendritic cell and natural killer cell functions. As potential modifiers of the impaired innate immunity, some principal nutraceuticals will be illustrated, such as micronutrients, pre-probiotics and polyphenols. In elderly, clinical trials with the above products are scanty, however, some encouraging effects on the recovery of innate immune cells have been reported. In addition, our own results obtained with symbiotics and polyphenols extracted from red wine or fermented grape marc suggest the potential ability of these substances to modulate the innate immune response in ageing, thus reducing the inflammaging which characterizes immune senescence.

  18. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

    Directory of Open Access Journals (Sweden)

    Saenger Paul

    2012-05-01

    Full Text Available Abstract The term small for gestational age (SGA refers to infants whose birth weights and/or lengths are at least two standard deviation (SD units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH/insulin-like growth factor (IGF-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR polymorphism. Uniparental disomy (UPD and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  19. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder.

    Science.gov (United States)

    Saenger, Paul; Reiter, Edward

    2012-05-15

    The term small for gestational age (SGA) refers to infants whose birth weights and/or lengths are at least two standard deviation (SD) units less than the mean for gestational age. This condition affects approximately 3%-10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD) and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH) therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  20. Colorimetric determinations of lithium levels in drop-volumes of human plasma for monitoring patients with bipolar mood disorder.

    Science.gov (United States)

    Qassem, M; Hickey, M; Kyriacou, P A

    2016-08-01

    Lithium preparations are considered the most reliable form of mood stabilizing medication for patients with Bipolar disorder. Nevertheless, lithium is a toxic element and its therapeutic range is extremely narrow, with levels of 0.61.0 mEq considered normal, whereas levels above 1.5 mEq are toxic. Thus unfortunately, many patients reach toxic levels that lead to unnecessary complications. It is believed that personal monitoring of blood lithium levels would benefit patients taking lithium medication. Therefore, our aim is to develop a personal lithium blood level analyzer for patients with bipolar mood disorder, and we report here our initial results of a colorimetric-based method used to test drop-volumes of human plasma that had been spiked with lithium. It was possible to validate results with standard flame photometry readings. Applying the Partial Least Squares (PLS) method on preprocessed spectra, therapeutic concentrations of lithium in a single drop can be predicted in a rapid manner, and furthermore, the calibration results were used to select effective wavelengths which were employed as inputs in Multiple Linear Regression (MLR). The simplified algorithms of this would prove useful when developing a personal lithium analyzer. Overall, both calibration methods gave high correlation and small error outputs with a R2= 0.99036 and RMSEC = 0.03778, and R2= 0.994148 and RMSEC= 0.0294404, for PLS and MLR methods, respectively. The results show that the spectrophotometric determination of blood lithium levels can be extended beyond laboratory applications and indicate the capability of this testing principle to be employed in a personal monitoring device. Future work will now focus on the technical development of a miniaturized system for measurement of lithium levels in blood with an acceptable level of accuracy and sensitivity.

  1. Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative disease.

    Science.gov (United States)

    Colangeli, S; Barbanti Brodàno, G; Gasbarrini, A; Bandiera, S; Mesfin, A; Griffoni, C; Boriani, S

    2015-06-01

    Pedicle screw and rod instrumentation has become the preferred technique for performing stabilization and fusion in the surgical treatment of lumbar spine degenerative disease. Rigid fixation leads to high fusion rates but may also contribute to stress shielding and adjacent segment degeneration. Thus, the use of semirigid rods made of polyetheretherketone (PEEK) has been proposed. Although the PEEK rods biomechanical properties, such as anterior load sharing properties, have been shown, there are few clinical studies evaluating their application in the lumbar spine surgical treatment. This study examined a retrospective cohort of patients who underwent posterior lumbar fusion for degenerative disease using PEEK rods, in order to evaluate the clinical and radiological outcomes and the incidence of complications.

  2. Stand-alone anterior lumbar interbody fusion for treatment of degenerative spondylolisthesis.

    Science.gov (United States)

    Rao, Prashanth J; Ghent, Finn; Phan, Kevin; Lee, Keegan; Reddy, Rajesh; Mobbs, Ralph J

    2015-10-01

    We sought to evaluate the clinical and radiologic efficacy of stand-alone anterior lumbar interbody fusion (ALIF) for low grade degenerative spondylolisthesis, the favoured surgical management approach at our institution. The optimal approach for surgical management of spondylolisthesis remains contentious. We performed a prospective analysis of all consecutive patients with low grade lumbar spondylolisthesis who underwent ALIF between 2009 and 2013 by a single surgeon (n=27). The mean age was 64.9 years with a male to female ratio of 14:13. There were 32 levels operated and the average preoperative spondylolisthesis was 14.8%, which reduced to 6.4% postoperatively and 9.4% at the latest follow-up (p=0001). Postoperative disc height was increased to 175% of preoperative values and was statistically significant (plumbar degenerative spondylolisthesis. Future studies should include adequately powered, prospective, multicentre registry studies with long term follow-up to allow a better assessment of the relative benefits and risks.

  3. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    Science.gov (United States)

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases.

  4. Acute pyogenic discitis in a degenerative intervertebral disc in an adult

    Directory of Open Access Journals (Sweden)

    Masamitsu Tanaka

    2010-08-01

    Full Text Available Masamitsu Tanaka1,2, Hiroshi Shimizu2, Yoshiyuki Yato1, Takashi Asazuma1, Koichi Nemoto11Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama; 2Department of Orthopedic Surgery, Self Defense Force Fukuoka Hospital, Kasuga, Fukuoka, JapanAbstract: A 35-year-old male who had been receiving conservative treatment for L4 isthmic spondylolisthesis suffered from pyogenic spondylodiscitis in the degenerative L4/L5 intervertebral disc space, which could be identified by comparison with previous images. Symptoms improved with conservative antibiotic treatment. Neovascularization may occur in the annulus fibrosus of a degenerative intervertebral disc, which may increase the risk of hematogenous infection, leading to “discitis” even in adults.Keywords: spondylodiscitis, spondylitis, discitis, isthmic spondylolisthesis, spondylolysis, intervertebral disc degeneration

  5. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

    DEFF Research Database (Denmark)

    Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje;

    2016-01-01

    clinics in Norway. PARTICIPANTS: 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. INTERVENTIONS: 12 week supervised exercise therapy alone or arthroscopic partial......OBJECTIVE: To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. DESIGN: Randomised controlled superiority trial. SETTING: Orthopaedic departments at two public hospitals and two physiotherapy...... months, muscle strength had improved in the exercise group (P≤0.004). No serious adverse events occurred in either group during the two year follow-up. 19% of the participants allocated to exercise therapy crossed over to surgery during the two year follow-up, with no additional benefit. CONCLUSION...

  6. Revisiting the application of integrated physiotherapy in degenerative-dystrophic diseases of the musculoskeletal system

    Directory of Open Access Journals (Sweden)

    Kotenko K.V.

    2014-12-01

    Full Text Available Aim. The authors described a comprehensive program of frozen shoulder treatment, including extracorporeal shock wave therapy and pelotherapy. Objective: To evaluate the effectiveness of the inclusion of extracorporeal shock wave therapy and pelotherapy in rehabilitation of patients with degenerative diseases of the musculoskeletal system. Materials and Methods: there had been examined 120 patients during the study. Results: The result of the application of complex physiotherapy normalized indicators of metabolic and electrolyte imbalances that are important in the formation of a therapeutic effect. Conclusion: The application of extracorporeal shock wave therapy and in combination with pelotherapy in patients with scapula-humeral periarthritis is the elimination of metabolic and electrolyte imbalance, which is important in degenerative diseases of the musculoskeletal system

  7. Degenerative disc disease in the lumbar spine: Another cause for focally reduced activity on marrow scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology); Miles, K.A. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Wraight, E.P. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Dixon, A.K. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Cambridge Univ. (United Kingdom))

    1992-05-01

    A patient is presented in whom a focal reduction in marrow activity in the lumbar spine on both leucocyte and nanocolloid marrow scintigraphy was subsequently shown to be due to fatty infiltration of marrow in association with disc degeneration. Degenerative disease in the lumbar spine has not been previously described as a cause of abnormal bone marrow distribution by such means and needs to be distinguished from a more serious pathology, such as malignant infiltration and vertebral infection, which it may mimic. In a retrospective review of 33 nanocolloid bone marrow and 117 leucocyte scintigrams, 8 showed a degree of reduced marrow activity in the lumbar spine consistent with that caused by degenerative changes. (orig.).

  8. A 12-Week Exercise Therapy Program in Middle-Aged Patients With Degenerative Meniscus Tears

    DEFF Research Database (Denmark)

    Stensrud, Silje; Roos, Ewa M.; Risberg, May Arna

    2012-01-01

    , progression, tolerance, and potential benefit from an exercise therapy program in these patients who have not had surgery. This study describes a progressive exercise therapy program aiming at improving neuromuscular function and muscle strength in middle-aged patients with degenerative meniscus tears......Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 STUDY DESIGN: Case Series. BACKGROUND: Exercise is a viable treatment alternative to arthroscopic partial meniscectomy in patients with degenerative meniscus tears. No study has reported in detail type of exercises...... global rating of change scale, isokinetic knee muscle strength tests, and 3 lower extremity performance tests. Post intervention there were clinically meaningful changes (greater than 10 points) in 16 of 20 patients on the KOOS knee related quality of life, 19 of 20 patients rated themselves as "a lot...

  9. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

    DEFF Research Database (Denmark)

    Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

    2016-01-01

    months, muscle strength had improved in the exercise group (P≤0.004). No serious adverse events occurred in either group during the two year follow-up. 19% of the participants allocated to exercise therapy crossed over to surgery during the two year follow-up, with no additional benefit. CONCLUSION......OBJECTIVE: To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. DESIGN: Randomised controlled superiority trial. SETTING: Orthopaedic departments at two public hospitals and two physiotherapy...... clinics in Norway. PARTICIPANTS: 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. INTERVENTIONS: 12 week supervised exercise therapy alone or arthroscopic partial...

  10. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

    DEFF Research Database (Denmark)

    Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

    2016-01-01

    clinics in Norway. PARTICIPANTS: 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. INTERVENTIONS: 12 week supervised exercise therapy alone or arthroscopic partial...... meniscectomy alone. MAIN OUTCOME MEASURES: Intention to treat analysis of between group difference in change in knee injury and osteoarthritis outcome score (KOOS4), defined a priori as the mean score for four of five KOOS subscale scores (pain, other symptoms, function in sport and recreation, and knee....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option.Trial registration www.clinicaltrials.gov (NCT01002794)....

  11. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

    DEFF Research Database (Denmark)

    Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

    2016-01-01

    clinics in Norway. Participants 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. Interventions 12 week supervised exercise therapy alone or arthroscopic partial...... meniscectomy alone. Main outcome measures Intention to treat analysis of between group difference in change in knee injury and osteoarthritis outcome score (KOOS 4), defined a priori as the mean score for four of five KOOS subscale scores (pain, other symptoms, function in sport and recreation, and knee....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option. Trial registration www.clinicaltrials.gov (NCT01002794)....

  12. Degenerative primer design and gene sequencing validation for select turkey genes.

    Science.gov (United States)

    Hutsko, Stephanie L; Lilburn, Michael S; Wick, Macdonald

    2016-06-01

    We successfully designed and validated degenerative primers for turkey genes MUC2, RPS13, TBP and TFF2 based on chicken sequences in order to use gene transcription analysis to evaluate (quantify) the mucin transcription to probiotic supplementation in turkeys. Primers were designed for the genes MUC2, TFF2, RPS13 and TBP using a degenerative primer design method based on the available Gallus gallus sequences. All primer sets, which produced a single PCR amplicon of the expected sizes, were cloned into the TOPO(®) vector and then transformed into TOP 10(®) competent cells. Plasmid DNA isolation was performed on the TOP10(®) cell culture and sent for sequencing. Sequences were analyzed using NCBI BLAST. All genes sequenced had over 90% homology with both the chicken and predicted turkey sequences. The sequences were used to design new 100% homologous primer sets for the genes of interest. © 2016 Poultry Science Association Inc.

  13. Modern approaches to diagnostics of combined degenerative hip and spine pathology

    Directory of Open Access Journals (Sweden)

    V. V. Khominets

    2014-01-01

    Full Text Available The results of standard radiographs of 90 patients with hip-spine syndrome associated with one unilateral or bilateral III stage hip osteoarthhrosis were analyzed with the aim to improve the diagnostics of pathological changes in the "hip joint-pelvis- spine" complex. 12 parameters of sagittal spinal-pelvic balance and 3 parameters of frontal one were studied and the degenerative changes in spinal motional segments were evaluated. The statistical processing of obtained data was made. It was stated that the most frequent variant of sagittal spinal-pelvic profile is hyperlordosic one, followed by formation of degenerative changes especially in dorsal regions of spine (р=0,076.The strategy of patient examination with hip-spine syndrome was established from clinical and radiographic positions.

  14. Degenerative processes in bioprosthetic mitral valves in juvenile pigs

    Directory of Open Access Journals (Sweden)

    Pedersen Torben B

    2011-05-01

    Full Text Available Abstract Background Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs. Materials The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation. Results Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00 and 1.20 (SD = ±0.25, respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55 and 6.51 mmHg (SD = ±2.57, respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium. Conclusions Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.

  15. Sleep Disorders in Childhood Neurogenetic Disorders

    Directory of Open Access Journals (Sweden)

    Laura Beth Mann Dosier

    2017-09-01

    Full Text Available Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dys