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Sample records for den diabetiske charcots

  1. Charcot Foot

    MedlinePlus

    ... help prevent recurrence of Charcot foot, development of ulcers, and possibly amputation. In cases with significant deformity, ... instructions for long-term treatment to prevent recurrences, ulcers, and amputation. and or or and or or, ...

  2. Before Charcot.

    PubMed

    Pearce, J M S

    2014-01-01

    From the time of Greco-Roman Medicine, the uncertain nature of hysterical illness was a fertile source of controversy. Because there were no testable objective signs of disease, the diverse ideas relating hysteria to the uterus and to psychological and physiological causes generated persisting polemics. Theories fluctuated chaotically, influenced by social changes of prosperity or deprivation, current attitudes, and issues of gender. Faced with a large number of patients with such illnesses as well as many with epilepsy, mental illnesses, and organic nervous disorders, Charcot set about investigating hysterics to determine what neurological abnormalities might explain them. His many predecessors, from Sydenham and Willis in the 17th century to Briquet and Bourneville in the 19th century, whose views are outlined in this chapter, both conditioned and influenced his efforts. Charcot succeeded in promoting his work at Salpêtrière, which for a time was respected throughout the world. PMID:25273484

  3. [The intimate Charcot].

    PubMed

    Bonduelle, M

    1994-01-01

    Charcot's first inner circle of relationships was at work at the Salpêtrière, face to face with his intern who Charcot then invited to his home. At the Clinic, Charcot gave his official lectures that attracted crowds, but the small circle of "his" students--interns, residents and other rare and privileges students saw some of the "best" moments, as long as they aquiesced totally and did not question the "maître". They all got together for dinner on Tuesday night at his sumptuous "hôtel" on Boulevard Saint-Germain, followed by a reception where they could meet writers, artists and politicians. When the outsiders had left, Charcot tightened together his inner circle, those he would invite to his summer home in Neuilly. Léon Daudet was one of these. He saw the art-lover, the enlightened connaisseur of classical literature. He saw Charcot let down his severe mask of a professor and become a pleasant joking man, yet his fascination with Charcot did not stop him from criticizing Charcot's materialism and anticlericalism. He also repudiated Charcot's autoritarism and depotism over his family (whom he adored) and recognized in Charcot a certain timidity and "proud malaise". These evenings, rare occasions in a life filled with work, went on long into the night in the solitary silence of his library. Only his long trips which he used as a "cure" broke the intimacy of his inner circle. His letters to his wife, who never accompanied him, offer a glimpse into the personality of this secret man. They let us perceive the effect of overwhelming scientific success and flattering applause, but also the shadow of susceptibility as seen by his daughter Jeanne who accompanied him on his last trips. He never gave up, never confided in others, yet he was a charmer, one whose silence was often a prelude to an explosion of rage. PMID:7754287

  4. [Charcot's epistemological concept].

    PubMed

    Lellouch, A

    1994-01-01

    Through a brilliant medical way, Charcot was, at the same time, rheumatologist, geriatric, clinician, pathologist - and mainly neuro-pathologist - ending as a psychiatrist (according to todays medical terminology). Here, we will point out how much scientific theory and philosophy may support an original concept very unusual during the second half of XIXth century medicine. Describing connection between biology and medicine according to Auguste Comte thoughte, the author is thoroughly going into the course introduced by Charcot: scientific medicine instead of empirical one; structural medical-anatomy against rudimentary approach and rising of experimental medicine; impact of human sciences on medical knowledge; appearance of specialists near general practitioners; idea of organic disturbances denying any 'faith healing". In fact, Charcot asserts that bedside instruction prevails against accurate sciences. PMID:11640482

  5. [Jean-martin charcot].

    PubMed

    Sakuta, Manabu

    2014-11-01

    Charcot created a system for the classification and diagnosis of neurological patients in the 1850s. His methodology consisted of listening to a patient's family history and present history, observing the patient scrupulously, and confirming lesions by autopsy once the patient was dead. He compared two different diseases in order to make their differences clear. Once he understood the fundamental form of a disease, he proceeded to study less perfect forms that had a single symptom. By this process, Charcot developed many new symptomatologies in Neurology. PMID:25407058

  6. Charcot foot syndrome.

    PubMed

    Jeffcoate, W J

    2015-06-01

    Charcot foot syndrome is an uncommon complication of diabetes but is potentially devastating in its consequences. Outcome is made worse by widespread professional ignorance leading to delayed diagnosis, but it is also hampered by lack of understanding of its causes and lack of treatments with proven effectiveness, other than offloading. There remains a desperate need for studies into its causes as well as comparative audit and trials designed to determine the best treatment for this difficult condition. Such work can probably only be effectively carried out through the establishment of multicentre networks. Nevertheless, improved understanding in recent years of the likely role of inflammatory pathways has raised awareness of the multiple ways in which the effects of neuropathy may be manifest in the development of the Charcot foot. This awareness is also leading to the realization that similar processes may conceivably contribute to the refractoriness of other foot diseases in diabetes, including both chronic unhealing ulcers and osteomyelitis. PMID:25818542

  7. Charcot-Marie-Tooth disease

    MedlinePlus

    Charcot-Marie-Tooth disease is a group of disorders passed down through families that affect the nerves outside the brain and ... Charcot-Marie-Tooth is one of the most common nerve-related disorders passed down through families (inherited). Changes to at least ...

  8. [How Charcot got his chair].

    PubMed

    Gelfand, T

    1994-01-01

    Charcot's career, as is well-known, reached a summit with his acquisition of the Faculty clinical chair of diseases of the nervous system inaugurated in 1882. Based upon previously untapped archival materials at the Charcot Library and the National Archives, this paper explores four questions: I. Was "Charcot's chair" really the first specialized chair for neurology?; 2. Was it founded specifically for Charcot?; 3. What role did the Faculty of Medicine play and did it offer any opposition?; 4. How important was the creation of the chair for the flourishing of the Salpêtrière school. Evidence is presented to show that Charcot considered a specialized chair in nervous diseases a high priority for his career and his school. Sometime around 1880, convinced of the importance of this project, he began to assemble arguments in its behalf from French and foreign sources, particularly from his German colleagues, Westphal and Erb. He learned that there were no precedents, not even in Berlin. Charcot's carefully prepared manuscript memoir presented a strong case for the "necessity" of the chair based on the recent progress and theoretical as well as practical importance of his subject. He described psychiatry, which already had a Faculty clinical chair, as but a "small part" of neuropathology and rejected the idea of combining the two disciplines. Although the project encountered opposition from several Faculty colleagues, who claimed that it was a personal favor for Charcot, powerful support from political allies such as Gambetta and Ferry ensured government funding. In fact, government action in behalf of the creation of the chair for Charcot preceded and surprised the medical Faculty. This paper shows the extent to which Charcot's own initiatives and arguments set the agenda and defined the role he envisaged for the new foundation at the center of the clinical research and teaching centre emerging under his direction at the Salpêtrière. PMID:11640483

  9. Charcot foot and ankle with osteomyelitis

    PubMed Central

    Donegan, Ryan; Sumpio, Bauer; Blume, Peter A.

    2013-01-01

    This paper presents a review of the current literature discussing topics of Charcot osteoarthropathy, osteomyelitis, diagnosing osteomyelitis, antibiotic management of osteomyelitis, and treatment strategies for management of Charcot osteoarthropathy with concurrent osteomyelitis. PMID:24098835

  10. Charcot-Marie-Tooth Disease

    MedlinePlus

    Charcot-Marie-Tooth disease (CMT) is a group of genetic nerve disorders. It is named after the three doctors who first identified it. ... a nerve biopsy. There is no cure. The disease can be so mild you don't realize ...

  11. Theater in professor Charcot's galaxy.

    PubMed

    Poirier, Jacques; Philippon, Jacques

    2013-01-01

    Jean-Martin Charcot, famous professor of the Chair of Clinic for Diseases of the Nervous System at Salpêtrière Hospital in Paris, was himself an artist, surrounded by artists, and adored the theater. His close colleague Charles Brown-Séquard was ridiculed by Georges Feydeau in a brief freakish monologue recited by Coquelin Cadet, from the Comédie-Française, concerning his claims to rejuvenate himself and others with animal testicle extracts. His friend and patient Alphonse Daudet had written many novels, short stories, and plays. Léon Daudet, Alphonse Daudet's son (and friend of Jean-Baptiste Charcot, the son of the professor), after having abandoned his medical studies, became a writer whose novel Les morticoles was a cruel satire of the medical profession. Among Charcot's pupils, Alfred Binet, Gilbert Ballet, Édouard Brissaud, and Joseph Babinski were particularly involved in the theater. Gilbert Ballet wrote the foreword to La folie au théâtre (Madness in Theatre) by André de Latour. Édouard Brissaud wrote a satiric play Le chèque (The Check), and Joseph Babinski, under the pseudonym of Olaf, was the coauthor with Palau of the drama Les détraquées (The Deranged Women). However, when all is said and done, perhaps the greatest actor in his entourage was Charcot himself. PMID:23485903

  12. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?".

    PubMed

    Teive, Hélio A G; Munhoz, Renato P; Simões, Jefferson C

    2012-04-01

    Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer. PMID:22510742

  13. Charcot spinal arthropathy in a diabetic patient.

    PubMed

    van Eeckhoudt, S; Minet, M; Lecouvet, F; Galant, C; Banse, X; Lambert, M; Lefèbvre, C

    2014-08-01

    We report a case of Charcot spinal arthropathy in a diabetic patient and emphasize the clinical reasoning leading to the diagnosis, discuss the differential diagnosis, and insist on the crucial role of the radiologist and pathologist which allows the distinction between Charcot spinal arthropathy and infectious or tumoural disorders of the spine. PMID:25012751

  14. Charcot-Marie-Tooth disease

    PubMed Central

    Sivera, Rafael; Vílchez, Juan Jesús; Martínez-Rubio, Dolores; Chumillas, María José; Vázquez, Juan Francisco; Muelas, Nuria; Bataller, Luis; Millán, José María; Palau, Fancesc; Espinós, Carmen

    2013-01-01

    Objectives: To determine the genetic distribution and the phenotypic correlation of an extensive series of patients with Charcot-Marie-Tooth disease in a geographically well-defined Mediterranean area. Methods: A thorough genetic screening, including most of the known genes involved in this disease, was performed and analyzed in this longitudinal descriptive study. Clinical data were analyzed and compared among the genetic subgroups. Results: Molecular diagnosis was accomplished in 365 of 438 patients (83.3%), with a higher success rate in demyelinating forms of the disease. The CMT1A duplication (PMP22 gene) was the most frequent genetic diagnosis (50.4%), followed by mutations in the GJB1 gene (15.3%), and in the GDAP1 gene (11.5%). Mutations in 13 other genes were identified, but were much less frequent. Sixteen novel mutations were detected and characterized phenotypically. Conclusions: The relatively high frequency of GDAP1 mutations, coupled with the scarceness of MFN2 mutations (1.1%) and the high proportion of recessive inheritance (11.6%) in this series exemplify the particularity of the genetic distribution of Charcot-Marie-Tooth disease in this region. PMID:24078732

  15. [Demonology and demonopathy under Charcot].

    PubMed

    Céard, J

    1994-01-01

    What an advantage, he, who is studying devil and witchcraft stories, would get with "Retrospective medicine" carried through the "Ecole de la Salpêtrière"? Those are collected in the Sister Jeanne des Anges autobiography plentiful annotations, printed by the "Bibliothèque Diabolique" from Bourneville (1886) and "Les démoniaques dans l'art", written by Charcot and Richer (1887). The first one is proposing to evoque the nun's symptoms as hysterical facts and to find every typical expression regarding that disease. It does not go thoroughly into the hallucinations content, that is to say the imaginative part of them, as well as contemporary people minding that hysteria remains unchanging year after year and that its cultural alterations are really uninteresting. Charcot and Richer's book asserts that the devilish is a devilish without fiend, that is why it is approving the Saint-Médard's convulsive people but, on the contrary, nothing is said about the bright witchcraft pictures. Then, despite its history, devilish contain is going hand to hand. Those historical studies are not trying to give a run down on a medical view of devilish approach but to make clear real hysterical knowledge; it means that before the medical deepening every one knows that dense disease. PMID:11640487

  16. An overview of the Charcot foot pathophysiology

    PubMed Central

    Kaynak, Gökhan; Birsel, Olgar; Güven, Mehmet Fatih; Öğüt, Tahir

    2013-01-01

    Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require in-depth investigations of its enigmatic nature to establish useful guidelines. Yet, this goal seems to be beyond reach, without a holistic view of the immense literature concerning the pathophysiology of the disorder. The primary objective of this article is to put together and review the recent advancements about the etiology and intrinsic mechanisms of diabetic Charcot foot. PMID:23919113

  17. Hysteria after Charcot: back to the future.

    PubMed

    Bogousslavsky, Julien

    2011-01-01

    The studies on hysteria and hypnotism probably constitute the most important long-term work of Jean-Martin Charcot and his school, starting around 1870 until Charcot's death in 1893. Désiré Bourneville, Charcot's sixth interne at La Salpêtrière, was probably instrumental in stimulating his mentor's interest in hysteria, while Charles Richet's 1875 article on somnambulism was the trigger for Charcot to introduce hypnotism into the management of hysterics. Albert Pitres, Paul Richer, Georges Gilles de la Tourette, Paul Sollier, Joseph Babinski, Sigmund Freud and Pierre Janet became the most famous of Charcot's collaborators on hysteria, either as 'guardians of the temple' (Richer, Gilles de la Tourette, who defended their mentor's concepts against Hippolyte Bernheim and the Nancy school in the dispute during the 1880-1890s), or in renewing the field in psychology (Janet and Freud, in the 1890s) or clinical neurology (Babinski in the 1900s). In 1908, a 'quarrel of hysteria' led several of Charcot's pupils into opposition with each other, from which Babinski was considered victorious against Charcot's successor Fulgence Raymond, despite the weaknesses of his theory on 'pithiatism'. During World War I, there was a new surge of interest in hysteria associated with war psycho-neuroses, and several students of Charcot became actively involved in medical military care (Sollier, Babinski, Gilbert Ballet, Achille Souques). Babinski's pupil Clovis Vincent developed a treatment called torpillage (torpedoing) against war hysteria, associating painful galvanic current discharges with 'persuasion', but this was dismissed after the soldiers, considering it as torture, rebelled. After World War I, the neurological and psychiatric interest in hysteria again faded away, and this condition largely went back to the no-man's land, where it had been before Charcot initiated his studies. A comprehensive look at the evolution of ideas on hysteria in the followers of Charcot shows that

  18. Jean-Martin Charcot and his legacy.

    PubMed

    Bogousslavsky, Julien

    2014-01-01

    Jean-Martin Charcot (1825-1893) rightly is considered the father of both modern neurology and psychiatry in France and much beyond. While he never was interested in mental disease and what was called 'alienism' at the time, his career at La Salpêtrière Hospital over 30 years was mainly marked by the development of a huge group of students which focused on the study and management of hysteria. When Charcot took office at the beginning of 1862, hysteria was a 'no-man's land', medically speaking, since neither the alienists nor the internists had much interest in this condition. At La Salpêtrière, these chronic patients were largely left to themselves before Désiré Bourneville, one of Charcot's first students, convinced his chief to care for them. Subsequently, the studies of Charcot with Paul Richer, Joseph Babinski, Georges Gilles de la Tourette, Paul Sollier, Pierre Janet, and many others allowed the condition to be addressed in detail. During his stay with Charcot in 1885-1866, Sigmund Freud, a young neuropathologist at the time, became fascinated by hysteria, an interest which probably was the main start of his interest in psychology. Charcot emphasized the concept of mental factors in hysteria, along with that of a 'dynamic' lesion, which accounted for the lack of neuropathological findings in the patients. While his ideas on hysteria and hypnotism were criticized after his death even by former pupils, such as Babinski, recent findings from functional studies using magnetic resonance imaging show how accurate and often visionary Charcot's thinking was in this field. PMID:25273488

  19. Jean-martin charcot pathologist, neurologist, psychiatrist and physician.

    PubMed

    Pandey, Sanjay

    2012-10-01

    Jean-Martin Charcot is known as father of modern neurology. Before him, neurology was only limited to select disorders like chorea. His contributions were not limited to neurology only, as he was instrumental in many new developments in the field of pathology, psychiatry, and internal medicine. Even after 100 years, Charcot`s clinical methods remain the pillar of modern neurology. PMID:23349597

  20. [Edouard Brissaud (1852-1909), Charcot's favorite pupil].

    PubMed

    Poirier, Jacques; Ricou, Philippe

    2010-01-01

    Edouard Brissaud's career and scientific work are deeply marked by the influence of professor Jean-Martin Charcot, Head of the Chair of clinics of nervous system diseases at the Salpêtrière. Brissaud was his "externe" in 1875 and his "interne" in 1879. In 1880, his medical thesis was presided over by Charcot, who also served as a jury member for his "agrégation" in 1886. Brissaud was the king pin and the cornerstone of the famous medical handbook (Traité de médecine), which was kindly supported by Charcot and Bouchard. In 1893, a few months before Charcot's death, Brissaud, encouraged by Charcot, founded the Revue neurologique with Pierre Marie. When, after Charcot's death, Brissaud, in charge of the interim of the Salpêtrière's Chair, paid a glowing tribute to him, in his first lecture. Charcot thought highly of Brissaud and was fond of him. Two unpublished letters from Charcot to Brissaud gave evidence of his attachment to him. In one of these letters, Charcot friendly discussed the medical handbook with Brissaud and left his son Jean-Baptiste Charcot, as an "interne", in the care of Brissaud. In the other letter, Charcot gave Brissaud an original observation of alcoholic paralysis and asked him what he thought of it. On the whole, as pertinently written by late professor Jean-Louis Signoret, "Edouard Brissaud was undoubtedly Charcot's favourite disciple". PMID:21560379

  1. Jean-Martin Charcot Pathologist, Neurologist, Psychiatrist and Physician

    PubMed Central

    Pandey, Sanjay

    2012-01-01

    Jean-Martin Charcot is known as father of modern neurology. Before him, neurology was only limited to select disorders like chorea. His contributions were not limited to neurology only, as he was instrumental in many new developments in the field of pathology, psychiatry, and internal medicine. Even after 100 years, Charcot`s clinical methods remain the pillar of modern neurology. PMID:23349597

  2. Charcot-Marie-Tooth disease

    PubMed Central

    Manganelli, Fiore; Nolano, Maria; Pisciotta, Chiara; Provitera, Vincenzo; Fabrizi, Gian M.; Cavallaro, Tiziana; Stancanelli, Annamaria; Caporaso, Giuseppe; Shy, Michael E.

    2015-01-01

    Objective: To evaluate, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes (CMT1A, late-onset CMT1B, and CMTX1), and rarer forms of CMT caused by mutations in RAB7 (CMT2B), TRPV4 (CMT2C), and GDAP1 (AR-CMT2K) genes. Methods: We investigated axonal loss by quantifying Meissner corpuscles and intrapapillary myelinated endings and evaluated morphometric changes in myelinated dermal nerve fibers by measuring fiber caliber, internodal, and nodal gap length. Results: The density of both Meissner corpuscles and intrapapillary myelinated endings was reduced in skin samples from patients with CMT1A and all the other CMT genotypes. Nodal gaps were larger in all the CMT genotypes though widening was greater in CMT1A. Perhaps an altered communication between axons and glia may be a common feature for multiple forms of CMT. Internodal lengths were shorter in all the CMT genotypes, and patients with CMT1A had the shortest internodes of all our patients. The uniformly shortened internodes in all the CMT genotypes suggest that mutations in both myelin and axon genes may developmentally impede internode formation. The extent of internodal shortening and nodal gap widening are likely both important in determining nerve conduction velocities in CMT. Conclusions: This study extends the information gained from skin biopsies on morphologic abnormalities in various forms of CMT and provides insights into potential pathomechanisms of axonal and demyelinating CMT. PMID:26362287

  3. Charcot foot associated with chronic alcohol abuse

    PubMed Central

    Arapostathi, Christina; Tentolouris, Nicholas; Jude, Edward B

    2013-01-01

    Two patients without a history of diabetes mellitus but with a history of chronic alcohol abuse were referred to our foot clinic due to pain and deformity of the midfoot. On examination both of the feet of the first patient and the left foot of the second patient were swollen and warm but all the inflammatory markers were negative. Subsequent imaging revealed Charcot deformity and the patients were treated with casting and special shoes. The temperature and the swelling of the feet after the offloading improved. x-Rays which were performed 1 and 2 years after the diagnosis did not show any progression of the Charcot deformity. PMID:23563675

  4. Migrating bone shards in dissecting Charcot joints.

    PubMed

    Forrester, D M; Magre, G

    1978-06-01

    Extensive periarticular calcification is characteristic of Charcot joints. Fragmentation of the articular margins of bone contributes to the bony detritus, but the majority forms de novo in the joint capsule. Occasionally the calcific debris is seen far removed from the joint. Dissection of a chronically distended joint along muscle planes is most commonly associated with the inflammatory joint disease of rheumatoid arthritis. Its occurrence in Charcot joints is documented by arthrography, which demonstrates continuity of the joint space and the distant calcifications. PMID:418652

  5. Surgical treatment of the Charcot foot.

    PubMed

    Pinzur, Michael S

    2016-01-01

    With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive-minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition. PMID:26813619

  6. Neurology outside Paris following Charcot.

    PubMed

    Moulin, Thierry; Clarac, François; Petit, Henri; Broussolle, Emmanuel

    2011-01-01

    The Middle Ages saw the development of numerous universities in the different provinces that later became the kingdom of France. In 1794, Napoleon I established 3 medical schools in Paris, Montpellier and Strasbourg, which were transformed into medical faculties in 1808. France had always been a highly centralized country, but during the 19th century, this trend started to change with the creation of medical faculties in Nancy (1872), Lille (1877), Lyon (1878), Bordeaux (1879), Toulouse (1891), Algiers (1910) and Marseille (1930). Following the creation of the 12 foundation courses, specialized chairs were progressively established in Paris, but for a long time this remained restricted to the French capital. However, with the emergence of medicine as an academic discipline in several towns outside Paris, came the development of neurology. This was greatly influenced by former students of Jean-Martin Charcot, local personalities, and the interactions between the two. Leading figures included Albert Pitres in Bordeaux, Léon Ingelrans in Lille, Eugène Devic and Jules Froment in Lyon, Lucien Cornil in Marseille, Joseph Grasset in Montpellier, and Marcel Riser in Toulouse. The interaction between French and Germanic medical communities also developed at this turbulent time under the influence of several great physicians such as Wilhelm Waldeyer, Adolf Kussmaul, and later Jean Alexandre Barré in Strasbourg, and Hippolyte Bernheim in Nancy. There are a number of other university towns outside Paris in which the development of neurology was probably influenced by the same interactions with psychiatry. It would be worth carrying out a thorough analysis of these towns in order to present an exhaustive overview of the development of neurology in France. PMID:20938155

  7. Charcot neuroarthropathy of the foot and ankle.

    PubMed

    Schon, L C; Easley, M E; Weinfeld, S B

    1998-04-01

    The goal of this study was to characterize Charcot neuroarthropathy of the foot and ankle by specific sites of involvement (ankle, hindfoot, midfoot, and forefoot), modes of presentation, methods of management, and outcome. A summary of treatment and results for 50 ankles, 22 hindfeet, 131 midfeet, and 18 forefeet is presented. Nondisplaced neuropathic ankle fractures typically healed uneventfully with casting and bracing. For displaced ankle fractures, closed reduction and casting generally resulted in loss of reduction and progressive deterioration; better results were obtained with open reduction and internal fixation, using supplemental Kirschner wires and screws. Ankles with Charcot neuroarthropathy and preexisting arthritis typically required arthrodesis. Of the ankles with neuropathic avascular talar necrosis, approximately 1/3 did well with nonoperative intervention and 2/3 required surgery. Chronic, unstable, malaligned Charcot ankles often required arthrodesis. Neuropathic calcaneal fractures were managed successfully nonoperatively. For feet with transverse tarsal joint involvement (Schon Type IV), management was more complex. Nonoperative treatment was successful for less than 1/2. Two thirds of the feet with midtarsus involvement (Schon Types I, II, and III) were managed successfully nonoperatively; 1/3 required surgery for recurrent ulceration, instability, or osteomyelitis. Half of the feet with forefoot neuroarthropathy required surgery for malalignment, ulceration, and/or difficulty with shoewear or braces. This review has established patterns of Charcot involvement of the foot and ankle with corresponding methods of treatment and subsequent responses. From this extensive clinical experience with 221 neuropathic fractures or Charcot joints, recommendations were derived to assist in selecting appropriate management options. PMID:9584374

  8. [Charcot and his legacy to medicine].

    PubMed

    Camacho Aguilera, José Francisco

    2012-01-01

    Jean-Martin Charcot (1825-1893) was a French physician whose professional life is divided into two phases: the first dedicated to neurology, and the second dedicated to the psychiatry area. Charcot is considered the father of modern neurology. In the Hospice de la Salpêtrière he began his research on neurological diseases, founded a laboratory of pathology (including microscopy and photography), and gave hospital classes based on pathological anatomy related to clinical manifestations based in the field of neurology. His research led to the description and study of different neurological diseases, such as multiple sclerosis, lateral amyotrophic sclerosis, hereditary motor and sensory neuropathy, motor ataxia, Parkinson`s disease, Gilles de la Tourette syndrome, epilepsy, visual aphasia and agnosia, to name a few. Some signs and diseases took their name as an eponym, and some are still mentioned in the current medicine, while others are left in oblivion. PMID:22820369

  9. The prefaces by Charcot: leitmotifs of an international career.

    PubMed

    Goetz, Christopher G

    2003-04-22

    The objective of this article was to examine the prefaces that Jean-Martin Charcot wrote for other colleagues' books and to evaluate these short essays from three perspectives: scientific material discussed, medicopolitical strategies revealed, and larger thematic issues developed. Charcot (1825-1893) was the most celebrated clinical neurologist of his epoch. In his mid and late career, he wrote very few manuscripts, delegating such work to junior colleagues or to Bourneville, who compiled Charcot's Complete Works. One particular source of direct writing from Charcot's mature career is the group of prefaces he composed for selected monographs authored by other colleagues. The prefaces from the Gasser tabulation (Bibliothèque Charcot, Paris) of Charcot's works were examined and analyzed in the context of Charcot's career. Of the 21 prefaces, 10 concerned books by other colleagues with whom he had not worked, and 11 introduced books of his students or direct colleagues. The prefaces concerned primarily two topics of direct medical interest to Charcot: localization studies of cortical and spinal cord diseases, and the combined subject of hysteria and hypnotism. In placing the works in scientific context, Charcot systematically emphasized the contributions of French neurologists, largely focusing on the Salpêtrière school and its (his) discoveries. Charcot used these prefaces to summarize the major thematic elements of his career, drafting the essays in the context of such topics as medical specialization, the concept of experimental medicine, and the prioritization of human studies over experimental laboratory medicine. Although an exhaustive reading of Charcot's entire opus is needed to provide a comprehensive view of his ideas, the short and pithy prefaces, comprising fewer than 60 pages, coalesce and distill the primary themes of his international career. PMID:12707438

  10. The Charcot foot: pathophysiology, diagnosis and classification.

    PubMed

    Trieb, K

    2016-09-01

    Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented. Cite this article: Bone Joint J 2016;98-B:1155-9. PMID:27587513

  11. Recognizing Charcot disease in a man with diabetes.

    PubMed

    Womack, Jamie M

    2016-05-01

    Charcot disease is a neurogenic osteoarthropathy that occurs in the foot and ankle following the loss of normal muscle tone, vascularization, and protective reflexes. Diabetes is its most common cause in the Western world. Fragmentation, destruction, and dislocation of the bones can occur spontaneously or after trauma. This article describes the care of a patient with Charcot disease. PMID:27124227

  12. Did Jean-Martin Charcot contribute to stroke?

    PubMed

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2010-01-01

    Stroke was never identified as a significant, autonomous field of activity of the emerging school of neurology at La Salpêtrière, which developed after the appointment of Jean-Martin Charcot (1825-1893) during the last days of 1861. However, stroke was already present in Charcot's first paper (1851), which dealt with a case of multiple organ cardiac embolism, including middle cerebral artery infarction, at a time when the studies of Rudolf Virchow on thromboembolism were unknown in France. A few years later, Charcot made a still up-to-date description of vascular intermittent claudication, which had only been reported in the horse. In the 1860s, Charcot and his pupils presented several major works dealing with cerebrovascular disease, including famous studies on miliary aneurysms in cerebral hemorrhage. This work was done with Charles Bouchard, at the time Charcot's 'interne', but who would become one of his 'political' opponents 2 decades later, when in 1892, as president of the 'agrégation' jury, he rejected the professorship application of 4 protégés of Charcot, including Joseph Babinski and Georges Gilles de la Tourette. Further work on cerebrovascular disease by Charcot included histological studies of brain 'softening', paraneoplastic cerebral arterial occlusion and consequences of stroke (e.g. arthropathies, vegetative changes, contractures and abnormal movements). Brain localization, one of Charcot's major neurological topics, was also largely based on stroke case studies. Charcot's work on stroke remains poorly recognized, but it demonstrates his unique skills in stimulating scientific work in younger colleagues, many of whom subsequently became major figures of neurology and psychiatry. PMID:20588046

  13. Jean-Baptiste Charcot, the French Antarctic expedition and scurvy.

    PubMed

    Teive, Hélio Afonso Ghizoni; Germiniani, Francisco Manoel Branco; Munhoz, Renato Puppi

    2014-07-01

    During the second expedition to the South Pole, Commander Jean-Baptiste Charcot and some members of the crew of "Pourquoi Pas?" developed symptoms suggestive of scurvy. The clinical picture was totally reversed after dietary changes. PMID:25054991

  14. Jean-Martin Charcot: neurologist by avocation, nephrologist by yearning.

    PubMed

    Eknoyan, Garabed

    2011-01-01

    In an age of medical advances and specialization, Jean-Martin Charcot (1825-1893) helped found the discipline of neurology and in 1882 was appointed the first Professor of Diseases of the Nervous System in France. As an investigator with broad interests and vast knowledge, Charcot contributed to several other disciplines. An early mentor and dominant figure in Charcot's formative years was Pierre Rayer (1793-1867), famous for his seminal contributions to the study of the kidney, who gifted to Charcot his passion for clinical pathological correlations and likely a yearning for the study of kidney diseases. Famous for the clarity and incisiveness of his formal teaching presentations, Charcot lectured on the kidney at the Faculty of Medicine in Paris in 1877. Translated into English and published as a book titled Lectures on Bright's Disease, those lectures became widely accessible and quoted in the literature through the 1940s. In addition, at a time when he was already concentrating on the study of neurological disorders, Charcot maintained his life-long interest in the kidney and published original studies on the pathological changes of the kidney in gout and experimental lead poisoning, as well as supporting a study of hysterical ischuria by his students. PMID:21614774

  15. Update on Charcot-Marie-Tooth Disease

    PubMed Central

    Patzkó, Ágnes; Shy, Michael E.

    2011-01-01

    Charcot-Marie-Tooth disease (CMT) disease encompasses a genetically heterogeneous group of inherited neuropathies, also known as hereditary motor and sensory neuropathies. CMT results from mutations in more than 40 genes expressed in Schwann cells and neurons causing overlapping phenotypes. The classic CMT phenotype reflects length-dependent axonal degeneration characterized by distal sensory loss and weakness, deep tendon reflex abnormalities, and skeletal deformities. Recent articles have provided insight into the molecular pathogenesis of CMT, which, for the first time, suggest potential therapeutic targets. Although there are currently no effective medications for CMT, multiple clinical trials are ongoing or being planned. This review will focus on the underlying pathomechanisms and diagnostic approaches of CMT and discuss the emerging therapeutic strategies. PMID:21080241

  16. The Charcot foot: medical and surgical therapy.

    PubMed

    Ulbrecht, Jan S; Wukich, Dane K

    2008-12-01

    Charcot neuro-osteoarthropathy (CN) is among the most devastating complications of neuropathy and now most commonly occurs in the feet of diabetic patients. Because it is relatively rare and because most patients and practitioners do not expect major bone pathology in the absence of significant pain, CN is often misdiagnosed as cellulitis, deep venous thrombosis, or gout. Also, radiographs early in the process are often relatively unremarkable. Although MRI findings are characteristic, treatment should not wait for the MRI result. The hot swollen erythematous neuropathic foot suspected to be CN should be emergently mechanically protected, usually in an irremovable total contact cast. Mechanical protection is the mainstay of conservative therapy, but surgical reconstruction of a deformed foot can usually also be successful. Unless diagnosed very early, significant decrements in quality of life result. Controlled studies are urgently needed to identify best practices. PMID:18990300

  17. Jules Bernard Luys in Charcot's penumbra.

    PubMed

    Parent, Martin; Parent, André

    2011-01-01

    Jules Bernard Luys (1828-1897) is a relatively unknown figure in 19th century French neuropsychiatry. Although greatly influenced by Jean-Martin Charcot (1825-1893), Luys worked in the shadow of the 'master of La Salpêtrière' for about a quarter of a century. When he arrived at this institution in 1862, he used microscopy and photomicrography to identify pathological lesions underlying locomotor ataxia and progressive muscular atrophy. He later made substantial contributions to our knowledge of normal human brain anatomy, including the elucidation of thalamic organization and the discovery of the subthalamic nucleus. Luys's name has long been attached to the latter structure (corps de Luys), which is at the center of our current thinking about the functional organization of basal ganglia and the physiopathology of Parkinson's disease. As head of the Maison de santé d'Ivry, Luys developed a highly original view of the functional organization of the normal human brain, while improving our understanding of the neuropathological and clinical aspects of mental illnesses. In 1886, Luys left La Salpêtrière and became chief physician at La Charité hospital. Following Charcot, whom he considered as the father of scientific hypnotism, Luys devoted the last part of his career to hysteria and hypnosis. However, Luys ventured too deeply into the minefield of hysteria. He initiated experiments as unconventional as the distant action of medication, and became one of the most highly caricatured examples of the fascination that hysteria exerted upon neurologists as well as laypersons at the end of the 19th century. PMID:20938152

  18. Jean-Martin Charcot's Role in the 19th Century Study of Music Aphasia

    ERIC Educational Resources Information Center

    Johnson, Julene K.; Lorch, Marjorie; Nicolas, Serge; Graziano, Amy

    2013-01-01

    Jean-Martin Charcot (1825-93) was a well-known French neurologist. Although he is widely recognized for his discovery of several neurological disorders and his research into aphasia, Charcot's ideas about how the brain processes music are less well known. Charcot discussed the music abilities of several patients in the context of his "Friday…

  19. Freud with Charcot: Freud's discovery and the question of diagnosis.

    PubMed

    Lepoutre, Thomas; Villa, François

    2015-04-01

    Although Charcot's seminal role in influencing Freud is widely stated, although Freud's trip to Paris to study with Charcot is well recognized as pivotal in his shift from neurological to psychopathological work, a key fact of the Freudian heuristic remains largely underestimated: namely, that Freud's psychopathological breakthrough, which gave birth to psychoanalysis, cannot be separated from his 'diagnostic preoccupation', which is a crucial and at times the first organizing principle of his earliest writings. The purpose of this article is therefore to reopen the question of diagnosis by following its development along the path leading from Charcot to Freud. The authors demonstrate that Freud's careful attention to diagnostic distinctions follows strictly in the direction of Charcot's 'nosological method'. More importantly, the article intends to identify the precise way in which his ideas operate in Freud's own work, in order to understand how Freud reinvests them to forge his own nosological system. If the authors trace the destiny of Charcot's lessons as they reach Freud's hands, it is the importance granted to mixed neuroses in Freud's psychopathology that allows them to pinpoint the role played by the diagnostic process in the rationality of psychoanalysis. PMID:25363538

  20. Etiology, pathophysiology and classifications of the diabetic Charcot foot

    PubMed Central

    Papanas, Nikolaos; Maltezos, Efstratios

    2013-01-01

    In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification. PMID:23705058

  1. [Rehabilitation of Charcot-Marie-Tooth Disease].

    PubMed

    Tajima, Fumihiro; Nakamura, Takeshi; Nishimura, Yukihide; Arakawa, Hideki; Kawasaki, Takashi; Ogawa, Takahiro; Nishiyama, Kazunari

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neuromuscular diseases causing progressive muscle weakness; contracture; deformity in the feet, legs, and hands; and impairments of ambulation and handgrip. Reduced physical ability can be attributed not only to the disease but also to physical deconditioning. Previously, most physicians in the field of rehabilitation were anxious about the hypothesis of overwork weakness in CMT, and did not conduct intensive exercise programs for patients with CMT. However, recent studies have reported that progressive resistance strengthening programs for lower extremities are feasible, safe, beneficial, and improve exercise intolerance and undue fatigue in patients with CMT. Although the improvement in exercise tolerance may be partly due to the reversal of deconditioning effect of related sedentary lifestyle, progressive resistance training and physical fitness can improve walking function, activities of daily living, and subjective perception of pain and fatigue in patients with CMT. To increase the daily physical function, some studies described the potential benefits of ankle-foot orthoses (AFOs); however, no control study supported it. So far, the training programs on CMT have been dependent on the exercise programs for able-bodied individuals. To increase the effects of rehabilitation, optimal programs that combine the training protocol and AFO strategies will have to be designed for patients with CMT. PMID:26764300

  2. [Pathology of Charcot-Marie-Tooth Disease].

    PubMed

    Oka, Nobuyuki

    2016-01-01

    Although genetic testing is available, nerve biopsy is useful in selected patients for the diagnosis of Charcot-Marie-Tooth disease (CMT). These are sporadic cases of hereditary neuropathy, or familial cases in which genetic testing is negative. CMT is caused by mutations of various genes. The pathological features of CMT have mostly been investigated using nerve biopsy, which may shed light on the presumed functions of mutated gene products. PMP22 duplication in CMT1A induces numerous large onion bulb lesions (OB). Compared to chronic inflammatory demyelinating polyradiculoneuropathy, the differential features of CMT1A are patchy distribution of OB and non-inflammatory lesions. CMT1B also manifests as OB, but presents abnormal compaction of myelin sheaths caused by uncompacted myelin or excessive myelin folding. CMT2 includes axonal neuropathies and many causative genes have been found. CMT2A (MFN2 mutation) shows abnormal mitochondria with a spherical morphology instead of tubular in the longitudinal direction. CMT4 consists of autosomal recessive forms with demyelinating pathology. Most subtypes have mutations of genes relating to myelin maintenance, and pathologically, they show abnormal folding of the myelin structure. PMID:26764296

  3. An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients

    ClinicalTrials.gov

    2015-04-28

    Charcot Marie Tooth Disease (CMT); Hereditary Sensory and Motor Neuropathy; Nerve Compression Syndromes; Tooth Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System

  4. Charcot Marie Tooth disease (CMT): historical perspectives and evolution.

    PubMed

    Kazamel, Mohamed; Boes, Christopher J

    2015-01-01

    Prior to Charcot and Marie's and Tooth's reports, patients with peroneal muscular atrophy had been described by Virchow, Eulenburg, Friedreich, Osler, and others. In February 1886, Charcot and Marie published their original description of five patients who had what they called Progressive Muscular Atrophy. They surmised that the lesion could be in the spinal cord. Three months later, Tooth presented his M.D. degree thesis entitled "Peroneal Type of Progressive Muscular Atrophy", to the University of Cambridge, UK. Tooth localized the pathology to the peripheral nerves. Dyck and Lambert (Arch Neurol 18:619-625, 1968) classified several CMT kinships based on differences in modes of inheritance, natural history, biochemical features, nerve conduction velocity, and pathologic characteristics. This article will focus on historical landmarks and major discoveries pertinent to the disease since its original description through the second half of the twentieth century. PMID:25201224

  5. Jean-Martin Charcot at the birth of Russian neurology.

    PubMed

    Vein, Alla A

    2011-01-01

    Russian neurology was virtually nonexistent in the middle of the 19th century which made a traineeship abroad an absolute necessity. Charcot and his school did not just offer professional training, but created the best minds, which would determine the direction of neurology and psychiatry in Russia for many decades. After returning home, young Russian doctors not only implemented everything they had learned in Western Europe, but proceeded to make their own original contributions. The most talented pupils of Charcot, including such prominent names as Kozhevnikov, Korsakov, Minor, Bekhterev and Darkshevich, became the founders of neurological schools in Russia. They laid the basis for the further development of neurology and psychiatry. Remarkably, though trained by the same teachers, each of these future 'founding fathers' of these neurological and psychiatric schools followed his own individual path which resulted in an undeniable diversity in Russian neurology and psychiatry during the period of their formation. PMID:21252555

  6. Charcot neuroarthropathy: An often overlooked complication of diabetes.

    PubMed

    Botek, Georgeanne; Anderson, Martha A; Taylor, Ryan

    2010-09-01

    In patients with long-standing, poorly controlled diabetes and peripheral neuropathy, a red, hot, swollen foot without open ulceration should raise the suspicion of Charcot neuroarthropathy, an often-overlooked diabetic foot complication. The authors discuss key diagnostic features and how to differentiate this condition from cellulitis, osteomyelitis, and other conditions. They review key elements of the workup and emphasize the importance of early diagnosis and prompt treatment to preserve a functioning foot. PMID:20810870

  7. Charcot arthropathy in ultrasound examination – a case report

    PubMed Central

    Nowakowska-Płaza, Anna; Walentowska-Janowicz, Marta; Chojnowski, Marek; Sudoł-Szopińska, Iwona

    2016-01-01

    This article presents a patient with a long history of type 1 diabetes mellitus complicated with neuropathy and Charcot disease. The most common cause of neuropathic osteoarthropathy, called Charcot osteoarthropathy, is poorly controlled diabetes. The clinical picture is characterized by considerable edema, redness and increased skin temperature with relatively slight pain due to injury to nerve fibers responsible for pain sensation. The differential diagnosis should include bacterial or autoimmune arthritis, arthritis associated with gout as well as venous thrombosis and injury. The contribution of a local inflammatory reaction and abnormal bone turnover with excessive osteoclast activity might play a role in the etiopathogenesis of this disease. As a result, osseous and articular destruction progresses rapidly leading to irreversible deformity of the foot. Avoiding weight-bearing and resting the foot in a specially selected plaster cast is the most important part of treatment. Patients with the aforementioned complaints are referred to radiologists for imaging examinations. An ultrasonographer should pay attention to changes typical of Charcot arthropathy, such as: inflammatory and destructive changes in joints of the foot, uneven contour of bones with thickening and periosteal hyperemia as well as soft tissue swelling. PMID:27446605

  8. Charcot arthropathy in ultrasound examination - a case report.

    PubMed

    Płaza, Mateusz; Nowakowska-Płaza, Anna; Walentowska-Janowicz, Marta; Chojnowski, Marek; Sudoł-Szopińska, Iwona

    2016-06-01

    This article presents a patient with a long history of type 1 diabetes mellitus complicated with neuropathy and Charcot disease. The most common cause of neuropathic osteoarthropathy, called Charcot osteoarthropathy, is poorly controlled diabetes. The clinical picture is characterized by considerable edema, redness and increased skin temperature with relatively slight pain due to injury to nerve fibers responsible for pain sensation. The differential diagnosis should include bacterial or autoimmune arthritis, arthritis associated with gout as well as venous thrombosis and injury. The contribution of a local inflammatory reaction and abnormal bone turnover with excessive osteoclast activity might play a role in the etiopathogenesis of this disease. As a result, osseous and articular destruction progresses rapidly leading to irreversible deformity of the foot. Avoiding weight-bearing and resting the foot in a specially selected plaster cast is the most important part of treatment. Patients with the aforementioned complaints are referred to radiologists for imaging examinations. An ultrasonographer should pay attention to changes typical of Charcot arthropathy, such as: inflammatory and destructive changes in joints of the foot, uneven contour of bones with thickening and periosteal hyperemia as well as soft tissue swelling. PMID:27446605

  9. Quality-of-life in Charcot-Marie-Tooth disease: the patient's perspective.

    PubMed

    Johnson, Nicholas E; Heatwole, Chad R; Dilek, Nuran; Sowden, Janet; Kirk, Callyn A; Shereff, Denise; Shy, Michael E; Herrmann, David N

    2014-11-01

    This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance of each symptom identified. Prevalence and symptom impact were analyzed by age, symptom duration, gender, Charcot-Marie-Tooth type, and employment status. 407 participants returned the survey, identifying foot and ankle weakness (99.7%) and impaired balance (98.6%) as the most prevalent themes. Foot and ankle weakness and limitations with mobility were the themes with the highest impact. Both symptom prevalence and impact gradually increased with age and symptom duration. Several themes were more prevalent in women with Charcot-Marie-Tooth, including activity limitations, pain, fatigue, hip-thigh weakness, and gastrointestinal issues. All of the themes, except emotional or body image issues, were more prevalent among unemployed individuals. There were minimal differences in symptom prevalence between Charcot-Marie-Tooth types. There are multiple symptoms that impact Charcot-Marie-Tooth quality-of-life in adults. These symptoms have different levels of importance, are readily recognized by patients, and represent critical areas of Charcot-Marie-Tooth health. PMID:25092060

  10. Charcot Arthropathy of the Lumbosacral Spine Mimicking a Vertebral Tumor after Spinal Cord Injury

    PubMed Central

    Son, Soo-Bum; Kim, Eun-Sang; Eoh, Whan

    2013-01-01

    Charcot spinal arthropathy is a rare, progressive type of vertebral joint degeneration that occurs in the setting of any preexisting condition characterized by decreased afferent innervation to the extent that normal protective joint sensation in the vertebral column is impaired. The authors report on a case of Charcot arthropathy of the lower lumbar spine mimicking a spinal tumor following cervical cord injury. PMID:24527202

  11. [Jean-Martin Charcot (1825-1893): a physician with multiple facets].

    PubMed

    Lellouch, Alain

    2013-12-01

    This work is registered in the year (2013) commemorating the 120 years since Jean-Martin Charcot's (1825-1893) death. Presently, the event takes place during 2013, in France, in Paris, at Hôpital de la Salpêtrière where Charcot practiced as medical chief of l'Hospice de la Vieillesse-Femmes, from 1862 until he died in 1893. The aim of the research is to show, from various examples and sources (printed and handwritten: fonds d'archives Charcot de la Salpêtrière) how talented Charcot was as a clinician, pathologist and microscopist, researcher and experimenter, teacher, artist, designer, cartoonist, polyglot and traveller), how varied his medical career was and how innovative his scientific method was. All this permitted Charcot to make an impressive number of medical discoveries in various fields which are today known as geriatrics and rheumatology, internal medicine, cardiology, neurology, psychiatry and paranormal processes. PMID:26035927

  12. Diabetic Lisfranc fracture-dislocations and Charcot neuroarthropathy.

    PubMed

    Levitt, Bradley A; Stapleton, John J; Zgonis, Thomas

    2013-04-01

    The goal with Lisfranc fracture-dislocations is to regain joint congruity and reestablish midfoot stability to avoid debilitating posttraumatic arthrosis and chronic pain in the sensate patient. In the diabetic population, dense peripheral neuropathy and/or vascular disease are equally important and may alter the surgical approach to traumatic tarsometatarsal injuries. The initial diagnosis in the diabetic population may be delayed due to subtle radiographic findings and/or patient unawareness of trauma in the insensate foot. Failure to initiate treatment in the early stages of acute diabetic neuropathic Lisfranc injuries can predispose the patient to midfoot instability, potential ulceration, infection, and Charcot neuroarthropathy. PMID:23465814

  13. Diabetic charcot neuroarthropathy of the foot and ankle with osteomyelitis.

    PubMed

    Ramanujam, Crystal L; Stapleton, John J; Zgonis, Thomas

    2014-10-01

    One of the most devastating foot and/or ankle complications in the diabetic population with peripheral neuropathy is the presence of Charcot neuroarthropathy (CN). In recent years, diabetic limb salvage has been attempted more frequently as opposed to major lower extremity amputation for CN of the foot and ankle with ulceration and/or deep infection. Treatment strategies for osteomyelitis in the diabetic population have evolved. This article reviews some of the most common surgical strategies recommended for the diabetic patient with CN of the foot and/or ankle and concomitant osteomyelitis. PMID:25281510

  14. Charcot and Les névroses traumatiques: scientific and historical reflections.

    PubMed

    Micale, M S

    1995-06-01

    Between 1878 and 1893, Jean-Martin Charcot published over twenty detailed case histories dealing with what he termed 'traumatic hysteria' and what today would be labelled the psychoneurology of trauma. Charcot's cases record a highly diverse clinique tableau of symptoms. Etiologically, Charcot posited a dual model of a hereditary diathèse, or constitutional predilection to nervous degeneration, and an environmental agent provocateur. Increasingly during the 1880s, he emphasized the role of 'psychical shock'. These writings of Charcot also exhibit many of the same, superb clinical qualities that distinguish his work on other medical topics. Charcot isolated several hystero-traumatic formations and provided outstanding clinical depictions of subgenres of the disorder, most notably brachial monoplegias. His clinical demonstrations of the differential diagnosis of organic and functional post-traumatic pathologies represent Charcot the virtuoso neurologist at his finest. Taken together, these writings offer a penetrating exploration of the complex and elaborate functional sequelae of minor bodily injury and the phenomenon of traumatic psychogenic somatic symptom-formation. The revival today of medical interest in psycho-traumatic pathology, including the traumatic origins of certain dissociative states, provides an important context for the renewed appreciation of Charcot's work in this area. PMID:11619017

  15. Chapter 15: Jean-Martin Charcot and the anatomo-clinical method of neurology.

    PubMed

    Goetz, Christopher G

    2010-01-01

    Jean-Martin Charcot (1825-1893) was the premier clinical neurologist of the 19th century. Charcot's research was anchored in the anatomo-clinical method, a two-part methodology that linked clinical signs with anatomical lesions. The first step of this method involved the careful documentation of clinical signs with longitudinal observation. At the time of death, the second step involved autopsy examination of the brain and spinal cord. With combined clinical and anatomical data, Charcot was able to suggest concrete clinical-anatomical correlations. This method helped to define the tracts and nuclei responsible for normal and abnormal neurological signs and was pivotal to a new classification of neurological diseases based on anatomy. The best-developed example of this method was Charcot's work with motor system degenerative disorders, specifically amyotrophic lateral sclerosis. These studies led to the international designation of amyotrophic lateral sclerosis as Charcot's disease. Other examples of the fruits of the anatomo-clinical method included several stroke syndromes and the linkage of specific signs to specific lesions in multiple sclerosis. The discipline fostered cortical localization theory, which moved neurologists away from the concept of the brain as a homogenous organ in preference to the concept that brain regions controlled specific motor, sensory and language functions. Charcot's attempts to apply his anatomo-clinical method to the knotty neurological diagnosis of hysteria led him to experiments and conclusions that drew criticism and even scorn from colleagues. These events tarnished Charcot's reputation at the close of his career. In the context of Charcot's extensive discoveries and lasting contributions, the anatomo-clinical method remains the anchor of modern neurological diagnosis and is Charcot's most important contribution to clinical neurology. PMID:19892118

  16. De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.

    PubMed

    Motley, William W; Palaima, Paulius; Yum, Sabrina W; Gonzalez, Michael A; Tao, Feifei; Wanschitz, Julia V; Strickland, Alleene V; Löscher, Wolfgang N; De Vriendt, Els; Koppi, Stefan; Medne, Livija; Janecke, Andreas R; Jordanova, Albena; Zuchner, Stephan; Scherer, Steven S

    2016-06-01

    We performed whole exome sequencing on a patient with Charcot-Marie-Tooth disease type 1 and identified a de novo mutation in PMP2, the gene that encodes the myelin P2 protein. This mutation (p.Ile52Thr) was passed from the proband to his one affected son, and segregates with clinical and electrophysiological evidence of demyelinating neuropathy. We then screened a cohort of 136 European probands with uncharacterized genetic cause of Charcot-Marie-Tooth disease and identified another family with Charcot-Marie-Tooth disease type 1 that has a mutation affecting an adjacent amino acid (p.Thr51Pro), which segregates with disease. Our genetic and clinical findings in these kindred demonstrate that dominant PMP2 mutations cause Charcot-Marie-Tooth disease type 1. PMID:27009151

  17. Patient Identification of the Symptomatic Impact of Charcot Marie Tooth Disease Type 1A

    PubMed Central

    Johnson, Nicholas E; Heatwole, Chad R.; Ferguson, Michele; Sowden, Janet E.; Jeanat, Shanie; Herrmann, David N.

    2013-01-01

    Objective The burden of Charcot Marie Tooth type 1A, the most common inherited peripheral neuropathy, including impact on patient quality of life is not well understood. This study aims to qualitatively describe the range of symptoms associated with Charcot Marie Tooth type 1A and impact on quality of life. Methods We performed qualitative interviews with 16 adult Charcot Marie Tooth type 1A patients. Each interview was analyzed using a qualitative framework technique to identify and index symptoms by theme. Results Sixteen patients provided 656 quotes. One hundred and forty-five symptoms of importance were identified representing 20 symptomatic themes. Symptoms associated with difficulty with mobility and ambulation, specific activity impairment, and emotional distress were the most frequently mentioned. Conclusions Multiple symptoms contribute to Charcot Marie Tooth type 1A disease burden, some previously under-recognized. Improved recognition of under-recognized symptoms will optimize patient care and quality of life. PMID:23965405

  18. Dens invaginatus (Type III B)

    PubMed Central

    Kallianpur, Shreenivas; Sudheendra, US; Kasetty, Sowmya; Joshi, Prathamesh

    2012-01-01

    Dens invaginatus or ‘dens in dente’ is a developmental malformation of the tooth resulting from infolding of the dental papilla before calcification. This article presents a case of dens invaginatus occurring in maxillary right lateral incisor of a 45-year-old male patient. The patient presented with pain and clinically missing maxillary right canine. The tooth was found to be non-vital. Radiographic examination revealed the tooth-in-tooth appearance of lateral incisor with a dilated pulp chamber. The crown of impacted canine was found within the pulp chamber of lateral incisor. Owing to this unique clinical presentation, both the lateral incisor and the impacted canine were extracted. Histopathologic examination confirmed the diagnosis of Dens invaginatus Type III B. A brief review on etiopathogenesis, radiographic features and treatment of dens invaginatus has also been included. PMID:22923901

  19. Jean-Martin Charcot's role in the 19th century study of music aphasia.

    PubMed

    Johnson, Julene K; Lorch, Marjorie; Nicolas, Serge; Graziano, Amy

    2013-05-01

    Jean-Martin Charcot (1825-93) was a well-known French neurologist. Although he is widely recognized for his discovery of several neurological disorders and his research into aphasia, Charcot's ideas about how the brain processes music are less well known. Charcot discussed the music abilities of several patients in the context of his 'Friday Lessons' on aphasia, which took place at the Salpêtrière Hospital in Paris in 1883-84. In his most comprehensive discussion about music, Charcot described a professional trombone player who developed difficulty copying music notation and playing his instrument, thereby identifying a new isolated syndrome of music agraphia without aphasia. Because the description of this case was published only in Italian by one of his students, Domenico Miliotti, there has been considerable confusion and under-acknowledgement of Charcot's ideas about music and the brain. In this paper, we describe Charcot's ideas regarding music and place them within the historical context of the growing interest in the neurological underpinnings of music abilities that took place in the 1880s. PMID:23576129

  20. Charcot foot in diabetes and an update on imaging.

    PubMed

    Ergen, Fatma Bilge; Sanverdi, Saziye Eser; Oznur, Ali

    2013-01-01

    Charcot neuroarthropathy (CN) is a serious complication of diabetes mellitus that can cause major morbidity including limb amputation. Since it was first described in 1883, and attributed to diabetes mellitus in 1936, the diagnosis of CN has been very challenging even for the experienced practitioners. Imaging plays a central role in the early and accurate diagnosis of CN, and in distinction of CN from osteomyelitis. Conventional radiography, computed tomography, nuclear medicine scintigraphy, magnetic resonance imaging, and positron emission tomography are the imaging techniques currently in use for the evaluation of CN but modalities other than magnetic resonance imaging appeared to be complementary. This study focuses on imaging findings of acute and chronic neuropathic osteoarthropathy in diabetes and discrimination of infected vs. non-infected neuropathic osteoarthropathy. PMID:24273635

  1. Charcot foot in diabetes and an update on imaging

    PubMed Central

    Ergen, Fatma Bilge; Sanverdi, Saziye Eser; Oznur, Ali

    2013-01-01

    Charcot neuroarthropathy (CN) is a serious complication of diabetes mellitus that can cause major morbidity including limb amputation. Since it was first described in 1883, and attributed to diabetes mellitus in 1936, the diagnosis of CN has been very challenging even for the experienced practitioners. Imaging plays a central role in the early and accurate diagnosis of CN, and in distinction of CN from osteomyelitis. Conventional radiography, computed tomography, nuclear medicine scintigraphy, magnetic resonance imaging, and positron emission tomography are the imaging techniques currently in use for the evaluation of CN but modalities other than magnetic resonance imaging appeared to be complementary. This study focuses on imaging findings of acute and chronic neuropathic osteoarthropathy in diabetes and discrimination of infected vs. non-infected neuropathic osteoarthropathy. PMID:24273635

  2. Two New Letters by Denning

    NASA Astrophysics Data System (ADS)

    Beech, Martin

    2010-06-01

    Two letters written by W. F. Denning to R. P. Greg in March and April of 1879 that had been tucked into the folds of an 1876 edition of the British Association for the Advancement of Science Reports were recently found at the Carnegie Institution in Washington D.C. The letters are wonderfully preserved, and offer us a snap-shot of the work being performed by a young Denning at the time when his influence in the field of meteor studies was in its ascendency. The contents of these two letters is analyzed and placed within context to Denning's other publications and private life.

  3. Charcot, la salpêtrière, and hysteria as represented in European literature.

    PubMed

    Koehler, Peter J

    2013-01-01

    In this chapter, I describe the influence of Jean-Martin Charcot (1825-1893), his neurological school at the Salpêtrière (Paris), and his teaching of hysteria on European literature. Many references to Charcot and descriptions of hysterical attacks are found not only in French naturalistic literature but also subsequently in naturalistic novels from other European countries (the Netherlands, Russia, Scandinavian countries, Spain, Italy, and Germany) and furthermore in novels written in new literary movements that followed naturalism. At first, objective descriptions were presented, but in the periods that followed, in particular during the past decades, criticism, rather than objective descriptions, became the motivation for continuing to use Charcot and his teaching of hysteria as inspiration for novels and plays, although Charcot as an admired founder of neurology did not quite disappear, even in recent novels. It is quite impressive to observe how Charcot and his demonstrations of hysterical attacks still resound throughout European literature, even after more than a century. PMID:24290478

  4. Jean-Martin Charcot and his vibratory chair for Parkinson disease.

    PubMed

    Goetz, Christopher G

    2009-08-11

    Vibration therapy is currently used in diverse medical specialties ranging from orthopedics to urology to sports medicine. The celebrated 19th-century neurologist, J.-M. Charcot, used vibratory therapy to treat Parkinson disease (PD). This study analyzed printed writings by Charcot and other writers on vibratory therapy and accessed unpublished notes from the Salpêtrière Hospital, Paris. Charcot lectured on several occasions on vibratory therapy and its neurologic applications. He developed a vibration chair for patients with PD after he observed that patients were more comfortable and slept better after a train or carriage ride. He replicated this experience by having patients undergo daily 30-minute sessions in the automated vibratory chair (fauteuil trépidant). His junior colleague, Gilles de la Tourette, extended these observations and developed a helmet that vibrated the head on the premise that the brain responded directly to the pulsations. Although after Charcot's death vibratory therapy was not widely pursued, vibratory appliances are reemerging in 21st century medicine and can be retested using adaptations of Charcot's neurologic protocols. PMID:19667323

  5. Édouard Brissaud, Fulgence Raymond and the succession of Charcot.

    PubMed

    Tatu, Laurent

    2011-01-01

    At the time of his death in 1893, Jean-Martin Charcot (1825-1893) had reigned supreme over neurology in Paris for some 10 years. The problem of finding a successor was not easy to solve, and it was initially agreed that a temporary replacement should be found. Édouard Brissaud (1852-1909), one of Charcot's students and close associates, was charged with this mission. With the support of some of Charcot's other former students, he held the position of chair for diseases of the nervous system for 1 year. In theory, there were a number of potential successors, but only three were officially declared: Édouard Brissaud, Jules Déjerine (1849-1917) and Fulgence Raymond (1844- 1910). Other students of Charcot such as Pierre Marie (1853-1940), Alix Joffroy (1844-1908), Joseph Babinski (1857-1932) and Georges Gilles de la Tourette (1857-1904) had to withdraw their candidature for various reasons. The election culminated in the appointment of Fulgence Raymond as Charcot's successor. Although such an impossible succession was beyond Raymond, his work in neurology, which is often unrecognised, made him one of the most important neurologists of the early 20th century. PMID:20938146

  6. ACQUIRED PES CAVUS IN CHARCOT-MARIE-TOOTH DISEASE

    PubMed Central

    Carvalho Maranho, Daniel Augusto; Volpon, José Batista

    2015-01-01

    Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of the forefoot, hindfoot or it may be a combination of both locations. Related deformities, mainly the varus and toe clawing require appropriate evaluation; clinical characteristics such as severity of the deformity, impairment of the muscular power, flexibility and patient's age are important characteristics in the treatment decision. Conservative treatment of the cavusvarus foot with physiotherapy, insoles and shoe modifications are reserved to young patients and mild deformities. However, there is a tendency of the deformity to become more severe over time because of the progressive feature of the underlying neurological condition. So, the surgical treatment by using classical techniques is performed in early stages. Most importantly is the identification of the primary and main components of each deformity to properly correct them, if possible. Muscular transfers are used to treat the dynamic unbalance, retracted structures should be either divided or lengthened and localized osteotomies should be preferred over arthrodeses, which are reserved for stiff and severely deformed feet in adults. PMID:27077056

  7. Modeling protein misfolding in charcot-marie-tooth disease.

    PubMed

    Theocharopoulou, Georgia; Vlamos, Panayiotis

    2015-01-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder. Recent advancements in molecular biology have elucidated the molecular bases of this genetically heterogeneous neuropathy. Still, the major challenge lies in determining the individual contributions by malfunctions of proteins to the disease's pathology. This paper reviews the identified molecular mechanisms underlying major forms of CMT disease. A growing body of evidence has highlighted the role of protein misfolding in demyelinating peripheral neuropathies and neurodegenerative diseases. Several hypotheses have been proposed to explain how misfolded aggregates induce neuronal damage. Current research focuses on developing novel therapeutic targets which aim to prevent, or even reverse the formation of protein aggregation. Interestingly, the role of the cellular defence mechanisms against accumulation of misfolded proteins may play a key role leading to novel strategies for treatment accelerating the clearance of their toxic early aggregates. Based on these findings we propose a model for describing in terms of a formal computer language, the biomolecular processes involving proteins associated with CMT disease. PMID:25417019

  8. Systematic review of exercise for Charcot-Marie-Tooth disease.

    PubMed

    Sman, Amy D; Hackett, Daniel; Fiatarone Singh, Maria; Fornusek, Ché; Menezes, Manoj P; Burns, Joshua

    2015-12-01

    Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and one of the most common neuromuscular disorders. Exercise may be beneficial to maintain strength and function for people with CMT, however, no comprehensive evaluation of the benefits and risks of exercise have been conducted. A systematic review was completed searching numerous electronic databases from earliest records to February 2015. Studies of any design including participants of any age with confirmed diagnosis of CMT that investigated the effects of exercise were eligible for inclusion. Of 13,301 articles identified following removal of duplicates, 11 articles including 9 unique studies met the criteria. Methodological quality of studies was moderate, sample sizes were small, and interventions and outcome measures used varied widely. Although the majority of the studies identified changes in one or more outcome measurements across exercise modalities, the majority were non-significant, possibly due to Type II errors. Significant effects described included improvements in strength, functional activities, and physiological adaptations following exercise. Despite many studies showing changes in strength and function following exercise, findings of this review should be met with caution due to the few studies available and moderate quality of evidence. Well-powered studies, harmonisation of outcome measures, and clearly described interventions across studies would improve the quality and comparability of the evidence base. The optimal exercise modality and intensity for people with CMT as well as the long-term safety of exercise remain unclear. PMID:26010435

  9. Dominant Charcot-Marie-Tooth syndrome and cognate disorders.

    PubMed

    Pareyson, Davide; Marchesi, Chiara; Salsano, Ettore

    2013-01-01

    Charcot-Marie-Tooth neuropathy (CMT) is a group of genetically heterogeneous disorders sharing a similar phenotype, characterized by wasting and weakness mainly involving the distal muscles of lower and upper limbs, variably associated with distal sensory loss and skeletal deformities. This chapter deals with dominantly transmitted CMT and related disorders, namely hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary neuralgic amyotrophy (HNA). During the last 20 years, several genes have been uncovered associated with CMT and our understanding of the underlying molecular mechanisms has greatly improved. Consequently, a precise genetic diagnosis is now possible in the majority of cases, thus allowing proper genetic counseling. Although, unfortunately, treatment is still unavailable for all types of CMT, several cellular and animal models have been developed and some compounds have proved effective in these models. The first trials with ascorbic acid in CMT type 1A have been completed and, although negative, are providing relevant information on disease course and on how to prepare for future trials. PMID:23931817

  10. The impossible succession of Charcot - the quest for a suitable heir.

    PubMed

    Tatu, Laurent; Bogousslavsky, Julien

    2011-01-01

    With the death of Jean-Martin Charcot (1825-1893) in 1893 came the impossible task of finding a suitable successor. The clinical chair for nervous system diseases was temporarily entrusted to Édouard Brissaud (1852-1909). There were a number of potential successors, but only three were officially declared: Brissaud, Jules Déjerine (1849-1917) and Fulgence Raymond (1844-1910). In the final vote, Raymond was appointed as Charcot's successor. Although this succession would prove too great a challenge for him, Raymond's work in neurology, which is often unrecognised, made him one of the most important French neurologists of the early 20th century. PMID:21412005

  11. Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

    PubMed

    Bogousslavsky, Julien; Boller, François

    2013-01-01

    Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician." PMID:24041281

  12. Charcot-Marie-Tooth disease and related inherited neuropathies.

    PubMed

    Murakami, T; Garcia, C A; Reiter, L T; Lupski, J R

    1996-09-01

    Charcot-Marie-Tooth disease (CMT) was initially described more than 100 years ago by Charcot, Marie, and Tooth. It was only recently, however, that molecular genetic studies of CMT have uncovered the underlying causes of most forms of the diseases. Most cases of CMT1 are associated with a 1.5-Mb tandem duplication in 17p11.2-p12 that encompasses the PMP22 gene. Although many genes may exist in this large duplicated region, PMP22 appears to be the major dosage-sensitive gene. CMT1A is the first autosomal dominant disease associated with a gene dosage effect due to an inherited DNA rearrangement. There is no mutant gene, but instead the disease phenotype results from having 3 copies of a normal gene. Furthermore, these findings suggest that therapeutic intervention in CMT1A duplication patients may be possible by normalizing the amount of PMP22 mRNA levels. Alternatively, CMT1A can be caused by mutations in the PMP22 gene. Other forms of CMT are associated with mutations in the MPZ (CMT1B) and Cx32 (CMTX) genes. Thus, mutations in different genes can cause similar CMT phenotypes. The related but more severe neuropathy, Dejerine-Sottas syndrome (DSS), can also be caused by mutations in the PMP22 and MPZ genes. All 3 genes thus far identified by CMT researchers appear to play an important role in the myelin formation or maintenance of peripheral nerves. CMT1A, CMT1B, CMTX, hereditary neuropathy with liability to pressure palsies (HNPP), and DSS have been called myelin disorders or "myelino-pathies." Other demyelinating forms, CMT1C and CMT-AR, may be caused by mutations of not yet identified myelin genes expressed in Schwann cells. The clinically distinct disease HNPP is caused by a 1.5-Mb deletion in 17p11.2-p12, which spans the same region duplicated in most CMT1A patients. Underexpression of the PMP22 gene causes HNPP just as overexpression of PMP22 causes CMT1A. Thus, 2 different phenotypes can be caused by dosage variations of the same gene. It is apparent that

  13. SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease

    PubMed Central

    Ghezzi, Daniele; Chassagne, Maïté; Mayençon, Martine; Padet, Sylvie; Melchionda, Laura; Rouvet, Isabelle; Lannes, Béatrice; Bozon, Dominique; Latour, Philippe; Zeviani, Massimo; Mousson de Camaret, Bénédicte

    2013-01-01

    Objective: To investigate whether mutations in the SURF1 gene are a cause of Charcot-Marie-Tooth (CMT) disease. Methods: We describe 2 patients from a consanguineous family with demyelinating autosomal recessive CMT disease (CMT4) associated with the homozygous splice site mutation c.107-2A>G in the SURF1 gene, encoding an assembly factor of the mitochondrial respiratory chain complex IV. This observation led us to hypothesize that mutations in SURF1 might be an unrecognized cause of CMT4, and we investigated SURF1 in a total of 40 unrelated patients with CMT4 after exclusion of mutations in known CMT4 genes. The functional impact of c.107-2A>G on splicing, amount of SURF1 protein, and on complex IV activity and assembly was analyzed. Results: Another patient with CMT4 was found to harbor 2 additional SURF1 mutations. All 3 patients with SURF1-associated CMT4 presented with severe childhood-onset neuropathy, motor nerve conduction velocities <25 m/s, and lactic acidosis. Two patients had brain MRI abnormalities, including putaminal and periaqueductal lesions, and developed cerebellar ataxia years after polyneuropathy. The c.107-2A>G mutation produced no normally spliced transcript, leading to SURF1 absence. However, complex IV remained partially functional in muscle and fibroblasts. Conclusions: We found SURF1 mutations in 5% of families (2/41) presenting with CMT4. SURF1 should be systematically screened in patients with childhood-onset severe demyelinating neuropathy and additional features such as lactic acidosis, brain MRI abnormalities, and cerebellar ataxia developing years after polyneuropathy. PMID:24027061

  14. Biomarkers research in neuromuscular disease Charcot-Marie-Tooth.

    PubMed

    Seco-Cervera, Marta; Ibañez-Cabellos, Jose Santiago; Garcia-Gimenez, Jose Luis; Espinos, Carmen; Palau, Francesc; Pallardo, Federico V

    2014-10-01

    Charcot-Marie-Tooth disease (CMT) (ORPHA166) is the most frequent hereditary neuropathy. CMT is a heterogeneous group of disorders which, despite some variability in their clinical features, share the same general phenotype, usually characterized by wasting and weakness of distal limb muscles, decreased to absent deep tendon reflexes, distal sensory loss, and frequent skeletal deformities. Despite the clinical and molecular description of this disease in the last 20 years, there is no effective drug or advanced therapy available. Here we have pretend the identification of metabolic and oxidative stress biomarkers in plasmas from patients with duplication at PMP22 gene, the most frequent mutation causing CMT, and clinically characterized as CMT1A. The samples were collected in the neuropathy units from "La Fe" Hospital of Valencia, "Bellvitge" Hospital of Barcelona, "La Paz" Hospital of Madrid, and "Virgen del Rocío" Hospital of Sevilla. The metabolic biomarkers research was performed using 2D-DIGE analysis (Typhoon TRIO, GE) and DeCyder software (GE). Protein identification was made by mass spectrometry by MALDI-TOF-TOF (ABSciex) and liquid Chromatography analysis (ABSciex). The oxidative stress biomarkers research consisted in carbonylated proteins analysis by reaction with DNPH and Dot-blot. Total antioxidant capacity and GSSG/GSH ratio were analyzed with Antioxidant Assay kit (Cayman) and Glutathione Fluorescent detection Kit (Arbor Assays), respectively. Finally now we are performing the MDA levels by HPLC-UV. We found 8, 13 and 36 proteins with differential expression in mild, moderate and severely affected patients, respectively compared with their own matched controls. Also we found differences on oxidative stress parameters between de different groups analyzed. Our results suggest differences in the oxidative stress profile between the studied phenotypes in CMT1A patients. PMID:26461392

  15. Charcot-Marie-Tooth disease and related peripheral neuropathies.

    PubMed

    De Jonghe, P; Timmerman, V; Nelis, E; Martin, J J; Van Broeckhoven, C

    1997-01-01

    Soon after the description of Charcot-Marie-Tooth disease (CMT) in 1886, it became apparent that this syndrome is clinically and genetically heterogeneous. Neuropathological and electrophysiological studies have further dissected this syndrome into distinct categories that are now classified in a complex nosology of the inherited peripheral neuropathies. The recent advent of molecular genetics has dramatically increased our understanding of the underlying disease mechanisms. Genetic linkage studies have identified at least 17 genetic loci for different types of inherited neuropathies although most genes involved still remain to be found. The application of molecular genetics has already had an important impact on clinical practice and genetic counselling. Three genes responsible for hereditary motor and sensory neuropathy type I (HMSNI) or CMT1 have been identified: peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ) for the autosomal dominant form and connexin 32 (Cx32) for the X-linked dominant variant. The PMP22 gene is also involved in the majority of families with hereditary neuropathy with liability to pressure palsies (HNPP). The observation of a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene, in CMT1 and the reciprocal deletion in the same region in HNPP has provided a novel disease paradigm for autosomal dominant disorders, i.e. the gene dosage mechanism. The study of phenotype-genotype correlations in transgenic animal models for PMP22, MPZ and Cx32 mutations will help elucidate the underlying disease mechanisms and will provide a basis for gene therapy and/or other therapeutic approaches such as treatment with neurotrophic growth factors. PMID:10975746

  16. Broca and Charcot's research on Jacques Inaudi: the psychological and anthropological study of a mental calculator.

    PubMed

    Nicolas, Serge; Guida, Alessandro; Levine, Zachary

    2014-01-01

    In the nineteenth century, French scientific institutions became interested in young "mental calculators," arithmetical prodigies able to quickly and accurately perform complex mental calculations. The first scientists to study mental calculators were phrenologists who sought to prove the existence of a calculating organ in the frontal lobe. Paul Broca introduced one such mental calculator, Jacques Inaudi, to the Anthropological Society of Paris in 1880. Broca attributed extraordinary faculty for mental calculation to memory functioning (the psychological hypothesis) rather than physiological difference (the phrenological hypothesis). In 1892, prominent French Academy of Sciences member Jean-Martin Charcot produced a noteworthy study of Inaudi on the organization's behalf. Charcot observed that Inaudi called upon auditory memory rather than visual memory in his mental calculations, unlike most mental calculators who preceded him. Like Broca, Charcot was skeptical of the phrenological hypothesis, though he noted that Inaudi's skull was markedly plagiocephalic. Interestingly, anthropological examination of Inaudi is consistent with the themes of modern cognitive neuroscience. Thus, Charcot seems to have anticipated present research on the localization of mental calculation and memory for numbers. 1. (1)The Academy of Sciences, founded in 1666 by Louis XIV (1638-1715) with the goal of contributing to the advancement and application of the sciences in France, was one of the earliest European scientific institutions. As a prestigious society, it played an active role in defining scientific and technological research policy as well as drafting and publishing official reports. PMID:24697632

  17. [PREGNANCY AND DELIVERY IN A PATIENT WITH CHARCOT-MARIE-TOOTH DISEASE].

    PubMed

    Pehlivanov, B; Matev, M

    2016-01-01

    We report a case of a 34 years old primigravida with Charcot-Marie-Tooth disease (CMTD). The course of pregnancy was uneventful with no deterioration of symptoms due to the disease. Performed amniocentesis showed healthy fetus. Planned cesarean section with spinal anesthesia was performed because of the restricted pelvis. The possible issues of combination pregnancy and CMTD are discussed. PMID:27514143

  18. Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A

    ERIC Educational Resources Information Center

    Bamford, Nigel S.; White, Klane K.; Robinett, Stephanie A.; Otto, Randolph K.; Gospe, Sidney M., Jr.

    2009-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and…

  19. Nerve Excitability Properties in Charcot-Marie-Tooth Disease Type 1A

    ERIC Educational Resources Information Center

    Nodera, Hiroyuki; Bostock, Hugh; Kuwabara, Satoshi; Sakamoto, Takashi; Asanuma, Kotaro; Jia-Ying, Sung; Ogawara, Kazue; Hattori, Naoki; Hirayama, Masaaki; Kaji, Ryuji

    2004-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is commonly considered a prototype of a hereditary demyelinating polyneuropathy. Apart from the myelin involvement, there has been little information on axonal membrane properties in this condition. Taking advantage of the uniform nature of the disease process, we undertook the "in vivo" assessment of…

  20. A case report of Charcot arthropathy caused by syringomyelia and Chiari malformation complicated with scoliosis

    PubMed Central

    2014-01-01

    Background Although Charcot arthropathy, also known as neuropathic arthropathy, of which early diagnosis and treatment is extremely difficult, associated with other cause factor has been widely described, Charcot arthropathy caused by syringomyelia and Chiari malformation complicated with scoliosis has never been described in the literature. Case presentation A 44-year-old male was hospitalized for diagnosis and treatment due to complaining the progressively swelling and limitation of motion in his left shoulder joint for 1 year. The patient has no significant past medical history except for scoliosis 8 years prior to his presentation to our clinic; He denied any constitutional symptoms, trauma, or pain in the upper extremities at this time of presentation. Based on history, physical and auxiliary examination, following diagnoses were made: Charcot arthropathy of the left shoulder, syringomyelia, Chiari malformation and scoliosis. Conclusion Once Charcot arthritis was found, it was mostly in advanced stage and very difficult to treat. So we recommended that if patient suffering from scoliosis visited in clinic, further examination such as magnetic resonance imaging (MRI) and regular follow-up should be carried out, and early-stage of this devastating disease caused by syringomyelia and Chiari malformation may be diagnosed easily. PMID:24886292

  1. Data Mining for Identifying Novel Associations and Temporal Relationships with Charcot Foot

    PubMed Central

    Munson, Michael E.; Wrobel, James S.; Holmes, Crystal M.; Hanauer, David A.

    2014-01-01

    Introduction. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. Methods. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9 codes). For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5). Results. We found 710 associations, 676 (95.2%) of which had a P value for the association less than 1.0 × 10−5 and 603 (84.9%) of which had an odds ratio > 5.0. There were 111 (15.6%) associations with a significant temporal relationship (P < 1.0 × 10−3). The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. Conclusion. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis. PMID:24868558

  2. MIDFOOT CHARCOT ARTHROPATHY IN DIABETIC PATIENTS: COMPLICATION OF AN EPIDEMIC DISEASE

    PubMed Central

    Ferreira, Ricardo Cardenuto; Gonçalez, Daniel Hidalgo; Filho, João Manoel Fonseca; Costa, Marco Túlio; Santin, Roberto Attilio Lima

    2015-01-01

    Objectives: To outline the epidemiological profile of diabetic patients with Charcot arthropathy affecting the midfoot alone or extending from the midfoot to the hindfoot; To assess the results from the treatment that these patients undergo, according to a preestablished protocol, over the medium term. Methods: We retrospectively evaluated 88 patients (110 extremities) with Charcot arthropathy of the midfoot. The minimum follow-up period was 12 months. We included 45 patients with Charcot arthropathy affecting the tarsal-metatarsal joints (51%); 20 patients in whom the talonavicular, calcaneocuboid and subtalar joints were affected (23%); and 23 patients in whom both the midfoot and hindfoot were affected (26%), as described by Brodsky and Trepman. We defined the treatment as successful when a functional foot was preserved; and unsuccessful when the foot was amputated. Results: From treating Charcot arthropathy primarily involving the midfoot were satisfactory in the cases of 75 patients (85%) treated according to our protocol. For the patients with severe lesions affecting both the midfoot and the hindfoot, a greater number of complex operations (i.e. arthrodesis) were needed in order to obtain the same overall rate of satisfactory results. The osteoarticular lesions originating in the midfoot probably extended progressively to the hindfoot because of delayed diagnosis with inadequate early treatment. Conclusion: It was possible to preserve a functional extremity in 85% of the patients. Severe lesions involving the midfoot and extending to the hindfoot required a greater number of surgical procedures to treat them. PMID:27047875

  3. Double Dens Invaginatus: Report of Three Cases

    PubMed Central

    Zengin, A. Zeynep; Sumer, A. Pinar; Celenk, Peruze

    2009-01-01

    Dens invaginatus results from an infolding of the outer surface of a tooth. The clinical importance of dens invaginatus results from the risk of pulpal disease. So, all clinicians should be aware of this anomaly. The presence of double dens invaginatus is extremely rare. This article presents three cases of double dens invaginatus in permanent maxillary lateral incisors, one with preventive restoration on its palatal surface. They were classified as double dens invaginatus because of two enamel lined invaginations presented in the crowns of these teeth. PMID:19262734

  4. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    PubMed

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  5. Risk factors of diabetic foot Charcot arthropathy: a case-control study at a Malaysian tertiary care centre

    PubMed Central

    Fauzi, Aishah Ahmad; Chung, Tze Yang; Latif, Lydia Abdul

    2016-01-01

    INTRODUCTION This study aimed to determine the risk factors of diabetic Charcot arthropathy of the foot among diabetic patients with and without foot problems. METHODS This was a case-control study involving diabetic patients attending the Diabetic Foot Care and Wound Management Clinic at University Malaya Medical Centre, Kuala Lumpur, Malaysia, from June 2010 to June 2011. Data on sociodemographic profiles, foot factors and diabetes characteristics was collected and analysed. RESULTS A total of 48 diabetic patients with Charcot arthropathy of the foot were identified. Data from these 48 patients was compared with those of 52 diabetic patients without foot problems. Up to 83.3% of patients with diabetic Charcot arthropathy presented with unilateral Charcot foot, most commonly located at the midfoot (45.8%). Patients with a history of foot problems, including foot ulcer, amputation, surgery or a combination of problems, had the highest (26-time) likelihood of developing Charcot arthropathy (odds ratio 26.4; 95% confidence interval 6.4–109.6). Other significant risk factors included age below 60 years, more than ten years’ duration of diabetes mellitus and the presence of nephropathy. CONCLUSION A history of prior diabetic foot problems is the greatest risk factor for developing diabetic Charcot arthropathy, compared with other risk factors such as diabetes characteristics and sociodemographic profiles. Preventive management of diabetic foot problems in the primary care setting and multidisciplinary care are of paramount importance, especially among chronic diabetic patients. PMID:27075668

  6. Lisfranc fracture-dislocation precipitating acute Charcot arthopathy in a neuropathic diabetic foot: a case report

    PubMed Central

    Yeoh, Joey; Muir, Kenneth Ross; Dissanayake, Ajith Munasinghe; Tzu-Chieh, Wendy Yu

    2008-01-01

    The Lisfranc injury is relatively uncommon yet remains popular in the literature due to its variable causative mechanisms and subtleties in radiographic features despite its potential for disabling long term outcomes if treatment is inadequate, inappropriate or delayed. These injuries are especially pertinent in diabetic patients, especially those with neuropathy, since they are more common, can lead to Charcot neuropathic joint, ulcers and have different causative mechanisms compared to the general population. We describe the case of a neuropathic diabetic patient who presented with a Lisfranc injury which precipitated the development of acute Charcot arthropathy in the right foot. The case serves to illustrate several salient points about the Lisfranc joint and related injuries in diabetic patients. PMID:18973700

  7. Intra-Articular Giant Heterotopic Ossification following Total Knee Arthroplasty for Charcot Arthropathy

    PubMed Central

    Tsuge, Shintaro; Aoki, Yasuchika; Sonobe, Masato; Shibata, Yoshifumi; Sasaki, Yu; Nakagawa, Koichi

    2013-01-01

    Although the Charcot arthropathy may be associated with serious complications, total knee arthroplasty (TKA) is the preferred choice of treatment by patients. This case report presents an 80-year-old man with intra-articular giant heterotopic ossification following loosening of femoral and tibial implants and femoral condylar fracture. He had undergone TKA because of Charcot neuropathy seven years ago and had been doing well since. Immediately after a left knee sprain, he became unable to walk. Because he had developed a skin ulcer on his left calf where methicillin-resistant Staphylococcus aureus was detected, we postponed revision surgery until the ulcer was completely healed. While waiting, intra-articular bony fragments grew larger and formed giant heterotopic ossified masses. Eventually, the patient underwent revision surgery, and two major ossified masses were carefully and successfully extirpated. It should be noted that intra-articular heterotopic giant ossification is a significant complication after TKA for neuropathic arthropathy. PMID:24151574

  8. De Novo duplication in Charcot-Marie-Tooth Type 1A

    SciTech Connect

    Mandich, P.; Bellone, E.; Ajmar, F.

    1996-09-01

    We read with interest the paper on {open_quotes}Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1A: First Report of a De Novo Duplication with a Maternal Origin,{close_quotes}. They reported their experience with 10 sporadic cases of Charcot-Marie-Tooth type 1A (CMT1A) in which it was demonstrated that the disease had arisen as the result of a de novo duplication. They analyzed the de novo-duplication families by using microsatellite markers and identified the parental origin of the duplication in eight cases. In one family the duplication was of maternal origin, whereas in the remaining seven cases it was of paternal origin. The authors concluded that their report was the first evidence of a de novo duplication of maternal origin, suggesting that this is not a phenomenon associated solely with male meiosis. 7 refs.

  9. Charcot neuroarthropathy in simultaneous kidney–pancreas transplantation: report of two cases

    PubMed Central

    del Vecchio, Jorge Javier; Raimondi, Nicolás; Rivarola, Horacio; Autorino, Carlos

    2013-01-01

    Charcot neuroarthropathy (CN) is considered a major complication in diabetes mellitus (DM), and it is estimated that 1% of diabetic patients may develop this complication. Simultaneous kidney–pancreas transplantation (SKPT) is one of the most effective therapies for patients with type 1 DM and end-stage diabetic nephropathy. Some cases with a Charcot-modified clinical presentation during the postoperative convalescence period after SKPT have been described. The clinical presentation may condition severe destructive lesions, and good practices include systematic follow-up. Based on the cases described, SKPT is one more entity that might lead to CN ‘foot-at-risk’. The aim of this article is to describe two cases of neuropathic arthropathy with rapid progression in the short term after SKPT. PMID:24003361

  10. Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

    PubMed

    Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

    2013-08-01

    In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. PMID:22285450

  11. Laparoscopic appendectomy in a pediatric patient with type 1 Charcot-Marie-Tooth disease.

    PubMed

    Heller, Joshua A; Marn, Richard Y

    2015-12-01

    A pediatric patient with type 1 Charcot-Marie-Tooth disease-a disorder associated with a demyelinating polyneuropathy-presented for laparoscopic appendectomy in the setting of acute appendicitis. Induction and maintenance of anesthesia were successfully managed without the use of any depolarizing or nondepolarizing neuromuscular blocking agents. The patient was successfully extubated at the completion of the procedure without any respiratory or neuromuscular sequelae, with excellent pain control and no postoperative nausea or vomiting. PMID:26403061

  12. Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

    SciTech Connect

    Fain, P.R.; Barker, D.F.; Chance, P.F. )

    1994-02-01

    Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

  13. Conservative and surgical treatment of the chronic Charcot foot and ankle

    PubMed Central

    Güven, Mehmet Fatih; Karabiber, Atakan; Kaynak, Gökhan; Öğüt, Tahir

    2013-01-01

    Charcot neuroarthropathy (CN) is a severe joint disease in the foot and ankle that can result in fracture, permanent deformity, and limb loss. It is a serious and potentially limb-threatening lower-extremity late complication of diabetes mellitus. The aim of this manuscript was to evaluate modern concepts of chronic CN through a review of the available literature and to integrate a perspective of management from the authors’ extensive experience. PMID:23919114

  14. Birth of modern psychiatry and the death of alienism: the legacy of Jean-Martin Charcot.

    PubMed

    Bogousslavsky, Julien; Moulin, Thierry

    2011-01-01

    At the time of Jean-Martin Charcot, Paris--the main center for studies on the nervous system and its disorders--was home to critical exchanges between the developing discipline of neurology and psychiatry. Contrary to the commonly held view, and in spite of an established tradition concerning mental diseases, emerging neurology had a much stronger influence on psychiatry ('alienism') than the reverse. This was largely due to the school built up by Jean-Martin Charcot himself, which was organized around the study and management of hysteria. Although Charcot always claimed to be uninterested in mental medicine, he stimulated the development of an original scientific approach to nervous system conditions, based on Claude Bernard's method, along with structured academic teaching. Conversely, alienism paradoxically remained stuck in organicism, after Antoine Bayle's report in 1822 of 'arachnitis' as the substratum of general paresis of the insane. Contrary to alienism, the young neurological school was capable of self-criticism, and progressively highlighted mental factors in hysteria. This led to the paradox that neurologists were active in a disease with no organic cerebral lesion, while alienists were postulating brain lesions in all mental disorders. Pushed by Charcot, the academic evolution led to the launch of a faculty chair of mental and brain diseases in 1875, which was taken over for nearly half a century by his direct pupils Benjamin Ball, Alix Joffroy and Gilbert Ballet, who held the position until 1916, supporting the development of modern psychiatry in general hospitals, while alienism progressively disappeared at the turn of the century. PMID:20938143

  15. The posteriorly tilted dens. A normal variation mimicking a fractured dens.

    PubMed

    Swischuk, L E; Hayden, C K; Sarwar, M

    1979-02-26

    The normal dens occasionally can be posteriorly tilted and in such cases, can mimic a fractured, posteriorly tilted, dens. Differentiation of the two conditions depends on: [1] knowledge that this normal variation of the dens occurs, and [2] demonstrating that no fracture exists. In many cases, this latter determination can be accomplished on plain films, but in other cases, laminography is required. PMID:431988

  16. Syringomyelia with Chiari I malformation presenting as hip charcot arthropathy: a case report and literature review.

    PubMed

    Memarpour, Roya; Tashtoush, Basheer; Issac, Lydia; Gonzalez-Ibarra, Fernando

    2015-01-01

    Neuroarthropathy (neuropathic osteoarthropathy), also known as Charcot joint, is a condition characterized by a progressive articular surface destruction in the setting of impaired nociceptive and proprioceptive innervation of the involved joint. It is seen most commonly in the foot and ankle secondary to peripheral neuropathy associated with diabetes mellitus. Cases of hip (Charcot) neuroarthropathy are rare and almost exclusively reported in patients with neurosyphilis (tabes dorsalis). We report a case of a 36-year-old man who presented to the emergency department complaining of right hip pain. On physical examination, pain and thermal sensory deficits were noted in the upper torso with a cape-like distribution, as well as signs of an upper motor neuron lesion in the left upper and lower extremities. A magnetic resonance imaging study (MRI) of the right hip showed evidence of early articular surface destruction and periarticular edema consistent with hip Charcot arthropathy. An MRI of the spine revealed an Arnold-Chiari type I malformation with extensive syringohydromyelia of the cervical and thoracic spine. PMID:25692057

  17. Syringomyelia with Chiari I Malformation Presenting as Hip Charcot Arthropathy: A Case Report and Literature Review

    PubMed Central

    Memarpour, Roya; Gonzalez-Ibarra, Fernando

    2015-01-01

    Neuroarthropathy (neuropathic osteoarthropathy), also known as Charcot joint, is a condition characterized by a progressive articular surface destruction in the setting of impaired nociceptive and proprioceptive innervation of the involved joint. It is seen most commonly in the foot and ankle secondary to peripheral neuropathy associated with diabetes mellitus. Cases of hip (Charcot) neuroarthropathy are rare and almost exclusively reported in patients with neurosyphilis (tabes dorsalis). We report a case of a 36-year-old man who presented to the emergency department complaining of right hip pain. On physical examination, pain and thermal sensory deficits were noted in the upper torso with a cape-like distribution, as well as signs of an upper motor neuron lesion in the left upper and lower extremities. A magnetic resonance imaging study (MRI) of the right hip showed evidence of early articular surface destruction and periarticular edema consistent with hip Charcot arthropathy. An MRI of the spine revealed an Arnold-Chiari type I malformation with extensive syringohydromyelia of the cervical and thoracic spine. PMID:25692057

  18. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.

    PubMed

    Sevilla, Teresa; Lupo, Vincenzo; Martínez-Rubio, Dolores; Sancho, Paula; Sivera, Rafael; Chumillas, María J; García-Romero, Mar; Pascual-Pascual, Samuel I; Muelas, Nuria; Dopazo, Joaquín; Vílchez, Juan J; Palau, Francesc; Espinós, Carmen

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a

  19. Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients

    PubMed Central

    Folestad, Agnetha; Ålund, Martin; Asteberg, Susanne; Fowelin, Jesper; Aurell, Ylva; Göthlin, Jan

    2015-01-01

    Background and purpose Charcot neuropathy is characterized by bone destruction in a foot leading to deformity, instability, and risk of amputation. Little is known about the pathogenic mechanisms. We hypothesized that the bone-regulating Wnt/β-catenin and RANKL/OPG pathways have a role in Charcot arthropathy. Patients and methods 24 consecutive Charcot patients were treated by off-loading, and monitored for 2 years by repeated foot radiography, MRI, and circulating levels of sclerostin, dickkopf-1, Wnt inhibitory factor-1, Wnt ligand-1, OPG, and RANKL. 20 neuropathic diabetic controls and 20 healthy controls served as the reference. Results Levels of sclerostin, Dkk-1 and Wnt-1, but not of Wif-1, were significantly lower in Charcot patients than in the diabetic controls at inclusion. Dkk-1 and Wnt-1 levels responded to off-loading by increasing. Sclerostin levels were significantly higher in the diabetic controls than in the other groups whereas Wif-1 levels were significantly higher in the healthy controls than in the other groups. OPG and RANKL levels were significantly higher in the Charcot patients than in the other groups at inclusion, but decreased to the levels in healthy controls at 2 years. OPG/RANKL ratio was balanced in all groups at inclusion, and it remained balanced in Charcot patients on repeated measurement throughout the study. Interpretation High plasma RANKL and OPG levels at diagnosis of Charcot suggest that there is high bone remodeling activity before gradually normalizing after off-loading treatment. The consistently balanced OPG/RANKL ratio in Charcot patients suggests that there is low-key net bone building activity by this pathway following diagnosis and treatment. Inter-group differences at diagnosis and changes in Wnt signaling following off-loading treatment were sufficiently large to be reflected by systemic levels, indicating that this pathway has a role in bone remodeling and bone repair activity in Charcot patients. This is of

  20. About medicine and the arts. Charcot and French literature at the fin-de-siècle.

    PubMed

    Koehler, P

    2001-03-01

    The relationship between medicine and the arts, literature in particular, has many aspects. One of the most obvious relations is the use of literature as a source for historical studies. Jean-Martin Charcot and his school often appear in French literature at the end of the 19th century. Several aspects will be highlighted in this study, including (1) the ideas about degenerative diseases in the work of Emile Zola, the main author of the naturalistic movement; (2) decadence and spiritism in two "transitional" novels by Joris Karl Huysmans, who, once supporter of the naturalistic movement, changed his ideas following observations of disease and cure that could not be explained in a scientific way. Charcot's work on hysteria and hypnosis, as well as Brown-Séquard's rejuvenation experiments with testicular extracts played an important role with this respect; (3) Charcot's relationship with the Daudets, in particular his treatment of Alphonse's tabes dorsalis and the ambivalent attitude of his son Léon Daudet towards Charcot; (4) the influence of the lectures at the Salpêtrière on the work of Guy de Maupassant, who attended the lessons in the mid-1880s. The reading of novels and biographies of these authors provides a part of the social context and the cultural atmosphere in Paris at the "fin-de-siècle" when Charcot and his school played an important role in medicine. Moreover, it shows the influence of medicine and science on society as recorded by writers. PMID:11446262

  1. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

    PubMed Central

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  2. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  3. Denning of grizzly bears in the Yellowstone National Park area

    USGS Publications Warehouse

    Judd, Steven L.; Knight, Richard R.; Blanchard, Bonnie M.

    1986-01-01

    Radiotelemetry was used to locate 101 grizzly bear (Ursus arctos) dens from 1975 to 1980; 35 dens were examined on the ground. Pregnant females denned in late October, and most other bears denned by mid-November. Duration of denning average 113, 132, and 170 days for males, females, and females with new cubs, respectively. Males emerged from mid-February to late March, followed by single females and females with yearlings and 2-year-olds. Females with new cubs emerged from early mid-April. Den sites were associated with moderate tree cover (26%-75% canopy cover) on 30°-60° slopes. Dens occurred on all aspects, although northerly exposures were most common. Grizzly bears usually dug new dens but occasionally used natural cavities or a den from a previous year. Males usually dug larger dens than females with young. Eight excavated and 2 natural dens of the 35 examined dens were used for more than 1 year.

  4. The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

    PubMed Central

    Schinke, Josua; Kolog Gulko, Miriam; Christmann, Martin; Valerius, Oliver; Stumpf, Sina Kristin; Stirz, Margarita; Braus, Gerhard H.

    2016-01-01

    DenA/DEN1 and the COP9 signalosome (CSN) represent two deneddylases which remove the ubiquitin-like Nedd8 from modified target proteins and are required for distinct fungal developmental programmes. The cellular DenA/DEN1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. DenA/DEN1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the C-terminal DenA/DEN1 phosphorylation pattern. Nuclear DenA/DEN1 is destabilized during fungal development by five of the eight CSN subunits which target nuclear DenA/DEN1 for degradation. DenA/DEN1 becomes stabilized as a phosphoprotein at S243/S245 during vegetative growth, which is necessary to support further asexual development. After the initial phase of development, the newly identified cytoplasmatic DenA/DEN1 interacting phosphatase DipA and an additional developmental specific C-terminal phosphorylation site at serine S253 destabilize DenA/DEN1. Outside of the nucleus, DipA is co-transported with DenA/DEN1 in the cytoplasm between septa and nuclei. Deletion of dipA resulted in increased DenA/DEN1 stability in a strain which is unresponsive to illumination. The mutant strain is dysregulated in cytokinesis and impaired in asexual development. Our results suggest a dual phosphorylation-dependent DenA/DEN1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm. PMID:27010942

  5. A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L

    PubMed Central

    Zhang, Ruxu; Zhang, Fufeng; Li, Xiaobo; Huang, Shunxiang; Zi, Xiaohong; Liu, Ting; Liu, Sanmei; Li, Xuning; Xia, Kun; Pan, Qian; Tang, Beisha

    2014-01-01

    We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141NHSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the K141NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141NHSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141NHSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the K141NHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease. PMID:25206829

  6. Ostectomy and Medial Plantar Artery Flap Reconstruction for Charcot Foot Ulceration Involving the Midfoot.

    PubMed

    Sato, Tomoya; Ichioka, Shigeru

    2016-01-01

    Charcot foot is a serious complication of diabetes, characterized by deformity and overlying ulceration. The condition most commonly affects the midfoot. However, little information is available on the use of a medial plantar artery flap to treat diabetic midfoot ulceration. The purpose of the present study was to evaluate the versatility of ostectomy and medial plantar flap reconstruction for midfoot plantar ulceration associated with rocker-bottom deformity secondary to Charcot foot. Four patients underwent ostectomy and medial plantar flap reconstruction. Before flap reconstruction, the devitalized soft tissues and bone were radically resected. After the infection had been controlled, the ulcerated portion was minimally excised, and the bony prominence underlying the ulcer was removed. A medial plantar artery flap was applied to the ulcer. The donor site was covered with a split-thickness skin graft or artificial dermis. In all patients, the ulcers healed and independent ambulation was achieved. However, 1 patient experienced ulcer recurrence, and subsequent infection necessitated a major amputation. Limb salvage is challenging in the setting of deformity and intractable plantar ulceration. The advantages of medial plantar artery flap reconstruction are that tissues with a rich blood supply are used to cover the exposed bone, and the flap can withstand the pressure and shear stress of the patient's body weight. However, a dominant artery in the foot is sacrificed. Therefore, the patency of the dorsalis pedis artery must be confirmed in every patient. The results of the present study have demonstrated that a medial plantar artery can be an effective alternative for diabetic patients with a plantar ulcer secondary to Charcot foot. PMID:26190780

  7. An Unusual Presentation of Charcot Arthropathy Caused by Syringomyelia Mimicking a Soft Tissue Tumor

    PubMed Central

    Atalar, Ebru; Ataoglu, Baybars

    2014-01-01

    Charcot arthropathy is a chronic, degenerative condition and is associated with decreased sensorial innervation. Numerous causes of this arthropathy have been described. Here we report a case of neuropathic arthropathy secondary to syringomyelia which was misdiagnosed as a soft tissue tumor and treated surgically and additionally with radiotherapy at another institution. The patient had clinical and radiological signs of syringomyelia, associated with a limited range of motion, swelling, and pain in the affected joint. Neuropathic arthropathy, although less common, should be considered in cases of unexplained joint swelling, pain, and limited range of motion of the affected joint. PMID:25126434

  8. Osteomyelitis or Charcot neuro-osteoarthropathy? Differentiating these disorders in diabetic patients with a foot problem.

    PubMed

    Ertugrul, Bulent M; Lipsky, Benjamin A; Savk, Oner

    2013-01-01

    Both osteomyelitis and Charcot neuro-osteoarthropathy (CN) are potentially limb-threatening complications of diabetic neuropathy, but they require quite different treatments. Almost all bone infections in the diabetic foot originate from an infected foot ulcer while diabetic osteoarthropathy is a non-infectious process in which peripheral neuropathy plays the critical role. Differentiating between diabetic foot osteomyelitis and CN requires careful evaluation of the patient, including the medical history, physical examination, selected laboratory findings, and imaging studies. Based on available studies, we review the approaches to the diagnostic differentiation of osteomyelitis from CN of the foot in diabetic patients. PMID:24205433

  9. Sport activity in Charcot-Marie-Tooth disease: A case study of a Paralympic swimmer.

    PubMed

    Vita, Giuseppe; La Foresta, Stefania; Russo, Massimo; Vita, Gian Luca; Messina, Sonia; Lunetta, Christian; Mazzeo, Anna

    2016-09-01

    This study reports the positive physical, emotional and psychosocial changes induced by sport activity in a Paralympic swimmer with Charcot-Marie-Tooth (CMT) type 4A. When we compared evaluations before initiating sport activity with those after five years of competitive activity, we found: i) increased proximal muscles strength of upper limbs; ii) augmented ability to propel wheelchair independently; iii) improved quality of life; iv) reduced trait anxiety and striking improvement of depression; v) enhanced self-esteem. Longitudinal studies in large cohorts to evaluate the positive effects of sport activity are needed to support provision of evidence-based advice to patients and families. PMID:27460291

  10. Osteomyelitis or Charcot neuro-osteoarthropathy? Differentiating these disorders in diabetic patients with a foot problem

    PubMed Central

    Ertugrul, Bulent M.; Lipsky, Benjamin A.; Savk, Oner

    2013-01-01

    Both osteomyelitis and Charcot neuro-osteoarthropathy (CN) are potentially limb-threatening complications of diabetic neuropathy, but they require quite different treatments. Almost all bone infections in the diabetic foot originate from an infected foot ulcer while diabetic osteoarthropathy is a non-infectious process in which peripheral neuropathy plays the critical role. Differentiating between diabetic foot osteomyelitis and CN requires careful evaluation of the patient, including the medical history, physical examination, selected laboratory findings, and imaging studies. Based on available studies, we review the approaches to the diagnostic differentiation of osteomyelitis from CN of the foot in diabetic patients. PMID:24205433

  11. [Charcot, working and 'Male Hysteria': A new approach to the Leçons du mardi (Tuesday Lessons) from the standpoint of psychodynamics of work].

    PubMed

    Molinier, Pascale

    2015-01-01

    This paper examines the role of work in Charcot's clinical teaching focusing on cases of male hysteria in The Tuesday's Lessons from 1887 to 1889. Today, we read the work of Charcot in a retrospective way as having ended in a failure: He would have missed the discovery of the sexual unconscious. From the perspective of psychodynamics of work, it appears an alternative way which was present in Charcot, though unfinished, opening on a possible development of a relationship between psychic and body. The role of work in traumatic hysteria has been forgotten by Freud's posterity and this obliteration continues today. PMID:27089167

  12. Reconstruction of Lisfranc joint dislocations secondary to Charcot neuroarthropathy using a plantar plate.

    PubMed

    Garchar, Dave; DiDomenico, Lawrence A; Klaue, Kaj

    2013-01-01

    Lisfranc joint dislocation secondary to Charcot arthropathy is a debilitating condition that often leads to ulceration and infection. After conservative treatment, such as bracing and appropriate shoe wear fail, the only option might be amputation. However, we have seen good clinical outcomes from applying a plate to the plantar (tension) side of the medial midfoot. In our retrospective study, 24 consecutive patients (25 feet) from April 1999 through July 2004 underwent Charcot reconstruction for Lisfranc dislocation. Clinical and radiographic follow-up examinations were performed every 3 weeks during the postoperative course. Union was achieved in 24 (96%) of the 25 feet. The average time to ambulation was 11.68 (range 7 to 20) weeks for the 24 patients. The average follow-up period was 38.0 (range 17 to 64) months. The union and interval to ambulation rates showed that a plate applied to the plantar aspect of the medial midfoot provides a strong, sturdy construct for arthrodesis and ambulation. PMID:23621976

  13. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q

    SciTech Connect

    Kwon, J.M.; Elliott, J.L.; Yee, W.C.

    1995-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy. In some families, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families with CMT2 do not show linkage with 1p markers, suggesting genetic heterogeneity in CMT2. We investigated linkage in a single large kindred with autosomal dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B) was mapped to the interval between the microsatellite markers D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and may ultimately lead to the identification of a gene defect that underlies the CMT2 phenotype. 21 refs., 3 figs., 1 tab.

  14. The memory of two great mental calculators: Charcot and Binet's neglected 1893 experiments.

    PubMed

    Nicolas, Serge; Gounden, Yannick; Levine, Zachary

    2011-01-01

    French neurologist Jean Martin Charcot (1825-1893) and French psychologist Alfred Binet (1857-1911) are almost unknown as investigators who conducted original and fascinating studies in the area of memory. In a series of 1893 experiments, they compared the performance of two expert mental calculators, Jacques Inaudi and Périclès Diamandi, in tasks that consisted of recalling digits. Inspired by Ribot's psychological work (1881), they believed in the existence of not one type of memory but several partial, special, and local memories, each devoted to a particular domain. In all arithmetical prodigies, memory for digits is abnormally developed compared with other memories. Inaudi was considered to be an auditory memory-based mental calculator; when memorizing digits, he did not rely onthe appearance of the items or create visual imagery of any kind. Rather, he remembered digits principally by their sounds. Inaudi's methods of calculation and memorization were original and different from those used by Diamandi, who was a typical visual memory-based mental calculator. The experiments presented in the 1893 article were among the first scientific demonstrations of the importance to psychology of studying different types of memory. The present work gives a translation of this pioneering experimental article on expert calculators by Charcot and Binet, instructive for the comprehension of normal memory. PMID:21834408

  15. Jean-Martin Charcot's house officers at La Salpêtrière Hospital.

    PubMed

    Walusinski, Olivier

    2011-01-01

    From the time he became chef de service at La Salpêtrière Hospital in 1866 until his death in 1893, Jean-Martin Charcot oversaw 32 house officers. Some of them became famous, such as D.M. Bourneville, E. Brissaud, P. Marie and G. Gilles de la Tourette. Others are less well known. The fact remains that Charcot knew how to surround himself with fine students and leverage their talents in order to make the neurological discoveries by which he would become famous throughout the world. Here, we present the biographies of H. Soulier (1862), J. Cotard (1865), R. Lépine (1867), A. Gombault (1872), A. Pierret (1874), A. Pitres (1876), P. Oulmont (1877), G. Guinon (1885), P. Blocq(1887), E. Huet (1888), E. Parmentier (1890) and A. Souques(1893). Each of these men with their unique paths and interests helped lay the foundations for the birth of neurology at the end of the 19th century in Paris. As Emile Littré said: 'La science de la Médecine, si elle ne veut pas être rabaissée au rang de métier, doit s'occuper de son histoire et soigner les vieux monuments que les temps passés lui ont légués', which could be translated as 'to avoid being reduced to a trade, the science of medicine must attend to its history and take care of the old monuments handed down by time'. PMID:20938144

  16. Copy Number Variations in a Population-Based Study of Charcot-Marie-Tooth Disease

    PubMed Central

    Høyer, Helle; Braathen, Geir J.; Eek, Anette K.; Nordang, Gry B. N.; Skjelbred, Camilla F.; Russell, Michael B.

    2015-01-01

    Copy number variations (CNVs) are important in relation to diversity and evolution but can sometimes cause disease. The most common genetic cause of the inherited peripheral neuropathy Charcot-Marie-Tooth disease is the PMP22 duplication; otherwise, CNVs have been considered rare. We investigated CNVs in a population-based sample of Charcot-Marie-Tooth (CMT) families. The 81 CMT families had previously been screened for the PMP22 duplication and point mutations in 51 peripheral neuropathy genes, and a genetic cause was identified in 37 CMT families (46%). Index patients from the 44 CMT families with an unknown genetic diagnosis were analysed by whole-genome array comparative genomic hybridization to investigate the entire genome for larger CNVs and multiplex ligation-dependent probe amplification to detect smaller intragenomic CNVs in MFN2 and MPZ. One patient had the pathogenic PMP22 duplication not detected by previous methods. Three patients had potentially pathogenic CNVs in the CNTNAP2, LAMA2, or SEMA5A, that is, genes related to neuromuscular or neurodevelopmental disease. Genotype and phenotype correlation indicated likely pathogenicity for the LAMA2 CNV, whereas the CNTNAP2 and SEMA5A CNVs remained potentially pathogenic. Except the PMP22 duplication, disease causing CNVs are rare but may cause CMT in about 1% (95% CI 0–7%) of the Norwegian CMT families. PMID:25648254

  17. Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2014-04-01

    We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) μm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) μm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone. PMID:24322885

  18. Polar bear maternity denning in the Beaufort Sea

    USGS Publications Warehouse

    Amstrup, S.; Gardner, C.

    1994-01-01

    The distribution of polar bears (Ursus maritimus) is circumpolar in the NOrthern Hemisphere, but known locations of maternal dens are concentrated in relatively few, widely scattered locations. Denning is either uncommon or unknown within gaps. To understand effects of industrial development and propose increases in hunting, the temporal and spatial distribution of denning in the Beaufort Sea must be known. We caputred and radiocollared polar bears between 1981 and 1991 and determined tht denning in the Beaufort Sea region was sufficient to account for the estimated population there. Of 90 dend, 48 were on drifting pack ice, 38 on land, and 4 on land-fast ice. The portions of dens on land was higher (P= 0.029) in later compared with earlier years of the study. Bears denning on pack ice drifting as far as 997 km (x=385km) while in dens. there was no difference in cun production by bears denning on land and pack ice (P =0.66). Mean entry and exit dates were 11 November and 5 April for land dens and 22 November and 26 March for pack-ice dens. Female polar bears captured in the Beaufort Sea appeared to be isolated from those caught eat of Cape Bathurst in Canada. Of 35 polar bears that denned along the mainland coast of Alaska and Canada 80% denned between 137 00'W snf 146 59'W. Bears followed to >1 den did not reuse sites and consecutive dens were 20-1,304 km apart. However radio-collared bears are largely faithful to substrate (pack-ice, land, and land-fast ice) and the general geographic area of previous dens. Bears denning on land may be vunerable to human activities such as hunting and industrial development. However, predictable denning chronology and alck of site fidelity indicate that many potential impacts on denning polar bears could be mitigated.

  19. Dragons' Den: promoting healthcare research and innovation.

    PubMed

    Mazhindu, Deborah; Gregory, Siobhan

    2015-07-01

    The changing health and social care landscape, and, in particular, the financial challenges affecting the NHS, can present difficulties for staff looking for funding to support innovation and new ways of working. One method of competitive tendering that is becoming more accepted as a way of allocating funds, encouraging staff engagement and developing innovation for research is a format based the BBC television series, Dragons' Den. This article describes how Hounslow and Richmond Community Healthcare NHS Trust, London, has developed a 'Dragons' Den initiative' of annual competitive research funding allocation to ensure that some of the most dynamic practice in the trust is captured. PMID:26135194

  20. Charcot-Marie-Tooth 1A concurrent with schwannomas of the spinal cord and median nerve.

    PubMed

    Kwon, Joo Young; Chung, Ki Wha; Park, Eun Kyung; Park, Sun Wha; Choi, Byung-Ok

    2009-08-01

    We identified Charcot-Marie-Tooth disease type 1A (CMT1A) in a family with schwannomas in the spinal cord and median nerve. The CMT1A in this family showed an autosomal dominant pattern, like other CMT patients with PMP22 duplication, and the family also indicated a possible genetic predisposition to schwannomas by 'mother-to-son' transmission. CMT1A is mainly caused by duplication of chromosome 17p11.2-p12 (PMP22 gene duplication). A schwannoma is a benign encapsulated tumor originating from a Schwann cell. A case of hereditary neuropathy with liability to pressure palsies (HNPP) concurrent with schwannoma has been previously reported. Although it seems that the co-occurrence of CMT1A and schwannomas in a family would be the result of independent events, we could not completely ignore the possibility that the coincidence of two diseases might be due to a shared genetic background. PMID:19654968

  1. Acute Charcot foot and diabetes: A primer for the vascular nurse.

    PubMed

    Foley, Anne M

    2016-03-01

    The clinical findings of the acute Charcot process includes a swollen, warm, and erythematous foot; although pain may be present, it is often mild and out of proportion to the clinical examination. The diagnosis is confirmed by radiologic imaging, and the diagnosis must be considered in any patient with diabetic neuropathy and unilateral foot swelling. Initial treatment calls for immediate immobilization of the foot. Failure to do so can lead to further foot damage, destruction, and possibly amputation. The patient with acute CN requires referral to a multidisciplinary team experienced in the care of the diabetic patient with this devastating condition. Patient education is a crucial component of the treatment plan when caring for a client with CN. PMID:26897350

  2. The diagnostic criteria for multiple sclerosis: From Charcot to McDonald.

    PubMed

    Gafson, Arie; Giovannoni, Gavin; Hawkes, Christopher H

    2012-01-01

    The history of diagnostic criteria for multiple sclerosis (MS) from Charcot to McDonald is reviewed. Although the criteria have evolved positively with each revision we think there is still room for improvement. It is proposed that the 2010 revision to the McDonald criteria should be used for research or drug trials and comprise two categories: 'MS' and 'Not MS'. McDonald 2010 could be used optionally for routine clinical purposes. The categories 'probable' and 'possible' are permissible for everyday clinical activity, particularly where there is limited access to MRI, but they would not be appropriate for research or drug trials. Future updates should make it mandatory to perform MRI of the brain, and possibly spinal cord, and the definition of 'an attack' should be revised to include information from physical examination or MRI. Finally, we suggest that certain paroxysmal symptoms (e.g. Lhermitte phenomenon) should be incorporated in any further revision. PMID:25876446

  3. [Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].

    PubMed

    Uno, S; Katayama, K; Dobashi, N; Hirano, A; Ogihara, A; Yamazaki, H; Usui, N; Kobayashi, T; Inoue, K; Kuraishi, Y

    1999-05-01

    A 44-year-old, previously healthy man with a diagnosis of non-Hodgkin's lymphoma (NHL, diffuse large B-cell type, stage IIA) was treated with combination chemotherapy including vincristine (VCR). After receiving a cumulative dose of VCR, he experienced rapid and marked weakening which progressed to quadriplegia and bulbar palsy. Prior to this therapy, the patient had no neurological problems, and his siblings were asymptomatic. Physical examination identified pes cavus (hollow foot), and electrodiagnostic studies showed markedly slower nerve conduction velocity of myelinated fibers, with abundant "onion bulb" formations. Chromosomal analysis detected 17p11.2-12 duplication, thus yielding a diagnosis of Charcot-Marie-Tooth (CMT) 1A. CMT disease is a familial neuromuscular disorder, and the incidence is approximately 1 in 2,500. We concluded that if CMT disease is diagnosed, vincristine should be avoided due to the potential severity of neurotoxicity to small doses. PMID:10390891

  4. Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease.

    PubMed

    Ohshita, Naohiro; Oka, Saeko; Tsuji, Kaname; Yoshida, Hiroaki; Morita, Shosuke; Momota, Yoshihiro; Tsutsumi, Yasuo M

    2016-01-01

    Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD. PMID:27269665

  5. [Therapy for Charcot-Marie-Tooth Disease: From the Standpoint of Neurologists].

    PubMed

    Nakagawa, Masanori

    2016-01-01

    To date, there is no approved pharmacologic treatment for any form of Charcot-Marie-Tooth disease (CMT). However, some clinical or preclinical trials for CMT1A have been undertaken, for example Neurotrophin-3, PXT3003, and neuregulin-1. Gene therapy for CMT1X, CMT2F and Giant axonal neuropathy using animal model or culture cells have been reported with some interesting results. Stem cell research for example iPS cells derived from patients with CMT2A or CMT2E, is being conducted to clarify the mechanism of CMT and find therapeutic clues. The development of new surrogate markers for clinical trials is also needed. Additionally, steps should be taken to improve the quality of life of patients with CMT, including pain control and life style enhancement. PMID:26764298

  6. Connexin mutations in X-linked Charcot-Marie-Tooth disease

    SciTech Connect

    Bergoffen, J. ); Scherer, S.S.; Wang, S.; Scott, M.; Bone, L.J.; Chen, K.; Lensch, M.W.; Fischbeck, K.H. ); Paul, D.L. ); Change, P.F. )

    1993-12-24

    X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry techniques, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32 plays an important role in peripheral nerve.

  7. Piet Mondrian's trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011.

    PubMed

    Steinman, Lawrence; Axtell, Robert C; Barbieri, Donald; Bhat, Roopa; Brownell, Sara E; de Jong, Brigit A; Dunn, Shannon E; Grant, Jacqueline L; Han, May H; Ho, Peggy P; Kuipers, Hedwich F; Kurnellas, Michael P; Ousman, Shalina S; Rothbard, Jonathan B

    2013-01-01

    Four questions were posed about multiple sclerosis (MS) at the 2011 Charcot Lecture, Oct. 22, 2011. 1. The Male/Female Disparity: Why are women developing MS so much more frequently than men? 2. Neuronal and Glial Protection: Are there guardian molecules that protect the nervous system in MS? 3. Predictive Medicine: With all the approved drugs, how can we rationally decide which one to use? 4. The Precise Scalpel vs. the Big Hammer for Therapy: Is antigen-specific therapy for demyelinating disease possible? To emphasize how our views on the pathogenesis and treatment of MS are evolving, and given the location of the talk in Amsterdam, Piet Mondrian's progressive interpretations of trees serve as a heuristic. PMID:23303879

  8. Critical Limb Ischemia in Association with Charcot Neuroarthropathy: Complex Endovascular Therapy for Limb Salvage

    SciTech Connect

    Palena, Luis Mariano; Brocco, Enrico; Manzi, Marco

    2013-05-09

    Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical and orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.

  9. A rare presentation of multiple dens invaginatus in maxillary dentition

    PubMed Central

    Purani, Jigar M; Purani, Hiral J

    2014-01-01

    Dens invaginatus is a developmental disturbance of the tooth and usually occurs in the maxillary lateral incisor of permanent dentition. In this article, a rare case of dens invaginatus affecting multiple permanent maxillary teeth is described. PMID:25085944

  10. A neurological bias in the history of hysteria: from the womb to the nervous system and Charcot.

    PubMed

    Mota Gomes, Marleide da; Engelhardt, Eliasz

    2014-12-01

    Hysteria conceptions, from ancient Egypt until the 19th century Parisian hospital based studies, are presented from gynaecological and demonological theories to neurological ones. The hysteria protean behavioral disorders based on nervous origin was proposed at the beginning, mainly in Great Britain, by the "enlightenment nerve doctors". The following personages are highlighted: Galen, William, Sydenham, Cullen, Briquet, and Charcot with his School. Charcot who had hysteria and hypnotism probably as his most important long term work, developed his conceptions, initially, based on the same methodology he applied to studies of other neurological disorder. Some of his associates followed him in his hysteria theories, mainly Paul Richer and Gilles de La Tourette who produced, with the master's support, expressive books on Salpêtrière School view on hysteria. PMID:25517645

  11. A literature-based guide to the conservative and surgical management of the acute Charcot foot and ankle

    PubMed Central

    Schade, Valerie L.; Andersen, Charles A.

    2015-01-01

    Acute Charcot neuroarthropathy of the foot and ankle presents with the insidious onset of a unilateral acutely edematous, erythematous, and warm lower extremity. The acute stages are typically defined as Eichenholtz Stage 1, or Stage 0, which was first described by Shibata et al. in 1990. The ultimate goal of treatment is maintenance of a stable, plantigrade foot which can be easily shod, minimizing the risk of callus, ulceration, infection, and amputation. The gold standard of treatment is non-weight-bearing immobilization in a total contact cast. Surgical intervention remains controversial. A review of the literature was performed to provide an evidenced-based approach to the conservative and surgical management of acute Charcot neuroarthropathy of the foot and ankle. PMID:25795102

  12. Charcot Foot

    MedlinePlus

    ... occur in people who have significant nerve damage (neuropathy). The bones are weakened enough to fracture, and ... patients with diabetes—a disease often associated with neuropathy—take preventive measures and seek immediate care if ...

  13. Marguerite Bottard (1822-1906), nurse under Jean-Martin Charcot, portrayed by G. Gilles de la Tourette.

    PubMed

    Walusinski, Olivier

    2011-01-01

    Hospitals in Paris underwent considerable change at the end of the 19th century. As they moved from providing accommodation to care, their mission shifted from helping to healing. The glorification of scientific progress, as opposed to religious obscurantism, affected all of French 'Republican' society, in particular a significant part of the medical profession, led by figures such as D.M. Bourneville, former interne (house officer) under J.M. Charcot and also his publisher. Bourneville helped bring about the creation of nursing schools and the gradual replacement of religious orders by educated secular nurses. Marguerite Bottard, Charcot's chief nurse made famous by A. Brouillet's painting 'Une leçon clinique à La Salpêtrière', would be glorified and decorated as a model for this movement. A letter by G. Gilles de la Tourette to Charcot's successor F. Raymond, never before published, illustrates this progressive current of thought and revisits the struggle to secularise hospitals under the Third Republic in France. At the same time, it renews interest in the exemplary career of a nurse whose name was recently given to a building at La Salpêtrière Hospital. PMID:21487229

  14. Dens Evaginatus: A Problem-Based Approach

    PubMed Central

    Ayer, A.; Vikram, M.; Suwal, P.

    2015-01-01

    Dens evaginatus is an uncommon developmental anomaly of human dentition characterized by the presence of tubercle on the occlusal surface of mandibular premolars and lingual surface of anterior teeth. Due to occlusal trauma this tubercle tends to fracture thus exposing the pathway to the pulp chamber of teeth. This case report is about the presentation of dens evaginatus in mandibular premolars bilaterally; among them tooth 44 was associated with chronic apical periodontitis. Fractured tubercle of three premolars was sealed with composite resin. Root canal treatment was performed with tooth 44. Routine endodontic treatment did not result in remission of infection. Therefore, culture and sensitivity tests were performed to identify the cause and modify treatment plan accordingly. Triple antibiotic paste was used as an intracanal medicament to disinfect the root canal that resulted in remission of infection. PMID:26779353

  15. Alfred Vulpian and Jean-Martin Charcot in each other's shadow? From Castor and Pollux at La Salpêtrière to neurology forever.

    PubMed

    Bogousslavsky, Julien; Walusinski, Olivier; Moulin, Thierry

    2011-01-01

    While Alfred Vulpian (1826-1887) is not completely forgotten, he cannot match the uninterrupted celebrity which Jean-Martin Charcot (1825-1893) still enjoys today. After becoming interne (residents) at the same institute in 1848, both were involved in shaping the cradle of what would become modern neurology. Both started work as chiefs at a La Salpêtrière service on January 1, 1862, making common rounds and studies, with several common publications. While their friendship remained 'for life', as stated by Charcot at Vulpian's funeral, their career paths differed. Vulpian progressed quicker and higher, being appointed full professor and elected at the Académie Nationale de Médecine and the Académie des Sciences several years before Charcot, as well as becoming dean of the Paris Faculty of Medicine. These positions also enabled him to support his friend Charcot in getting appointed full clinical professor and becoming the first holder of the chair of Clinique des Maladies du Système Nerveux in 1882. Before studying medicine, Vulpian had worked in physiology with Pierre Flourens, and his career always remained balanced between physiology and neurology, with remarkable papers. He introduced Charcot to optic microscopy during their La Salpêtrière years, indirectly helping him to become his successor to the chair of pathological anatomy in 1872. While Vulpian succeeded so well in local medical affairs, Charcot spent his time building up a huge clinical service and a teaching 'school' at La Salpêtrière, which he never left for over 31 years until his death. This 'school' progressively became synonymous with clinical neurology itself and perpetuated the master's memory for decades. Vulpian never had such support, although Jules Déjerine was his pupil and Joseph Babinski was his interne before becoming Charcot's chef de clinique (chief of staff) in 1885. This unusual switch in Parisian medicine contributed to Charcot's unaltered celebrity over more than a century

  16. Respiratory dysfunction in Charcot-Marie-Tooth disease type 1A.

    PubMed

    de Carvalho Alcântara, Mônica; Nogueira-Barbosa, Marcello H; Fernandes, Regina Maria França; da Silva, Geruza Alves; Lourenço, Charles Marques; Sander, Heide H; Marques Junior, Wilson

    2015-05-01

    We aimed to investigate the relationship between neurological compromise, respiratory parameters in wakefulness and in sleep, physiology, and morphology of phrenic nerves in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). Sixteen patients with CMT1A were evaluated by spirometry, maximal expiratory and maximal inspiratory pressures (MEP, MIP), polysomnography, phrenic nerve compound muscle action potential (CMAP), and ultrasonography (roots C3,C4,C5 and phrenic nerves). Clinical disability was measured with Charcot-Marie-Tooth neuropathy score (CMT-NS; range 0-36). Two control groups, comprising 30 individuals matched for age, sex, and body mass index, were used for comparison. Ten patients were female (62%), mean age was 37.88 years (range 24-76); and CMT-NS range was 7-34. MIP was reduced in five (31%) and MEP in 12 patients (75%), although only one had restrictive respiratory dysfunction in spirometry. Apnoea-hypopnea index (AHI) was significantly higher in patients (12.01 ± 11.57/h × 5.89 ± 8.36/h; p value = 0.05) and increased in REM sleep compared with NREM (9.94 ± 10.96/h × 19.13 ± 19.93/h; p value = 0.01). There were significant correlations between CMT-NS and AHI (Pearson = 0.69; p value = 0.03); CMT-NS and MIP (Pearson = -0.691, p value = 0.003); and CMT-NS and MEP (Pearson = -0.603, p value = 0.013). Also, AHI showed negative correlation with MIP (Pearson = -0.52, p value = 0.036) and MEP (Pearson = -0.55, p value = 0.026). Phrenic nerves were enlarged in ultrasonography in all patients and presented significant correlations with CMAPs (right: Pearson = -0.554, p value = 0.026; left: Pearson = -0.558, p value = 0.025). We suggest that axonal degeneration of nerves directed to muscles of respiration might explain the high prevalence of respiratory weakness in patients with CMT1A. Clinical manifestations are frequent during sleep, where the diaphragm alone can only partially surpass the overload in breathing apparatus. PMID:25761374

  17. Coexistence of Charcot-Marie-Tooth disease type 1A and anti-MAG neuropathy.

    PubMed

    Piscosquito, Giuseppe; Salsano, Ettore; Ciano, Claudia; Palamara, Luisa; Morbin, Michela; Pareyson, Davide

    2013-06-01

    At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate. PMID:23781967

  18. A brief review of recent Charcot-Marie-Tooth research and priorities

    PubMed Central

    Ekins, Sean; Litterman, Nadia K.; Arnold, Renée J.G.; Burgess, Robert W.; Freundlich, Joel S.; Gray, Steven J.; Higgins, Joseph J.; Langley, Brett; Willis, Dianna E.; Notterpek, Lucia; Pleasure, David; Sereda, Michael W.; Moore, Allison

    2015-01-01

    This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases. PMID:25901280

  19. Charcot-Marie-Tooth (CMT) disease 1A with superimposed inflammatory polyneuropathy in children.

    PubMed

    Desurkar, A; Lin, J-P; Mills, K; Al-Sarraj, S; Jan, W; Jungbluth, H; Wraige, E

    2009-04-01

    Charcot-Marie-Tooth (CMT) disease is genetically heterogeneous and subdivided into demyelinating (CMT 1) and axonal (CMT 2) types based on neurophysiology findings. CMT1A, the commonest form associated with duplication of the PMP22 segment on chromosome 17p, often arises in childhood but is generally a slowly progressive disease. We report 2 children presenting with clinical features of an acute inflammatory demyelinating polyneuropathy (AIDP) who were subsequently diagnosed with underlying CMT1A. Both children had neurophysiology and histopathology features consistent with CMT1. Immunoglobulin treatment was initiated considering the evidence of superimposed inflammation and appeared to modify disease progression. Our findings indicate that CMT1A predisposes to a superimposed inflammatory neuropathy. Recognition of this association is difficult, particularly in children without clear family history, but of great importance as immunomodulatory treatment may improve outcome. In addition, we postulate that an underlying genetic polyneuropathy should be suspected if the recovery from AIDP is slower than expected, or incomplete. PMID:19809938

  20. Charcot-Marie-Tooth disease: frequency of genetic subtypes in a Southern Italy population.

    PubMed

    Manganelli, Fiore; Tozza, Stefano; Pisciotta, Chiara; Bellone, Emilia; Iodice, Rosa; Nolano, Maria; Geroldi, Alessandro; Capponi, Simona; Mandich, Paola; Santoro, Lucio

    2014-12-01

    The objective of this study is to assess the genetic distribution of Charcot-Marie-Tooth (CMT) disease in Campania, a region of Southern Italy. We analyzed a cohort of 197 index cases and reported the type and frequency of mutations for the whole CMT population and for each electrophysiological group (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]) and for familial and isolated CMT cases. Genetic diagnosis was achieved in 148 patients (75.1%) with a higher success rate in HNPP and CMT1 than CMT2. Only four genes (PMP22, GJB1, MPZ, and GDAP1) accounted for 92% of all genetically confirmed CMT cases. In CMT1, PMP22 duplication was the most common mutation while the second gene in order of frequency was MPZ in familial and SH3TC2 in isolated cases. In CMT2, GJB1 was the most frequent mutated gene and GJB1 with GDAP1 accounted for almost 3/4 of genetically defined CMT2 patients. The first gene in order of frequency was GJB1 in familial and GDAP1 in isolated cases. In HNPP, the majority of patients harbored the PMP22 gene deletion. The novelty of our data is the relatively high frequency of SH3TC2 and GDAP1 mutations in demyelinating and axonal forms, respectively. These epidemiological data can help in panel design for our patients' population. PMID:25429913

  1. Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing

    PubMed Central

    Høyer, Helle; Braathen, Geir J.; Busk, Øyvind L.; Holla, Øystein L.; Svendsen, Marit; Hilmarsen, Hilde T.; Strand, Linda; Skjelbred, Camilla F.; Russell, Michael B.

    2014-01-01

    Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81 CMT families. Gene mutations had previously been identified in 22 families; the remaining 59 families were analysed by next-generation sequencing. Thirty-two CMT genes and 19 genes causing other inherited neuropathies were included in a custom panel. Variants were classified into five pathogenicity classes by genotype-phenotype correlations and bioinformatics tools. Gene mutations, classified certainly or likely pathogenic, were identified in 37 (46%) of the 81 families. Point mutations in known CMT genes were identified in 21 families (26%), whereas four families (5%) had point mutations in other neuropathy genes, ARHGEF10, POLG, SETX, and SOD1. Eleven families (14%) carried the PMP22 duplication and one family carried a MPZ duplication (1%). Most mutations were identified not only in known CMT genes but also in other neuropathy genes, emphasising that genetic analysis should not be restricted to CMT genes only. Next-generation sequencing is a cost-effective tool in diagnosis of CMT improving diagnostic precision and time efficiency. PMID:25025039

  2. Perk Ablation Ameliorates Myelination in S63del-Charcot-Marie-Tooth 1B Neuropathy.

    PubMed

    Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D'Antonio, Maurizio; Feltri, Maria L; Wrabetz, Lawrence

    2016-04-01

    In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot-Marie-Tooth disease type 1B (CMT1B)-S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment:Perkhaploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/- compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition,Perkdeficiency in other cells may contribute to demyelination in a non-Schwann-cell autonomous manner. PMID:27095827

  3. Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

    SciTech Connect

    Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. ); Brooks, D.G.; Ravetch, J.V. ); Trofatter, J.A. )

    1993-11-15

    The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

  4. Oral Health, Temporomandibular Disorder, and Masticatory Performance in Patients with Charcot-Marie-Tooth Type 2

    PubMed Central

    Rezende, Rejane L. S.; Bonjardim, Leonardo R.; Neves, Eduardo L. A.; Santos, Lidiane C. L.; Nunes, Paula S.; Garcez, Catarina A.; Souza, Cynthia C.; Araújo, Adriano A. S.

    2013-01-01

    Background. The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD) and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2). Methods and Results. The average number of decayed, missing, and filled teeth (DMFT) for both groups, control (CG) and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P = 0.227). The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P = 0.899). The prevalence of self-reported TMD was 33.3% and 38.9% (P = 0.718) in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG) and 22.2% (CMT2), without significant difference between groups (P = 0.162). The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7%) and temporalis (CG = 19.0%; GCMT2 = 33.3%) muscle pain. The geometric mean diameter (GMD) was not significantly different between groups (CG = 4369; CMT2 = 4627, P = 0.157). Conclusion. We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance. PMID:24391462

  5. Charcot Neuroarthropathy in Patients With Diabetes: An Updated Systematic Review of Surgical Management.

    PubMed

    Schneekloth, Brian J; Lowery, Nicholas J; Wukich, Dane K

    2016-01-01

    Charcot neuroarthropathy (CN) of the foot and ankle is a demanding clinical dilemma, and surgical management can be very complicated. Historically, the evidence guiding surgical management of CN has been small retrospective case series and expert opinions. The purpose of the present report was to provide a systematic review of studies published from 2009 to 2014 and to review the indications for surgery. A Medline search was performed, and a systematic review of studies discussing the surgical management of CN was undertaken. Thirty reports fit the inclusion criteria for our study, including 860 patients who had undergone a surgical procedure for the treatment of CN. The surgical procedures included amputation, arthrodesis, debridement of ulcers, drainage of infections, and exostectomy. The midfoot was addressed in 26.9% of cases, the hindfoot in 41.6%, and the ankle in 38.4%. Of the 30 studies, 24 were retrospective case series (level 4), 4 were controlled retrospective studies (level 3), and 2 were level II studies. The overall amputation rate was 8.9%. The quality of the published data on the surgical management of CN has improved during the past several years. Evidence concerning the timing of treatment and the use of different fixation methods remains inconclusive. PMID:26810129

  6. Severe phenotypes in a Charcot-Marie-Tooth 1A patient with PMP22 triplication.

    PubMed

    Kim, Sung Min; Lee, Jinho; Yoon, Bo Ram; Kim, Ye Jin; Choi, Byung-Ok; Chung, Ki Wha

    2015-02-01

    Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous hereditary motor and sensory neuropathy signified by a distal symmetric polyneuropathy. The most frequent subtype is type 1A (CMT1A) caused by duplication in chromosome 17p12 that includes PMP22. This study reports a woman with a family history of CMT1A due to PMP22 duplication. However, she presented with a more severe phenotype than her sibling or ancestors and was found to have a PMP22 triplication instead of the duplication. This was caused by de novo mutation on her affected mother's duplication chromosome. Her lower limb magnetic resonance imaging revealed severe diffused atrophy and fatty replacement. However, her affected sister with typical PMP22 duplication showed almost intact lower limb. Triplication patient's median motor nerve conduction velocity was far lower compared with her sister. Her onset age was faster (8 years) than her sister (42 years). CMT1A triplication might be generated by a female-specific chromosomal rearrangement mechanism that is different from the frequent paternal-originated CMT1A duplication. It also suggests that the wide phenotypic variation of CMT1A might be partly caused by unstable genomic rearrangement, including PMP22 triplication. PMID:25500726

  7. Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

    PubMed

    Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

    2008-07-01

    Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination. PMID:18425620

  8. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.

    PubMed

    Cottenie, Ellen; Kochanski, Andrzej; Jordanova, Albena; Bansagi, Boglarka; Zimon, Magdalena; Horga, Alejandro; Jaunmuktane, Zane; Saveri, Paola; Rasic, Vedrana Milic; Baets, Jonathan; Bartsakoulia, Marina; Ploski, Rafal; Teterycz, Pawel; Nikolic, Milos; Quinlivan, Ros; Laura, Matilde; Sweeney, Mary G; Taroni, Franco; Lunn, Michael P; Moroni, Isabella; Gonzalez, Michael; Hanna, Michael G; Bettencourt, Conceicao; Chabrol, Elodie; Franke, Andre; von Au, Katja; Schilhabel, Markus; Kabzińska, Dagmara; Hausmanowa-Petrusewicz, Irena; Brandner, Sebastian; Lim, Siew Choo; Song, Haiwei; Choi, Byung-Ok; Horvath, Rita; Chung, Ki-Wha; Zuchner, Stephan; Pareyson, Davide; Harms, Matthew; Reilly, Mary M; Houlden, Henry

    2014-11-01

    Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels. PMID:25439726

  9. Mutation of SIMPLE in Charcot-Marie-Tooth 1C alters production of exosomes.

    PubMed

    Zhu, Hong; Guariglia, Sara; Yu, Raymond Y L; Li, Wenjing; Brancho, Deborah; Peinado, Hector; Lyden, David; Salzer, James; Bennett, Craig; Chow, Chi-Wing

    2013-06-01

    Charcot-Marie-Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis. PMID:23576546

  10. Characteristics of demyelinating Charcot-Marie-Tooth disease with concurrent diabetes mellitus

    PubMed Central

    Yu, Zhiliang; Wu, Xiaohua; Xie, Huijun; Han, Ying; Guan, Yangtai; Qin, Yong; Zheng, Huimin; Jiang, Jianming; Niu, Zhenmin

    2014-01-01

    Purpose: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with concurrent diabetes mellitus (DM) is rare. The purpose of this study is to explore the genetic, clinical and pathological characteristics of the patients with CMT and concurrent DM. Methods: We investigated gene mutations (the peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide-induced tumor necrosis factor-α factor gene, early growth response gene and the neurofilament light chain gene loci) of a relatively large and typical Chinese family with CMT1 and concurrent DM2. From the literature, we also retrieved all reported families and single cases with CMT and concurrent DM. We comprehensively analyzed the characteristics of total 33 patients with CMT and concurrent DM, and further compared these characteristics with those of patients of diabetic peripheral neuropathy (DPN). Results: Patients with CMT and concurrent DM had some relatively independent characteristics and pathogenic mechanisms. So we designated that kind of characteristic demyelinating CMT which accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT. Conclusion: CMT is an etiologic factor of DM, even though the intrinsic association between CMT and DM still remains further exploration. PMID:25120817

  11. Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease

    PubMed Central

    Madorsky, Irina; Opalach, Katherine; Waber, Amanda; Verrier, Jonathan D.; Solmo, Chelsea; Foster, Thomas; Dunn, William A; Notterpek, Lucia

    2009-01-01

    Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance. PMID:19320048

  12. A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

    PubMed Central

    2013-01-01

    Background Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria. Methods To identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed. Results WES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn’t exhibit any other symptoms of the previously reported HADHB patients. Conclusions These data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB. PMID:24314034

  13. A pilot study of proximal strength training in Charcot-Marie-Tooth disease.

    PubMed

    Ramdharry, Gita M; Pollard, Alexander; Anderson, Cheryl; Laurá, Matilde; Murphy, Sinead M; Dudziec, Magdalena; Dewar, Elizabeth L; Hutton, Elspeth; Grant, Robert; Reilly, Mary M

    2014-12-01

    Gait analysis of people with Charcot-Marie-Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single-blinded cross over design to investigate the effect of a 16-week home-based programme of resistance training on hip flexor muscle strength. Measures of walking endurance, gait speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based on American College of Sports Medicine recommendations. A mixed effects model was used for analysis. Twenty-six people finished the study, with average reported exercise participation of 93%. No negative effects of exercise were observed. Significant increase in hip flexor muscle strength was observed on the left, but not the right. No changes were observed in walking speed and endurance measures. This pilot study of home-based resistance training showed a modest improvement in hip strength but only on one side. The lack of a more significant improvement and no improvement in walking measures suggests that this training protocol may not be optimal for people with CMT and that patients may need to stratified differently for training studies in CMT. PMID:25582960

  14. Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

    PubMed

    Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

    2014-12-15

    Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment. PMID:25454638

  15. Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

    PubMed

    Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

    2015-11-19

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies. PMID:26423936

  16. Neural and Molecular Features on Charcot-Marie-Tooth Disease Plasticity and Therapy

    PubMed Central

    Juárez, Paula; Palau, Francesc

    2012-01-01

    In the peripheral nervous system disorders plasticity is related to changes on the axon and Schwann cell biology, and the synaptic formations and connections, which could be also a focus for therapeutic research. Charcot-Marie-Tooth disease (CMT) represents a large group of inherited peripheral neuropathies that involve mainly both motor and sensory nerves and induce muscular atrophy and weakness. Genetic analysis has identified several pathways and molecular mechanisms involving myelin structure and proper nerve myelination, transcriptional regulation, protein turnover, vesicle trafficking, axonal transport and mitochondrial dynamics. These pathogenic mechanisms affect the continuous signaling and dialogue between the Schwann cell and the axon, having as final result the loss of myelin and nerve maintenance; however, some late onset axonal CMT neuropathies are a consequence of Schwann cell specific changes not affecting myelin. Comprehension of molecular pathways involved in Schwann cell-axonal interactions is likely not only to increase the understanding of nerve biology but also to identify the molecular targets and cell pathways to design novel therapeutic approaches for inherited neuropathies but also for most common peripheral neuropathies. These approaches should improve the plasticity of the synaptic connections at the neuromuscular junction and regenerate cell viability based on improving myelin and axon interaction. PMID:22745917

  17. Charcot-Marie-Tooth 1A: A narrative review with clinical and anatomical perspectives.

    PubMed

    McGrath, M C

    2016-07-01

    Charcot-Marie-Tooth 1A (CMT1A) is regarded as the most common hereditary peripheral neurodegenerative disorder. This narrative review highlights perspectives around the historically well-established and characteristic anatomical manifestations of CMT1A seen in the feet, legs and hands, in addition to a clinical diagnosis that may be confirmed by electrophysiology, genetic or molecular markers together with the presence of a typical family history. A less well-known perspective is the potential for systemic manifestations and wider complication. The condition is characterised by a progressive clinical picture with unmistakable anatomical and neurological features that have been described since the late 19th century. There remains no cure although supportive, rehabilitative, and surgical regimes may provide helpful management or amelioration of symptoms. Most recently, the emergence of a pleotherapeutic approach suggests distinct promise. Future research focused on a detailed elucidation of the underlying molecular mechanisms underpinning myelin and axonal function may eventually hold the key to successful treatment of CMT1A. Genetic modification would potentially present a cure. Clin. Anat. 29:547-554, 2016. © 2015 Wiley Periodicals, Inc. PMID:26457477

  18. Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice

    PubMed Central

    Gouveri, Evanthia; Papanas, Nikolaos

    2011-01-01

    Charcot osteoarthropathy (COA) is a potentially limbthreatening condition that mainly affects diabetic patients with neuropathy. In everyday practice, it presents as a red, hot, swollen foot, usually painless, and is frequently triggered by trivial injury. Its etiology is traditionally attributed to impairment of either the autonomic nervous system, leading to increased blood flow and bone resorption, or of the peripheral nervous system, whereby loss of pain and protective sensation render the foot susceptible to repeated injury. More recently, excessive local inflammation is thought to play a decisive role. Diagnosis is based on clinical manifestation and imaging studies (plain X-rays, bone scan, Magnetic Resonance Imaging). The mainstay of management is immediate off-loading, while surgery is usually reserved for chronic cases with irreversible deformities and/or joint instability. The aim of this review is to provide an overview of COA in terms of pathogenesis, classification and clinical presentation, diagnosis and treatment, with an emphasis on the high suspicion required by clinicians for timely recognition to avoid further complications. PMID:21691556

  19. How do Mutations in GJB1 Cause X-linked Charcot-Marie-Tooth Disease?

    PubMed Central

    Kleopa, Kleopas A.; Abrams, Charles K.; Scherer, Steven S.

    2012-01-01

    The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most common form of hereditary motor and sensory neuropathy. The clinical phenotype is characterized by progressive weakness, atrophy, and sensory abnormalities that are most pronounced in the distal extremities. Some patients have CNS manifestations. Affected males have moderate to severe symptoms, whereas heterozygous females are usually less affected. Neurophysiology shows intermediate slowing of conduction and length-dependent axonal loss. Nerve biopsies show more prominent axonal degeneration than de/remyelination. Mutations in GJB1, the gene that encodes the gap junction (GJ) protein connexin32 (Cx32) cause CMT1X; more than 400 different mutations have been described. Many Cx32 mutants fail to form functional GJs, or form GJs with abnormal biophysical properties. Schwann cells and oligodendrocytes express Cx32, and the GJs formed by Cx32 play an important role in the homeostasis of myelinated axons. Animal models of CMT1X demonstrate that loss of Cx32 in myelinating Schwann cells causes a demyelinating neuropathy. Effective therapies remain to be developed. PMID:22771394

  20. Linkage localization of X-linked Charcot-Marie-Tooth disease

    SciTech Connect

    Bergoffen, J. Univ. of Pennsylvania, Philadelphia ); Trofatter, J.; Haines, J.L. ); Pericak-Vance, M.A. ); Chance, P.F. ); Fischbeck, K.H. )

    1993-02-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.

  1. Mutational studies in X-linked Charcot-Marie-Tooth disease (CMTX)

    SciTech Connect

    Cherryson, A.K.; Yeung, L.; Kennerson, M.L.; Nicholson, G.A.

    1994-09-01

    Charcot-Marie-Tooth disease, also known as hereditary motor and sensory neuropathy (HMSN), is a heterogeneous group of slowly progressive disorders of the peripheral nerve. X-linked CMT (CMTX) is characterized by slow motor nerve conduction velocities in affected males and the presence of mildly affected or normal carrier females with intermediate or normal nerve conduction velocities. CMTX, which has an incidence of 3.1 per 100,000 and accounts for approximately 10% of CMT cases, has been mapped to Xq13. One of the genes lying in this region, connexin 32, has been found to contain alterations in individuals affected with X-linked CMT. We have identified our X-linked families from dominant type 1 CMT families using the clinical criteria given above. These families were screened for point mutations in connexin 32. We have identified three missense mutations, a G{r_arrow}A transition at amino acid 35 (valine to methionine), a C{r_arrow}G transition at amino acid 158 (proline to alanine) and a T{r_arrow}A transition at amino acid 182 (serine to threonine). Another family showed a 18 bp deletion, which removed the amino acid 111 to 116 inclusive (histidine, glycine, aspartic acid, proline, leucine, histidine).

  2. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease

    PubMed Central

    Liao, Yi-Chu; Liu, Yo-Tsen; Tsai, Pei-Chien; Chang, Chia-Ching; Huang, Yen-Hua; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Background Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT) type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive. Methodology and Principal Findings Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability. Conclusion GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies. PMID:26244500

  3. Linkage localization of X-linked Charcot-Marie-Tooth disease.

    PubMed Central

    Bergoffen, J; Trofatter, J; Pericak-Vance, M A; Haines, J L; Chance, P F; Fischbeck, K H

    1993-01-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers--AR, PGKP1, DXS453, and DXYS1X--in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 (theta = 0). PMID:8430694

  4. Quantum dot-based diabetic foot mapping for diagnosing osteomyelitis and Charcot neuroarthropathy.

    PubMed

    Yousefi, Farzaneh; Nabipour, Iraj; Kalantarhormozi, Mohammadreza; Assadi, Tahereh; Raeisi, Alireza; Assadi, Majid

    2015-07-01

    The location of osteomyelitis is very important in Charcot neuroarthropathy (CN), especially when a physician is considering amputation of the affected extremity. In diabetic CN, the presence of osteomyelitis is likely. Thus, to identify the infected tissue that needs to be removed, the specific area of infection must be correctly identified. Both CN and osteomyelitis have high mortality rates, but osteomyelitis is more life threatening and needs aggressive treatment. We propose a QD-based method for distinguishing CN with sterile inflammation from osteomyelitis that does not require multiple and frequent imaging modalities. The method utilizes two different colored QDs (i.e., red and green). The red QD is attached to a UBI, an antimicrobial peptide, which attaches to bacteria, enabling their detection. The green QD is attached to MDP, which accumulates in areas of inflammation. When these QDs are injected intravenously at the same time, the red QD-UBI accumulates in infected areas and attaches to bacteria, and the green QD-MDP accumulates both in areas with sterile inflammation and infected areas. The accumulation of only green QDs in the suspect extremity signifies a sterile inflammation process (CN). However, the accumulation of both the red and green QDs signify infectious and inflammation processes (i.e., osteomyelitis or a soft tissue infection, depending on the location). In the latter case, the treatment needs to be more intensive, with even amputation considered. PMID:25801484

  5. Vestibular impairment in Charcot-Marie-Tooth disease type 4C.

    PubMed

    Pérez-Garrigues, Herminio; Sivera, Rafael; Vílchez, Juan Jesús; Espinós, Carmen; Palau, Francesc; Sevilla, Teresa

    2014-07-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is a hereditary neuropathy with prominent unsteadiness. The objective of the current study is to determine whether the imbalance in CMT4C is caused only by reduced proprioceptive input or if vestibular nerve involvement is an additional factor. We selected 10 CMT4C patients and 10 age-matched and sex-matched controls. We performed a comprehensive evaluation of the vestibular system, including video Head Impulse Test, bithermal caloric test, galvanic stimulation test and skull vibration-induced nystagmus test. None of the patients experienced dizziness, spontaneous or gaze-evoked nystagmus, but all had significant vestibular impairment when tested when compared to controls. Seven had completely unexcitable vestibular systems and abnormal vestibuloocular reflex. There was no correlation between the degree of vestibulopathy and age or clinical severity. Significant vestibular impairment is a consistent finding in CMT4C and is present early in disease evolution. The profound imbalance that is so disabling in these patients may result from a combination of proprioceptive loss and vestibular neuropathy, and this would modify the recommended rehabilitation strategies. PMID:24614092

  6. A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

    PubMed Central

    Hyun, Young Se; Kwak, Geon; Choi, Yu-Ri; Yeo, Ha Kyung; Jwa, Dong Hwan; Kim, Eun Ja; Mo, Won Min; Nam, Soo Hyun; Kim, Sung Min; Yoo, Jeong Hyun; Koo, Heasoo; Park, Hwan Tae; Chung, Ki Wha; Choi, Byung-Ok

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy. PMID:26828946

  7. Behavioural profiling of a murine Charcot-Marie-Tooth disease type 1A model.

    PubMed

    Norreel, J C; Jamon, M; Riviere, G; Passage, E; Fontes, M; Clarac, F

    2001-04-01

    Different features of motor behaviour were studied on a transgenic mouse model of Charcot-Marie-Tooth's disease (CMT). Mutants with 4 or 7 copies of the human PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A were compared with control animals. The aim of the study was to validate this transgenic model and to characterise the impairments occurring in the various lines. Three main types of analysis were performed in 2-month-old mice without any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA protocol) demonstrated that only a few motor deficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video-tracking system was performed and revealed that the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, splay test and rotarod test. Even in lines with a significantly limited copy number of the transgene, we observed and quantified impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of this human pathology and will certainly be useful for therapeutic procedures and for theoretical studies on this disease. PMID:11328356

  8. Charcot-Marie-Tooth type 1A disease from patient to laboratory.

    PubMed

    Perveen, Shazia; Mannan, Shazia; Hussain, Abrar; Kanwal, Sumaira

    2015-02-01

    Charcot-Marie-Tooth (CMT) disease is a well-known neural or spinal type of muscular atrophy. It is the most familiar disease within a group of conditions called Hereditary Motor and Sensory Neuropathies (HMSN). The disease was discovered by three scientists several years ago. Several genes are involved as the causative agents for the disease. Hundreds of causative mutations have been found and research work for the identification of a novel locus and for the treatment of CMT1A is going on. This review article was planned to gather information on CMT disease and updates on its treatment.National Center for Biotechnology Information (NCBI) and PubMed were searched for data retrieval. Molgen database, which is the exclusive site for CMT mutation, was the other source of articles. Different aspects of the CMT disease were compared.Advancements in the finding of the causative gene, discovery of the novel Loci are the current issues in this regard.CMT disease is incurable, but researchers are trying to get some benefits from different natural compounds and several therapeutic agents.Various groups are working on the treatment projects of CMT1A. Major step forward in CMT research was taken in 2004 when ascorbic acid was used for transgenic mice treatment. Gene therapy for constant neurotrophin-3 (NT- 3) delivery by secretion by muscle cells for the CMT1A is also one of the possible treatments under trial. PMID:25842560

  9. [Phenotypes of Charcot-Marie-Tooth Syndrome and Differential Diagnosis Focused in Inflammatory Neuropathies].

    PubMed

    Iijima, Masahiro

    2016-01-01

    Charcot-Marie-Tooth disease (CMT), the most frequent form of inherited neuropathy, is a genetically heterogeneous syndrome of the peripheral nervous system with a rather homologous clinical phenotype (slowly progressive distal weakness and muscle atrophy, skeletal deformities, and areflexia in each limb). CMT1 is the autosomal-dominant demyelinating form, and CMT1A (mostly PMP22 duplication) is the most frequent subtype, followed by CMTX1, HNPP (hereditary neuropathy with liability to pressure palsies), CMT1B, or CMT2. As CMT is characterized by slowly progressive motor and sensory disturbances in each limb, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) occasionally. Some points can distinguish demyelinating CMT from CIDP. CMT1 patients do not show the conduction block that is frequent in CIDP. In addition, ultrasonographic findings are useful because CMT1 suggests diffuse enlargement of peripheral nerves, whereas CIDP is characterized by asymmetrical or focal enlargement of peripheral nerves. Some CMT1 cases show favorable responses to immunomodulating therapeutics such as corticosteroids, IVIg, and plasma exchange. Such CIDP-like CMT1 (especially CMT1B or CMT2A) shows moderate to high levels of cerebrospinal fluid protein and infiltrated inflammatory macrophages. PMID:26764297

  10. [Treatment for Patients with Charcot-Marie-Tooth Disease: Orthopaedic Aspects].

    PubMed

    Watanabe, Kota

    2016-01-01

    The orthopedic manifestations in patients with Charcot-Marie-Tooth disease include deformity and dysfunction of the extremities and spine. Conservative treatment is the first choice. Orthosis and rehabilitation can improve function, and are important for the prevention of joint contractures. Foot problems are most commonly observed and require surgical treatment. Foot deformities include pes cavus, cavovarus, claw toes, or drop foot. Single or combined surgeries selected for soft tissues are plantar release, tendon transfer, or Achilles tendon lengthening, and those for bones are osteotomies and joint fusions. The upper limb initially demonstrates loss of power of the intrinsic hand muscles followed by symmetrical atrophy of the forearm muscle groups. The typical hand deformity is claw hand. Tendon transfer, joint fusion, soft tissue release, or nerve decompression procedures are performed for correction of hand deformities. Acetabular dysplasia in the hip joints is sometimes observed and osteotomy is selected as surgical treatment in such cases. The associated spinal deformity is scoliosis with or without kyphosis. Similar to treatment of idiopathic scoliosis, posterior spinal fusion is performed in patients with progressive spinal deformities. PMID:26764299

  11. Charcot neuroarthropathy after simultaneous pancreas-kidney transplantation: risk factors, prevalence, and outcome.

    PubMed

    García Barrado, Fernando; Kuypers, Dirk R; Matricali, Giovanni A

    2015-08-01

    We retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas-kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre-transplant values of HbA1c , received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992-1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999-2012) received lower doses of corticosteroids as part of their tacrolimus-based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre-transplant diabetic control and the use of high-dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended. PMID:26033225

  12. Postural stabilization and balance assessment in Charcot-Marie-Tooth 1A subjects.

    PubMed

    Lencioni, T; Rabuffetti, M; Piscosquito, G; Pareyson, D; Aiello, A; Di Sipio, E; Padua, L; Stra, F; Ferrarin, M

    2014-09-01

    The aim of the present study was to assess postural stabilization skill in adult subjects affected by Charcot-Marie-Tooth disease (CMT) type 1A. For this purpose ground reaction force (GRF) was measured by means of a piezoelectric force platform during the sit-to-stand (STS) movement, until a steady state erect posture was achieved. Specific indexes to quantify Centre of Mass acceleration, both during postural stabilization and during quiet standing, were computed using a mathematical model. Forty-seven CMT1A subjects were recruited for the study, and the control group was formed by forty-one age- and sex-matched healthy subjects. The results show that CMT1A subjects are less stable than controls during the quiet stance. Greater difficulty (high values of Yinf, the final instability rate) to maintain erect posture appears to be mainly associated with plantar-flexor muscle weakness, rather than to damage of the proprioceptive system. The worst performances shown by CMT1A subjects in the stabilization phase (high values of I, the global index of postural stabilization performance) seem to be associated with reduced muscle strength and the loss of large sensory nerve fibres. Distal muscle weakness appears to affect both postural stabilization and quiet erect posture. The presented protocol and the analysis of postural stabilization parameters provide useful information on CMT1A balance disorders. PMID:25082324

  13. Denning behaviour of non-gravid wolves, Canis lupus

    USGS Publications Warehouse

    Mech, L.D.; Phillips, M.K.; Smith, D.W.; Kreeger, T.J.

    1996-01-01

    Wild wolves (Canis lupus) that had produced pups in earlier years but were not currently pregnant, and ovariectomized captive wolves, dug dens during and after the whelping season even though they produced no pups. These observations suggest that den digging is not a function of pregnancy or of ovarian estrogen or progesterone. We hypothesize that increasing prolactin in spring elicits or mediates den-digging behavior.

  14. Jean Martin Charcot (1825-93) and John Hughlings Jackson (1835-1911): neurology in France and England in the 19th century.

    PubMed

    Silvester, Alexander

    2009-11-01

    In 1862 Jean Martin Charcot was appointed Physician at the Salpêtrière Hospital in Paris, and simultaneously John Hughlings Jackson was appointed as assistant physician at the National Hospital for the Paralysed and Epileptic, Queen Square, London. Both men made significant contributions to the development of neurology, many of which remain important to contemporary neurologists. The achievements and the work of Charcot and Hughlings Jackson are considered in the light of their respective localities and medical education, and the structure of hospital institutions and political allegiances are compared in the late 19th century in France and Britain. PMID:20029079

  15. Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease.

    PubMed

    Boffeli, Troy J; Tabatt, Jessica A

    2015-01-01

    Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5. PMID:25131389

  16. Diabetic Charcot neuroarthropathy: The diagnosis must be considered in all diabetic neuropathic patients presenting with a hot, swollen foot.

    PubMed

    Al-Busaidi, Ibrahim S; Mason, Rhett; Lunt, Helen

    2015-10-16

    The diagnosis of diabetic Charcot neuroarthropathy (CN) is challenging. This is especially true early in the disease process, when its classical presentation of an acutely inflamed foot may masquerade as other more common lower limb conditions. Prompt diagnosis and appropriate treatment reduces the risk of CN causing permanent incapacitating foot deformity or amputation. We report two cases in which the diagnosis was delayed, resulting in long-term sequelae. These cases highlight the importance of considering CN in patients with diabetic peripheral neuropathy, who present with a red, hot, and swollen foot. PMID:26645758

  17. Misunderstanding of foot drop in a patient with charcot-marie-tooth disease and lumbar disk herniation.

    PubMed

    Han, Youngmin; Kim, Kyoung-Tae; Cho, Dae-Chul; Sung, Joo-Kyung

    2015-04-01

    We report the case of 57-year-old woman diagnosed with Charcot-Marie-Tooth (CMT) disease and lumbar disk herniation (LDH). She had left leg weakness and foot numbness, foot deformity (muscle atrophy, high arch, and clawed toes). The lumbar spine MRI showed LDH at L4-5. Additionally, electrophysiology results were consistent with chronic peripheral motor-sensory polyneuropathy (axonopathy). In genetic testing, 17p11.2-p12 duplication/deletions characteristic of CMT disease were observed. We confirmed the patient's diagnosis as CMT disease and used conservative treatment. PMID:25932299

  18. View east along Wolf Den Road showing residences on the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View east along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

  19. View northwest along Wolf Den Road showing residences on the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View northwest along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

  20. Dens in dente in a six year old doberman pinscher.

    PubMed

    DeForge, D H

    1992-09-01

    Developmental abnormalities of tooth shape and form are rare. Identification of dens in dente is made by radiographic and clinical examination. Pulpitis, pulp necrosis and periapical inflammation can be associated with this abnormality. The tooth should be evaluated for endodontic therapy. A review of the literature related to dens in dente is described with the findings in a doberman pinscher. PMID:1290603

  1. Clinical and genetic spectra in a series of Chinese patients with Charcot-Marie-Tooth disease.

    PubMed

    Wang, Rui; He, Jin; Li, Jin-Jing; Ni, Wang; Wu, Zhi-Ying; Chen, Wan-Jin; Wang, Yi

    2015-12-01

    The aim of this study was to determine the clinical features and frequencies of genetic subtypes in a series of patients with Charcot-Marie-Tooth (CMT) disease from Eastern China. Patients were divided into three subtypes, CMT1, CMT2 and hereditary neuropathy with liability to pressure palsy (HNPP), according to their electrophysiological manifestations. Multiplex ligation-dependent probe analysis (MLPA) was performed to detect duplications/deletions in the PMP22 gene. The coding regions and splice sites of the GJB1, MPZ, MFN2 and GDAP-1 genes were determined by direct sequencing. Among the 148 patients in the study, 37.2% of the cases had mutations in genes assessed. The mutation detection rate was higher in patients with family histories than in spontaneous cases. PMP22 duplication (13.5%) was predominant in this group of patients, followed by PMP22 deletion (11.5%), and point mutations in GJB1 (8.8%), MPZ (2.0%) and MFN2 (0.7%). Three novel mutations (c.151T>C and c.310 A>G in GJB1 and c.1516 C>G in MFN2) were detected. A small deletion in PMP22 exon 4 was detected in a patient with severe CMT1. Genetic tests have great value in CMT patients with family histories. The frequency of PMP22 duplications was lower in Asian patients than in others. We suggest that genetic testing strategies in CMT patients should be primarily based on electromyography data. PMID:26454100

  2. Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease

    SciTech Connect

    Su, Y.; Zhang, H.; Madrid, R.

    1994-09-01

    Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses is to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.

  3. Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases

    PubMed Central

    Dethrage, Lindsey M.; Gore, John C.; Smith, Seth A.; Li, Jun

    2014-01-01

    Objective: The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases. Methods: MTR was measured in the SN of patients with CMT type 1A (CMT1A, n = 10), CMT type 2A (CMT2A, n = 3), hereditary neuropathy with liability to pressure palsies (n = 3), and healthy controls (n = 21). Additional patients without a genetically confirmed subtype (n = 4), but whose family histories and electrophysiologic tests were consistent with CMT, were also included. The relationship between MTR and clinical neuropathy scores was assessed, and the interscan and inter-rater reliability of MTR was estimated. Results: Mean volumetric MTR values were significantly decreased in the SN of patients with CMT1A (33.8 ± 3.3 percent units) and CMT2A (31.5 ± 1.9 percent units) relative to controls (37.2 ± 2.3 percent units). A significant relationship between MTR and disability scores was also detected (p = 0.01 for genetically confirmed patients only, p = 0.04 for all patients). From interscan and inter-rater reliability analyses, proximal nerve MTR values were repeatable at the slicewise and mean volumetric levels. Conclusions: MTR measurements may be a viable biomarker of proximal nerve pathology in patients with CMT. PMID:25253751

  4. Prevalence of Peripheral Arterial Disease in Patients With Diabetic Charcot Neuroarthropathy.

    PubMed

    Wukich, Dane K; Raspovic, Katherine M; Suder, Natalie C

    2016-01-01

    Charcot neuroarthropathy (CN) is a serious complication of diabetes mellitus (DM) that can lead to pedal ulceration, infection, hospitalization, and amputation. Peripheral arterial disease (PAD) is also found in patients with diabetic foot disease; however, its prevalence in patients with CN has not been extensively evaluated. The aim of the present study was to evaluate the prevalence of PAD in a group of patients with CN (with and without ulceration) and compare this to a group of patients with diabetic foot ulceration (DFU) and no CN. We compared the lower extremity noninvasive arterial testing results of 85 patients with DM and CN with those from a group of 126 patients with DFU and no CN. No statistically significant differences were found in age, gender, type of DM (1 versus 2), insulin use, duration of DM, or history of dialysis between our study and control groups. The prevalence of PAD in the patients with CN was 40%. Compared with patients with DFUs, the patients with CN were less likely to have PAD (odds ratio 0.48, 95% confidence interval 0.28 to 0.85; p = .0111), ischemia (odds ratio 0.33, 95% confidence interval 0.16 to 0.69; p = .0033), or the need for revascularization (odds ratio 0.27, 95% confidence interval 0.10 to 0.73; p = .0097). Critical limb ischemia (great toe pressure <30 mm Hg) was 82% less likely in patients with CN than in patients with DFU. PAD in patients with CN is not uncommon; however, ischemia and the need for revascularization were significantly less likely than in patients with DFU without CN. PMID:27020760

  5. Innovative quantitative testing of hand function in Charcot-Marie-Tooth neuropathy.

    PubMed

    Alberti, Maria A; Mori, Laura; Francini, Luca; Poggi, Ilaria; Monti Bragadin, Margherita; Bellone, Emilia; Grandis, Marina; Maggi, Giovanni; Reni, Lizia; Sormani, Maria P; Tacchino, Andrea; Padua, Luca; Prada, Valeria; Bove, Marco; Schenone, Angelo

    2015-12-01

    To describe a new test to quantitatively evaluate hand function in patients affected by Charcot-Marie-Tooth neuropathy (CMT). The sensor-engineered glove test (SEGT) was applied to CMT patients (N: 26) and compared with a cohort of healthy controls (HC, N: 26). CMT patients were further divided into subjects with clinically normal (group 1) or impaired hand (group 2) function. The SEGT parameters evaluated were touch duration, inter-tapping interval, and movement rate parameters of two different sequences: finger tapping (FT) and index-medium-ring-little (IMRL) performed at self-paced mode (SPM) and maximum velocity (MV). Hand function and strength were assessed by the 9-hole peg test (9HPT) and dynamometry. Disability of patients was measured by the CMT neuropathy score. CMT patients had significantly worst performances at SEGT than controls regarding the rate of execution of both FT (at MV) and IMRL sequences (at SPM and MV). The rate parameter at MV in IMRL sequence showed a significant trend of decreasing in its average between HC (n: 26, rate = 3.08 ± 0.52 Hz), group 1 (n: 9, rate = 2.64 ± 0.66 Hz) and group 2 (n: 17, rate = 2.19 ± 0.45 Hz) (p for trend <0.001). No correlations were found with either 9HPT, dynamometry, electrophysiology, and the CMT neuropathy score. The SEGT test is sensitive to show hand dysfunction in CMT patients, with and without clinically impaired hands. PMID:26456943

  6. Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy.

    PubMed

    Thomas, Florian P; Guergueltcheva, Velina; Gondim, Francisco A A; Tournev, Ivailo; Rao, Chitharanjan V; Ishpekova, Boryana; Kinsella, Laurence J; Pan, Yi; Geller, Thomas J; Litvinenko, Ivan; De Jonghe, Peter; Scherer, Steven S; Jordanova, Albena

    2016-03-01

    Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5-45.6 m/s in the US family and 24.7-57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations. PMID:26725087

  7. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

    PubMed Central

    Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

    2014-01-01

    Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can

  8. Balance and muscle power of children with Charcot-Marie-Tooth

    PubMed Central

    Silva, Tais R.; Testa, Amanda; Baptista, Cyntia R. J. A.; Marques, Wilson; Mattiello-Sverzut, Ana C.

    2014-01-01

    BACKGROUND: In certain diseases, functional constraints establish a greater relationship with muscle power than muscle strength. However, in hereditary peripheral polyneuropathies, no such relationship was found in the literature. OBJECTIVE: In children with Charcot-Marie-Tooth (CMT), to identify the impact of muscle strength and range of movement on the static/dynamic balance and standing long jump based on quantitative and functional variables. METHOD: The study analyzed 19 participants aged between 6 and 16 years, of both genders and with clinical diagnoses of CMT of different subtypes. Anthropometric data, muscle strength of the lower limbs (hand-held dynamometer), ankle and knee range of movement, balance (Pediatric Balance Scale) and standing long jump distance were obtained by standardized procedures. For the statistical analysis, Pearson and Spearman correlation coefficients were used. RESULTS: There was a strong positive correlation between balance and the muscle strength of the right plantar flexors (r=0.61) and dorsiflexors (r=0.59) and a moderate correlation between balance and the muscle strength of inversion (r=0.41) and eversion of the right foot (r=0.44). For the long jump and range of movement, there was a weak positive correlation with right and left plantar flexion (r=0.20 and r=0.12, respectively) and left popliteal angle (r=0.25), and a poor negative correlation with left dorsiflexion (r=-0.15). CONCLUSIONS: The data on the patients analyzed suggests that the maintenance of distal muscle strength favors performance during balance tasks, while limitations in the range of movement of the legs seem not to be enough to influence the performance of the horizontal long jump. PMID:25076001

  9. Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients★

    PubMed Central

    Li, Xiaobo; Zi, Xiaohong; Li, Lin; Zhan, Yajing; Huang, Shunxiang; Li, Jin; Li, Xuning; Li, Xigui; Hu, Zhengmao; Xia, Kun; Tang, Beisha; Zhang, Ruxu

    2012-01-01

    We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced. PMID:25337104

  10. Late Corrective Arthrodesis in Nonplantigrade Diabetic Charcot Midfoot Disease Is Associated with High Complication and Reoperation Rates

    PubMed Central

    Wussow, Annekatrin

    2015-01-01

    Introduction. Charcot arthropathy may lead to a loss of osteoligamentous foot architecture and consequently loss of the plantigrade alignment. In this series of patients a technique of internal corrective arthrodesis with maximum fixation strength was provided in order to lower complication rates. Materials/Methods. 21 feet with severe nonplantigrade diabetic Charcot deformity Eichenholtz stages II/III (Sanders/Frykberg II/III/IV) and reconstructive arthrodesis with medial and additional lateral column support were retrospectively enrolled. Follow-up averaged 4.0 years and included a clinical (AOFAS score/PSS), radiological, and complication analysis. Results. A mean of 2.4 complications/foot occurred, of which 1.5/foot had to be solved surgically. 76% of feet suffered from soft tissue complications; 43% suffered hardware-associated complications. Feet with only 2 out of 5 high risk criteria according to Pinzur showed significantly lower complication counts. Radiographs revealed a correct restoration of all foot axes postoperatively with superior fixation strength medially. Conclusion. Late corrective arthrodesis with medial and lateral column stabilization in the nonplantigrade stages of neuroosteoarthropathy can provide reasonable reconstruction of the foot alignment. Nonetheless, overall complication/reoperation rates were high. With separation into low/high risk criteria a helpful guide in treatment choice is provided. This trial is registered with German Clinical Trials Register (DRKS) under number DRKS00007537. PMID:26000309

  11. The chair of mental and brain diseases: Charcot's pupils--Benjamin Ball, Alix Joffroy and Gilbert Ballet.

    PubMed

    Tiberghien, Denis

    2011-01-01

    Benjamin Ball (1833-1893), Alix Joffroy (1844-1908) and Gilbert Ballet (1853-1916) were three pupils of the great Charcot (1825-1893). They were successive holders of the chair for mental illness and encephalon at its creation in 1877 until the First World War: Benjamin Ball from 1877 to 1893, Alix Joffroy from 1893 to 1908, and Gilbert Ballet from 1908 to 1916. After describing the context surrounding the creation of this chair and the choice of its representative and successors, we will examine their neurological work on the brain derived from a method influenced by a current of thought careful to list the symptoms of the disease and to look for the anatomical causes in the brain. The renowned 19th century French neurologist Jean-Martin Charcot was a huge influence. With their acquired experience and progress in the fields of morphology and histology and cerebral cortex functioning, they greatly contributed to the evolution of neurological, clinical anatomical and psychological-physiological findings--thus allowing certain pathologies to be considered as organic diseases rather than neurotic symptoms--while all the time recognizing the importance of the cortical cell in mental illness. PMID:20938145

  12. Dens evaginatus: case reports and review of the literature.

    PubMed

    Ponnambalam, Yoganathan; Love, Robert M

    2006-06-01

    Dens evaginatus is a developmental anomaly that produces a tubercle on the occlusal or palatal or lingual surfaces of teeth. The tubercle, which often contains pulp tissue, can cause occlusal interference, and pulpal pathology is a common sequel of attrition or fracture of the evagination. It affects a number of tooth types, but most commonly the premolar teeth of people of oriental ethnicity. Early diagnosis and management of dens evaginatus are important to maintain pulp vitality. This article describes three cases of dens evaginatus with different presentations. PMID:16773794

  13. Dens invaginatus: review, relevance, and report of 3 cases.

    PubMed

    Khan, Suleman Abbas; Khan, Saima Yunus; Bains, Vivek K; Bains, Rhythm; Loomba, Kapil

    2012-01-01

    Dens invaginatus is a rare developmental morphoanatomical variation resulting from the infolding of the dental papilla before biological mineralization that allows the invagination of inner dental epithelium. Permanent maxillary lateral incisors are most commonly affected, and the condition is frequently bilateral, but it may also prevail in permanent maxillary central incisors. The purpose of this paper was to provide an overview of the etiopathogenesis, frequency of occurrence, and clinical and radiographic features and to discuss 3 dens invaginatus cases. PMID:23433617

  14. Patterns of den occupation by the spotted hyaena (Crocuta crocuta)

    USGS Publications Warehouse

    Boydston, E.E.; Kapheim, K.M.; Holekamp, K.E.

    2006-01-01

    Spotted hyaenas utilize isolated natal dens (NDs) and communal dens (CDs) for rearing their cubs. Here we describe patterns of natal and CD occupation by hyaenas belonging to one well-studied clan in the Maasai Mara National Reserve during a 10-year period. Locations of 98 den sites that were used as natal or CDs by hyaenas in the study clan were digitized in a Geographic Information System, and the duration of use of each den site, frequency of re-use, and distances involved in den moves were quantified. Hyaenas moved their CD monthly on average. Most CD sites were occupied only once during the study, but several sites were used repeatedly. On rare occasions, the movement of hyaenas to a new den site could be attributed to a disturbance event at the CD, but factors regularly prompting hyaenas to move to new CD sites were unclear. High-ranking female hyaenas were more likely to rear their cubs from birth in a CD than low-ranking females. Low-ranking females almost always utilized isolated NDs for the first few weeks of a litter's development, and low-ranking females transferred their cubs over longer distances than did high-ranking females. ?? 2006 East African Wild Life Society.

  15. The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease.

    PubMed Central

    Meggouh, F; Benomar, A; Rouger, H; Tardieu, S; Birouk, N; Tassin, J; Barhoumi, C; Yahyaoui, M; Chkili, T; Brice, A; LeGuern, E

    1998-01-01

    X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified the first de novo mutation of the Cx32 gene, consisting of a deletion of a G residue at position 499 in the Cx32 open reading frame. This previously unreported mutation produces a frameshift at position 147 in the protein and introduces a premature stop codon (TAG) at nucleotide 643, which results in the production of a truncated Cx32 molecule. This mutation illustrates the risk of an erroneous diagnosis of autosomal recessive CMT, especially in populations where consanguineous unions are frequent, and its consequences for genetic counselling, which can be avoided by molecular analysis. Images PMID:9541114

  16. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family.

    PubMed

    Sun, A-Ping; Tang, Lu; Liao, Qin; Zhang, Hui; Zhang, Ying-Shuang; Zhang, Jun

    2015-10-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases. PMID:26692872

  17. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

    PubMed Central

    Sun, A-ping; Tang, Lu; Liao, Qin; Zhang, Hui; Zhang, Ying-shuang; Zhang, Jun

    2015-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases. PMID:26692872

  18. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

    SciTech Connect

    Ionasescu, V.; Ionasescu, R.; Searby, C.

    1996-06-14

    We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.

  19. Jean-Martin Charcot, father of modern neurology: an homage 120 years after his death.

    PubMed

    Gomes, Marleide da Mota; Engelhardt, Eliasz

    2013-10-01

    Jean-Martin Charcot was a pioneer in a variety of subjects, including nervous system diseases; anatomy; physiology; pathology; and diseases of ageing, joints, and lungs. His medical achievements were mainly based on his anatomopathological proficiency, his observation, and his personal thoroughness that favored the delineation of the nosology of the main neurological diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, peroneal muscular atrophy, and hysteria/epilepsy. The link of this anatomoclinical method with iconographic representations and theatrical lessons, and the rich bibliographical documentations, carried out in a crowded barn for diseased people--Salpetrière Hospital, were the basis of his achievements, which are still discussed 120 years after his death. PMID:24212522

  20. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots

    PubMed Central

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-01-01

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review. PMID:23853192

  1. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots.

    PubMed

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-01-01

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review. PMID:23853192

  2. A chronic leg ulcer presenting with Charcot-Marie-Tooth disease and type 2 diabetes: a case report.

    PubMed

    Ren, Haitao; You, Chuangang; Han, Chunmao

    2013-03-01

    Charcot-Marie-Tooth (CMT) disease is characterized by hereditary sensorimotor polyneuropathy with foot deformity, sensorineural hearing loss, moderate developmental delay, and gait disturbance. CMT presenting with type 2 diabetes and an ulcer has not been reported. This article reports a man who presented with the symptoms mentioned above and also with a leg ulcer and type 2 diabetes. He was diagnosed with CMT disease based on family history and genetic testing. A skin defect in the left leg had manifested for more than 1 year, and results of initial fasting plasma glucose revealed type 2 diabetes. The evolution of these manifestations, coupled with a slowly progressive weakness, numbness, muscular wasting, and sensory impairment, strongly suggested the co-occurrence of 3 different diseases in the same individual. PMID:23446367

  3. Den use by arctic foxes (Alopex lagopus) in a subarctic region of western Alaska

    USGS Publications Warehouse

    Anthony, R.M.

    1996-01-01

    Distribution, abundance, and use of arctic fox dens located in coastal tundra communities of the Yukon-Kuskokwim delta were determined in studies from 1985 to 1990. Dens were denser and less complex than those described in studies conducted above the Arctic Circle. Eighty-three dens of varying complexity were found in the 52-km2 study area. Nineteen dens were used by arctic foxes for whelping or rearing pups. Three females relocated litters to multiple dens; a maximum of four dens were used concurrently by pups from one litter. Although red foxes were common in the region, their use of dens in the study area was minimal. Differences in vegetation at den sites and nearby unoccupied sites were minimal. Furthermore, den sites could not be distinguished from non-den sites during aerial surveys.

  4. Denning chronology and design of effective bear management units

    USGS Publications Warehouse

    Inman, R.M.; Costello, C.M.; Jones, D.E.; Inman, K.H.; Thompson, B.C.; Quigley, H.B.

    2007-01-01

    Reports on the effectiveness of using late fall hunting seasons to reduce the proportion of female black bears (Ursus americanus) in the harvest are limited, and the geographic scale over which the technique functions as intended has not been examined. During 1992-2000, we radio-equipped black bears in New Mexico, USA, obtained estimates of 175 den entry and 137 den emergence dates, and used New Mexico Department of Game and Fish harvest data (1985-2000) to test for differences in proportion of females in the harvest relative to denning chronology. Bears in northern New Mexico entered dens earlier and emerged later than bears in southern New Mexico (P ??? 0.001). In northern New Mexico bears displayed the typical pattern of earlier entry and later emergence by reproductive females, proportion of females in the harvest varied over time as expected, and late fall seasons were effective (P ??? 0.10). In contrast, denning chronology did not differ by sex in southern New Mexico, proportion of females in the harvest did not change over time, and late fall seasons were not effective (P ??? 0.18). Manipulation of hunting season dates to influence female mortality can be an effective tool, however our study provides an example of an area where denning chronology did not differ by sex and late seasons were not effective. We also observed regional differences in timing of entrance and emergence, which suggest that scale of application may be key. In management jurisdictions that encompass ecologically distinct areas, cover a wide range of latitudes, or are mountainous, successful use of the technique may depend on knowledge of denning chronology at multiple locations and appropriate designation of hunting unit boundaries, season dates, and data analysis units.

  5. Crime, hysteria and belle époque hypnotism: the path traced by Jean-Martin Charcot and Georges Gilles de la Tourette.

    PubMed

    Bogousslavsky, Julien; Walusinski, Olivier; Veyrunes, Denis

    2009-01-01

    Hysteria and hypnotism became a favorite topic of studies in the fin de siècle neurology that emerged from the school organized at La Salpêtrière by Jean-Martin Charcot, where he had arrived in 1861. Georges Gilles de la Tourette started working with Charcot in 1884 and probably remained his most faithful student, even after his mentor's death in 1893. This collaboration was particularly intense on 'criminal hypnotism', an issue on which Hippolyte Bernheim and his colleagues from the Nancy School challenged the positions taken by the Salpêtrière School. Bernheim claimed that hypnotism was not a diagnostic feature of hysteria and that there were real-life examples of murders suggested under hypnosis, while hypnosis susceptibility was identified with hysteria by Charcot and Gilles de la Tourette, who saw rape as the only crime associated with hypnotism. The quarrel was particularly virulent during a series of famous criminal cases which took place between 1888 and 1890. At the time, it was considered that La Salpêtrière had succeeded over Nancy, since the role of hypnotism was discarded during these famous trials. However, the theories of Charcot and Gilles de la Tourette were also damaged by the fight, which probably triggered the conceptual evolution leading to Joseph Babinski's revision of hysteria in 1901. Gilles de la Tourette's strong and public interest in hypnotism nearly cost him his life, when a young woman who claimed to have been hypnotized against her will shot him in the head at his own home in 1893. It was subsequently shown that hypnotism had nothing to do with it. The delusional woman was interned at Sainte-Anne for mental disturbance, thus escaping trial. Ironically, Gilles de la Tourette may have been partly responsible, since he had been one of the strongest proponents of placing mentally-ill criminals in asylums instead of prisons. PMID:19602893

  6. Who was first to diagnose and report neuropathic arthropathy of the foot and ankle: Jean-Martin Charcot or Herbert William Page?

    PubMed

    Sanders, Lee J; Edmonds, Michael E; Jeffcoate, William J

    2013-09-01

    In November 1883, Jean-Martin Charcot and Charles Féré reported on bone and joint disease of the foot in cases of tabes dorsalis, and referred to the condition as 'pied tabétique'--a disabling neuropathic osteoarthropathy that we usually now refer to as the Charcot foot. Charcot had originally described neuropathic osteoarthropathy in more proximal joints in 1868, and in his 1883 paper with Féré stated that involvement of the short bones and small joints of the foot had not yet been described. They emphasised in the paper that one of their cases was the first ever observed, two years earlier, in 1881. It is relevant, however, that it was in this same year that involvement of the foot by tabetic arthropathy was presented to the International Medical Congress in London by an English surgeon, Herbert William Page. We believe that Page was the first to diagnose and to report a case of tabetic neuropathic osteoarthropathy in which the bones of the foot and ankle were involved. He was also the first to propose a link between the tabetic foot and disease of the peripheral nerves, as opposed to the central nervous system. PMID:23765185

  7. Remote identification of polar bear maternal den habitat in northern Alaska

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Ambrosius, K.J.

    2001-01-01

    Polar bears (Ursus maritimus) give birth in dens of ice and snow to protect their altricial young. During the snow-free season, we visited 25 den sites located previously by radiotelemetry and characterized the den site physiognomy. Seven dens occurred in habitats with minimal relief. Eighteen dens (72%) were in coastal and river banks. These "banks" were identifiable on aerial photographs. We then searched high-resolution aerial photographs (n = 3000) for habitats similar to those of the 18 dens. On aerial photos, we mapped 1782 km of bank habitats suitable for denning. Bank habitats comprised 0.18% of our study area between the Colville River and the Tamayariak River in northern Alaska. The final map, which correctly identified 88% of bank denning habitat in this region, will help minimize the potential for disruptions of maternal dens by winter petroleum exploration activities.

  8. Detecting denning polar bears with Forward-Looking Infrared (FLIR) imagery

    USGS Publications Warehouse

    Amstrup, Steven C.; York, G.; McDonald, T.L.; Nielson, R.; Simac, K.

    2004-01-01

    Polar bears give birth in snow dens in midwinter and remain in dens until early spring. The survival and development of cubs is dependent on a stable environment within the maternal den. To mitigate potential disruption of polar bear denning by existing and proposed petroleum activities, we used forward-looking infrared (FLIR) viewing to try to detect heat rising from dens.We flew transects over dens of radio-collared females with FLIR imager-equipped aircraft, recorded weather conditions at each observation, and noted whether the den was detected.We surveyed 23 dens on 67 occasions (1 to 7 times each). Nine dens were always detected, and 10 dens visited more than once were detected on some flights but not on others. Four dens were never detected (17 percent), but three of those were visited only under marginal conditions. The odds of detecting a den were 4.8 times greater when airborne moisture (snow, blowing snow, fog, etc.) was absent than when it was present, and they increased 3-fold for every 1?C increase in temperature-dew point spread. The estimated probability of detecting dens in sunlight was 0. Data suggested that FLIR surveys conducted during optimal conditions for detection can produce detection rates approaching 90 percent and thus can be an important management and mitigation tool. polar bear, infrared imagery, maternal denning, human impacts, management

  9. American black bear denning behavior: Observations and applications using remote photography

    USGS Publications Warehouse

    Bridges, A.S.; Fox, J.A.; Olfenbuttel, C.; Vaughan, M.B.

    2004-01-01

    Researchers examining American black bear (Ursus americanus) denning behavior have relied primarily on den-site visitation and radiotelemetry to gather data. Repeated den-site visits are time-intensive and may disturb denning bears, possibly causing den abandonment, whereas radiotelemetry is sufficient only to provide gross data on den emergence. We used remote cameras to examine black bear denning behavior in the Allegheny Mountains of western Virginia during March-May 2003. We deployed cameras at 10 den sites and used 137 pictures of black bears. Adult female black bears exhibited greater extra-den activity than we expected prior to final den emergence, which occurred between April 12 and May 6, 2003. Our technique provided more accurate den-emergence estimation than previously published methodologies. Additionally, we observed seldom-documented behaviors associated with den exits and estimated cub age at den emergence. Remote cameras can provide unique insights into denning ecology, and we describe their potential application to reproductive, survival, and behavioral research.

  10. Habitat characteristics of polar bear terrestrial maternal den sites in northern Alaska

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Fischbach, Anthony S.

    2003-01-01

    Polar bears (Ursus maritimus) give birth to and nurture their young in dens of ice and snow. During 1999-2001, we measured the structure of 22 dens on the coastal plain of northern Alaska after polar bear families had evacuated their dens in the spring. During the summers of 2001 and 2002, we revisited the sites of 42 maternal and autumn exploratory dens and recorded characteristics of the under-snow habitat. The structure of polar bear snow dens was highly variable. Most were simple chambers with a single entrance/egress tunnel. Others had multiple chambers and additional tunnels. Thickness of snow above and below dens was highly variable, but most dens were overlain by less than 1 m of snow. Dens were located on, or associated with, pronounced landscape features (primarily coastal and river banks, but also a lake shore and an abandoned oil field gravel pad) that are readily distinguished from the surrounding terrain in summer and catch snow in early winter. Although easily identified, den landforms in northern Alaska were more subtle than den habitats in many other parts of the Arctic. The structure of polar bear dens in Alaska was strikingly similar to that of dens elsewhere and has remained largely unchanged in northern Alaska for more than 25 years. Knowledge of den structure and site characteristics will allow resource managers to identify habitats with the greatest probability of holding dens. This information may assist resource managers in preventing negative impacts of mineral exploration and extraction on polar bears.

  11. Prophylactic treatment of dens evaginatus using mineral trioxide aggregate.

    PubMed

    Koh, E T; Ford, T R; Kariyawasam, S P; Chen, N N; Torabinejad, M

    2001-08-01

    Two case reports with dens evaginatus are presented. Each patient had one tooth affected. There was a prominent tubercle on the occlusal surface of the mandibular second premolar. Under local anesthesia and rubber dam isolation a partial pulpotomy was conducted and mineral trioxide aggregate was placed. After 6 months the teeth were removed as part of planned orthodontic treatment. Histological examination of these teeth showed an apparent continuous dentin bridge formation in both teeth, and the pulps were free of inflammation. These cases show that mineral trioxide aggregate can be used as an alternative to existing materials in the proplylactic treatment of dens evaginatus. PMID:11501594

  12. Denning habits of free-ranging dogs reveal preference for human proximity.

    PubMed

    Sen Majumder, Sreejani; Paul, Manabi; Sau, Shubhra; Bhadra, Anindita

    2016-01-01

    Dens are crucial in the early development of many mammals, making den site selection an important component of parental care in such species. Resource availability and shelter from predators primarily govern den selection. Species inhabiting human-dominated landscapes typically den away from human disturbance, often shifting dens to avoid humans during the early life of their young. Domesticated dogs have evolved in human proximity over centuries, being bred and reared in human homes for generations. While pets rely on their owners for shelter and care, free-ranging dogs roam uncared, and typically whelp in dens. We conducted a study on 148 free-ranging dog dens in India to understand their denning habits. Distance from resources influenced den choice, but anthropogenic disturbance did not. Dens were found in areas of high human activity, and begging from humans was preferred over scavenging. A study on 15 pregnant females revealed that females actively searched for denning sites, rejecting several intermediate ones before selecting the final den. We propose that the obvious preference of dogs for denning close to humans is a behavioural adaptation that helps them to survive in the urban landscape, in spite of the high human induced mortality during the early life of pups. PMID:27535214

  13. Denning habits of free-ranging dogs reveal preference for human proximity

    PubMed Central

    Sen Majumder, Sreejani; Paul, Manabi; Sau, Shubhra; Bhadra, Anindita

    2016-01-01

    Dens are crucial in the early development of many mammals, making den site selection an important component of parental care in such species. Resource availability and shelter from predators primarily govern den selection. Species inhabiting human-dominated landscapes typically den away from human disturbance, often shifting dens to avoid humans during the early life of their young. Domesticated dogs have evolved in human proximity over centuries, being bred and reared in human homes for generations. While pets rely on their owners for shelter and care, free-ranging dogs roam uncared, and typically whelp in dens. We conducted a study on 148 free-ranging dog dens in India to understand their denning habits. Distance from resources influenced den choice, but anthropogenic disturbance did not. Dens were found in areas of high human activity, and begging from humans was preferred over scavenging. A study on 15 pregnant females revealed that females actively searched for denning sites, rejecting several intermediate ones before selecting the final den. We propose that the obvious preference of dogs for denning close to humans is a behavioural adaptation that helps them to survive in the urban landscape, in spite of the high human induced mortality during the early life of pups. PMID:27535214

  14. Den-site characteristics of black bears in Rocky Mountain National Park, Colorado

    USGS Publications Warehouse

    Baldwin, R.A.; Bender, L.C.

    2008-01-01

    We compared historic (1985-1992) and contemporary (2003-2006) black bear (Ursus americanus) den locations in Rocky Mountain National Park (RMNP), Colorado, USA, for habitat and physiographic attributes of den sites and used maximum entropy modeling to determine which factors were most influential in predicting den-site locations. We observed variability in the relationship between den locations and distance to trails and elevation over rime. Locations of historic den sites were most associated with slope, elevation, and covertype, whereas contemporary sites were associated with slope, distance to roads, aspect, and canopy height. Although relationships to covariates differed between historic and contemporary periods, preferred den-site characteristics consistently included steep slopes and factors associated with greater snow depth. Distribution of den locations shifted toward areas closer to human developments, indicating little negative influence of this factor on den-site selection by black bears in RMNP.

  15. Steroid-dependent sensorineural hearing loss in a patient with Charcot-Marie-Tooth disease showing auditory neuropathy.

    PubMed

    Maeda, Yukihide; Kataoka, Yuko; Sugaya, Akiko; Kariya, Shin; Kobayashi, Katsuhiro; Nishizaki, Kazunori

    2015-06-01

    Charcot-Marie-Tooth disease (CMT) is the most common form of hereditary sensorimotor neuropathy and sometimes involves disorders of the peripheral auditory system. We present a case of steroid-dependent auditory neuropathy associated with CMT, in which the patient experienced 3 episodes of acute exacerbation of hearing loss and successful rescue of hearing by prednisolone. An 8-year-old boy was referred to the otolaryngology department at the University Hospital. He had been diagnosed with CMT type 1 (demyelinating type) at the Child Neurology Department and was suffering from mild hearing loss due to auditory neuropathy. An audiological diagnosis of auditory neuropathy was confirmed by auditory brainstem response and distortion-product otoacoustic emissions. At 9 years and 0 months old, 9 years and 2 months old, and 10 years and 0 months old, he had experienced acute exacerbations of hearing loss, each of which was successfully rescued by intravenous or oral prednisolone within 2 weeks. Steroid-responsive cases of CMT have been reported, but this is the first case report of steroid-responsive sensorineural hearing loss in CMT. The present case may have implications for the mechanisms of action of glucocorticoids in the treatment of sensorineural hearing loss. PMID:25440412

  16. Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission

    PubMed Central

    Huber, Nina; Guimaraes, Sofia; Schrader, Michael; Suter, Ueli; Niemann, Axel

    2013-01-01

    Mitochondria and peroxisomes can be fragmented by the process of fission. The fission machineries of both organelles share a set of proteins. GDAP1 is a tail-anchored protein of mitochondria and induces mitochondrial fragmentation. Mutations in GDAP1 lead to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy, and affect mitochondrial dynamics. Here, we show that GDAP1 is also targeted to peroxisomes mediated by the import receptor Pex19. Knockdown of GDAP1 leads to peroxisomal elongation that can be rescued by re-expressing GDAP1 and by missense mutated forms found in CMT patients. GDAP1-induced peroxisomal fission is dependent on the integrity of its hydrophobic domain 1, and on Drp1 and Mff, as is mitochondrial fission. Thus, GDAP1 regulates mitochondrial and peroxisomal fission by a similar mechanism. However, our results reveal also a more critical role of the amino-terminal GDAP1 domains, carrying most CMT-causing mutations, in the regulation of mitochondrial compared to peroxisomal fission. PMID:23628762

  17. Recurrent Episodes of Stroke-Like Symptoms in a Patient with Charcot-Marie-Tooth Neuropathy X Type 1

    PubMed Central

    Wu, Ning; Said, Sarita; Sabat, Shyamsunder; Wicklund, Matthew; Stahl, Mark C.

    2015-01-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor sensory neuropathy, is a heterogeneous group of disorders best known for causing inherited forms of peripheral neuropathy. The X-linked form, CMTX1, is caused by mutations in the gap junction protein beta 1 (GJB1) gene, expressed both by peripheral Schwann cells and central oligodendrocytes. Central manifestations are known but are rare, and there are few case reports of leukoencephalopathy with transient or persistent neurological deficits in patients with this CMT subtype. Here, we report the case of a man with multiple male and female family members affected by neuropathy who carries a pathologic mutation in GJB1. He has experienced three transient episodes with variable neurological deficits over the course of 7 years with corresponding changes on magnetic resonance imaging (MRI). This case illustrates CMT1X as a rare cause of transient neurological deficit and demonstrates the evolution of associated reversible abnormalities on MRI over time. To the best of our knowledge, this report provides the longest period of serial imaging in a single patient with this condition in the English language literature. PMID:26955336

  18. Mechanism, Prevalence, and More Severe Neuropathy Phenotype of the Charcot-Marie-Tooth Type 1A Triplication

    PubMed Central

    Liu, Pengfei; Gelowani, Violet; Zhang, Feng; Drory, Vivian E.; Ben-Shachar, Shay; Roney, Erin; Medeiros, Adam C.; Moore, Rebecca J.; DiVincenzo, Christina; Burnette, William B.; Higgins, Joseph J.; Li, Jun; Orr-Urtreger, Avi; Lupski, James R.

    2014-01-01

    Copy-number variations cause genomic disorders. Triplications, unlike deletions and duplications, are poorly understood because of challenges in molecular identification, the choice of a proper model system for study, and awareness of their phenotypic consequences. We investigated the genomic disorder Charcot-Marie-Tooth disease type 1A (CMT1A), a dominant peripheral neuropathy caused by a 1.4 Mb recurrent duplication occurring by nonallelic homologous recombination. We identified CMT1A triplications in families in which the duplication segregates. The triplications arose de novo from maternally transmitted duplications and caused a more severe distal symmetric polyneuropathy phenotype. The recombination that generated the triplication occurred between sister chromatids on the duplication-bearing chromosome and could accompany gene conversions with the homologous chromosome. Diagnostic testing for CMT1A (n = 20,661 individuals) identified 13% (n = 2,752 individuals) with duplication and 0.024% (n = 5 individuals) with segmental tetrasomy, suggesting that triplications emerge from duplications at a rate as high as ∼1:550, which is more frequent than the rate of de novo duplication. We propose that individuals with duplications are predisposed to acquiring triplications and that the population prevalence of triplication is underascertained. PMID:24530202

  19. Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.

    PubMed

    Tan, Christopher A; Rabideau, Marina; Blevins, Amy; Westbrook, Marjorie Jody; Ekstein, Tali; Nykamp, Keith; Deucher, Anne; Harper, Amy; Demmer, Laurie

    2016-06-01

    Pathogenic variants in the mitofusin 2 gene (MFN2) are the most common cause of autosomal dominant Charcot-Marie-Tooth (CMT2) disease, which is typically characterized by axonal sensorimotor neuropathy. We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2. A review of the literature reveals that sporadic and familial cases of compound heterozygous or homozygous pathogenic MFN2 variants have been infrequently described, which indicates that MFN2 can also be inherited in a recessive manner. This case highlights several clinical findings not typically associated with MFN2 pathogenic variants, including young age of onset and rapidly progressing diaphragmatic paresis that necessitated tracheostomy and mechanical ventilation, and adds to the growing list of features identified in autosomal recessive MFN2-related CMT2. Our patient with MFN2-related CMT2 expands the clinical and mutational spectrum of individuals with autosomal recessive CMT2 and identifies a new clinical feature that warrants further observation. © 2016 Wiley Periodicals, Inc. PMID:26955893

  20. An essential role of MAG in mediating axon-myelin attachment in Charcot-Marie-Tooth 1A disease

    PubMed Central

    Kinter, Jochen; Lazzati, Thomas; Schmid, Daniela; Zeis, Thomas; Erne, Beat; Lützelschwab, Roland; Steck, Andreas J.; Pareyson, Davide; Peles, Elior; Schaeren-Wiemers, Nicole

    2012-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy caused by the duplication of the PMP22 gene. Demyelination precedes the occurrence of clinical symptoms that correlate with axonal degeneration. It was postulated that a disturbed axon-glia interface contribute to altered myelination consequently leading to axonal degeneration. In this study, we examined the expression of MAG and Necl4, two critical adhesion molecules that are present at the axon-glia interface, in sural nerve biopsies of CMT1A patients and in peripheral nerves of mice overexpressing human PMP22, an animal model for CMT1A. We show an increase in the expression of MAG and a strong decrease of Necl4 in biopsies of CMT1A patients as well as in CMT1A mice. Expression analysis revealed that MAG is strongly upregulated during peripheral nerve maturation, whereas Necl4 expression remains very low. Ablating MAG in CMT1A mice results in separation of axons from their myelin sheath. Our data show that MAG is important for axon-glia contact in a model for CMT1A, and suggest that its increased expression in CMT1A disease has a compensatory role in the pathology of the disease. Thus, we demonstrate that MAG together with other adhesion molecules such as Necl4 is important in sustaining axonal integrity. PMID:22940629

  1. PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

    PubMed

    Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

    2013-10-15

    Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

  2. A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.

    PubMed

    Tamiya, Gen; Makino, Satoshi; Hayashi, Makiko; Abe, Akiko; Numakura, Chikahiko; Ueki, Masao; Tanaka, Atsushi; Ito, Chizuru; Toshimori, Kiyotaka; Ogawa, Nobuhiro; Terashima, Tomoya; Maegawa, Hiroshi; Yanagisawa, Daijiro; Tooyama, Ikuo; Tada, Masayoshi; Onodera, Osamu; Hayasaka, Kiyoshi

    2014-09-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. PMID:25152455

  3. A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease

    PubMed Central

    Tamiya, Gen; Makino, Satoshi; Hayashi, Makiko; Abe, Akiko; Numakura, Chikahiko; Ueki, Masao; Tanaka, Atsushi; Ito, Chizuru; Toshimori, Kiyotaka; Ogawa, Nobuhiro; Terashima, Tomoya; Maegawa, Hiroshi; Yanagisawa, Daijiro; Tooyama, Ikuo; Tada, Masayoshi; Onodera, Osamu; Hayasaka, Kiyoshi

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247−10_247−6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. PMID:25152455

  4. The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes

    SciTech Connect

    Dyer, K.D. |; Handen, J.S.; Rosenberg, H.F.

    1997-03-01

    The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of {beta}-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon. In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire {beta}-galactoside binding site encoded by exon III. We have isolated CLC {beta}-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the {beta}-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. 35 refs., 3 figs.

  5. NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.

    PubMed

    Berciano, José; García, Antonio; Peeters, Kristien; Gallardo, Elena; De Vriendt, Els; Pelayo-Negro, Ana L; Infante, Jon; Jordanova, Albena

    2015-05-01

    The purpose of the study was to describe a pedigree with NEFL E396K mutation associated with a novel dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) phenotype. The pedigree comprised four patients over two generations, aged between 35 and 59 years, who have been serially evaluated since 1993. Their clinical picture was characterized by pes cavus, sensorimotor neuropathy and spastic gait. Both older patients showed ascending leg weakness to involve pelvic musculature. CMT neuropathy score ranged from 14 to 26 (moderate to severe disease). Electrophysiology showed uniform nerve conduction slowing in the intermediate range, both in distal and proximal nerve segments. Multimodal evoked potential and blink reflex studies revealed abnormalities indicative of central sensorimotor pathway dysfunction. On imaging studies of lower-limb musculature, there was massive atrophy of intrinsic foot muscles and to a lesser degree of calves and thighs predominating in muscles innervated by tibial and sciatic nerves. In both patients exhibiting waddling gait, there was atrophy of pelvic muscles mainly involving gluteus medius, gluteus minimus and piriformis. We conclude that NEFL E396K mutation may manifest with a novel DI-CMT phenotype, characterized by simultaneous involvement of the peripheral and central nervous system. PMID:25877835

  6. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    SciTech Connect

    Denton, P.; Gere, S.; Wolpert, C.

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  7. Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, Type 2B

    SciTech Connect

    Vance, J.M.; Speer, M.C.; Stajich, J.M.

    1996-07-01

    Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named {open_quotes}CMT2B.{close_quotes} We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck (1993). Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in most CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that {open_quotes}all [patients] had characteristic findings in their physical examinations, including... evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers,{close_quotes} it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. 16 refs., 1 tab.

  8. Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach

    PubMed Central

    Zimoń, Magdalena; Battaloǧlu, Esra; Parman, Yesim; Erdem, Sevim; Baets, Jonathan; De Vriendt, Els; Atkinson, Derek; Almeida-Souza, Leonardo; Deconinck, Tine; Ozes, Burcak; Goossens, Dirk; Cirak, Sebahattin; Van Damme, Philip; Shboul, Mohammad; Voit, Thomas; Van Maldergem, Lionel; Dan, Bernard; El-Khateeb, Mohammed S.; Guergueltcheva, Velina; Lopez-Laso, Eduardo; Goemans, Nathalie; Masri, Amira; Züchner, Stephan; Timmerman, Vincent; Topaloǧlu, Haluk; De Jonghe, Peter

    2016-01-01

    Autosomal recessive forms of Charcot-Marie-Tooth disease (ARCMT) are rare but severe disorders of the peripheral nervous system. Their molecular basis is poorly understood due to the extensive genetic and clinical heterogeneity, posing considerable challenges for patients, physicians, and researchers. We report on the genetic findings from a systematic study of a large collection of 174 independent ARCMT families. Initial sequencing of the three most common ARCMT genes (ganglioside-induced differentiation protein 1—GDAP1, SH3 domain and tetratricopeptide repeats-containing protein 2—SH3TC2, histidine-triad nucleotide binding protein 1—HINT1) identified pathogenic mutations in 41 patients. Subsequently, 87 selected nuclear families underwent single nucleotide polymorphism (SNP) genotyping and homozygosity mapping, followed by targeted screening of known ARCMT genes. This strategy provided molecular diagnosis to 22 % of the families. Altogether, our unbiased genetic approach identified pathogenic mutations in ten ARCMT genes in a total of 41.3 % patients. Apart from a newly described founder mutation in GDAP1, the majority of variants constitute private molecular defects. Since the gene testing was independent of the clinical phenotype of the patients, we identified mutations in patients with unusual or additional clinical features, extending the phenotypic spectrum of the SH3TC2 gene. Our study provides an overview of the ARCMT genetic landscape and proposes guidelines for tackling the genetic heterogeneity of this group of hereditary neuropathies. PMID:25231362

  9. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success

    PubMed Central

    Timmerman, Vincent; Strickland, Alleene V.; Züchner, Stephan

    2014-01-01

    Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs. PMID:24705285

  10. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker.

    PubMed

    Nobbio, Lucilla; Visigalli, Davide; Radice, Davide; Fiorina, Elisabetta; Solari, Alessandra; Lauria, Giuseppe; Reilly, Mary M; Santoro, Lucio; Schenone, Angelo; Pareyson, Davide

    2014-06-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A. PMID:24812204

  11. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    PubMed

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies. PMID:26786738

  12. Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

    PubMed

    Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

    2016-02-17

    Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A. PMID:26599234

  13. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease

    PubMed Central

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-01-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status. PMID:27162595

  14. Grizzly bear denning chronology and movements in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Haroldson, Mark A.; Ternent, Mark A.; Gunther, Kerry A.; Schwartz, Charles C.

    2002-01-01

    Den entrance and emergence dates of grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem are important to management agencies that wish to minimize impacts of human activities on bears. Current estimates for grizzly bear denning events use data that were collected from 1975–80. We update these estimates by including data obtained from 1981–99. We used aerial telemetry data to estimate week of den entry and emergence by determining the midpoint between the last known active date and the first known date denned, as well as the last known date denned and the first known active date. We also investigated post emergence movement patterns relative to den locations. Mean earliest and latest week of den entry and emergence were also determined. Den entry for females began during the fourth week in September, with 90% denned by the fourth week of November. Earliest den entry for males occurred during the second week of October, with 90% denned by the second week of December. Mean week of den entry for known pregnant females was earlier than males. Earliest week of den entry for known pregnant females was earlier than other females and males. Earliest den emergence for males occurred during the first week of February, with 90% of males out of dens by the fourth week of April. Earliest den emergence for females occurred during the third week of March; by the first week of May, 90% of females had emerged. Male bears emerged from dens earlier than females. Denning period differed among classes and averaged 171 days for females that emerged from dens with cubs, 151 days for other females, and 131 days for males. Known pregnant females tended to den at higher elevations and, following emergence, remained at higher elevation until late May. Females with cubs remained relatively close (<3 km) to den sites until the last 2 weeks in May. Timing of denning events was similar to previous estimates for this and other grizzly bear populations in the southern Rocky

  15. Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.

    PubMed

    Lupo, Vincenzo; García-García, Francisco; Sancho, Paula; Tello, Cristina; García-Romero, Mar; Villarreal, Liliana; Alberti, Antonia; Sivera, Rafael; Dopazo, Joaquín; Pascual-Pascual, Samuel I; Márquez-Infante, Celedonio; Casasnovas, Carlos; Sevilla, Teresa; Espinós, Carmen

    2016-03-01

    Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies. PMID:26752306

  16. Duchenne, Charcot and Babinski, three neurologists of La Salpetrière Hospital, and their contribution to concepts of the central organization of motor synergy.

    PubMed

    Clarac, François; Massion, Jean; Smith, Allan M

    2009-11-01

    Many currently accepted notions of motor control originate from a few seminal concepts developed in the latter half of the 19th century (see Bennett and Hacker, 2002). The goal of this review is to retrace some current ideas about motor control back to the thought of three French neurologists of Hospital of the Salpetrière hospital in Paris during the latter half of the 19th century and early 20th century (Fig. 1): Guillaume Duchenne de Boulogne (1806-1875), Jean-Martin Charcot (1825-1893), and Joseph Babinski (1857-1932). A common theoretical and methodological thread unites these three men as Charcot was taught neurology by Duchenne, and Babinski was trained by Charcot. The influential concepts developed by these pioneering French neurologists have been neglected for nearly a century and only rediscovered recently. We intend to highlight how these astute clinicians used their meticulous clinical observations of patients to reveal novel and original perspectives of motor co-ordination. Between 1850 and 1930, all three men played a major role in developing and shaping the entire field of normal and pathological motor control in addition to making important contributions to three major scientific issues; the centralist view of muscle sense, the emerging concept of muscle synergy in voluntary movements and in locomotion and finally the specific role of the cerebellum in muscle synergy. The important contributions of these men will be considered in the context of other significant schools of neurology from other countries. Finally, the concept of cerebellar asynergy as proposed by Babinski anticipated the development of the internal models which much later were able to provide a theoretical basis for understanding the mechanism of learned motor co-ordination involving the cerebellum. PMID:19766718

  17. Selection of den sites by black bears in the southern Appalachians

    USGS Publications Warehouse

    Reynolds-Hogland, M. J.; Mitchell, M.S.; Powell, R.A.; Brown, D.C.

    2007-01-01

    We evaluated selection of den sites by American black bears (Ursus americanus) in the Pisgah Bear Sanctuary, western North Carolina, by comparing characteristics of dens at 53 den sites with availability of habitat characteristics in annual home ranges of bears and in the study area. We also tested whether den-site selection differed by sex, age, and reproductive status of bears. In addition, we evaluated whether the den component of an existing habitat model for black bears predicted where bears would select den sites. We found bears selected den sites far from gravel roads, on steep slopes, and at high elevations relative to what was available in both annual home ranges and in the study area. Den-site selection did not differ by sex or age, but it differed by reproductive status. Adult females with cubs preferred to den in areas that were relatively far from gravel roads, but adult females without cubs did not. The habitat model overestimated the value of areas near gravel roads, underestimated the value of moderately steep areas, and did not include elevation as a predictor variable. Our results highlight the importance of evaluating den selection in terms of both use and availability of den characteristics. ?? 2007 American Society of Mammalogists.

  18. A female black bear denning habitat model using a geographic information system

    USGS Publications Warehouse

    Clark, J.D.; Hayes, S.G.; Pledger, J.M.

    1998-01-01

    We used the Mahalanobis distance statistic and a raster geographic information system (GIS) to model potential black bear (Ursus americanus) denning habitat in the Ouachita Mountains of Arkansas. The Mahalanobis distance statistic was used to represent the standard squared distance between sample variates in the GIS database (forest cover type, elevation, slope, aspect, distance to streams, distance to roads, and forest cover richness) and variates at known bear dens. Two models were developed: a generalized model for all den locations and another specific to dens in rock cavities. Differences between habitat at den sites and habitat across the study area were represented in 2 new GIS themes as Mahalanobis distance values. Cells similar to the mean vector derived from the known dens had low Mahalanobis distance values, and dissimilar cells had high values. The reliability of the predictive model was tested by overlaying den locations collected subsequent to original model development on the resultant den habitat themes. Although the generalized model demonstrated poor reliability, the model specific to rock dens had good reliability. Bears were more likely to choose rock den locations with low Mahalanobis distance values and less likely to choose those with high values. The model can be used to plan the timing and extent of management actions (e.g., road building, prescribed fire, timber harvest) most appropriate for those sites with high or low denning potential. 

  19. Raccoon (Procyon lotor) diurnal den use within an intensively managed forest in central West Virginia

    USGS Publications Warehouse

    Owen, Sheldon F.; Berl, Jacob L.; Edwards, John W.; Ford, W. Mark; Wood, Petra Bohall

    2015-01-01

    Intensive forest management may influence the availability of suitable den sites for large den-seeking species, such as Procyon lotor (Raccoon). As part of a Raccoon ecology study on an industrial forest in the Allegheny Mountains of central West Virginia, we radio-tracked 32 Raccoons to 175 diurnal den sites to determine relative use of dens that included cavity trees, rock dens, log piles, slash piles, and exposed limbs. Patterns of den use significantly differed between sexes and among seasons. Overall, we recorded 58 cavity dens in 12 tree species with 7 maternal dens found in 5 tree species. Raccoons selected larger-diameter den trees than available cavity trees and non-cavity trees. Because the abundance of suitable tree cavities is known to influence Raccoon densities and recruitment at fine spatial scales and female Raccoons in this study used tree cavities as maternal den sites, the continued harvest of large-diameter trees (i.e., those capable of developing den cavities) without replacement may impact Raccoon recruitment within intensively managed forests throughout the central Appalachians.

  20. The 5' regulatory sequence of the PMP22 in the patients with Charcot-Marie-Tooth disease.

    PubMed

    Sinkiewicz-Darol, Elena; Kabzińska, Dagmara; Moszyńska, Izabela; Kochański, Andrzej

    2010-01-01

    Little is known about the molecular background of clinical variability of Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A and HNPP disorders result from duplication and deletion of the PMP22 gene respectively. In a series of studies performed on affected animal transgenic models of CMT1A disease, expression of the PMP22 gene (gene dosage) was shown to correlete with severity of CMT course (gene dosage effect). In this study we hypothesized that single nucleotide polymorphisms (SNPs) located within the 5' regulatory sequence of PMP22 gene may be responsible for the CMT1A/HNPP clinical variability. We have sequenced the PMP22 5' upstream regulatory sequence in a group of 45 CMT1A/HNPP patients harboring the PMP22 duplication (37) /deletion (8). We have identified five SNPs in the regulatory sequence of the PMP22 gene. Three of them i.e. -819C>T, -4785G>T, -4800C>T were detected both in the patients and in the control group. Thus, their pathogenic role in the regulation of the expression of the PMP22 gene seems not to be significant. Two SNPs i.e. -4210T>C and -4759T>A were found only in the CMT patients. Their role in the regulation of the PMP22 gene expression can not be excluded. Additionally we have detected the Thr118Met variant in exon 4 of the PMP22 gene, which was previously reported by other authors, in one patient. We conclude that the 5' regulatory sequence of the PMP22 gene is conserved at the nucleotiode level, however rarely occurring SNPs variant in the PMP22 regulatory sequence may be associated with the gene dosage effect. PMID:20842290

  1. Efficacy of focal mechanic vibration treatment on balance in Charcot-Marie-Tooth 1A disease: a pilot study.

    PubMed

    Pazzaglia, Costanza; Camerota, F; Germanotta, M; Di Sipio, E; Celletti, C; Padua, L

    2016-07-01

    Patients affected by Charcot-Marie-Tooth (CMT) disease experience an impaired balance. Although the causes of the postural instability are not fully understood, somatosensory system seems to play a key role. Mechanical vibration seems to act on the somatosensory system and to improve its function. The aim of our study was to evaluate the effects of focal mechanical vibration (fMV) on the balance of CMT 1A patients. We enrolled 14 genetically confirmed CMT 1A patients (8 female and 6 male, mean age 492 years, range 32-74, mean duration of disease: 13 years, range 1-30). Patients underwent a 3-day fMV treatment on quadriceps and triceps surae and were evaluated before the treatment as well as 1 week and 1 month after the end of the treatment. The primary outcome measure was the Berg Balance Scale (BBS) and the secondary were the Dynamic Gait Index (DGI), the 6 Min Walking Test (6MWT), the muscular strength of lower limbs, the Quality of Life (QoL) questionnaire and the stabilometric variables. The statistical analysis showed a significant modification of the BBS due to the effect of treatment (p < 0.05). A significant modification was also found in the DGI (p < 0.05). Concerning the stabilometric variables we found significant changes only for the eyes closed condition; in particular, a significant decrease was found in VelocityML (p < 0.05) and Sway path length (p < 0.05). The fMV treatment applied on lower limbs of CMT 1A patients determined an improvement of balance as detected by the BBS. The concurrent improvement of stabilometric variables in the eyes closed condition only suggests that fMV acts mostly on somatosensory afferences. Further studies are needed to confirm these data on a larger sample of CMT patients. PMID:27177999

  2. Exome Sequencing Identifies GNB4 Mutations as a Cause of Dominant Intermediate Charcot-Marie-Tooth Disease

    PubMed Central

    Soong, Bing-Wen; Huang, Yen-Hua; Tsai, Pei-Chien; Huang, Chien-Chang; Pan, Hung-Chuan; Lu, Yi-Chun; Chien, Hsin-Ju; Liu, Tze-Tze; Chang, Ming-Hong; Lin, Kon-Ping; Tu, Pang-Hsien; Kao, Lung-Sen; Lee, Yi-Chung

    2013-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited neuropathies. Mutations in approximately 45 genes have been identified as being associated with CMT. Nevertheless, the genetic etiologies of at least 30% of CMTs have yet to be elucidated. Using a genome-wide linkage study, we previously mapped a dominant intermediate CMT to chromosomal region 3q28–q29. Subsequent exome sequencing of two affected first cousins revealed heterozygous mutation c.158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gβ4), to cosegregate with the CMT phenotype in the family. Further analysis of GNB4 in an additional 88 unrelated CMT individuals uncovered another de novo mutation, c.265A>G (p.Lys89Glu), in this gene in one individual. Immunohistochemistry studies revealed that Gβ4 was abundant in the axons and Schwann cells of peripheral nerves and that expression of Gβ4 was significantly reduced in the sural nerve of the two individuals carrying the c.158G>A (p.Gly53Asp) mutation. In vitro studies demonstrated that both the p.Gly53Asp and p.Lys89Glu altered proteins impaired bradykinin-induced G-protein-coupled-receptor (GPCR) signaling, which was facilitated by the wild-type Gβ4. This study identifies GNB4 mutations as a cause of CMT and highlights the importance of Gβ4-related GPCR signaling in peripheral-nerve function in humans. PMID:23434117

  3. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

    PubMed Central

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

  4. [An autopsy case of neuronal type Charcot-Marie-Tooth disease (HMSN type II) with nerve deafness and psychiatric symptoms].

    PubMed

    Yoshimura, I; Yoshimura, N; Hanazono, T; Usutani, S; Muramoto, Y; Fukushima, Y

    1992-06-01

    The clinical and pathological findings of a 41-year-old male patient with atypical Charcot-Marie-Tooth disease were reported. There were 3 cases of subarachnoid haemorrhage, 2 nerve deafness and 2 hereditary motor and sensory neuropathy (HMSN) in his family. He had suffered from progressive nerve deafness since 5 years old and gait disturbance since 37 years old. He had been admitted to the psychiatric hospital 3 times because of hallucinatory-delusional state and behavior abnormalities. Neurological examinations at 39 years old revealed that he had mental deterioration (IQ 66), nerve deafness, diffuse muscle atrophy, most marked distally, sensory disturbance, areflexia, positive Romberg's sign, orthostatic hypotension, dysphagia and slurred speech. MCV of median nerve was 27.8 m/sec, and SCV was not evoked. EEG revealed nonspecific dysfunction of the brain. He died of ileus-like condition at 41 years old. General autopsy showed haemorrhagic infarction of the jejunum and ileum due to compression of the superior mesenteric artery and vein by an adhesion band of connective tissue formed after previous appendectomy. Neuropathological examinations revealed axonal degeneration and loss of myelinated fibers with schwannosis of anterior and posterior spinal nerve roots as well as peripheral nerves. The posterior roots were more severely affected than the anterior ones. Ganglion cells of the posterior root ganglia showed remarkable degeneration and loss. There was severe degeneration of the posterior columns, especially in the gracilis, of the spinal cord. Nerve cells in the anterior horns and Clarke's columns also displayed conspicuous atrophy or central chromatolysis followed by gliosis. There was slight degeneration of the posterior spinocerebellar tracts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1389565

  5. Mutational analysis of the myelin protein zero (MPZ) gene associated with Charcot-Marie-Tooth neuropathy type 1B

    SciTech Connect

    Roa, B.B.; Warner, L.E.; Lupski, J.R.

    1994-09-01

    The MPZ gene that maps to chromosome 1q22q23 encodes myelin protein zero, which is the most abundant peripheral nerve myelin protein that functions as a homophilic adhesion molecule in myelin compaction. Association of the MPZ gene with the dysmyelinating peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS) was previously demonstrated by MPZ mutations identified in CMT1B and in rare DSS patients. In this study, the coding region of the MPZ gene was screened for mutations in a cohort of 74 unrelated patients with either CMT type 1 or DSS who do not carry the most common CMT1-associated molecular lesion of a 1.5 Mb DNA duplication on 17p11.2-p12. Heteroduplex analysis detected base mismatches in ten patients that were distributed over three exons of MPZ. Direct sequencing of PCR-amplified genomic DNA identified a de novo MPZ mutation associated with CMT1B that predicts an Ile(135)Thr substitution. This finding further confirms the role of MPZ in the CMT1B disease process. In addition, two polymorphisms were identified within the Gly(200) and Ser(228) codons that do not alter the respective amino acid residues. A fourth base mismatch in MPZ exon 3 detected by heteroduplex analysis is currently being characterized by direct sequence determination. Previously, four unrelated patients in this same cohort were found to have unique point mutations in the coding region of the PMP22 gene. The collective findings on CMT1 point mutations could suggest that regulatory region mutations, and possibly mutations in CMT gene(s) apart from the MPZ, PMP22 and Cx32 genes identified thus far, may prove to be significant for a number of CMT1 cases that do not involve DNA duplication.

  6. Pedal bone density, strength, orientation, and plantar loads preceding incipient metatarsal fracture after Charcot neuroarthropathy: 2 case reports

    PubMed Central

    Gutekunst, David J.; Sinacore, David R.

    2014-01-01

    Study Design Case reports Background Charcot neuroarthropathy (CN) is a progressive, non-infective, inflammatory destruction of bones and joints leading to foot deformities and plantar ulceration. Though individuals with CN typically have low areal bone mineral density (aBMD), little is known regarding changes in volumetric bone mineral density (vBMD), bone geometry, joint mal-alignment, and biomechanical loads preceding fracture. Case Description Two females, aged 45 and 54 years at the onset of an acute non-fracture CN event, received regular physical therapy with wound care and total contact casting. Both enrolled in a larger research study that included plantar pressure assessment and quantitative computed tomography (QCT) at enrollment and 3, 6, and 12 months later. The women sustained mid-diaphyseal fifth metatarsal fracture 10–11 months after enrollment. QCT image analysis techniques were used to measure vBMD; bone geometric indices reflecting strength in compression, bending, and cortical buckling; and 3-dimensional bone-to-bone orientation angles reflecting foot deformity. Outcomes Fifth metatarsal mid-diaphyseal vBMD decreased during off-loading treatment from 0 to 3 months, then increased to above baseline levels by 6 months. All geometric strength indices improved from baseline through 6 months. Plantar loading in the lateral midfoot increased preceding fracture, concomitant with alterations in bone orientation angles which suggest progressive development of metatarsus adductus and equinovarus foot deformity. Discussion Fractures may occur when bone strength decreases or when biomechanical loading increases. Incipient fracture was preceded by increased loading in the lateral midfoot, but not by reductions in vBMD or geometric strength indices, suggesting that loading played a greater role in fracture. Moreover, the progression of foot deformities may be causally linked to the increased plantar loading. Level of evidence Therapy, level 4 PMID:24256173

  7. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies.

    PubMed

    van Paassen, Barbara W; van der Kooi, Anneke J; van Spaendonck-Zwarts, Karin Y; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

  8. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

    SciTech Connect

    Tan, C.; Ainsworth, P. |

    1994-09-01

    Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions, while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.

  9. Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

    PubMed

    Mathis, Stéphane; Corcia, Philippe; Tazir, Meriem; Camu, William; Magdelaine, Corinne; Latour, Philippe; Biberon, Julien; Guennoc, Anne-Marie; Richard, Laurence; Magy, Laurent; Funalot, Benoît; Vallat, Jean-Michel

    2014-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.4 megabase CMT1A duplication and atypical presentation (electrophysiological, clinical or pathological): a 10 year-old girl with tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent paresthesiae and block conduction on the electrophysiological study; a 46 year-old woman with transient recurrent nerve palsies mimicking HNPP. These observations highlight the wide spectrum of CMT1A and the overlap between CMT1A and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases. PMID:24792522

  10. Long-term analyses of innervation and neuromuscular integrity in the Trembler-J mouse model of Charcot-Marie-Tooth disease.

    PubMed

    Nicks, Jessica Renee; Lee, Sooyeon; Kostamo, Kathryne Ann; Harris, Andrew Benford; Sookdeo, Amanda M; Notterpek, Lucia

    2013-10-01

    A large fraction of hereditary demyelinating neuropathies, classified as Charcot-Marie-Tooth disease type 1A, is associated with misexpression of peripheral myelin protein 22. In this study, we characterized morphologic and biochemical changes that occur with diseaseprogression in neuromuscular tissue of Trembler-J mice, a spontaneous rodent model of Charcot-Marie-Tooth disease type 1A. Using age-matched, 2- and 10-month-old, wild-type and Trembler-J mice, we observed neuromuscular deficits that progress from distal to proximal regions. The impairments in motor performance are underlined by degenerative events at distal nerve segments and structural alterations at nerve-muscle synapses. Furthermore, skeletal muscle of affected mice showed reduced myofiber diameter, increased expression of the muscle atrophy marker muscle ring-finger protein 1, and fiber type switching. A dietary intervention of intermittent fasting attenuated these progressive changes and supported distal nerve myelination and neuromuscular junction integrity. In addition to the well-characterized demyelination aspects of this model, our investigations identified distinct degenerative events in distal nerves and muscle of affected neuropathic mice. Therefore, therapeutic studies aimed at slowing or reversing the neuropathic features of these disorders should include the examination of muscle tissue, as well as neuromuscular contact sites. PMID:24042197

  11. Landward and eastward shift of Alaskan polar bear denning associated with recent sea ice changes

    USGS Publications Warehouse

    Fischbach, A.S.; Amstrup, Steven C.; Douglas, D.C.

    2007-01-01

    Polar bears (Ursus maritimus) in the northern Alaska region den in coastal areas and on offshore drifting ice. We evaluated changes in the distribution of polar bear maternal dens between 1985 and 2005, using satellite telemetry. We determined the distribution of maternal dens occupied by 89 satellite collared female polar bears between 137°W and 167°W longitude. The proportion of dens on pack ice declined from 62% in 1985–1994 to 37% in 1998–2004 (P = 0.044) and among pack ice dens fewer occurred in the western Beaufort Sea after 1998. We evaluated whether hunting, attraction to bowhead whale remains, or changes in sea ice could explain changes in den distribution. We concluded that denning distribution changed in response to reductions in stable old ice, increases in unconsolidated ice, and lengthening of the melt season. In consort, these changes have likely reduced the availability and quality of pack ice denning habitat. Further declines in sea ice availability are predicted. Therefore, we expect the proportion of polar bears denning in coastal areas will continue to increase, until such time as the autumn ice retreats far enough from shore that it precludes offshore pregnant females from reaching the Alaska coast in advance of denning.

  12. Selection of wolf dens in relation to winter territories in northeastern Minnesota

    USGS Publications Warehouse

    Ciucci, P.; Mech, L.D.

    1992-01-01

    Locations of wolf (Canus lupus) dens in the Superior National Forest in northeastern Minnesota from 1969 through 1988 were analyzed in relation to winter territories. Dens situated within the central 60% of the territories were randomly located relative to territory centers. However, only 10.5% (2) of the dens were located within a 1-km-wide strip inside the territory boundaries, indicating possible avoidance of neighboring packs. A negative relationship (r2 = 0.27; P 1 year, and possibly the availability of a stable food source helped determine den location.

  13. Post-den emergence behavior of polar bears (Ursus maritimus) in Northern Alaska

    USGS Publications Warehouse

    Smith, T.S.; Partridge, S.T.; Amstrup, Steven C.; Schliebe, S.

    2007-01-01

    We observed polar bear (Ursus maritimus) maternity den sites on Alaska’s North Slope in March 2002 and 2003 in an effort to describe bears’ post-den emergence behavior. During 40 sessions spanning 459 h, we observed 8 adults and 14 dependent cubs outside dens for 37.5 h (8.2% of total observation time). There was no significant difference between den emergence dates in 2002 (mean = 15 Mar ± 4.1 d) and 2003 (mean = 21 Mar ± 2.1 d). Following initial den breakout, polar bears remained at their den sites for 1.5 to 14 days (mean = 8.1 ± 5.1 d). The average length of stay in dens between emergent periods was significantly shorter in 2002 (1.79 h) than in 2003 (4.82 h). While outside, adult bears were inactive 49.5% of the time, whereas cubs were inactive 13.4% of the time. We found no significant relationships between den emergence activity and weather. Adult polar bears at den sites subjected to industrial activity exhibited significantly fewer bouts of vigilance than denned bears in undisturbed areas (t = -5.5164, df = 4, p= 0.00). However, the duration of vigilance behaviors at sites near industrial activity was not significantly shorter than at the other sites studied (t = -1.8902, df = 4, p = 0.07). Results for these bears were within the range of findings in other studies of denned polar bears.

  14. Charcot-Marie-Tooth neuropathy due to a novel EGR2 gene mutation with mild phenotype--usefulness of human mapping chip linkage analysis in a Czech family.

    PubMed

    Safka Brožková, Dana; Nevšímalová, Soňa; Mazanec, Radim; Rautenstrauss, Bernd; Seeman, Pavel

    2012-08-01

    Charcot-Marie-Tooth neuropathies (CMT) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system. Selection of candidate disease genes for mutation analysis is sometimes difficult since more than 40 genes and loci are known to be associated with CMT neuropathies. Hence a Czech family Cz-CMT with demyelinating type of autosomal dominant CMT disease was investigated by genome-wide linkage analysis by means of single-nucleotide polymorphism (SNP) arrays. Among 35 regions with linkage, five carried known CMT genes. In the final result a novel early growth response 2 - missense mutation c.1235 A>G, p.Glu412Gly was found. Surprisingly, the more severely affected proband carried an additional heterozygous myelin protein zero variant p.Asp246Asn detected previously, which may modify the phenotype. However, this MPZ variant is benign in heterozygous state alone, because it is also carried by the patient's healthy father. PMID:22546699

  15. Spinal and bulbar muscular atrophy and Charcot-Marie-Tooth type 1A: Co-existence of two rare neuromuscular genetic diseases in the same patient.

    PubMed

    Sagnelli, Anna; Scaioli, Vidmer; Piscosquito, Giuseppe; Salsano, Ettore; Dalla Bella, Eleonora; Gellera, Cinzia; Pareyson, Davide

    2015-10-01

    Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by a trinucleotide CAG repeat expansion in the androgen receptor gene; it is clinically characterized by adult-onset, slowly progressive weakness and atrophy mainly affecting proximal limb and bulbar muscles. Charcot-Marie-Tooth disease type 1A is an autosomal dominant polyneuropathy due to peripheral myelin protein 22 gene duplication and characterized by slowly progressive distal limb muscle weakness, atrophy and sensory loss with foot deformities. Here we report the co-occurrence of both neuromuscular genetic diseases in the same male patient. Difficulties in climbing stairs and jaw weakness were presenting symptoms consistent with SBMA. However, predominant distal weakness and bilateral pes cavus were rather suggestive of a hereditary polyneuropathy. The combination of two diseases, even if extremely rare, should be considered in the presence of atypical symptoms; in the case of genetic diseases this event may have important implications on family members' counseling. PMID:26298608

  16. Novel FH mutation in a patient with cutaneous leiomyomatosis associated with cutis verticis gyrata, eruptive collagenoma and Charcot-Marie-Tooth disease.

    PubMed

    Marque, M; Gardie, B; Bressac de Paillerets, B; Rustin, P; Guillot, B; Richard, S; Bessis, D

    2010-12-01

    Multiple cutaneous and uterine leiomyomatosis (MCUL)/hereditary leiomyomatosis and renal cell cancer (HLRCC) (OMIM 150800/OMIM 605839) is a rare hereditary disorder leading to the development of benign cutaneous and uterine smooth muscle tumours in young adults.(1,2) This disease is characterized by an increased risk of developing renal cell carcinomas.(3) It results from dominantly inherited autosomal mutations in the fumarate hydratase (FH) gene.(4) This gene encodes a Krebs cycle enzyme, present in both cytosolic and mitochondrial compartments, and probably acts as a tumour suppressor gene. We report a 22-year-old man affected by cutaneous leiomyomatosis associated with cutis verticis gyrata, disseminated collagenoma and Charcot-Marie-Tooth disease, who was harbouring the novel FH gene mutation c.821C > T, p.Ala274Val. PMID:20560959

  17. Metabolite profile of a mouse model of Charcot-Marie-Tooth type 2D neuropathy: implications for disease mechanisms and interventions.

    PubMed

    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H; Currie, Meagan E; Norberg, Sara N; Evsikov, Alexei V; Miers, Kathy E; Seburn, Kevin L; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J; Burgess, Robert W

    2016-01-01

    Charcot-Marie-Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot-Marie-Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite 'fingerprint' we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

  18. Early-Onset Osteoarthritis, Charcot-Marie-Tooth Like Neuropathy, Autoimmune Features, Multiple Arterial Aneurysms and Dissections: An Unrecognized and Life Threatening Condition

    PubMed Central

    Aubart, Mélodie; Gobert, Delphine; Aubart-Cohen, Fleur; Detaint, Delphine; Hanna, Nadine; d’Indya, Hyacintha; Lequintrec, Janine-Sophie; Renard, Philippe; Vigneron, Anne-Marie; Dieudé, Philippe; Laissy, Jean-Pierre; Koch, Pierre; Muti, Christine; Roume, Joelle; Cusin, Veronica; Grandchamp, Bernard; Gouya, Laurent; LeGuern, Eric; Papo, Thomas; Boileau, Catherine; Jondeau, Guillaume

    2014-01-01

    Background Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. Methods All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. Results Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren’s disease, rheumatoid arthritis, Hashimoto’s disease, or isolated autoantibodies- were found in 36% of patients. Interpretation SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot

  19. Polar bear maternal den habitat in the Arctic National Wildlife Refuge, Alaska

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Ambrosius, K.J.

    2006-01-01

    Polar bears (Ursus maritimus) give birth during mid-winter in dens of ice and snow. Denning polar bears subjected to human disturbances may abandon dens before their altricial young can survive the rigors of the Arctic winter. Because the Arctic coastal plain of Alaska is an area of high petroleum potential and contains existing and planned oil field developments, the distribution of polar bear dens on the plain is of interest to land managers. Therefore, as part of a study of denning habitats along the entire Arctic coast of Alaska, we examined high-resolution aerial photographs (n = 1655) of the 7994 km2 coastal plain included in the Arctic National Wildlife Refuge (ANWR) and mapped 3621 km of bank habitat suitable for denning by polar bears. Such habitats were distributed uniformly and comprised 0.29% (23.2 km2) of the coastal plain between the Canning River and the Canadian border. Ground-truth sampling suggested that we had correctly identified 91.5% of bank denning habitats on the ANWR coastal plain. Knowledge of the distribution of these habitats will help facilitate informed management of human activities and minimize disruption of polar bears in maternal dens.

  20. Kin selection in den sharing develops under limited availability of tree hollows for a forest marsupial

    PubMed Central

    Banks, Sam C.; Lindenmayer, David B.; McBurney, Lachlan; Blair, David; Knight, Emma J.; Blyton, Michaela D. J.

    2011-01-01

    Animal social behaviour is not static with regard to environmental change. Flexibility in cooperative resource use may be an important response to resource decline, mediating the impacts of resource availability on fitness and demography. In forest ecosystems, hollow trees are key den resources for many species, but are declining worldwide owing to forestry. Altered patterns of den sharing may mediate the effects of the decline of this resource. We studied den-sharing interactions among hollow-dependent Australian mountain brushtail possums to investigate how spatial variation in hollow tree availability affects resource sharing and kin selection. Under reduced den availability, individuals used fewer dens and shared them less often. This suggests increased territoriality in the presence of resource competition. Further, there was a switch from kin avoidance to kin preference with decreasing hollow tree availability. This was driven primarily by a change in den sharing among siblings. The inclusive fitness benefits of den sharing with kin are likely to increase under resource-limiting conditions, but are potentially outweighed by the benefits of associating with non-relatives (avoidance of inbreeding or pathogen transmission) where dens are abundant. We discuss how predictions from social evolutionary theory can contribute to understanding animal responses to landscape change. PMID:21288953

  1. Den site activity patterns of adult male and female swift foxes, Vulpes velox, in Northwestern Texas

    USGS Publications Warehouse

    Lemons, P.R.; Ballard, W.B.; Sullivan, R.M.; Sovada, M.A.

    2003-01-01

    Activity of Swift Foxes (Vulpes velox) at den sites was studied in northwestern Texas during pup rearing seasons in 2000 and 2001 to determine role of males in parental care. Twenty-four percent of radio-collared females with a potential to breed successfully raised pups to eight weeks of age. We intensively monitored presence and absence of male and female Swift Foxes at two den sites each year. Females were present >2.6 times more at den sites than males during the pup rearing season. Female and male Swift Foxes largely stayed at dens during diurnal hours and were active away from dens during nocturnal and crepuscular hours. Females and males spent 12.4% and 3.0% more time at dens before pups emerged, than after pups emerged, respectively. Following depredation of one male parent, the female spent 29% less time at the den site. Decrease in time spent at the den by the female following loss of her mate suggested that loss of one parent might severely impact recruitment of Swift Foxes. Our observations indicated that intense Coyote (Canis latrans) depredation may severely impact pup-rearing success as well as the parental care within Swift Fox family groups.

  2. Dens invaginatus in an impacted mesiodens: a morphological study.

    PubMed

    Cantín, M; Fonseca, G M

    2013-01-01

    Dens invaginatus (DI) is a dental anomaly originated from invagination of the enamel organ into the dental papilla, during odontogenesis. DI may be associated with other abnormalities such as dysmorphic mesiodens, and this unusual condition may be detected by chance on the conventional radiography. However, the three-dimensional nature and the exact morphological patterns of DI are impossible to appreciate from this method. We present a morphological study of impacted mesiodens in a 9-year-old girl, which the three coronal invaginations were detected only by Cone-Beam Computed Tomography (CBCT) in the pre-surgical examination. CBCT, radiographic and microscopic reproductions allow transfer of images to facilitate cooperation of working groups, examination as well as for teaching purposes. PMID:24322044

  3. Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for the DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus in Fujian, China.

    PubMed

    Guo, Xiao-Xia; Li, Chun-Xiao; Zhang, Ying-Mei; Xing, Dan; Dong, Yan-De; Zhang, Heng-Duan; Qin, Cheng-Feng; Zhao, Tong-Yan

    2016-09-01

    Dengue is an acute, emerging, infectious disease transmitted by Aedes mosquitoes that has become a serious global public health problem. The DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus were originally isolated from the serum of a patient with dengue fever in Fujian Province, China, in 1999. Our data provide the first assessment of the vector competence of Aedes mosquitoes with respect to the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus. There were significant differences in the replication rates of these two viral strains in Aedes albopictus and Aedes aegypti (P<0.05); replication of the DEN2-FJ10 strain was greater in Ae. aegypti than in Ae. albopictus 5 days post infection whereas replication of the DEN2-FJ11 was greater in Ae. albopictus than in Ae. aegypti 7 days post infection. The replicative ability of the DEN2-FJ11 strain was greater than that of the DEN2-FJ10 strain in infected Ae. albopictus. In infected Ae. aegypti, rapid proliferation of the DEN2-FJ10 strain occurred earlier than in the DEN2-FJ11 strain. There were no significant differences in the midgut and salivary gland infection rates of Ae. albopictus and Ae. aegypti with respect to either viral strain. Although the DEN2-FJ10 and DEN2-FJ11 strains differ in their virulence to neonatal rats, there was no significant difference in the ability of either Ae. albopictus or Ae. aegypti to transmit the DEN2-FJ10 and DEN2-FJ10 strains of the dengue 2 virus (P>0.05). In summary, our results indicate that Ae. albopictus and Ae. aegypti mosquitoes are moderately competent vectors of the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus and provide the first evidence of the effect of these two viral strains on the vector competence of mosquitoes in China. PMID:27260668

  4. Grizzly bear denning and potential conflict areas in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Podruzny, Shannon; Cherry, Steve; Schwartz, Charles C.; Landenburger, Lisa

    2002-01-01

    Increasing winter use of steep, high-elevation terrain by backcountry recreationists has elevated concern about disturbance of denning grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem (GYE). To help identify areas where such conflicts might occur, we developed a spatially explicit model to predict potential denning areas in the GYE. Using a scan area of 630 m around each location, we assigned site attributes to 344 den locations of radio-trackedg rizzly bears from 1975-99. Attributesi dentified as predictorsf or the analysis included elevation, slope, an index of solar radiation, and forest cover. We used the Mahalanobis distance statistic to model the similarity between sites used by denning bears and each cell in the data layers. We used the final Mahalanobis distance model to produce maps of the study area. Potential denning habitat, based upon the model, is abundantw ithin the GYE. Ourr esultsc an be used by land managementa gencies to identifyp otentialc onflict sites and minimize effects of regulated activities on denning grizzly bears. We illustrate how the Gallatin National Forest (GNF) used the model to examine the overlap between potential snowmobile use areas and potential denning habitat as part of a Biological Assessment submitted to the U.S. Fish and Wildlife Service.

  5. Management of dens in dente associated with a chronic periapical lesion.

    PubMed

    Mehta, Vivek; Raheja, Anupama; Singh, Rajeev Kumar

    2015-01-01

    Dens in dente is characterised as a developmental anomaly resulting from invagination of the enamel organ into the dental papilla. It is a rare malformation of teeth, showing a wide spectrum of morphological variations such as gemination, microdontia, taurodontism, dentinogenesis imperfecta, supernumerary tooth and hyperplasias, resulting frequently in early pulp necrosis. Maxillary lateral incisors are the commonest teeth to be affected by dental malformations-supernumerary tooth, talon cusp, congenitally missing tooth and dens in dente. We describe the management of a case of dens in dente in a maxillary lateral incisor with a periradicular lesion. PMID:26655667

  6. Den Entry Behavior in Scandinavian Brown Bears: Implications for Preventing Human Injuries

    PubMed Central

    Sahlén, Veronica; Friebe, Andrea; Sæbø, Solve; Swenson, Jon E; Støen, Ole-Gunnar

    2015-01-01

    Encounters between Scandinavian brown bears (Ursus arctos) and humans that result in human injuries and fatalities typically coincide with den entry in October and November, and commonly occur near a den. Our aim was to determine when bears arrive at their dens, identify potential predictors of this event, document behavior and activity associated with this period, and attempt to explain the increased risk of bear-caused human injuries in this period. We analyzed global positioning system (GPS) location and activity data from brown bears in south-central Sweden, using generalized linear mixed models, statistical process control, and activity analyses. Bears arrived at their den sites between 6 October and 1 December. Timing varied by reproductive category, bear age, and year. Half of all bears significantly reduced their activity before arriving at the den area: on average 2,169 m away from the den and 1.8 days before arrival. The other half reduced their activity after arriving at the den area. The latter bears took longer time to reach hibernation activity levels, but we did not find a difference in the start date of hibernation between the 2 groups. Bears also appeared to be sensitive to disturbance in this period, with higher den abandonment rates than later in winter, particularly for males and for bears that had not visited their den sites previously. Den entry occurred from October to December, with high variability and poor predictability of its timing. Therefore, restricting hunting or other recreation activities to reduce risk of injury by bears and disturbing bears probably would be both impractical and ineffective. Our findings can be used to educate hunters about bear behavior at this time of year. Many people associate dens with an increased risk of a bear responding aggressively to disturbance to defend its den, but our results indicate that other behavioral, and possibly physiological, changes in this period also may be involved. © 2014 The

  7. Conventional Treatment of Maxillary Incisor Type III Dens Invaginatus with Periapical Lesion: A Case Report

    PubMed Central

    Borges, Álvaro Henrique; Semenoff Segundo, Alex; Nadalin, Michele Regina; Pedro, Fábio Luís Miranda; da Cruz Filho, Antônio Miranda; Sousa-Neto, Manoel Damião

    2011-01-01

    Dens invaginatus is a developmental dental anomaly clinically characterized by a palatine furrow that can be limited to the coronal pulp or may extend to the radicular apex. The purpose of this paper was to present a clinical case of type III dens invaginatus, identified on the maxillary right central incisor in anterior periapical radiographs, in which the tooth was submitted to conventional endodontic treatment. The results obtained after five years of clinical and radiographic followup demonstrated that conventional endodontic treatment is a clinically viable alternative in cases of type III dens invaginatus. PMID:21991460

  8. [Immediate implant loading using DenTi implants--our long-term experience. Part 2: Experience with DenTi implants as reflected in the literature].

    PubMed

    István, Vajdovich; Mihály, Bandula; Péter, Bóka; Zsuzsanna, Tóth

    2006-12-01

    Immediate loading of dental implants have been widely used to retain and support cross-arch partial dentures. 3-6 months after implantation the osseointegration is established. This period may be shortened with immediate loading of implants. The purpose of this study was to compare the long term experience of immediate loading of DenTi implants and the results reported in available literature. The most relevant articles were selected from current available literature. The influencing factors of success of immediate loading (surgery,- host,- implant and occlusion-related factors) were investigated and discussed in this article. The result of the evaluation showed that the success rate of the immediate loaded DenTi implants with large grit sandblasted treatment and acid etched surface was higher than 95 %. The success rate of the immediate loaded DenTi implants is similar to the ones reported in the available literature. PMID:17444128

  9. The homeopathy of kin selection: an evaluation of Van den Berghe's sociobiological approach to ethnic nepotism.

    PubMed

    Brigandt, Ingo

    2001-09-01

    The present discussion of sociobiological approaches to ethnic nepotism takes Pierre van den Berghe's theory as a starting point. Two points, which have not been addressed in former analyses, are considered to be of particular importance. It is argued that the behavioral mechanism of ethnic nepotism -- as understood by van den Berghe -- cannot explain ethnic boundaries and attitudes. In addition, I show that van den Berghe's central premise concerning ethnic nepotism is in contradiction to Hamilton's formula, the essential principle of kin selection theory. It is further discussed how other approaches that make reference to ethnic nepotism are related to van den Berghe's account and its problems. I conclude with remarks on the evolutionary explanation of ethnic phenomena. PMID:16859334

  10. Sex steroid and prolactin profiles in male American black bears (Ursus americanus) during denning.

    PubMed

    Tsubota, T; Garshelis, D L; Nelson, R A; Bahr, J M

    1999-01-01

    Serum sex steroid and prolactin profiles were examined in the male American black bear, Ursus americanus during denning. Sera collected in December and the following March from 8 denning male black bears in Minnesota, U.S.A. were assayed for testosterone, estradiol-17 beta and prolactin. Eight bears were confirmed to be the denning mode based on a serum urea to creatinine ratio less than 10. Serum testosterone concentrations tended to increase from December to the subsequent March whereas serum estradiol-17 beta concentrations tended to decrease during this period. There were few changes in serum prolactin concentrations between December and March. These findings suggest that spermatogenesis and testicular steroidogenesis initiated during denning may be influenced by changes in serum sex steroid concentrations in the American black bear. PMID:10027172

  11. Nonsurgical endodontic management of dens invaginatus with open apex: A case report

    PubMed Central

    Rani, Nidhi; Sroa, Renu B

    2015-01-01

    Dens invaginatus is a rare malformation with a widely varied morphology. It typically affects permanent maxillary lateral incisors, central incisors, and premolars. This article demonstrates rapid management of type II dens invagination with open apex and large periradicular lesion using calcium hydroxide as intracanal medicament for 1-week followed by apical plug formation with mineral trioxide aggregate Plus and lateral condensation of Gutta-percha. At 24-month follow-up, the patient was asymptomatic and lesion was entirely resolved. PMID:26751206

  12. Cell cycle progression in denV-transfected murine fibroblasts exposed to ultraviolet radiation.

    PubMed

    Kusewitt, D F; Budge, C L; Nolla, H A; Edwards, B S; Ley, R D

    1992-09-01

    Repair-proficient murine fibroblasts transfected with the denV gene of bacteriophage T4 repaired 70-80% of pyrimidine dimers within 24 h after exposure to 150 J/m2 ultraviolet radiation (UVR) from an FS-40 sunlamp. Under the same conditions, control cells repaired only about 20% of UVR-induced pyrimidine dimers. After UVR exposure, both control and denV-transfected cells exhibited some degree of DNA-synthesis inhibition, as determined by flow cytometric analysis of cell-cycle kinetics in propidium iodide-stained cells. DenV-transfected cells had a longer and more profound S phase arrest than control cells, but both control and denV-transfected cells had largely recovered from UVR effects on cell-cycle kinetics by 48 h after UVR exposure. Inhibition of DNA synthesis by UVR was also measured by determining post-UVR incorporation of bromodeoxyuridine (BrdU). The amount of BrdU incorporated was quantitated by determining with flow cytometry the quenching of Hoechst dye 33342 by BrdU incorporated in cellular DNA. DenV-transfected cells showed more marked inhibition of BrdU incorporation after low fluences of UVR than control cells. Differences between denV-transfected and control cells in cell-cycle kinetics following UVR exposure may be related to differences in mechanisms of repair when excision repair of pyrimidine dimers is initiated by endonuclease V instead of cellular repair enzymes. PMID:1380650

  13. Remote identification of maternal polar bear (Ursus maritimus) denning habitat on the Colville River Delta, Alaska

    NASA Astrophysics Data System (ADS)

    Blank, Justin J.

    High resolution digital aerial photographs (1 foot pixel size) of the Colville River Delta, Alaska were examined in 3D, with the use of a digital photogrammetric workstation. Topographic features meeting the criteria required for adequate snow accumulation, and subsequent construction of terrestrial polar bear maternal dens, were identified and digitized into an ArcGIS line shapefile. Effectiveness, efficiency, and accuracy were improved when compared to previous polar bear denning habitat efforts which utilized contact photo prints and a pocket stereoscope in other geographic areas of northern Alaska. Accuracy of photograph interpretation was systematically evaluated visually from the air with the use of a helicopter and physically on the ground. Results show that the mapping efforts were successful in identifying den habitat 91.3% of the time. Knowledge denning habitat can improve and inform decision making by managers and regulators when considering travel and development in the study area. An understanding of polar bear denning habitat extent and location will be a crucial tool for planning activities within the study area in a way that minimizes conflicts with maternal dens.

  14. Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens

    PubMed Central

    Gharajehdaghipour, Tazarve; Roth, James D.; Fafard, Paul M.; Markham, John H.

    2016-01-01

    Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra. PMID:27045973

  15. Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens.

    PubMed

    Gharajehdaghipour, Tazarve; Roth, James D; Fafard, Paul M; Markham, John H

    2016-01-01

    Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ(15)N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra. PMID:27045973

  16. A Rare Case of Crowned Dens Syndrome Mimicking Aseptic Meningitis

    PubMed Central

    Takahashi, Teruyuki; Minakata, Yugo; Tamura, Masato; Takasu, Toshiaki; Murakami, Marohito

    2013-01-01

    Background Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Microcrystal-line deposition most often consists of calcium pyrophosphate dehydrate crystals and/or hydroxyapatite crystals. Case Presentation This report describes the case of an 89-year-old woman who presented with sudden onset, high fever, severe occipital headache, and neck stiffness. A laboratory examination revealed a markedly elevated white blood cell count (11,100/µl) and C-reactive protein level (23.8 mg/dl). These clinical findings suggested severe infection such as meningitis with sepsis. However, the results of blood culture, serum endotoxin, and procalcitonin were all negative, and cerebrospinal fluid studies revealed only a slight abnormality. The patient was first diagnosed with meningitis and treated with antiviral and antibiotic agents as well as non-steroidal anti-inflammatory drugs, but they only had limited effects. A cervical plain computed tomography (CT) scan and its three-dimensional (3D) reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. On the basis of the CT findings, the patient was diagnosed as a severe case of CDS and was immediately treated with corticosteroids. The patient's condition drastically improved within a week after one course of corticosteroid therapy. Conclusion Some atypical symptoms of CDS are misleading and may be misdiagnosed as meningitis, as happened in our case. A CT scan, especially a 3D-CT scan, is necessary and useful for a definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for fever, headache, and cervical pain of unknown origin. PMID:23569451

  17. Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A.

    PubMed

    Kawalec, Maria; Zabłocka, Barbara; Kabzińska, Dagmara; Neska, Jacek; Beręsewicz, Małgorzata

    2014-01-01

    Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot-Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve axons. The precise mechanism by which mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is a hypothesis suggesting the involvement of reduced expression of a homologous protein, mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein expression profiles in different mouse tissues, with special attention paid to dorsal root ganglia (DRGs), as parts of the peripheral nervous system. Quantitative measurement relating to mRNA revealed that expression of the Mfn2 gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system samples and other tissues studied. This result was further supported by Western blot evaluation. Both these sets of data confirm the hypothesis that the cellular consequences of mutations in the mitofusin 2 gene can mostly be manifested in the peripheral nervous system. PMID:25574749

  18. Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation.

    PubMed

    Said, Gérard; Lacroix, Catherine; Planté-Bordeneuve, Violaine; Messing, Bernard; Slama, Abdelhamid; Crenn, Pascal; Nivelon-Chevallier, Annie; Bedenne, Laurent; Soichot, Pierre; Manceau, E; Rigaud, Daniel; Guiochon-Mantel, Anne; Matuchansky, Claude

    2005-06-01

    We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy. PMID:15742109

  19. Long-Range Structural Effects of a Charcot-Marie-Tooth Disease-Causing Mutation in Human Glycyl-TRNA Synthetase

    SciTech Connect

    Xie, W.; Nangle, L.A.; Zhang, W.; Schimmel, P.; Yang, X.-L.

    2009-06-04

    Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located {approx}30 {angstrom} away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.

  20. INF2 mutations associated with dominant inherited intermediate Charcot-Marie-Tooth neuropathy with focal segmental glomerulosclerosis in two Chinese patients.

    PubMed

    Jin, Suqin; Wang, Wei; Wang, Renbin; Lv, He; Zhang, Wei; Wang, Zhaoxia; Jiao, Jinsong; Yuan, Yun

    2015-01-01

    Recently, mutations in the inverted formin 2 (INF2) gene have been indentified in patients with dominant inherited intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) with focal segmental glomerulosclerosis (FSGS). We report clinical and nerve pathological changes in two Chinese patients. Case 1 is 27 years old and presented with distal muscle weakness and atrophy of legs at the age of 13 and renal failure at the age of 26. Three of his family members died due to pure renal failure. Case 2 is 22 years old and presented with distal muscle weakness and atrophy of the legs with transient attacks of difficulty in speaking at age 17. Proteinuria was found by routine urine test at the same time. Sural nerve biopsy revealed moderate-to-severe loss of myelinated fibers with union bulbs and regeneration clusters in both patients. Ultrastructurally, numerous elongated extensions of Schwann cells of unmyelinated fibers could be seen in both patients. INF2 gene mutation screening revealed c.451 T>C in case 1 and c.341 G>A in case 2. This is the first report of Chinese patients with INF2-related DI-CMT. The c.451 T>C mutant was responsible for both isolated FSGS and a dual phenotype of FSGS and neuropathy within one family. Intrafamilial variability can be found with the same INF2 mutation. The CNS manifestations further broadened the clinical spectrum of INF2- associated disorders. PMID:25943269

  1. Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3.

    PubMed

    Brewer, Megan H; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P; Menezes, Manoj P; Ryan, Monique M; Farrar, Michelle A; Mowat, David; Subramanian, Gopinath M; Young, Helen K; Zuchner, Stephan; Reddel, Stephen W; Nicholson, Garth A; Kennerson, Marina L

    2016-07-01

    With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

  2. Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

    PubMed Central

    Brewer, Megan H.; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P.; Ryan, Monique M.; Subramanian, Gopinath M.; Young, Helen K.; Zuchner, Stephan; Reddel, Stephen W.; Nicholson, Garth A.; Kennerson, Marina L.

    2016-01-01

    With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

  3. Examining hand dominance using dynamometric grip strength testing as evidence for overwork weakness in Charcot-Marie-Tooth disease: a systematic review and meta-analysis.

    PubMed

    Roberts-Clarke, Daniel; Fornusek, Che; Fiatarone Singh, Maria A; Burns, Joshua; Hackett, Daniel A

    2016-09-01

    This systematic review with a meta-analysis of studies was carried out to evaluate the potential of overwork weakness on the basis of grip strength of dominant and nondominant hands in individuals with Charcot-Marie-Tooth disease (CMT). Numerous electronic databases were searched from the earliest records to February 2016. Studies of any design including participants older than 18 years of age with a confirmed diagnosis of CMT that measured grip strength of both hands using dynamometric testing were eligible for inclusion. Of 12 593 articles identified following removal of duplicates, five articles fulfilled the criteria. A total of 166 participants, mostly with CMT1 or CMT2, were described from the studies included. Hand and finger pinch grip strength for the dominant compared with the nondominant hand was not statistically different. There is no definitive evidence that preferential use of the dominant hand in CMT impairs function relative to the nondominant hand. Thus, robust exercise trials of progressive resistance training are needed to understand the extent of adaptations possible and provide evidence of the safety of such regimens. PMID:27177353

  4. The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro.

    PubMed

    Lin, Tai-An; Kourteva, Galina; Hilton, Holly; Li, Hongli; Tare, Nadine S; Carvajal, Valerie; Hang, Julie S; Wei, Xin; Renzetti, Louis M

    2010-11-01

    CRTH2 is one of the prostaglandin D₂ receptors and plays a proinflammatory role in allergic diseases. Gene expression markers in whole blood induced by CRTH2 activation have not previously been reported. Using microarray analyses of 54 675 genes, we revealed modest gene expression changes in human whole blood stimulated in vitro by a selective CRTH2 agonist, DK-PGD₂. Five genes were found to exhibit 1.5- to 2.6-fold changes in expression. The expression of Charcot-Leyden crystal protein/galectin-10 (CLC/Gal-10) in particular was consistently enhanced in human whole blood stimulated by DK-PGD₂, as confirmed by quantitative real-time polymerase chain reaction analyses. DK-PGD(2)-induced increases in blood CLC/Gal-10 mRNA levels were largely attenuated by the CRTH2 antagonist CAY10471.Thus, the DK-PGD₂-induced CLC/Gal-10 mRNA level can serve as a potential marker for monitoring pharmacodynamic effects of blood exposure to CRTH2 modulating agents. PMID:20858065

  5. A novel synonymous mutation in the MPZ gene causing an aberrant splicing pattern and Charcot-Marie-Tooth disease type 1b.

    PubMed

    Corrado, L; Magri, S; Bagarotti, A; Carecchio, M; Piscosquito, G; Pareyson, D; Varrasi, C; Vecchio, D; Zonta, A; Cantello, R; Taroni, F; D'Alfonso, S

    2016-08-01

    Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy with a heterogeneous genetic background. Here, we describe two CMT1B families with a mild sensory-motor neuropathy and a novel synonymous variant (c.309G > T, p.G103G) in exon 3 of the MPZ gene. Next generation sequencing analysis on a 94 CMT gene panel showed no mutations in other disease genes. In vitro splicing assay and mRNA expression analysis indicated that the c.309T variant enhances a cryptic donor splice site at position c.304 resulting in the markedly increased expression of the r.304_448del alternative transcript in patients' cells. This transcript is predicted to encode a truncated P0 protein (p.V102Cfs11*) lacking the transmembrane domain, thus suggesting a possible haploinsufficiency mechanism for this mutation. This is the third reported synonymous MPZ variant associated with CMT1 and affecting splicing. These data confirm the functional impact of synonymous variants on MPZ splicing and their possible role as disease-causing mutations rather than silent polymorphisms. PMID:27344971

  6. Expression of a dynamin 2 mutant associated with Charcot-Marie-Tooth disease leads to aberrant actin dynamics and lamellipodia formation.

    PubMed

    Yamada, Hiroshi; Kobayashi, Kinue; Zhang, Yubai; Takeda, Tetsuya; Takei, Kohji

    2016-08-15

    Specific mutations in dynamin 2 are linked to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy. However, the effects of these mutations on dynamin function, particularly in relation to the regulation of the actin cytoskeleton remain unclear. Here, selected CMT-associated dynamin mutants were expressed to examine their role in the pathogenesis of CMT in U2OS cells. Ectopic expression of the dynamin CMT mutants 555Δ3 and K562E caused an approximately 50% decrease in serum stimulation-dependent lamellipodia formation; however, only K562E caused aberrations in the actin cytoskeleton. Immunofluorescence analysis showed that the K562E mutation resulted in the disappearance of radially aligned actin bundles and the simultaneous appearance of F-actin clusters. Live-cell imaging analyses showed F-actin polymers of decreased length assembled into immobile clusters in K562E-expressing cells. The K562E dynamin mutant colocalized with the F-actin clusters, whereas its colocalization with clathrin-coated pit marker proteins was decreased. Essentially the same results were obtained using another cell line, HeLa and NG108-15 cells. The present study is the first to show the association of dynamin CMT mutations with aberrant actin dynamics and lamellipodia, which may contribute to defective endocytosis and myelination in Schwann cells in CMT. PMID:27328317

  7. The influence of somatosensory and muscular deficits on postural stabilization: Insights from an instrumented analysis of subjects affected by different types of Charcot-Marie-Tooth disease.

    PubMed

    Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Bovi, Gabriele; Calabrese, Daniela; Aiello, Alessia; Di Sipio, Enrica; Padua, Luca; Diverio, Manuela; Pareyson, Davide; Ferrarin, Maurizio

    2015-08-01

    Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder. CMT1 is primarily demyelinating, CMT2 is primarily axonal, and CMTX1 is characterized by both axonal and demyelinating abnormalities. We investigated the role of somatosensory and muscular deficits on quiet standing and postural stabilization in patients affected by different forms of CMT, comparing their performances with those of healthy subjects. Seventy-six CMT subjects (CMT1A, CMT2 and CMTX1) and 41 healthy controls were evaluated during a sit-to-stand transition and the subsequent quiet upright posture by means of a dynamometric platform. All CMT patients showed altered balance and postural stabilization compared to controls. Multivariate analysis showed that in CMT patients worsening of postural stabilization was related to vibration sense deficit and to dorsi-flexor's weakness, while quiet standing instability was related to the reduction of pinprick sensibility and to plantar-flexor's weakness. Our results show that specific sensory and muscular deficits play different roles in balance impairment of CMT patients, both during postural stabilization and in static posture. An accurate evaluation of residual sensory and muscular functions is therefore necessary to plan for the appropriate balance rehabilitation treatment for each patient, besides the CMT type. PMID:26028275

  8. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

    PubMed

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases. PMID:25462154

  9. Pathogenic mechanisms underlying X-linked Charcot-Marie-Tooth neuropathy (CMTX6) in patients with a pyruvate dehydrogenase kinase 3 mutation.

    PubMed

    Perez-Siles, Gonzalo; Ly, Carolyn; Grant, Adrienne; Drew, Alexander P; Yiu, Eppie M; Ryan, Monique M; Chuang, David T; Tso, Shih-Chia; Nicholson, Garth A; Kennerson, Marina L

    2016-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. An X-linked form of CMT (CMTX6) is caused by a missense mutation (R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. PDK3 is one of 4 isoenzymes that negatively regulate the activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation of its first catalytic component pyruvate dehydrogenase (designated as E1). Mitochondrial PDC catalyses the oxidative decarboxylation of pyruvate to acetyl CoA and links glycolysis to the energy-producing Krebs cycle. We have previously shown the R158H mutation confers PDK3 enzyme hyperactivity. In this study we demonstrate that the increased PDK3 activity in patient fibroblasts (PDK3(R158H)) leads to the attenuation of PDC through hyper-phosphorylation of E1 at selected serine residues. This hyper-phosphorylation can be reversed by treating the PDK3(R158H) fibroblasts with the PDK inhibitor dichloroacetate (DCA). In the patient cells, down-regulation of PDC leads to increased lactate, decreased ATP and alteration of the mitochondrial network. Our findings highlight the potential to develop specific drug targeting of the mutant PDK3 as a therapeutic approach to treating CMTX6. PMID:27388934

  10. Despotism and Risk of Infanticide Influence Grizzly Bear Den-Site Selection

    PubMed Central

    Libal, Nathan S.; Belant, Jerrold L.; Leopold, Bruce D.; Wang, Guiming; Owen, Patricia A.

    2011-01-01

    Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations ( = 1,412 m, SE = 52) and steeper slopes ( = 21.9°, SE = 1.1) than adult male (elevation:  = 1,209 m, SE = 76; slope:  = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring. PMID:21935378

  11. Despotism and risk of infanticide influence grizzly bear den-site selection.

    PubMed

    Libal, Nathan S; Belant, Jerrold L; Leopold, Bruce D; Wang, Guiming; Owen, Patricia A

    2011-01-01

    Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations (mean= 1,412 m, SE = 52) and steeper slopes (mean = 21.9°, SE = 1.1) than adult male (elevation: mean = 1,209 m, SE = 76; slope: mean = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring. PMID:21935378

  12. Heading for the hills: risk avoidance drives den site selection in African wild dogs.

    PubMed

    Jackson, Craig R; Power, R John; Groom, Rosemary J; Masenga, Emmanuel H; Mjingo, Ernest E; Fyumagwa, Robert D; Røskaft, Eivin; Davies-Mostert, Harriet

    2014-01-01

    Compared to their main competitors, African wild dogs (Lycaon pictus) have inferior competitive abilities and interspecific competition is a serious fitness-limiting factor. Lions (Panthera leo) are the dominant large carnivore in African savannah ecosystems and wild dogs avoid them both spatially and temporally. Wild dog young are particularly vulnerable and suffer high rates of mortality from lions. Since lions do not utilize all parts of the landscape with an equal intensity, spatial variation in lion densities can be exploited by wild dogs both during their general ranging behaviour, but more specifically when they are confined to a den with vulnerable young. Since patches of rugged terrain are associated with lower lion densities, we hypothesized that these comparatively safe habitats should be selected by wild dogs for denning. We investigated the relationship between the distribution of 100 wild dog den sites and the occurrence of rugged terrain in four wild dog populations located in Tanzania, Zimbabwe and South Africa. A terrain ruggedness index was derived from a 90 m digital elevation model and used to map terrain ruggedness at each site. We compared characteristics of actual and potential (random) den sites to determine how wild dogs select den sites. The distributions of wild dog dens were strongly associated with rugged terrain and wild dogs actively selected terrain that was more rugged than that available on average. The likelihood of encountering lions is reduced in these habitats, minimizing the risk to both adults and pups. Our findings have important implications for the conservation management of the species, especially when assessing habitat suitability for potential reintroductions. The simple technique used to assess terrain ruggedness may be useful to investigate habitat suitability, and even predict highly suitable denning areas, across large landscapes. PMID:24918935

  13. NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.

    PubMed

    Berciano, José; Peeters, Kristien; García, Antonio; López-Alburquerque, Tomás; Gallardo, Elena; Hernández-Fabián, Arantxa; Pelayo-Negro, Ana L; De Vriendt, Els; Infante, Jon; Jordanova, Albena

    2016-02-01

    The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. By then, a working diagnosis of sporadic early onset cerebellar ataxia with peripheral neuropathy was established. Screening of mutations associated with SCA and autosomal recessive cerebellar ataxias was negative. Her son showed a mild phenotype characterized by delayed motor milestones, and lower-limb hypotonia and areflexia. Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia. PMID:26645395

  14. Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease.

    PubMed

    Bergamin, Giorgia; Boaretto, Francesca; Briani, Chiara; Pegoraro, Elena; Cacciavillani, Mario; Martinuzzi, Andrea; Muglia, Maria; Vettori, Andrea; Vazza, Giovanni; Mostacciuolo, Maria Luisa

    2014-09-01

    Charcot-Marie-Tooth (CMT) diseases include a group of clinically heterogeneous inherited neuropathies subdivided into demyelinating (CMT1), axonal (CMT2) and intermediate CMT forms. CMTs are associated with different genes, although mutations in some of these genes may cause both clinical pictures. To date, more than 50 CMT genes have been identified, but more than half of the cases are due to mutations in MFN2, MPZ, GJB1 and PMP22. The aim of this study was to estimate the frequency of disease mutations of these four genes in the axonal form of CMT in order to evaluate their effectiveness in the molecular diagnosis of CMT2 patients. A cohort of 38 CMT2 Italian subjects was screened for mutations in the MFN2, MPZ and GJB1 genes by direct sequencing and for PMP22 rearrangements using the MLPA technique. Overall, we identified 15 mutations, 8 of which were novel: 11 mutations (28.9 %) were in the MFN2 gene, 2 (5.3 %) in MPZ and 2 (5.3 %) in PMP22. No mutations were found in GJB1. Two patients showed rearrangements in the PMP22 gene, which is commonly associated with CMT1 or HNPP phenotypes thus usually not tested in CMT2 patients. By including this gene in the analysis, we reached a molecular diagnosis rate of 39.5 %, which is one of the highest reported in the literature. Our findings confirm the MFN2 gene as the most common cause of CMT2 and suggest that PMP22 rearrangements should be considered in the molecular diagnosis of CMT2 patients. PMID:24819634

  15. Mutation analysis of PMP22 in Slovak patients with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies.

    PubMed

    Resko, Peter; Radvansky, Jan; Odnogova, Zuzana; Baldovic, Marian; Minarik, Gabriel; Polakova, Helena; Palffy, Roland; Kadasi, Ludevit

    2011-12-01

    Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies are the most commonly inherited neurological disorders in humans, characterized by clinical and genetic heterogeneity. The most prevalent clinical entities belonging to this group of disorders are CMT type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A and HNPP are predominantly caused by a 1.5 Mb duplication and deletion in the chromosomal region 17p11.2, respectively, and less frequently by other mutations in the peripheral myelin protein 22 (PMP22) gene. Despite being relatively common diseases, they haven't been previously studied in the Slovak population. Therefore, the aim of this study was to identify the spectrum and frequency of PMP22 mutations in the Slovak population by screening 119 families with CMT and 2 families with HNPP for causative mutations in this gene. The copy number determination of PMP22 resulted in the detection of CMT1A duplication in 40 families and the detection of HNPP deletion in 7 families, 6 of which were originally diagnosed as CMT. Consequent mutation screening of families without duplication or deletion using dHPLC and sequencing identified 6 single base changes (3 unpublished to date), from which only c.327C>A (Cys109X) present in one family was provably causative. These results confirm the leading role of PMP22 mutation analysis in the differential diagnosis of CMT and show that the spectrum and frequency of PMP22 mutations in the Slovak population is comparable to that seen in the global population. PMID:22131320

  16. Developing an evidence-based clinical pathway for the assessment, diagnosis and management of acute Charcot Neuro-Arthropathy: a systematic review

    PubMed Central

    2013-01-01

    Background Charcot Neuro-Arthropathy (CN) is one of the more devastating complications of diabetes. To the best of the authors’ knowledge, it appears that no clinical tools based on a systematic review of existing literature have been developed to manage acute CN. Thus, the aim of this paper was to systematically review existing literature and develop an evidence-based clinical pathway for the assessment, diagnosis and management of acute CN in patients with diabetes. Methods Electronic databases (Medline, PubMed, CINAHL, Embase and Cochrane Library), reference lists, and relevant key websites were systematically searched for literature discussing the assessment, diagnosis and/or management of acute CN published between 2002-2012. At least two independent investigators then quality rated and graded the evidence of each included paper. Consistent recommendations emanating from the included papers were then fashioned in a clinical pathway. Results The systematic search identified 267 manuscripts, of which 117 (44%) met the inclusion criteria for this study. Most manuscripts discussing the assessment, diagnosis and/or management of acute CN constituted level IV (case series) or EO (expert opinion) evidence. The included literature was used to develop an evidence-based clinical pathway for the assessment, investigations, diagnosis and management of acute CN. Conclusions This research has assisted in developing a comprehensive, evidence-based clinical pathway to promote consistent and optimal practice in the assessment, diagnosis and management of acute CN. The pathway aims to support health professionals in making early diagnosis and providing appropriate immediate management of acute CN, ultimately reducing its associated complications such as amputations and hospitalisations. PMID:23898912

  17. LITAF Mutations Associated with Charcot-Marie-Tooth Disease 1C Show Mislocalization from the Late Endosome/Lysosome to the Mitochondria

    PubMed Central

    Ferreira Lacerda, Andressa; Hartjes, Emily; Brunetti, Craig R.

    2014-01-01

    Charcot-Marie-Tooth (CMT) disease is one of the most common heritable neuromuscular disorders, affecting 1 in every 2500 people. Mutations in LITAF have been shown to be causative for CMT type 1C disease. In this paper we explore the subcellular localization of wild type LITAF and mutant forms of LITAF known to cause CMT1C (T49M, A111G, G112S, T115N, W116G, L122V and P135T). The results show that LITAF mutants A111G, G112S, W116G, and T115N mislocalize from the late endosome/lysosome to the mitochondria while the mutants T49M, L122V, and P135T show partial mislocalization with a portion of the total protein present in the late endosome/lysosome and the remainder of the protein localized to the mitochondria. This suggests that different mutants of LITAF will produce differing severity of disease. We also explored the effect of the presence of mutant LITAF on wild-type LITAF localization. We showed that in cells heterozygous for LITAF, CMT1C mutants T49M and G112S are dominant since wild-type LITAF localized to the mitochondria when co-transfected with a LITAF mutant. Finally, we demonstrated how LITAF transits to the endosome and mitochondria compartments of the cell. Using Brefeldin A to block ER to Golgi transport we demonstrated that wild type LITAF traffics through the secretory pathway to the late endosome/lysosome while the LITAF mutants transit to the mitochondria independent of the secretory pathway. In addition, we demonstrated that the C-terminus of LITAF is necessary and sufficient for targeting of wild-type LITAF to the late endosome/lysosome and the mutants to the mitochondria. Together these data provide insight into how mutations in LITAF cause CMT1C disease. PMID:25058650

  18. Lack of GDAP1 Induces Neuronal Calcium and Mitochondrial Defects in a Knockout Mouse Model of Charcot-Marie-Tooth Neuropathy

    PubMed Central

    Civera-Tregón, Azahara; Yndriago, Laura; Pla-Martin, David; Zenker, Jennifer; Cuevas-Martín, Carmen; Estela, Anna; Sánchez-Aragó, María; Forteza-Vila, Jerónimo; Cuezva, José M.; Chrast, Roman; Palau, Francesc

    2015-01-01

    Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs) in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria–endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis. PMID:25860513

  19. Association of the Charcot-Marie-Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance).

    PubMed

    Boora, Ganesh K; Kulkarni, Amit A; Kanwar, Rahul; Beyerlein, Peter; Qin, Rui; Banck, Michaela S; Ruddy, Kathryn J; Pleticha, Josef; Lynch, Cynthia A; Behrens, Robert J; Züchner, Stephan; Loprinzi, Charles L; Beutler, Andreas S

    2015-10-15

    The predisposition of patients to develop polyneuropathy in response to toxic exposure may have a genetic basis. The previous study Alliance N08C1 found an association of the Charcot-Marie-Tooth disease (CMT) gene ARHGEF10 with paclitaxel chemotherapy induced peripheral neuropathy (CIPN) related to the three non-synonymous, recurrent single nucleotide variants (SNV), whereby rs9657362 had the strongest effect, and rs2294039 and rs17683288 contributed only weakly. In the present report, Alliance N08CA was chosen to attempt to replicate the above finding. N08CA was chosen because it is the methodologically most similar study (to N08C1) performed in the CIPN field to date. N08CA enrolled patients receiving the neurotoxic chemotherapy agent paclitaxel. Polyneuropathy was assessed by serial repeat administration of the previously validated patient reported outcome instrument CIPN20. A study-wide, Rasch type model was used to perform extreme phenotyping in n=138 eligible patients from which "cases" and "controls" were selected for genetic analysis of SNV performed by TaqMan PCR. A significant association of ARHGEF10 with CIPN was found under the pre-specified primary endpoint, with a significance level of p=0.024. As in the original study, the strongest association of a single SNV was seen for rs9657362 (odds ratio=3.56, p=0.018). To further compare results across the new and the previous study, a statistical "classifier" was tested, which achieved a ROC area under the curve of 0.60 for N08CA and 0.66 for N08C1, demonstrating good agreement. Retesting of the primary endpoint of N08C1 in the replication study N08CA validated the association of ARHGEF10 with CIPN. PMID:26143528

  20. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    SciTech Connect

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. ); Middleton, L.T. )

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  1. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMT1A duplication

    SciTech Connect

    Wise, C.A.; Davis, S.N.; Heju, Z.; Pentao, L.; Patel, P.I.; Lupski, J.R. ); Garcia, C.A. )

    1993-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: Measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)[sub n] repeats, and detection of a junction fragment by pulsed-field gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, the authors conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies. 61 refs., 4 figs.

  2. Prevalence and origin of De Novo duplications in Charcot-Marie-Tooth disease type 1A: First report of a De Novo duplication with a maternal origin

    SciTech Connect

    Blair, I.P.; Nash, J.; Gordon, M.J.; Nicholson, G.A.

    1996-03-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that {>=}10% of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus. 41 refs., 2 figs.

  3. Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease

    PubMed Central

    Hara, Taichi; Hashimoto, Yukiko; Akuzawa, Tomoko; Hirai, Rika; Kobayashi, Hisae; Sato, Ken

    2014-01-01

    Peripheral myelin protein 22 (PMP22) resides in the plasma membrane and is required for myelin formation in the peripheral nervous system. Many PMP22 mutants accumulate in excess in the endoplasmic reticulum (ER) and lead to the inherited neuropathies of Charcot-Marie-Tooth (CMT) disease. However, the mechanism through which PMP22 mutants accumulate in the ER is unknown. Here, we studied the quality control mechanisms for the PMP22 mutants L16P and G150D, which were originally identified in mice and patients with CMT. We found that the ER-localised ubiquitin ligase Hrd1/SYVN1 mediates ER-associated degradation (ERAD) of PMP22(L16P) and PMP22(G150D), and another ubiquitin ligase, gp78/AMFR, mediates ERAD of PMP22(G150D) as well. We also found that PMP22(L16P), but not PMP22(G150D), is partly released from the ER by loss of Rer1, which is a Golgi-localised sorting receptor for ER retrieval. Rer1 interacts with the wild-type and mutant forms of PMP22. Interestingly, release of PMP22(L16P) from the ER was more prominent with simultaneous knockdown of Rer1 and the ER-localised chaperone calnexin than with the knockdown of each gene. These results suggest that CMT disease-related PMP22(L16P) is trapped in the ER by calnexin-dependent ER retention and Rer1-mediated early Golgi retrieval systems and partly degraded by the Hrd1-mediated ERAD system. PMID:25385046

  4. Tolerability and efficacy study of P2X7 inhibition in experimental Charcot-Marie-Tooth type 1A (CMT1A) neuropathy.

    PubMed

    Sociali, Giovanna; Visigalli, Davide; Prukop, Thomas; Cervellini, Ilaria; Mannino, Elena; Venturi, Consuelo; Bruzzone, Santina; Sereda, Michael W; Schenone, Angelo

    2016-11-01

    Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy for which pharmacological treatments are not yet available. An abnormally high intracellular Ca(2+) concentration was observed in Schwann cells (SC) from CMT1A rats, caused by the PMP22-mediated overexpression of the P2X7 purinoceptor. The purpose of this study was to investigate the tolerability and therapeutic potential of a pharmacological antagonist of the P2X7 receptor (A438079) in CMT1A. A438079 ameliorated in vitro myelination of organotypic DRG cultures from CMT1A rats. Furthermore, we performed an experimental therapeutic trial in PMP22 transgenic and in wild-type rats. A preliminary dose-escalation trial showed that 3mg/kg A438079 administered via intraperitoneal injection every 24h for four weeks was well tolerated by wild type and CMT1A rats. Affected rats treated with 3mg/kg A438079 revealed a significant improvement of the muscle strength, when compared to placebo controls. Importantly, histologic analysis revealed a significant increase of the total number of myelinated axons in tibial nerves. Moreover, a significant decrease of the hypermyelination of small caliber axons and a significant increase of the frequency and diameter of large caliber myelinated axons was highlighted. An improved distal motor latencies was recorded, whereas compound muscle action potentials (CMAP) remained unaltered. A438079 reduced the SC differentiation defect in CMT1A rats. These results show that pharmacological inhibition of the P2X7 receptor is well tolerated in CMT1A rats and represents a proof-of-principle that antagonizing this pathway may correct the molecular derangements and improve the clinical phenotype in the CMT1A neuropathy. PMID:27431093

  5. Progression of motor axon dysfunction and ectopic Nav1.8 expression in a mouse model of Charcot-Marie-Tooth disease 1B.

    PubMed

    Rosberg, Mette R; Alvarez, Susana; Klein, Dennis; Nielsen, Finn Cilius; Martini, Rudolf; Levinson, S Rock; Krarup, Christian; Moldovan, Mihai

    2016-09-01

    Mice heterozygously deficient for the myelin protein P0 gene (P0+/-) develop a slowly progressing neuropathy modeling demyelinating Charcot-Marie-Tooth disease (CMT1B). The aim of the study was to investigate the long-term progression of motor dysfunction in P0+/- mice at 3, 7, 12 and 20months. By comparison with WT littermates, P0+/- showed a decreasing motor performance with age. This was associated with a progressive reduction in amplitude and increase in latency of the plantar compound muscle action potential (CMAP) evoked by stimulation of the tibial nerve at ankle. This progressive functional impairment was in contrast to the mild demyelinating neuropathy of the tibial nerve revealed by histology. "Threshold-tracking" studies showed impaired motor axon excitability in P0+/- from 3months. With time, there was a progressive reduction in threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus associated with increasing resting I/V slope and increasing strength-duration time constant. These depolarizing features in excitability in P0+/- as well as the reduced CMAP amplitude were absent in P0+/- NaV1.8 knockouts, and could be acutely reversed by selective pharmacologic block of NaV1.8 in P0+/-. Mathematical modeling indicated an association of altered passive cable properties with a depolarizing shift in resting membrane potential and increase in the persistent Na(+) current in P0+/-. Our data suggest that ectopic NaV1.8 expression precipitates depolarizing conduction failure in CMT1B, and that motor axon dysfunction in demyelinating neuropathy is pharmacologically reversible. PMID:27215377

  6. Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model

    PubMed Central

    Hatting, M; Spannbauer, M; Peng, J; Al Masaoudi, M; Sellge, G; Nevzorova, Y A; Gassler, N; Liedtke, C; Cubero, F J; Trautwein, C

    2015-01-01

    Chronic liver inflammation is a crucial event in the development and growth of hepatocellular carcinoma (HCC). Compelling evidence has shown that interleukin-6 (IL-6)/gp130-dependent signaling has a fundamental role in liver carcinogenesis. Thus, in the present study we aimed to investigate the role of gp130 in hepatocytes for the initiation and progression of HCC. Hepatocyte-specific gp130 knockout mice (gp130Δhepa) and control animals (gp130f/f) were treated with diethylnitrosamine (DEN). The role of gp130 for acute injury (0–144 h post treatment), tumor initiation (24 weeks) and progression (40 weeks) was analyzed. After acute DEN-induced liver injury we observed a reduction in the inflammatory response in gp130Δhepa animals as reflected by decreased levels of IL-6 and oncostatin M. The loss of gp130 slightly attenuated the initiation of HCC 24 weeks after DEN treatment. In contrast, 40 weeks after DEN treatment, male and female gp130Δhepa mice showed smaller tumors and reduced tumor burden, indicating a role for hepatocyte-specific gp130 expression during HCC progression. Oxidative stress and DNA damage were substantially and similarly increased by DEN in both gp130f/f and gp130Δhepa animals. However, gp130Δhepa livers revealed aberrant STAT5 activation and decreased levels of transforming growth factor-β (TGFβ), pSMAD2/3 and SMAD2, whereas phosphorylation of STAT3 at Tyr705 and Ser727 was absent. Our results indicate that gp130 deletion in hepatocytes reduces progression, but not HCC initiation in the DEN model. Gp130 deletion resulted in STAT3 inhibition but increased STAT5 activation and diminished TGF-dependent signaling. Hence, blocking gp130 in hepatocytes might be an interesting therapeutic target to inhibit the growth of HCC. PMID:25741592

  7. Treatment of Dens Invagination in a Maxillary Lateral Incisor: A Case Report

    PubMed Central

    Heydari, Azar; Rahmani, Mona

    2015-01-01

    Dens invagination is a developmental anomaly requiring specific treatment approaches. Oehler's Type III dens in dente, extends into the root and perforates at the apical area or lateral surface of the root. In this case endodontic treatment of the invaginated tooth was carried out through the central lumen of the invagination with calcium hydroxide without manipulation of the main pulp canal, thereby leaving the tooth vital. The 18-month follow-up examinations were indicative of treatment success; the periapical lesion resolved completely and the tooth remained vital. Conclusion: Information about the three dimensional anatomy of the teeth especially those with an abnormality is necessary for a successful treatment. PMID:26213545

  8. Mapping polar bear maternal denning habitat in the National Petroleum Reserve -- Alaska with an IfSAR digital terrain model

    USGS Publications Warehouse

    Durner, George M.; Simac, Kristin; Amstrup, Steven C.

    2013-01-01

    The National Petroleum Reserve–Alaska (NPR-A) in northeastern Alaska provides winter maternal denning habitat for polar bears (Ursus maritimus) and also has high potential for recoverable hydrocarbons. Denning polar bears exposed to human activities may abandon their dens before their young are able to survive the severity of Arctic winter weather. To ensure that wintertime petroleum activities do not threaten polar bears, managers need to know the distribution of landscape features in which maternal dens are likely to occur. Here, we present a map of potential denning habitat within the NPR-A. We used a fine-grain digital elevation model derived from Interferometric Synthetic Aperture Radar (IfSAR) to generate a map of putative denning habitat. We then tested the map’s ability to identify polar bear denning habitat on the landscape. Our final map correctly identified 82% of denning habitat estimated to be within the NPR-A. Mapped denning habitat comprised 19.7 km2 (0.1% of the study area) and was widely dispersed. Though mapping denning habitat with IfSAR data was as effective as mapping with the photogrammetric methods used for other regions of the Alaskan Arctic coastal plain, the use of GIS to analyze IfSAR data allowed greater objectivity and flexibility with less manual labor. Analytical advantages and performance equivalent to that of manual cartographic methods suggest that the use of IfSAR data to identify polar bear maternal denning habitat is a better management tool in the NPR-A and wherever such data may be available.

  9. First evidence of gregarious denning in opossums (Didelphimorphia, Didelphidae), with notes on their social behaviour

    PubMed Central

    Astúa, Diego; Carvalho, Rafael A.; Maia, Paula F.; Magalhães, Arthur R.; Loretto, Diogo

    2015-01-01

    The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother–pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena. PMID:26085500

  10. "Where's the Bear? Over There!"--Creative Thinking and Imagination in Den Making

    ERIC Educational Resources Information Center

    Canning, Natalie

    2013-01-01

    This small scale research project examines opportunities for creative thinking and imagination through den making in a rural private day nursery with its own woodland area on the borders of England and Wales in the UK. The research is underpinned by sociocultural theory and is an ethnographic study of non-participant observations of children aged…

  11. The Influence of the Outdoor Environment: Den-Making in Three Different Contexts

    ERIC Educational Resources Information Center

    Canning, Natalie

    2010-01-01

    This small-scale research examined den-making in three different settings in the UK. The research consisted of non-participant, narrative observations of children aged between 3- and 5-years and early years practitioners involved in supporting them in their play. Content analysis revealed common themes: the impact of the environment on the way…

  12. First report of captive New Guinea dingo (Canis dingo hallstromi) den-digging and parental behavior.

    PubMed

    Koler-Matznick, Janice; Stinner, Mindy

    2011-01-01

    New Guinea dingoes (NGDs) (Canis dingo hallstromi; Troughton [1957] Proc Roy Soc new South Wells 1955-1956:93-94) have been kept in zoos since 1956. Almost nothing is known of their wild behavior. These observations of a captive pair are the first documentation of natal den-digging and parental behavior for this taxon. The main den, excavated near the top of a 1.5 m hill, consisted of a rounded chamber about 50.8 cm deep, with an entrance about 30.5 cm high and 40.6 cm wide. The dam frequently moved the pups from the natal den to secondary locations for short periods during the day and then back to the den, starting when the pups were 2 weeks old. When the pups were between 5 and 12 weeks of age, both parents regularly regurgitated for them. The sire expressed escalating threat behavior toward the male pup starting when the pup was 5 months old, and the female began threatening the female pups at about 6 months of age. Rejection of same-sex offspring is usual for captive NGDs as the next breeding season approaches. PMID:21154450

  13. Effect of age on respiratory carcinogenesis with diethyl-nitrosamine (DEN) in hamsters

    SciTech Connect

    Stinson, S.F.; Saffiotti, U.

    1986-03-01

    Groups of male and female Syrian golden hamsters were given 12 weekly s.c. injections of 10 mg/kg DEN beginning at 1 day (85 animals) or 8 weeks (70 animals) of age, and were held for lifetime observation. In hamsters receiving DEN from birth, the first respiratory tumors were observed at 15 experimental weeks; all animals were dead by 66 weeks with a 99% respiratory tumor incidence. Of these hamster, 87% developed carcinomas or adenomas in the nasal cavities, 75% papillomas of the trachea, larynx or extrapulmonary bronchi and 7% adenomas or adenocarcinomas of the peripheral lung. Hamsters given DEN from 8 weeks of age first showed respiratory tumors after 25 weeks with a 96% incidence by 62 weeks when all had died. Of these hamsters, 24% developed carcinomas or adenomas in the nasal cavities, 91% papillomas of the trachea, larynx or bronchi, and 9% adenomas or adenocarcinomas of the peripheral lung. In comparison, the nasal tumors in the first group were more anaplastic and invaded the brain more frequently than in the second. These results indicate that the nasal mucosa of newborns is more sensitive to carcinogenesis with DEN than is that of adults, while there appears to be little age-related susceptibility of the epithelium of the airways or lung. A serial sacrifice experiment is currently under way to study the cells of origin of the various tumors using immuno-histochemical and electron microscopic techniques.

  14. First evidence of gregarious denning in opossums (Didelphimorphia, Didelphidae), with notes on their social behaviour.

    PubMed

    Astúa, Diego; Carvalho, Rafael A; Maia, Paula F; Magalhães, Arthur R; Loretto, Diogo

    2015-06-01

    The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother-pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena. PMID:26085500

  15. DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions.

    PubMed

    Karyala, Prashanthi; Metri, Rahul; Bathula, Christopher; Yelamanchi, Syam K; Sahoo, Lipika; Arjunan, Selvam; Sastri, Narayan P; Chandra, Nagasuma

    2016-09-01

    Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue-human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue-human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/). PMID:27618709

  16. The Dens: Normal Development, Developmental Variants and Anomalies, and Traumatic Injuries.

    PubMed

    O'Brien, William T; Shen, Peter; Lee, Paul

    2015-01-01

    Accurate interpretation of cervical spine imagining can be challenging, especially in children and the elderly. The biomechanics of the developing pediatric spine and age-related degenerative changes predispose these patient populations to injuries centered at the craniocervical junction. In addition, congenital anomalies are common in this region, especially those associated with the axis/dens, due to its complexity in terms of development compared to other vertebral levels. The most common congenital variations of the dens include the os odontoideum and a persistent ossiculum terminale. At times, it is necessary to distinguish normal development, developmental variants, and developmental anomalies from traumatic injuries in the setting of acute traumatic injury. Key imaging features are useful to differentiate between traumatic fractures and normal or variant anatomy acutely; however, the radiologist must first have a basic understanding of the spectrum of normal developmental anatomy and its anatomic variations in order to make an accurate assessment. This review article attempts to provide the basic framework required for accurate interpretation of cervical spine imaging with a focus on the dens, specifically covering the normal development and ossification of the dens, common congenital variants and their various imaging appearances, fracture classifications, imaging appearances, and treatment options. PMID:26199787

  17. The Dens: Normal Development, Developmental Variants and Anomalies, and Traumatic Injuries

    PubMed Central

    O’Brien, William T; Shen, Peter; Lee, Paul

    2015-01-01

    Accurate interpretation of cervical spine imagining can be challenging, especially in children and the elderly. The biomechanics of the developing pediatric spine and age-related degenerative changes predispose these patient populations to injuries centered at the craniocervical junction. In addition, congenital anomalies are common in this region, especially those associated with the axis/dens, due to its complexity in terms of development compared to other vertebral levels. The most common congenital variations of the dens include the os odontoideum and a persistent ossiculum terminale. At times, it is necessary to distinguish normal development, developmental variants, and developmental anomalies from traumatic injuries in the setting of acute traumatic injury. Key imaging features are useful to differentiate between traumatic fractures and normal or variant anatomy acutely; however, the radiologist must first have a basic understanding of the spectrum of normal developmental anatomy and its anatomic variations in order to make an accurate assessment. This review article attempts to provide the basic framework required for accurate interpretation of cervical spine imaging with a focus on the dens, specifically covering the normal development and ossification of the dens, common congenital variants and their various imaging appearances, fracture classifications, imaging appearances, and treatment options. PMID:26199787

  18. Systemic inflammation disrupts oligodendrocyte gap junctions and induces ER stress in a model of CNS manifestations of X-linked Charcot-Marie-Tooth disease.

    PubMed

    Olympiou, Margarita; Sargiannidou, Irene; Markoullis, Kyriaki; Karaiskos, Christos; Kagiava, Alexia; Kyriakoudi, Styliana; Abrams, Charles K; Kleopa, Kleopas A

    2016-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is a common form of inherited neuropathy resulting from different mutations affecting the gap junction (GJ) protein connexin32 (Cx32). A subset of CMT1X patients may additionally present with acute fulminant CNS dysfunction, typically triggered by conditions of systemic inflammation and metabolic stress. To clarify the underlying mechanisms of CNS phenotypes in CMT1X we studied a mouse model of systemic inflammation induced by lipopolysaccharide (LPS) injection to compare wild type (WT), connexin32 (Cx32) knockout (KO), and KO T55I mice expressing the T55I Cx32 mutation associated with CNS phenotypes. Following a single intraperitoneal LPS or saline (controls) injection at the age of 40-60 days systemic inflammatory response was documented by elevated TNF-α and IL-6 levels in peripheral blood and mice were evaluated 1 week after injection. Behavioral analysis showed graded impairment of motor performance in LPS treated mice, worse in KO T55I than in Cx32 KO and in Cx32 KO worse than WT. Iba1 immunostaining revealed widespread inflammation in LPS treated mice with diffusely activated microglia throughout the CNS. Immunostaining for the remaining major oligodendrocyte connexin Cx47 and for its astrocytic partner Cx43 revealed widely reduced expression of Cx43 and loss of Cx47 GJs in oligodendrocytes. Real-time PCR and immunoblot analysis indicated primarily a down regulation of Cx43 expression with secondary loss of Cx47 membrane localization. Inflammatory changes and connexin alterations were most severe in the KO T55I group. To examine why the presence of the T55I mutant exacerbates pathology even more than in Cx32 KO mice, we analyzed the expression of ER-stress markers BiP, Fas and CHOP by immunostaining, immunoblot and Real-time PCR. All markers were increased in LPS treated KO T55I mice more than in other genotypes. In conclusion, LPS induced neuroinflammation causes disruption of the main astrocyte

  19. Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells.

    PubMed

    Horn, Michael; Baumann, Reto; Pereira, Jorge A; Sidiropoulos, Páris N M; Somandin, Christian; Welzl, Hans; Stendel, Claudia; Lühmann, Tessa; Wessig, Carsten; Toyka, Klaus V; Relvas, João B; Senderek, Jan; Suter, Ueli

    2012-12-01

    Studying the function and malfunction of genes and proteins associated with inherited forms of peripheral neuropathies has provided multiple clues to our understanding of myelinated nerves in health and disease. Here, we have generated a mouse model for the peripheral neuropathy Charcot-Marie-Tooth disease type 4H by constitutively disrupting the mouse orthologue of the suspected culprit gene FGD4 that encodes the small RhoGTPase Cdc42-guanine nucleotide exchange factor Frabin. Lack of Frabin/Fgd4 causes dysmyelination in mice in early peripheral nerve development, followed by profound myelin abnormalities and demyelination at later stages. At the age of 60 weeks, this was accompanied by electrophysiological deficits. By crossing mice carrying alleles of Frabin/Fgd4 flanked by loxP sequences with animals expressing Cre recombinase in a cell type-specific manner, we show that Schwann cell-autonomous Frabin/Fgd4 function is essential for proper myelination without detectable primary contributions from neurons. Deletion of Frabin/Fgd4 in Schwann cells of fully myelinated nerve fibres revealed that this protein is not only required for correct nerve development but also for accurate myelin maintenance. Moreover, we established that correct activation of Cdc42 is dependent on Frabin/Fgd4 function in healthy peripheral nerves. Genetic disruption of Cdc42 in Schwann cells of adult myelinated nerves resulted in myelin alterations similar to those observed in Frabin/Fgd4-deficient mice, indicating that Cdc42 and the Frabin/Fgd4-Cdc42 axis are critical for myelin homeostasis. In line with known regulatory roles of Cdc42, we found that Frabin/Fgd4 regulates Schwann cell endocytosis, a process that is increasingly recognized as a relevant mechanism in peripheral nerve pathophysiology. Taken together, our results indicate that regulation of Cdc42 by Frabin/Fgd4 in Schwann cells is critical for the structure and function of the peripheral nervous system. In particular, this

  20. Importance of Native Grassland Habitat for Den-Site Selection of Indian Foxes in a Fragmented Landscape

    PubMed Central

    Punjabi, Girish Arjun; Chellam, Ravi; Vanak, Abi Tamim

    2013-01-01

    Fragmentation of native habitats is now a ubiquitous phenomenon affecting wildlife at various scales. We examined selection of den-sites (n = 26) by Indian foxes (Vulpes bengalensis) in a highly modified short-grassland landscape in central India (Jan-May, 2010). At the scale of the home-range, defined by an 800 m circular buffer around den sites, we examined the effect of land-cover edges and roads on selection of sites for denning using a distance-based approach. At the smaller den-area scale, defined by a 25 m x 25 m plot around den and paired available sites, the effect of microhabitat characteristics was examined using discrete-choice models. Indian foxes selected den-sites closer to native grasslands (t = -9.57, P < 0.001) and roads (t = -2.04, P = 0.05) than random at the home-range scale. At the smaller scale, abundance of rodents and higher visibility increased the odds of selection of a site by eight and four times respectively, indicating resource availability and predator avoidance to be important considerations for foxes. Indian foxes largely chose to den in human-made structures, indicated by the proportion of dens found in earthen bunds (0.69) and boulder piles (0.27) in the study area. With agricultural expansion and human modification threatening native short-grassland habitats, their conservation and effective management in human-dominated landscapes will benefit the Indian fox. The presence of some human-made structures within native grasslands would also be beneficial for this den-dependent species. We suggest future studies examine the impact of fragmentation and connectivity of grasslands on survival and reproductive success of the Indian fox. PMID:24098494

  1. Combined endodontic and surgical management of a mandibular lateral incisor with a rare type of dens invaginatus.

    PubMed

    Chaniotis, Antonios M; Tzanetakis, Giorgos N; Kontakiotis, Evangelos G; Tosios, Konstantinos I

    2008-10-01

    Dens invaginatus is a developmental malformation of teeth that most commonly affects permanent maxillary lateral incisors. Presence of dens invaginatus in mandibular permanent teeth is relatively rare. The purpose of this report is to describe the combined nonsurgical and surgical management of a mandibular lateral incisor associated with a rare type of dens invaginatus. Pulp involvement of the malformed tooth, periapical abscess, and severe periodontal destruction were observed. The signs (sinus tracts) and symptoms ceased after completion of the treatment. Satisfactory healing of the periradicular lesion was observed at the 6-month and 2-year follow-up examinations. PMID:18793933

  2. Expression of the denV gene of coliphage T4 in UV-sensitive rad mutants of Saccharomyces cerevisiae

    SciTech Connect

    Valerie, K.; Fronko, G.; Henderson, E.E.; de Riel, J.K.

    1986-10-01

    A plasmid containing the denV gene from bacteriophage T4, under the control of the yeast alcohol dehydrogenase I (ADC1) promoter, conferred a substantial increase in UV resistance in the UV-sensitive Saccharomyces cerevisiae mutants rad1-2 and rad3-2. The UV resistance of the denV+ yeast cells was cell cycle dependent and correlated well with the level of the denV gene product as measured by immunoblotting and by a photoreversal assay for pyrimidine dimer-DNA glycosylase activity.

  3. HyDEn: A Hybrid Steganocryptographic Approach for Data Encryption Using Randomized Error-Correcting DNA Codes

    PubMed Central

    Regoui, Chaouki; Durand, Guillaume; Belliveau, Luc; Léger, Serge

    2013-01-01

    This paper presents a novel hybrid DNA encryption (HyDEn) approach that uses randomized assignments of unique error-correcting DNA Hamming code words for single characters in the extended ASCII set. HyDEn relies on custom-built quaternary codes and a private key used in the randomized assignment of code words and the cyclic permutations applied on the encoded message. Along with its ability to detect and correct errors, HyDEn equals or outperforms existing cryptographic methods and represents a promising in silico DNA steganographic approach. PMID:23984392

  4. HyDEn: a hybrid steganocryptographic approach for data encryption using randomized error-correcting DNA codes.

    PubMed

    Tulpan, Dan; Regoui, Chaouki; Durand, Guillaume; Belliveau, Luc; Léger, Serge

    2013-01-01

    This paper presents a novel hybrid DNA encryption (HyDEn) approach that uses randomized assignments of unique error-correcting DNA Hamming code words for single characters in the extended ASCII set. HyDEn relies on custom-built quaternary codes and a private key used in the randomized assignment of code words and the cyclic permutations applied on the encoded message. Along with its ability to detect and correct errors, HyDEn equals or outperforms existing cryptographic methods and represents a promising in silico DNA steganographic approach. PMID:23984392

  5. CheckDen, a program to compute quantum molecular properties on spatial grids.

    PubMed

    Pacios, Luis F; Fernandez, Alberto

    2009-09-01

    CheckDen, a program to compute quantum molecular properties on a variety of spatial grids is presented. The program reads as unique input wavefunction files written by standard quantum packages and calculates the electron density rho(r), promolecule and density difference function, gradient of rho(r), Laplacian of rho(r), information entropy, electrostatic potential, kinetic energy densities G(r) and K(r), electron localization function (ELF), and localized orbital locator (LOL) function. These properties can be calculated on a wide range of one-, two-, and three-dimensional grids that can be processed by widely used graphics programs to render high-resolution images. CheckDen offers also other options as extracting separate atom contributions to the property computed, converting grid output data into CUBE and OpenDX volumetric data formats, and perform arithmetic combinations with grid files in all the recognized formats. PMID:19447056

  6. Misconceptions in Van den Broeck's representation of misconceptions about learning disability research.

    PubMed

    Willson, Victor L; Reynolds, Cecil R

    2002-01-01

    The methods and conclusions of Van den Broeck (in this issue) are evaluated from two perspectives: (a) statistical considerations and (b) theoretical models of IQ and achievement, specifically reading achievement. We consider the statistical model proposed by Van den Broeck for the regression-based discrepancy model (RDM) to be either irrelevant or conceptually inconsistent with current models of IQ and achievement. The resulting simulation produced exemplar cases that are not realistic in terms of practice. The theoretical representations of IQ and achievement were, in our understanding, inconsistent with contemporary models of either. We suggest that acceptable models support the use of the RDM as it has been proposed by us and by others as one component of the determination of the presence or absence of a learning disability. PMID:15493317

  7. Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A

    SciTech Connect

    Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N.

    1996-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.

  8. Excision repair characteristics of denV-transformed xeroderma pigmentosum cells.

    PubMed

    Ley, R D; Applegate, L A; de Riel, J K; Henderson, E E

    1989-03-01

    Introduction of the denV gene of phage T4, encoding the pyrimidine dimer-specific endonuclease V, into xeroderma pigmentosum cells XP12RO(M1) was reported to result in partial restoration of colony-forming ability and excision repair synthesis. We have further characterized 3 denV-transformed XP clones in terms of rates of excision of pyrimidine dimers and size of the resulting resynthesized regions following exposure to 100 J/m2 from an FS-40 sunlamp. In the denV-transformed XP cells we observed 50% dimer removal within 3-6 h after UV exposure as compared to no measurable removal in the XP12RO(M1) line and 50% dimer excision after 18 h in the GM637A human, control cells. Dimer removal was assayed with Micrococcus luteus UV-endonuclease in conjunction with sedimentation of treated DNA in alkaline sucrose gradients. The size of the resulting repaired regions was determined by the bromouracil photolysis technique. Based on the photolytic sensitivity of DNA repaired in the presence of bromodeoxyuridine, we calculated that the excision of a dimer in the GM637A cells appears to be accompanied by the resynthesis of a region approximately 95 nucleotides in length. Conversely, the resynthesized regions in the denV-transformed clones were considerably smaller and were estimated to be between 13 and 18 nucleotides in length. These results may indicate that either the endonuclease that initiated dimer repair dictated the size of the resynthesized region or that the long-patch repair observed in the normal cells resulted from the repair of non-dimer DNA lesions. PMID:2918865

  9. Case study of total energy system, Sher-Den Mall, Sherman, Texas

    SciTech Connect

    Myrtetus, G.B.; Levey, M.D.

    1980-12-01

    The Sher-Den Mall shopping center receives all of its electricity and heating and cooling energy from a total energy plant located within the shopping center proper. Four engine-generator units are fueled primarily by natural gas, with some fuel oil use. The following are presented: initial corporate planning, investigation, and feasibility studies; a description of the total energy system; capital costs; plant operations, and revenue structure. Tables, figures, exhibits, and equipment specification lists are presented. (MHR)

  10. Technische Systeme für den Herzersatz und die Herzunterstützung

    NASA Astrophysics Data System (ADS)

    Schöb, Reto; Loree, Howard M.

    Herzkrankheiten verursachen allein in den Vereinigten Staaten jährlich mehr als 700’000 Todesfälle. Ungefähr 3 Millionen Patienten in den U.S.A. leiden gemäss der American Heart Association (AHA) und dem National Heart, Lung and Blood Institute (NHLBI) an kongestivem Herzversagen (Congestive Heart Failure, CHF), welches eine chronische, sehr entkräftende und degenerative Krankheit ist: Das Herz ist dabei unfähig, hinreichend Blut zu den Organen des Körpers zu pumpen. Über 400’000 Fälle von CHF werden jedes Jahr diagnostiziert. Ähnliche Zahlen werden für Europa und Japan zusammen geschätzt. Basierend auf Daten vom AHA und NHLBI beträgt die fünfjährige Überlebensrate für CHF-Patienten lediglich etwa 50% [1]. 70’000-120’000 dieser Patienten könnten von einer Herzverpflanzung profitieren. 1999 wurden in den USA aber nur 2185 Herztransplantationen durchgeführt während die Warteliste über 4000 Patienten beträgt [2]. Ein akuter Mangel an Spenderherzen und die enormen Kosten (250’000-400’000 USD pro Patient) sind die begrenzenden Faktoren für Herztransplantationen [3]. Dies bedeutet, dass eine riesige Anzahl von Patienten durch ein zuverlässiges und verschleissfreies, nichtthrombotisches, total implantierbares, künstliches Herz gerettet werden könnten. Bis heute jedoch kein derartiges Implantat kommerziell verfügbar.

  11. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.

    PubMed

    Mannil, Manoj; Solari, Alessandra; Leha, Andreas; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Walter, Maggie C; Rautenstrauss, Bernd; Schnizer, Tuuli J; Schenone, Angelo; Seeman, Pavel; Kadian, Chandini; Schreiber, Olivia; Angarita, Natalia G; Fabrizi, Gian Maria; Gemignani, Franco; Padua, Luca; Santoro, Lucio; Quattrone, Aldo; Vita, Giuseppe; Calabrese, Daniela; Young, Peter; Laurà, Matilde; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Shy, Michael E; Reilly, Mary M; Pareyson, Davide; Sereda, Michael W

    2014-11-01

    This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures - the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry - further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials. PMID:25085517

  12. [Failed compression osteosynthesis of the dens axis treated by anterior C1-C2 transarticular stabilisation. Case report].

    PubMed

    Kočiš, J; Kelbl, M

    2011-01-01

    We describe the case of an 80-year-old female patient who had undergone anterior C1-C2 transarticular stabilisation and was subsequently treated by the triple-screw method for failed compression osteosynthesis of a AO type III dens axis fracture. Key words: dens axis, upper cervical spine fracture, eldery, triple screw technique, anterior transarticular C1-C2 stabilisation. PMID:21729645

  13. Catalogue of polar bear (Ursus maritimus) maternal den locations in the Beaufort Sea and neighboring regions, Alaska, 1910-2010

    USGS Publications Warehouse

    Durner, George M.; Fischbach, Anthony S.; Amstrup, Steven C.; Douglas, David C.

    2010-01-01

    This report presents data on the approximate locations and methods of discovery of 392 polar bear (Ursus maritimus) maternal dens found in the Beaufort Sea and neighboring regions between 1910 and 2010 that are archived by the U.S. Geological Survey, Alaska Science Center, Anchorage, Alaska. A description of data collection methods, biases associated with collection method, primary time periods, and spatial resolution are provided. Polar bears in the Beaufort Sea and nearby regions den on both the sea ice and on land. Standardized VHF surveys and satellite radio telemetry data provide a general understanding of where polar bears have denned in this region over the past 3 decades. Den observations made during other research activities and anecdotal reports from other government agencies, coastal residents, and industry personnel also are reported. Data on past polar bear maternal den locations are provided to inform the public and to provide information for natural resource agencies in planning activities to avoid or minimize interference with polar bear maternity dens.

  14. [Charcot arthropathy and diabetic foot].

    PubMed

    López-Gavito, E; Parra-Téllez, P; Vázquez-Escamilla, J

    2016-01-01

    Diabetes mellitus is a major chronic degenerative disease, which currently is taking on alarming proportions in the population of our country. Neuropathic arthropathy is one of the most interesting degenerative joint disorders and increasingly common within the orthopedic pathology. It is defined as a progressive degenerative arthropathy, chronic and affecting one or more peripheral joints, and develops as a result of the lack of sensory perception normal in the innervation of joints. As a result the joints of the feet are subjected to trauma and repetitive injury causing a neurotraumatic effect with progressive damage to the joints of the hindfoot, midfoot and forefoot. Diagnosis includes a proper medical history, careful examination of the affected limb, conventional X-ray, scintigraphy, computed tomography and magnetic resonance imaging in some cases. Conservative treatment includes: drugs, rest of the affected limb, and the use of appliances like total-contact cast, orthotics or special shoes. Surgical treatment depends on the stage of the disease, and may require one or more surgical procedures, in order to achieve a full foot plantar support to prevent ulcers. One of the surgeries performed most often is the fusion of damaged joints. Surgery must be performed only in the coalescence phase of the disease, using internal, or external fixation or both. PMID:27627777

  15. Charcot-Marie-Tooth Disease

    MedlinePlus

    ... 2,500 people. CMT affects your peripheral nerves. Peripheral nerves carry movement and sensation signals between the brain and spinal cord and the rest of the body. Symptoms usually start around the teen years. Foot problems such as high arches or hammertoes can ...

  16. Charcot-Marie-Tooth disease

    MedlinePlus

    ... nerve dysfunction; Neuropathy - peroneal (hereditary); Hereditary motor and sensory neuropathy ... Saunders; 2012:chap 76. Sarnat HB. Hereditary motor-sensory neuropathies. In: Kliegman RM, Stanton BF, St Geme ...

  17. Charcot-Marie-Tooth Disease

    MedlinePlus

    ... States. CMT, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, comprises a ... and spinal cord and supply the muscles and sensory organs in the limbs. A typical feature includes ...

  18. Charcot-Marie-Tooth Disease

    MedlinePlus

    ... a different neuropathy distinct from CMT1A called hereditary neuropathy with predisposition to pressure palsy (HNPP) is caused ... PMP-22 gene result in episodic, recurrent demyelinating neuropathy. CMT1B is an autosomal dominant disease caused by ...

  19. Protective effect of Punica granatum peel and Vitis vinifera seeds on DEN-induced oxidative stress and hepatocellular damage in rats.

    PubMed

    Kumar, Ashok K; Vijayalakshmi, K

    2015-01-01

    This study was designed to find out the efficacy of ethanol extracts of Punica granatum peel and Vitis vinifera seeds on diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular damage in Wistar rats. Rats were divided into four groups. The first group served as normal control, and the second group received DEN at a dose of 200 mg/kg body weight by single intraperitoneal administration. The third one received DEN as in DEN-treated group and co-treated with 400 mg/kg P. granatum peel extract. The final group also received DEN and co-treated with 400 mg/kg V. vinifera seed extract. DEN administration to rats resulted in significantly elevated levels of serum SGPT, SGOT, ALP, and GGT which is indicative of hepatocellular damage. DEN-induced oxidative stress was confirmed by elevated levels of lipid peroxides and decreased activities of superoxide dismutase, catalase, and glutathione peroxidase in the serum and liver tissues. The status of non-enzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione were also found to be decreased in serum and tissues of DEN-administered rats. Co-treatment with the P. granatum peel and V. vinifera seed extracts orally for 12 weeks significantly reversed the DEN-induced alterations in the serum and liver tissues. PMID:25304489

  20. Dens Axis Vertebroplasty Combined with C 3 Vertebral Body Arthroplasty. Case Study.

    PubMed

    Guzik, Grzegorz

    2015-01-01

    Spinal tumors are most commonly located in the thoracic and lumbar spine, less commonly in the cervical section of the spine. Diagnosis is usually late and surgery is not radical. Myeloma is one of the most frequent metastatic spinal tumors. Surgical treatment of osteolytic lesions in the spine involves posterior and anterior stabilization, full or partial tumorectomies as well as decompression of neural structures. Bone cement injection has been increasingly used in plastic surgery of vertebral bodies and is most frequently performed percutaneously in the thoracic and lumbar spine. Cervical vertebroplasty can be performed both percutaneously and after anterior exposure of the spine. The dens axis can also be approached transorally. The safest surgical technique seems to be the Southwick approach, which allows exposure of the spine at C2-Th2 and, if necessary, can be extended both proximally and distally. Cemented cervical vertebroplasty, especially dens axis vertebroplasty, shows good results, yet this technique has rarely been described in the literature. It has the advantage of early patient mobility and little limitation of motion of the spine. Cervical vertebroplasty can be successfully combined with other procedures utilizing the same surgical approach in a single-stage operation. Post-resection anterior stabilization of the cervical spine with plates and vertebral body prosthesis allows for good stability of the spine and makes it possible to restore the spinal axis and curvatures. PMID:26468178

  1. Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

    2010-03-01

    Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9. PMID:20084675

  2. Wie verstehen Schülerinnen und Schüler den Begriff der Unendlichkeit?

    NASA Astrophysics Data System (ADS)

    Schimmöller, Tabea

    Wie Hilbert bereits feststellte, wirkt die Idee der Unendlichkeit, wie keine andere, schon seit Zeiten sehr anregend und fruchtbar auf den Verstand und bewegt das Gemüt der Menschen. Der Begriff der Unendlichkeit bedarf aber auch, wie kein anderer, der Aufklärung, denn mit ihm eröffnet sich ein weites Feld, welches nicht nur aus vielen verschiedenen Definitionen besteht, sondern auch aus völlig unterschiedlichen Disziplinen. Physiker suchen immer dringender nach einer "Theorie für Alles" oder einer "Weltformel", Kosmologen beschäftigen sich unter anderem mit der Ewigkeit des Universums, Theologen interessiert eher die Unendlichkeit Gottes, Philosophen diskutieren unter anderem Grenzfragen zwischen Naturwissenschaft und Philosophie und die Mathematiker versuchen den Paradoxien des Unendlichen einen Sinn zu geben. Und so wird ersichtlich, dass nichts abstrakter ist als das Unendliche: Obwohl die Unendlichkeit für die unterschiedlichsten Wissenschaften von großer Bedeutung ist, "[ist] in der Wirklichkeit das Unendliche nirgends zu finden, [egal] was für Erfahrungen und Beobachtungen und welcherlei Wissenschaft wir auch heranziehen".

  3. Management of Oehler's Type III Dens Invaginatus Using Cone Beam Computed Tomography.

    PubMed

    Ranganathan, Jaya; Rangarajan Sundaresan, Mohan Kumar; Ramasamy, Srinivasan

    2016-01-01

    Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT) are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler's classification (1957) for Dens Invaginatus (DI) into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler's Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation. PMID:27069697

  4. Management of Oehler's Type III Dens Invaginatus Using Cone Beam Computed Tomography

    PubMed Central

    Ranganathan, Jaya; Rangarajan Sundaresan, Mohan Kumar; Ramasamy, Srinivasan

    2016-01-01

    Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT) are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler's classification (1957) for Dens Invaginatus (DI) into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler's Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation. PMID:27069697

  5. Structure of a Complex between Nedd8 and the Ulp/Senp Protease Family Member Den1

    SciTech Connect

    Reverter, David; Wu, Kenneth; Erdene, Tudeviin Gan; Pan, Zhen-Qiang; Wilkinson, Keith D.; Lima, Christopher D.

    2010-07-20

    The Nedd8 conjugation pathway is conserved from yeast to humans and is essential in many organisms. Nedd8 is conjugated to cullin proteins in a process that alters SCF E3 ubiquitin ligase activity, and it is presumed that Nedd8 deconjugation would reverse these effects. We now report the X-ray structures of the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8 aldehyde, thus revealing a model for the tetrahedral transition state intermediate generated during proteolysis. Although Den1 is closely related to the SUMO-specific protease family (Ulp/Senp family), structural analysis of the interface suggests determinants involved in Nedd8 selectivity by Den1 over other ubiquitin-like family members and suggests how the Ulp/Senp architecture has been modified to interact with different ubiquitin-like modifiers.

  6. Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication

    PubMed Central

    Ichiyama, Koji; Lee, Ching Hua; Eyo, Zhi Wen; Ebina, Hirotaka; Takahashi, Hirotaka; Takahashi, Chikako; Tan, Beng Hui; Hishiki, Takayuki; Ohba, Kenji; Matsuyama, Toshifumi; Koyanagi, Yoshio; Tan, Yee-Joo; Sawasaki, Tatsuya; Chu, Justin Jang Hann; Vasudevan, Subhash G.; Sano, Kouichi; Yamamoto, Naoki

    2016-01-01

    Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells. PMID:26735137

  7. Remote identification of potential polar bear maternal denning habitat in northern Alaska using airborne LiDAR

    NASA Astrophysics Data System (ADS)

    Jones, B. M.; Durner, G. M.; Stoker, J.; Shideler, R.; Perham, C.; Liston, G. E.

    2013-12-01

    Polar bear (Ursus maritimus) populations throughout the Arctic are being threatened by reductions in critical sea ice habitat. Throughout much of their range, polar bears give birth to their young in winter dens that are excavated in snowdrifts. New-born cubs, which are unable to survive exposure to Arctic winter weather, require 2-3 months of the relatively warm, stable, and undisturbed environment of the den for their growth. In the southern Beaufort Sea (BS), polar bears may den on the Alaskan Arctic Coastal Plain (ACP).The proportion of dens occurring on land has increased because of reductions in stable multi-year ice, increases in unconsolidated ice, and lengthening of the fall open-water period. Large portions of the ACP are currently being used for oil and gas activities and proposed projects will likely expand this footprint in the near future. Since petroleum exploration and development activities increase during winter there is the potential for human activities to disturb polar bears in maternal dens. Thus, maps showing the potential distribution of terrestrial denning habitat can help to mitigate negative interactions. Prior remote sensing efforts have consisted of manual interpretation of vertical aerial photography and automated classification of Interferometric Synthetic Aperture (IfSAR) derived digital terrain models (DTM) (5-m spatial resolution) focused on the identification of snowdrift forming landscape features. In this study, we assess the feasibility of airborne Light Detection and Ranging (LiDAR) data (2-m spatial resolution) for the automated classification of potential polar bear maternal denning habitat in a 1,400 km2 area on the central portion of the ACP. The study region spans the BS coast from the Prudhoe Bay oilfield in the west to near Point Thompson in the east and extends inland from 10 to 30 km. Approximately 800 km2 of the study area contains 19 known den locations, 51 field survey sites with information on bank height and

  8. Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family.

    PubMed

    Leal, Alejandro; Berghoff, Corinna; Berghoff, Martin; Del Valle, Gerardo; Contreras, Carlos; Montoya, Olga; Hernández, Erick; Barrantes, Ramiro; Schlötzer-Schrehardt, Ursula; Neundörfer, Bernhard; Reis, André; Rautenstrauss, Bernd; Heuss, Dieter

    2003-08-01

    Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation. On neurological examination the heterozygous parents and their homozygous children both showed distal sensory deficits. The mother and the siblings displayed impaired deep tendon reflexes and mild sensory ataxia. The homozygous individuals were more severely affected with an earlier age of onset, distal motor weakness, and pupillary abnormalities. Electrophysiological studies revealed both signs of demyelination and axonal nerve degeneration. The sural nerve biopsy of one sibling showed thinly myelinated nerve fibers, onion bulb formation, and clusters of regenerating fibers. On electron microscopy axonal degeneration and decompaction of inner myelin layers were found. This Costa Rican family shows phenotypic variability depending on the homozygous or heterozygous state of the Tyr145Ser mutation carriers. PMID:12845552

  9. Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-α6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C.

    PubMed

    Vijay, Sauparnika; Chiu, Meagan; Dacks, Joel B; Roberts, Rhys C

    2016-07-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is one of the commonest autosomal recessive inherited peripheral neuropathies and is associated with mutations in the Rab11 effector, SH3TC2. Disruption of the SH3TC2-Rab11 interaction is the molecular abnormality underlying this disease. However, why SH3TC2 mutations cause an isolated demyelinating neuropathy remains unanswered. Here we show that SH3TC2 is an exclusive Schwann cell protein expressed late in myelination and is downregulated following denervation suggesting a functional role in myelin sheath maintenance. We support our data with an evolutionary cell biological analysis showing that the SH3TC2 gene, and its paralogue SH3TC1, are derived from an ancestral homologue, the duplication of which occurred in the common ancestor of jawed vertebrates, coincident with the appearance of Schwann cells and peripheral axon myelination. Furthermore, we report that SH3TC2 associates with integrin-α6, suggesting that aberrant Rab11-dependent endocytic trafficking of this critical laminin receptor in myelinated Schwann cells is connected to the demyelination seen in affected nerves. Our study therefore highlights the inherent evolutionary link between SH3TC2 and peripheral nerve myelination, pointing also towards a molecular mechanism underlying the specific demyelinating neuropathy that characterizes CMT4C. PMID:27068304

  10. Acute non-ambulatory tetraparesis with absence of the dens in two large breed dogs: case reports with a radiographic study of relatives

    PubMed Central

    2013-01-01

    Background Non-ambulatory tetraparesis with an absence of the dens of C2 (axis) has not previously been reported in large breed dogs. An absence or hypoplasia of the dens has been reported in both small, medium and large breed dogs, but not in closely related animals. Methods Two young large-breed dogs (a German shepherd and a Standard poodle) both with an acute onset of non-ambulatory tetraparesis were subjected to physical, neurological and radiographic examinations. Both dogs were euthanased and submitted for postmortem examination within one week of onset of clinical signs. To investigate possible heritability of dens abnormalities, oblique radiographs of the cranial cervical vertebrae were taken of nine and eighteen dogs related to the German shepherd and the Standard poodle, respectively. Results Absence of the dens, atlantoaxial instability and extensive spinal cord injury was found in both case dogs. Radiographs revealed a normal dens in both parents and in the seven littermates of the German shepherd. An absence or hypoplasia of the dens was diagnosed in six relatives of the Standard poodle. Conclusions Atlantoaxial subluxation with cervical spinal cord injury should be considered as a differential diagnosis in non-ambulatory tetraparetic young large breed dogs. Absence of the dens and no history of external trauma increase the likelihood for this diagnosis. This study provides evidence to suggest that absence or hypoplasia of the dens is inherited in an autosomal way in Standard poodle dogs. PMID:23591104

  11. The "crowned dens" revisited: imaging findings in calcium crystal deposition diseases around the odontoid.

    PubMed

    Viana, Sergio L; Fernandes, João L; De Araújo Coimbra, Pablo P; De Mendonça, José L F; Freitas, Flávia M O; De Carvalho Barbosa Viana, Maria A

    2010-10-01

    The so-called "crowned dens" is a peculiar manifestation of calcium crystal deposition diseases, either caused by calcium pyrophosphate dihydrate or caused by calcium hydroxiapatite crystals, characterized by the presence of calcific deposits around the odontoid, often showing a crown-like configuration on imaging. It has protean clinical and radiological pictures, and care should be taken to avoid misinterpretation and diagnostic errors. Although asymptomatic in many patients, this entity may present as a predominantly algic or febrile condition, and in some cases, signs of compression of the spinal cord may be the major complaint. The detection of calcifications in the periodontoid tissues is the key to the diagnosis, erosive osseous changes, and variably calcified soft-tissue masses being occasionally associated. Computed tomography is the most important imaging study to be performed in this setting. PMID:19344369

  12. Erythronium dens-canis L. (Liliaceae): an unusual case of change of leaf mottling.

    PubMed

    La Rocca, Nicoletta; Pupillo, Paolo; Puppi, Giovanna; Rascio, Nicoletta

    2014-01-01

    Erythronium dens-canis is an early-flowering understory lily of southern Europe with two leaves and a single flower, although a number of plants have only one leaf and do not flower. The leaves are mottled with silvery flecks and brown patches, that gradually vanish turning to a lively green color. The nature and function of this striking variegation pattern were investigated in differently colored leaf parts following the springtime color change. Tissue organization was examined by light and electron microscopy; photosynthetic pigments were analyzed by spectrophotometry and HPLC; chlorophyll fluorescence parameters were evaluated by MINI-PAM. The results showed that brown patches originated in vacuolar anthocyanins in the subepidermal cell layer while air spaces between the upper epidermis and underlying chlorenchyma resulted in silvery flecks. The two leaf areas did not differ in photosynthetic pigments, chloroplast organization and photosynthetic parameters (F(v)/F(m), NPQ, rETR). Greening of brown patches due to anthocyanin resorption was faster in non-flowering plants than in flowering ones, occurring only when young fruits were developing. Anthocyanin disappearance did not change the structural-functional features of photosynthetic tissues. As a whole the results suggest that the anthocyanin pigmentation of E. dens-canis leaves does not affect the photosynthetic light use and has no photoprotective function. It is proposed that the complex leaf color pattern may act as a camouflage to escape herbivores, while the reflective silvery spots may have a role in attracting pollinators of this early-flowering species. PMID:24291157

  13. Distribution of dens used by radiocollared San Joaquin kit fox on Naval Petroleum Reserve No. 1, Kern County, California, 1980-1987

    SciTech Connect

    O'Farrell, T.P.; Tabor, S.P.; Kato, T.T.

    1987-09-01

    Locations of 945 dens used by radiocollared San Joaquin kit foxes (Vulpes macrotis mutica) on or adjacent to the US Department of Energy's Naval Petroleum Reserve No. 1 (NPR-1) in western Kern County, California between 1980-1987 were recorded on maps and stored within a computer-compatible data base. Most (516 of 887) typical subterranean dens of this endangered species were found in undeveloped portions of 65 sections, but most (41 of 58) atypical dens (dens in man-made structures) were found in developed portions of 26 sections. Program managers can plan construction, maintenance, and operational activities on NPR-1 in ways that avoid potential conflicts with the conservation of kit fox dens by using the section maps provided in this report or by accessing the computerized data base through the Endangered Species Contractor, EG and G Energy Measurements, Inc. 20 refs., 3 figs, 1 tab.

  14. Rater Biases in Genetically Informative Research Designs: Comment on Bartels, Boomsma, Hudziak, van Beijsterveldt, and van den Oord (2007)

    ERIC Educational Resources Information Center

    Hoyt, William T.

    2007-01-01

    Rater biases are of interest to behavior genetic researchers, who often use ratings data as a basis for studying heritability. Inclusion of multiple raters for each sibling pair (M. Bartels, D. I. Boomsma, J. J. Hudziak, T. C. E. M. van Beijsterveldt, & E. J. C. G. van den Oord, 2007) is a promising strategy for controlling bias variance and may…

  15. Enhanced pyrimidine dimer repair in cultured murine epithelial cells transfected with the denV gene of bacteriophage T4.

    PubMed

    Kusewitt, D F; Budge, C L; Ley, R D

    1994-04-01

    The patch size for excision repair of ultraviolet radiation (UV)-induced pyrimidine dimers was determined in cultured murine epithelial cells with normal and enhanced pyrimidine dimer repair capabilities. Cells with enhanced pyrimidine dimer repair were produced by transfecting 308 cells with the denV gene of bacteriophage T4; this gene encodes the enzyme endonuclease V. Pyrimidine dimer repair following exposure to UV from an FS-40 sunlamp was determined by micrococcal dimer-specific nuclease digestion and alkaline sucrose ultracentrifugation. Patch size ws estimated based on the photolytic lability of bromodeoxyuridine-substituted DNA. Excision repair of UV-induced pyrimidine dimers in denV-transfected 308 cells was enhanced two- to threefold. Production of mRNA from the denV gene in cell lines with enhanced repair was confirmed by RNA blotting. In control cells, the patch size for excision repair of DNA photoproducts was estimated to be 34 nucleotides per photoproduct removed; in denV-transfected cells, a smaller average patch size of 10-16 nucleotides per photoproduct removed was calculated. Thus, endonuclease V activity appears to alter not only the extent, but also the nature of excision repair in UV-exposed mammalian epithelial cells. PMID:8151125

  16. Absence of the dens in a 9.5-year-old rottweiler with non-progressive clinical signs

    PubMed Central

    Patton, Kristin M.; Almes, Kelli M.; de Lahunta, Alexander

    2010-01-01

    Absence of the dens is rarely described in large breed dogs. In this rottweiler, mild neurological deficits seen at 6 mo of age did not progress for the 9.5 y of the dog’s life despite lack of surgical intervention. This finding underscores the marked differences between small and large breeds. PMID:21119869

  17. Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits

    PubMed Central

    Johnson, Barbara W.; Goodman, Christin H.; Jee, Youngmee; Featherstone, David A.

    2016-01-01

    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JE Detect™ MAC-ELISA (JE Detect), a differential testing algorithm was developed in which samples tested by JE Detect with positive results were subsequently tested by the DEN Detect™ MAC-ELISA (DEN Detect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JE Detect and DEN Detect and were classified as JE− (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JE Detect and DEN Detect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID:26856911

  18. An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy

    PubMed Central

    Achilli, Francesca; Bros-Facer, Virginie; Williams, Hazel P.; Banks, Gareth T.; AlQatari, Mona; Chia, Ruth; Tucci, Valter; Groves, Michael; Nickols, Carole D.; Seburn, Kevin L.; Kendall, Rachel; Cader, Muhammed Z.; Talbot, Kevin; van Minnen, Jan; Burgess, Robert W.; Brandner, Sebastian; Martin, Joanne E.; Koltzenburg, Martin; Greensmith, Linda; Nolan, Patrick M.; Fisher, Elizabeth M. C.

    2009-01-01

    SUMMARY Mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system in humans, described clinically as Charcot-Marie-Tooth type 2D or distal spinal muscular atrophy type V. Here, we characterise a new mouse mutant, GarsC201R, with a point mutation that leads to a non-conservative substitution within GARS. Heterozygous mice with a C3H genetic background have loss of grip strength, decreased motor flexibility and disruption of fine motor control; this relatively mild phenotype is more severe on a C57BL/6 background. Homozygous mutants have a highly deleterious set of features, including movement difficulties and death before weaning. Heterozygous animals have a reduction in axon diameter in peripheral nerves, slowing of nerve conduction and an alteration in the recovery cycle of myelinated axons, as well as innervation defects. An assessment of GARS levels showed increased protein in 15-day-old mice compared with controls; however, this increase was not observed in 3-month-old animals, indicating that GARS function may be more crucial in younger animals. We found that enzyme activity was not reduced detectably in heterozygotes at any age, but was diminished greatly in homozygous mice compared with controls; thus, homozygous animals may suffer from a partial loss of function. The GarsC201R mutation described here is a contribution to our understanding of the mechanism by which mutations in tRNA synthetases, which are fundamentally important, ubiquitously expressed enzymes, cause axonopathy in specific sets of neurons. PMID:19470612

  19. Recombinant soluble gp130 protein reduces DEN-induced primary hepatocellular carcinoma in mice

    PubMed Central

    Hong, Jing; Wang, Hang; Shen, Guoying; Lin, Da; Lin, Yanxue; Ye, Nanhui; Guo, Yashan; Li, Qiaoling; Ye, Nanhui; Deng, Chengjun; Meng, Chun

    2016-01-01

    IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Soluble gp130 (sgp130) is known to be a natural inhibitor of the trans-signaling pathway. In the present study, our goal was to investigate whether recombinant sgp130 could suppress the initiation and progression of HCC in mouse models. Our results demonstrate that sgp130 induced an apoptosis of HepG2 cells and inhibited the clonogenicity of HepG2 in vitro. Moreover, the IL-6 trans-signaling pathway is significantly suppressed by sgp130 as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. In the DEN-induced HCC mouse model, intravenous injection of sgp130 attenuated hepatic fibrosis at 16 weeks and reduced the initiation and progression of primary HCC at 36 weeks. Furthermore, our results also demonstrate that intravenous administration of sgp130 significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice. PMID:27080032

  20. A comprehensive photometric study of dynamically evolved small van den Bergh-Hagen open clusters

    NASA Astrophysics Data System (ADS)

    Piatti, Andrés E.

    2016-09-01

    We present results from Johnson UBV, Kron-Cousins RI and Washington CT1T2 photometries for seven van den Bergh-Hagen (vdBH) open clusters, namely, vdBH 1, 10, 31, 72, 87, 92, and 118. The high-quality, multi-band photometric data sets were used to trace the cluster stellar density radial profiles and to build colour-magnitude diagrams (CMDs) and colour-colour (CC) diagrams from which we estimated their structural parameters and fundamental astrophysical properties. The clusters in our sample cover a wide age range, from ˜ 60 Myr up to 2.8 Gyr, are of relatively small size (˜ 1 - 6 pc) and are placed at distances from the Sun which vary between 1.8 and 6.3 kpc, respectively. We also estimated lower limits for the cluster present-day masses as well as half-mass relaxation times (tr). The resulting values in combination with the structural parameter values suggest that the studied clusters are in advanced stages of their internal dynamical evolution (age/tr ˜ 20 - 320), possibly in the typical phase of those tidally filled with mass segregation in their core regions. Compared to open clusters in the solar neighbourhood, the seven vdBH clusters are within more massive (˜ 80 - 380M$⊙$), with higher concentration parameter values (c ˜ 0.75-1.15) and dynamically evolved ones.

  1. Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment.

    PubMed

    Cozzani, E; Basso, D; Cimmino, M A; Larosa, M; Burlando, M; Rongioletti, F; Drago, F; Parodi, A

    2016-08-01

    Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA. PMID:27335228

  2. An unusual morphological anomaly in an incisor crown. Anterior dens evaginatus.

    PubMed

    Llena-Puy, Mari Carmen; Forner-Navarro, Leopoldo

    2005-01-01

    Exophytic growth of a portion of the tissue structure is one of the various clinical manifestations of the morphological anomalies that can affect the crown of the anterior teeth. The crown form disorder presented in this paper consists of an asymptomatic bulge on part of the vestibular surface of the tooth, due to enamel and dentine growth, with no radiological evidence of the pulp having extended into the protrusion of mineralised tissues. In this case, it only affects one tooth and is not associated with any other dental morphology or structure disorder, or with any of the syndromes that have been described in association with this anomaly. The term to describe this situation in the anterior teeth is not clearly defined in the relevant literature, which employs various names such as talon cusp, accentuated cingulum (when it affects the lingual or palatal surface) or dens evaginatus (evaginated tooth, evaginated odontome), the term that is always used when it is present in the posterior teeth. PMID:15627903

  3. Polar bear mother-offspring interactions in maternity dens in captivity.

    PubMed

    van Gessel, Chad

    2015-01-01

    Two female polar bears at Dierenrijk Zoo in the Netherlands were monitored at their maternity den one day before the birth of their cubs and three days postpartum. Each bear was monitored for 96 hr to document behaviour and vocalisations. The goal was to obtain insight into the differences between the mother that lost her litter and the other that successfully reared her cubs. Six groups of cub vocalisations were identified: Comfort, Discomfort, Distress, Nursing Attempts, Nursing, and No Vocalisation. Maternal vocalisations were split into three groups: Calm, Grooming, and Stress. Maternal behaviours were also split into three groups: Active, Rest, and Stress. The unsuccessful mother produced more stress vocalisations before and during the birth of her cub, whereas the successful mother appeared less stressed. Vocalisations indicate that the cub that died tried to nurse but was unsuccessful. The unsuccessful mother showed less stress as her cub got weaker and vocalised less. From this I suggest that maternal stress was a factor in cub mortality. PMID:26252623

  4. Conservative management of dens evaginatus and attached supernumerary tooth/odontome in mandibular premolar with dual radiolucencies

    PubMed Central

    Shah, Naseem; Jadhav, Ganesh Ranganath; Mittal, Priya; Logani, Ajay

    2015-01-01

    Recently, an innovative, nonsurgical regenerative endodontic treatment protocol “SealBio” was introduced to manage mature nonvital permanent teeth with periapical lesions. This paper explains the management of an unusual case of dens evaginatus and an attached supernumerary tooth/an odontome associated with two distinct radiolucencies in a mandibular premolar with “SealBio” technique and discusses the various hypotheses on the pathogenesis of unusual malformation and associated pericervical cyst-like radiolucency in the involved tooth. PMID:26604586

  5. Diethylnitrosamine (DEN) induces irreversible hepatocellular carcinogenesis through overexpression of G1/S-phase regulatory proteins in rat.

    PubMed

    Park, Dae-Hun; Shin, Jae Wook; Park, Seung-Kee; Seo, Jae-Nam; Li, Lan; Jang, Ja-June; Lee, Min-Jae

    2009-12-15

    Hepatocellular carcinoma (HCC) is the fifth most frequent cause of cancer deaths in males and was the third most frequent cause of cancer deaths in 2007 throughout the world. The incidence rate is 2-3 times higher in developing countries than in developed countries. Animal models have enabled study of the mechanism of HCC and the development of possible strategies for treatment. Diethylnitrosamine (DEN) is a representative chemical carcinogen with the potential to cause tumors in various organs, including the liver, skin, gastrointestinal tract, and respiratory system. Specifically in HCC, DEN is a complete carcinogen. Many lines of evidence have demonstrated a relationship between carcinogenesis and cell cycle regulation. In this study we found that cell cycle regulatory proteins were critically involved in cancer initiation and promotion by DEN. Cyclin D1, cyclin E, cdk4, and p21(CIP1/WAF1) are factors whose expression levels may be useful as criteria for the classification of hepatic disease. In particular, cdk4 had a pivotal role in the transition to the neoplastic stage. In conclusion, we suggest that changes in the level of cdk4 may be useful as a biomarker for detection of HCC. PMID:19822196

  6. Steppe lion remains imported by Ice Age spotted hyenas into the Late Pleistocene Perick Caves hyena den in northern Germany

    NASA Astrophysics Data System (ADS)

    Diedrich, Cajus G.

    2009-05-01

    Upper Pleistocene remains of the Ice Age steppe lion Panthera leo spelaea (Goldfuss, 1810) have been found in the Perick Caves, Sauerland Karst, NW Germany. Bones from many hyenas and their imported prey dating from the Lower to Middle Weichselian have also been recovered from the Perick Cave hyena den. These are commonly cracked or exhibit deep chew marks. The absence of lion cub bones, in contrast to hyena and cave bear cub remains in the Perick Caves, and other caves of northern Germany, excludes the possibility that P. leo spelaea used the cave for raising cubs. Only in the Wilhelms Cave was a single skeleton of a cub found in a hyena den. Evidence of the chewing, nibbling and cracking of lion bones and crania must have resulted from the importation and destruction of lion carcasses (4% of the prey fauna). Similar evidence was preserved at other hyena den caves and open air sites in Germany. The bone material from the Perick and other Central European caves points to antagonistic hyena and lion conflicts, similar to clashes of their modern African relatives.

  7. Korrelationsstatistischer Vergleich zweier Schulleistungstests fur den Unterricht in Englisch an Hauptschulen (Comparison by Statistical Correlation of Two English Achievement Tests for Intermediate Schools)

    ERIC Educational Resources Information Center

    Koch, Holger; Scheibner-Herzig, Gudrun

    1971-01-01

    Expanded version of a lecture given at a meeting of the Teachers of Modern Languages in Colleges of Education (Tagung der Fachdidaktiker fur neuere Sprachen an den Padagogischen Hochschulen), October 1, 1970 in Luneburg, West Germany. (RS)

  8. ‘Neanderthal bone flutes’: simply products of Ice Age spotted hyena scavenging activities on cave bear cubs in European cave bear dens

    PubMed Central

    Diedrich, Cajus G.

    2015-01-01

    Punctured extinct cave bear femora were misidentified in southeastern Europe (Hungary/Slovenia) as ‘Palaeolithic bone flutes’ and the ‘oldest Neanderthal instruments’. These are not instruments, nor human made, but products of the most important cave bear scavengers of Europe, hyenas. Late Middle to Late Pleistocene (Mousterian to Gravettian) Ice Age spotted hyenas of Europe occupied mainly cave entrances as dens (communal/cub raising den types), but went deeper for scavenging into cave bear dens, or used in a few cases branches/diagonal shafts (i.e. prey storage den type). In most of those dens, about 20% of adult to 80% of bear cub remains have large carnivore damage. Hyenas left bones in repeating similar tooth mark and crush damage stages, demonstrating a butchering/bone cracking strategy. The femora of subadult cave bears are intermediate in damage patterns, compared to the adult ones, which were fully crushed to pieces. Hyenas produced round–oval puncture marks in cub femora only by the bone-crushing premolar teeth of both upper and lower jaw. The punctures/tooth impact marks are often present on both sides of the shaft of cave bear cub femora and are simply a result of non-breakage of the slightly calcified shaft compacta. All stages of femur puncturing to crushing are demonstrated herein, especially on a large cave bear population from a German cave bear den. PMID:26064624

  9. 'Neanderthal bone flutes': simply products of Ice Age spotted hyena scavenging activities on cave bear cubs in European cave bear dens.

    PubMed

    Diedrich, Cajus G

    2015-04-01

    Punctured extinct cave bear femora were misidentified in southeastern Europe (Hungary/Slovenia) as 'Palaeolithic bone flutes' and the 'oldest Neanderthal instruments'. These are not instruments, nor human made, but products of the most important cave bear scavengers of Europe, hyenas. Late Middle to Late Pleistocene (Mousterian to Gravettian) Ice Age spotted hyenas of Europe occupied mainly cave entrances as dens (communal/cub raising den types), but went deeper for scavenging into cave bear dens, or used in a few cases branches/diagonal shafts (i.e. prey storage den type). In most of those dens, about 20% of adult to 80% of bear cub remains have large carnivore damage. Hyenas left bones in repeating similar tooth mark and crush damage stages, demonstrating a butchering/bone cracking strategy. The femora of subadult cave bears are intermediate in damage patterns, compared to the adult ones, which were fully crushed to pieces. Hyenas produced round-oval puncture marks in cub femora only by the bone-crushing premolar teeth of both upper and lower jaw. The punctures/tooth impact marks are often present on both sides of the shaft of cave bear cub femora and are simply a result of non-breakage of the slightly calcified shaft compacta. All stages of femur puncturing to crushing are demonstrated herein, especially on a large cave bear population from a German cave bear den. PMID:26064624

  10. A Rare Case of Parkinson's Disease with Severe Neck Pain Owing to Crowned Dens Syndrome

    PubMed Central

    Takahashi, Teruyuki; Tamura, Masato; Osabe, Keiichi; Tamiya, Takashi; Miki, Kenji; Yamaguchi, Mai; Akira, Kanno; Kamei, Satoshi; Takasu, Toshiaki

    2014-01-01

    Background Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and neck pain. Laboratory examination revealed marked elevations of white blood cells (10,100/µl) and C-reactive protein (CRP; 8.63 mg/dl). She was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The patient was treated with antiparkinsonism drugs, antibiotic agents and nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical plain computed tomography (CT) scanning detected remarkable crown-like calcification surrounding the odontoid process. Based on CT findings, the patient was diagnosed as having CDS with PD, and was immediately treated with corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83 mg/dl) of the patient were drastically improved within a week by the additional corticosteroid therapy. Conclusion Severe neck rigidity and bradykinesia in this patient might have strengthened the chondrocalcinosis around the odontoid process. Cervical plain CT scan is necessary and useful for the definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for musculoskeletal pain related to rigidity and bradykinesia in PD. PMID:24926265

  11. A Probabilistic Wake Vortex Lateral Transport Model Using Data from SFO and DEN

    NASA Technical Reports Server (NTRS)

    Mellman, George R.; Delisi, Donald P.

    2008-01-01

    In a previous report, we considered the behavior of the lateral position of vortices as a function of time after vortex formation for Out of Ground Effects (OGE) data for aircraft landing at San Francisco International Airport (SFO). We quantified the spread in lateral position as a function of time and examined how predictable lateral position is under a variety of assumptions. The combination of spread and predictability allowed us to derive probability distribution functions (PDFs) for lateral position given observed crosswind (CW) velocities. In this study, we examine the portability of these PDFs with respect to other landing sites. To this end, we consider OGE data obtained by the Federal Aviation Administration for landings at Denver International Airport (DEN) between 04/05/2006 and 06/03/2006. We consider vortices from both B733 (Boeing 737 models 200-500) and B757 (Boeing 757) aircraft. The data set contains 635 B733 landings and 506 B757 landings. The glide slope altitude for these measurements was 280 m, determined by the average initial vortex observation adjusted for a 3-second delay in the initial observation. The comparable SFO altitude was 158 m. We note that the principal mechanism for lateral transport in the OGE regime is advection by the ambient wind. This implies that a simple crosswind correction may be effective in explaining much of the variation in the lateral transport data. In this study, we again consider the use of ASOS data and average Lidar crosswind data over the vortex altitude range to predict vortex location as a function of time.

  12. Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

    PubMed Central

    Anastasio, Natascia; Ben-Omran, Tawfeg; Teebi, Ahmad; Ha, Kevin C.H.; Lalonde, Emilie; Ali, Rehab; Almureikhi, Mariam; Der Kaloustian, Vazken M.; Liu, Junhui; Rosenblatt, David S.; Majewski, Jacek; Jerome-Majewska, Loydie A.

    2010-01-01

    Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes. PMID:20887961

  13. Predicting movements of female polar bears between summer sea ice foraging habitats and terrestrial denning habitats of Alaska in the 21st century: Proposed methodology and pilot assessment

    USGS Publications Warehouse

    Bergen, Scott; Durner, George M.; Douglas, David C.; Amstrup, Steven C.

    2007-01-01

    Polar bears (Ursus maritimus) require the relative warmth and stability afforded by snow dens for successful reproduction. Pregnant bears must travel from foraging habitats on the sea ice to land in autumn to establish winter dens. Data of sea ice extent and composition from satellite-acquired passive microwave (PMW) imagery show a reduction in summer sea ice extent throughout the Arctic from 1979-2006. Additionally, General Circulation Models (GCM) predict that Arctic sea ice extent will continue to diminish throughout the 21st century. Greater energetic demands will be placed on pregnant polar bears in the future if they travel greater distances from summer forage habitats to traditional denning habitats on land. We developed an approach for estimating how much these distances may change by modeling autumn movement paths of polar bears using the observational PMW record of sea ice distribution and sea ice projections of 5 GCMs during the 21st century. Over the 1979-2006 PMW record, polar bears returning to Alaska to den have experienced an annual increase in travel of > 6 km/year—an increase of >168 km over the 28 year period. Based on GCM sea ice projections during 2001-2060, the average increase in the distance required to reach traditional Alaskan denning regions was estimated to increase > 16 km/year. Distances traveled, and therefore, energetic demands, will likely vary among the different circumpolar sub-populations of polar bears.

  14. Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.

    PubMed

    Niederhoffer, Karen Y; Fahiminiya, Somayyeh; Eydoux, Patrice; Mawson, John; Nishimura, Gen; Jerome-Majewska, Loydie A; Patel, Millan S

    2016-09-01

    Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc. PMID:27375131

  15. Geothermal Project Den Haag - 3-D models for temperature prediction and reservoir characterization

    NASA Astrophysics Data System (ADS)

    Mottaghy, D.; Pechnig, R.; Willemsen, G.; Simmelink, H. J.; Vandeweijer, V.

    2009-04-01

    In the framework of the "Den Haag Zuidwest" geothermal district heating system a deep geothermal installation is projected. The target horizon of the planned doublet is the "Delft sandstone" which has been extensively explored for oil- and gas reservoirs in the last century. In the target area, this upper Jurassic sandstone layer is found at a depth of about 2300 m with an average thickness of about 50 m. The study presented here focuses on the prediction of reservoir temperatures and production behavior which is crucial for planning a deep geothermal installation. In the first phase, the main objective was to find out whether there is a significant influence of the 3-dimensional structures of anticlines and synclines on the temperature field, which could cause formation temperatures deviating from the predicted extrapolated temperature data from oil and gas exploration wells. To this end a regional model was set up as a basis for steady state numerical simulations. Since representative input parameters are decisive for reliable model results, all available information was compiled: a) the subsurface geometry, depth and thickness of the stratigraphic layers known from seismic data sets 2) borehole geophysical data and c) geological and petrographical information from exploration wells. In addition 50 cuttings samples were taken from two selected key wells in order to provide direct information on thermal properties of the underlying strata. Thermal conductivity and rock matrix density were measured in the laboratory. These data were combined with a petrophysical log analysis (Gamma Ray, Sonic, Density and Resistivity), which resulted in continuous profiles of porosity, effective thermal conductivity and radiogenetic heat production. These profiles allowed to asses in detail the variability of the petrophysical properties with depth and to check for lateral changes between the wells. All this data entered the numerical simulations which were performed by a 3-D

  16. Role of phosphorylated histone H3 serine 10 in DEN-induced deregulation of Pol III genes and cell proliferation and transformation

    PubMed Central

    Zhong, Shuping

    2013-01-01

    The products of Pol III genes (RNA polymerase III-dependent genes), such as tRNAs and 5S rRNA, are elevated in both transformed and tumor cells suggesting that they play a crucial role in tumorigenesis. An increase in Brf1 (TFIIIB-related factor 1), a subunit of TFIIIB, augments Pol III gene transcription and is sufficient for cell transformation and tumor formation. We have demonstrated that enhancement of Brf1 and Pol III gene expression is associated with the occurrences of hepatocellular carcinoma (HCC) in mice. This suggests that Brf1 may be a key molecule during HCC development. Diethylnitrosamine (DEN), a chemical carcinogen, has been used to induce HCC in rodents. To determine the role of Brf1 and the epigenetic-regulating events in cell proliferation and transformation, hepatocytes were treated with DEN. The results indicate that DEN increases proliferation and transformation of AML-12 cells. DEN enhanced Brf1 expression and tRNALeu and 5S rRNA transcription, as well as H3S10ph (phosphorylation of histone H3 serine 10). Interestingly, DEN-induced Pol III gene transcription and H3S10ph in tumor cells of liver are significantly higher than in non-tumor cells. Inhibition of H3S10ph by H3S10A attenuates the induction of Brf1 and Pol III genes. Further analysis indicates that H3S10ph occupies the promoters of Brf1 and Pol III genes to modulate their expression. Blocking H3S10ph represses cell proliferation and transformation. These results demonstrate that DEN induces H3S10ph, which mediate Brf1 expression, including but not limited Brf1-dependent genes, to upregulate Pol III gene transcription, resulting in an increase in cell proliferation and transformation. PMID:23774401

  17. Charcot-Marie-Tooth and Related Diseases

    MedlinePlus

    ... to restore normal myelin maintenance. One scientist is conducting laboratory experiments to see whether a compound called heat shock protein 90 might be therapeutic in the type 1A form of CMT, while others are conducting an MDA- funded clinical trial to test the ...

  18. Learning about Charcot-Marie-Tooth Disease

    MedlinePlus

    ... A searchable database from the National Center for Biotechnology Information. eMedicine Journal [emedicine.medscape.com] There are ... of Neurological Disorders and Stroke National Center for Biotechnology Information [ncbi.nlm.nih.gov] An information page ...

  19. The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis

    PubMed Central

    Bigsby, Robert M.; Caperell-Grant, Andrea

    2011-01-01

    Mice treated neonatally with diethylnitrosamine (DEN) develop liver tumors in a male-dominant manner, reflecting the male bias in human hepatocellular carcinoma. Evidence suggests that estrogen, androgen, prolactin (PRL) and growth hormone (GH) modify liver tumorigenesis. We determined the roles of estrogen receptor-α (ERα) and prolactin receptor (PRLR) using receptor null mice, ERαKO (C57Bl/6J) and PRLR-KO (129Ola-X-C57BL/6), in the neonatal-DEN model of liver tumorigenesis. In both mouse strains, females had reduced tumorigenesis compared with males (P < 0.01), regardless of ERα or PRLR status. Tumorigenesis was not affected by ovariectomy in C57Bl/6J mice but it was increased by ovariectomy in the mixed strain, 129Ola-X-C57BL/6, regardless of PRLR status. ERαKO males had 47% fewer tumors than ERα wild-type males (P < 0.01). On the other hand, estradiol treatment protected against tumorigenesis in males only in the presence of ERα. As evidenced by liver gene expression, lack of ERα did not alter the pattern of GH secretion in males but resulted in the male GH pattern in females. These observations indicate that ERα is not required for lower tumorigenesis in females, but it is required for the protective effects of exogenously delivered estradiol. Unexpectedly, the results indicate that ERα plays a role in promotion of liver tumors in males. In addition, it can be concluded that sex differences in liver tumorigenesis cannot be explained by the sexually dimorphic pattern of GH secretion. The results also rule out PRL as the mediator of the protective effect of the ovaries. PMID:21606321

  20. Comment to the Article by van Arensbergen and van den Besselaar "The Selection of Scientific Talent in the Allocation of Research Grants"

    ERIC Educational Resources Information Center

    Maessen, K. M. H.

    2012-01-01

    The article entitled "The selection of scientific talent in the allocation of research grants" by van Arensbergen and van den Besselaar published in "Higher Education Policy" 25/3 (2012) is based on research that both researchers carried out on behalf of The Netherlands Organisation for Scientific Research. In this comment, we want to address…

  1. Protective Effect of Ethanolic Extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA Induced Liver Necrosis in Wistar Albino Rats

    PubMed Central

    2014-01-01

    This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis. PMID:25136566

  2. Protective effect of ethanolic extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA induced liver necrosis in Wistar Albino rats.

    PubMed

    Poornima, Kannappan; Chella Perumal, Palanisamy; Gopalakrishnan, Velliyur Kanniappan

    2014-01-01

    This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis. PMID:25136566

  3. Sclerocornea in a Patient with Van Den Ende–Gupta Syndrome Homozygous for a SCARF2 Microdeletion

    PubMed Central

    Migliavacca, Michele P.; Sobreira, Nara L. M.; Antonialli, Graziela P.M.; Oliveira, Mariana M.; Melaragno, Maria Isabel S.A.; Casteels, Ingele; de Ravel, Thomy; Brunoni, Decio; Valle, David; Perez, Ana Beatriz A.

    2015-01-01

    Van den Ende–Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553–559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2011] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2. PMID:24478002

  4. [Presence of the dinoflagellates Ceratium dens, C. fusus and C. furca (Gonyaulacales: Ceratiaceae) in Golfo de Nicoya, Costa Rica].

    PubMed

    Vargas-Montero, Maribelle; Freer, Enrique

    2004-09-01

    Harmful Algae Blooms (HAB) are a frequent phenomenon in the Gulf of Nicoya, Costa Rica, as in other parts of the world. The morphology and physiology of these microalgae are important because HAB species have adaptive characteristics. The production of high concentrations of paralytic toxins by Ceratium dinoflagellates has only been documented at the experimental level. However, this genus has been associated with the mortality of aquatic organisms, including oyster and shrimp larva, and fish, and with decreased water quality. Recently, fishermen reported massive mortality of encaged fish near Tortuga Island (Gulf of Nicoya). Samples were taken from an algal bloom that had produced an orange coloration and had a strong foul-smelling odor. Ultrastructural details were examined with scanning electron microscopy. The dinoflagellates Ceratium dens, C. furca and C. fusus were found in samples taken at the surface. The cell count revealed four million cells of this genus per liter. The morphological variability of these species is high; therefore electron microscopy is an useful tool in the ultrastructural study of these organisms. This is the first time that three Ceratium species are reported concurrently producing harmful blooms in Costa Rica. PMID:17465124

  5. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    NASA Astrophysics Data System (ADS)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  6. A Rare Case of Type III Dens Invaginatus in a Mandibular Second Premolar and Its Nonsurgical Endodontic Management by Using Cone-beam Computed Tomography: A Case Report.

    PubMed

    Agrawal, Pritesh Kisanlal; Wankhade, Jyoti; Warhadpande, Manjusha

    2016-04-01

    Invaginated teeth present technical difficulties in clinical management because of their abnormal anatomic configuration. Endodontic clinical management of type III dens invaginatus can be greatly enhanced by newer techniques and materials such as cone-beam computed tomography (CBCT), mineral trioxide aggregate, and platelet-rich fibrin. This case report presents a 13-year-old male patient with type III dens invaginatus (DI) in left mandibular second premolar with history of recurrent swelling. Pulp testing revealed no response with the tooth. Dens invaginatus type III with an immature apex and periapical lesion was seen on radiograph. The case was diagnosed as Oehlers type III DI with pulp necrosis and chronic apical abscess. The treatment was planned and performed by using CBCT imaging. CBCT was performed to see the canal anatomy and to know the size of periapical lesion. Root canal treatment was completed in 2 visits. Calcium hydroxide dressing was placed in the first visit. In the second visit MTA was used for apexification in the main canal, and warm vertical compaction technique with gutta-percha was used in the invaginated canal. At the 2-year reevaluation, the patient was asymptomatic, and his tooth had remained functional since the treatment was completed. Radiographic assessment of the tooth showed significant osseous healing of the preoperative lesion. Three-dimensional imaging is a valuable tool for endodontic management of teeth with complex internal anatomy. PMID:26874642

  7. DensToolKit: A comprehensive open-source package for analyzing the electron density and its derivative scalar and vector fields

    NASA Astrophysics Data System (ADS)

    Solano-Altamirano, J. M.; Hernández-Pérez, Julio M.

    2015-11-01

    DensToolKit is a suite of cross-platform, optionally parallelized, programs for analyzing the molecular electron density (ρ) and several fields derived from it. Scalar and vector fields, such as the gradient of the electron density (∇ρ), electron localization function (ELF) and its gradient, localized orbital locator (LOL), region of slow electrons (RoSE), reduced density gradient, localized electrons detector (LED), information entropy, molecular electrostatic potential, kinetic energy densities K and G, among others, can be evaluated on zero, one, two, and three dimensional grids. The suite includes a program for searching critical points and bond paths of the electron density, under the framework of Quantum Theory of Atoms in Molecules. DensToolKit also evaluates the momentum space electron density on spatial grids, and the reduced density matrix of order one along lines joining two arbitrary atoms of a molecule. The source code is distributed under the GNU-GPLv3 license, and we release the code with the intent of establishing an open-source collaborative project. The style of DensToolKit's code follows some of the guidelines of an object-oriented program. This allows us to supply the user with a simple manner for easily implement new scalar or vector fields, provided they are derived from any of the fields already implemented in the code. In this paper, we present some of the most salient features of the programs contained in the suite, some examples of how to run them, and the mathematical definitions of the implemented fields along with hints of how we optimized their evaluation. We benchmarked our suite against both a freely-available program and a commercial package. Speed-ups of ∼2×, and up to 12× were obtained using a non-parallel compilation of DensToolKit for the evaluation of fields. DensToolKit takes similar times for finding critical points, compared to a commercial package. Finally, we present some perspectives for the future development

  8. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes

    PubMed Central

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka

    2016-01-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

  9. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    PubMed

    Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

    2016-05-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

  10. Paleoenvironmental and Human Behavioral Implications of the Boegoeberg 1 Late Pleistocene Hyena Den, Northern Cape Province, South Africa

    NASA Astrophysics Data System (ADS)

    Klein, Richard G.; Cruz-Uribe, Kathryn; Halkett, David; Hart, Tim; Parkington, John E.

    1999-11-01

    Boegoeberg 1 (BOG1) is located on the Atlantic coast of South Africa, 850 km north of Cape Town. The site is a shallow rock shelter in the side of a sand-choked gully that was emptied by diamond miners. Abundant coprolites, chewed bones, and partially digested bones implicate hyenas as the bone accumulators. The location of the site, quantity of bones, and composition of the fauna imply it was a brown hyena nursery den. The abundance of Cape fur seal bones shows that the hyenas had ready access to the coast. Radiocarbon dates place the site before 37,000 14C yr ago, while the large average size of the black-backed jackals and the presence of extralimital ungulates imply cool, moist conditions, probably during the early part of the last glaciation (isotope stage 4 or stage 3 before 37,000 14C yr ago) or perhaps during one of the cooler phases (isotope substages 5d or 5b) within the last interglaciation. Comparisons of the BOG1 seal bones to those from regional Middle Stone Age (MSA) and Later Stone Age (LSA) archeological sites suggest (1) that hyena and human seal accumulations can be distinguished by a tendency for vertebrae to be much more common in a hyena accumulation and (2) that hyena and LSA accumulations can be distinguished by a tendency for hyena-accumulated seals to represent a much wider range of individual seal ages. Differences in the way hyenas and people dismember, transport, and consume seal carcasses probably explain the contrast in skeletal part representation, while differences in season of occupation explain the contrast in seal age representation. Like modern brown hyenas, the BOG1 hyenas probably occupied the coast year-round, while the LSA people focused their coastal visits on the August-October interval when nine-to-eleven-month-old seals were abundant. The MSA sample from Klasies River Mouth Cave 1 resembles BOG1 in seal age composition, suggesting that unlike LSA people, MSA people obtained seals more or less throughout the year.

  11. Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti.

    PubMed

    Sujitha, Vasu; Murugan, Kadarkarai; Paulpandi, Manickam; Panneerselvam, Chellasamy; Suresh, Udaiyan; Roni, Mathath; Nicoletti, Marcello; Higuchi, Akon; Madhiyazhagan, Pari; Subramaniam, Jayapal; Dinesh, Devakumar; Vadivalagan, Chithravel; Chandramohan, Balamurugan; Alarfaj, Abdullah A; Munusamy, Murugan A; Barnard, Donald R; Benelli, Giovanni

    2015-09-01

    Dengue is an arthropod-borne viral infection mainly vectored through the bite of Aedes mosquitoes. Recently, its transmission has strongly increased in urban and semi-urban areas of tropical and sub-tropical regions worldwide, becoming a major international public health concern. There is no specific treatment for dengue. Its prevention and control solely depends on effective vector control measures. In this study, we proposed the green-synthesis of silver nanoparticles (AgNP) as a novel and effective tool against the dengue serotype DEN-2 and its major vector Aedes aegypti. AgNP were synthesized using the Moringa oleifera seed extract as reducing and stabilizing agent. AgNP were characterized using a variety of biophysical methods including UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and sorted for size categories. AgNP showed in vitro antiviral activity against DEN-2 infecting vero cells. Viral titer was 7 log10 TCID50/ml in control (AgNP-free), while it dropped to 3.2 log10 TCID50/ml after a single treatment with 20 μl/ml of AgNP. After 6 h, DEN-2 yield was 5.8 log10 PFU/ml in the control, while it was 1.4 log10 PFU/ml post-treatment with AgNP (20 μl/ml). AgNP were highly effective against the dengue vector A. aegypti, with LC50 values ranging from 10.24 ppm (I instar larvae) to 21.17 ppm (pupae). Overall, this research highlighted the concrete potential of green-synthesized AgNP in the fight against dengue and its primary vector A. aegypti. Further research on structure-activity relationships of AgNP against other dengue serotypes is urgently required. PMID:26063530

  12. Endodontic Management of a Mandibular Incisor Exhibiting Concurrence of Fusion, Talon Cusp and Dens Invaginatus using CBCT as a Diagnostic Aid

    PubMed Central

    Kumar, Varun

    2016-01-01

    Teeth with aberrant anatomy present a challenge to the endodontist. Advanced tools like cone beam computed tomography aid in exploring the details of endodontic architecture in such cases. The aim of this case report is to highlight the advantage of CBCT in endodontic management of teeth with multiple dental anomalies. A mandibular lateral incisor associated with an extraoral sinus tract revealed unusual clinical anatomy. A provisional diagnosis of type III dens in dente was made based on radiographic findings. Considering the complex anatomy, CBCT was advised to get a confirmatory diagnosis. The anatomic details revealed by CBCT differed significantly from the provisional diagnosis. A final diagnosis of concurrence of fusion with a supernumerary tooth, talon cusp and type II dens invaginatus was established and endodontic treatment of the concerned tooth was carried out. Non-surgical endodontic treatment resulted in successful resolution of the sinus tract and healing of the periapical lesion. CBCT, thus proves to be an excellent diagnostic tool for management of teeth with unusual anatomy, paving way for a conservative treatment free of endodontic mishaps. PMID:27042591

  13. Cone-Beam Computed Tomography-Guided Management of C-Shaped Type III Dens Invaginatus With Peri-invagination Periodontitis in a Maxillary Canine: A Case Report.

    PubMed

    Mittal, Priya; Jadhav, Ganesh R; Syed, Shibli; Bhujbal, Nikita D

    2016-06-01

    Dens invaginatus (DI) is a developmental anomaly seen infrequently in maxillary canines. This article describes cone-beam computed tomography-guided nonsurgical management of type III (subtype B) DI in a permanent maxillary canine associated with a sinus tract and peri-invagination periodontitis in a 17-year-old female. After gaining access to the root canal, thorough chemo-mechanical preparation was performed and usage of intracanal medicament of calcium hydroxide was prescribed for 3 weeks, during which the sinus tract healed completely. Obturation was completed by a technique of down-packing master-cone gutta-percha, followed by backfilling with thermoplasticized gutta-percha. At 12-months follow-up, the patient was asymptomatic with complete resolution of the sinus tract and radiographic evidence of healing of periapical pathology. PMID:27525733

  14. Morphological and molecular investigations of a microsporidium infecting the European grape vine moth, Lobesia botrana Den. et Schiff., and its taxonomic determination as Cystosporogenes legeri nov. comb.

    PubMed

    Kleespies, Regina G; Vossbrinck, Charles R; Lange, Martin; Jehle, Johannes A

    2003-07-01

    We have isolated a microsporidium from a laboratory stock of the European grape vine moth, Lobesia botrana Den. et Schiff. (Lepidoptera, Tortricidae). Screening of this stock showed an infection rate of more than 90%, whereas field collected larvae from three different locations in Rhineland-Palatinate (Germany) did not demonstrate any signs of infection. Light and electron microscopic investigations of infected insects showed that gross pathology, morphology, and ultrastructure of the microsporidium are similar to those described earlier for Pleistophora legeri. Comparative phylogenetic analysis of the small subunit rDNA using maximum likelihood, maximum parsimony, and neighbour joining distance methods showed that our isolate was closely related to Cystosporogenes operophterae. Based on our morphological and molecular investigations we propose to rename this species Cystosporogenes legeri nov. comb. PMID:12877831

  15. Factors Affecting Date of Implantation, Parturition, and Den Entry Estimated from Activity and Body Temperature in Free-Ranging Brown Bears

    PubMed Central

    Friebe, Andrea; Evans, Alina L.; Arnemo, Jon M.; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E.; Zedrosser, Andreas

    2014-01-01

    Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human. PMID:24988486

  16. Factors affecting date of implantation, parturition, and den entry estimated from activity and body temperature in free-ranging brown bears.

    PubMed

    Friebe, Andrea; Evans, Alina L; Arnemo, Jon M; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E; Zedrosser, Andreas

    2014-01-01

    Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human. PMID:24988486

  17. Effekt einer ad libitum verzehrten fettreduzierten Kost, reich an Obst, Gemüse und Milchprodukten auf den Blutdruck bei Borderline-Hypertonikern

    NASA Astrophysics Data System (ADS)

    Möseneder, Jutta M.

    2002-01-01

    In der randomisierten, multizentrischen DASH-Studie (Dietary Approaches to Stop Hy-pertension), die unter kontrollierten Bedingungen stattfand, führte eine fettreduzierte Mischkost, reich an Obst, Gemüse und Milchprodukten, bei Borderline-Hypertonikern zu einer signifikanten Blutdrucksenkung. Während der Studienphase wurden Körpermasse, Natrium-Aufnahme sowie Alkoholzufuhr aufgrund der bekannten Einflussnahme auf den Blutdruck konstant gehalten. In der eigenen Pilot-Studie sollte untersucht werden, ob das Ergebnis der DASH-Studie (i) mit deutschen Hypertonikern und (ii) unter habituellen Ernährungs- und Lebensbedingungen mit regelmäßig durchgeführter Ernährungsberatung und ad libitum Verzehr anstelle des streng kontrollierten Studienansatzes bestätigt werden kann. Eine Konstanz der Körpermasse, der Natrium-Urinausscheidung (unter diesem Studienansatz valider als die Aufnahme) und des Alkoholkonsums wurde vorausgesetzt. Die Studienpopulation setzte sich aus 53 übergewichtigen Probanden mit einer nicht medikamentös therapierten Borderline-Hypertonie und ohne Stoffwechselerkrankungen zusammen. Die Studienteilnehmer wurden randomisiert entweder der Idealgruppe mit einer fettarmen Kost reich an Milchprodukten, Obst und Gemüse (ähnlich der DASH-Idealgruppe) oder der Kontrollgruppe mit habitueller Ernährungsweise zugeteilt. Über einen Zeitraum von fünf Wochen wurde den Probanden etwa 50% ihres täglichen Lebensmittelbedarfes entsprechend ihrer Gruppenzugehörigkeit kostenfrei zur Verfügung gestellt. Gelegenheitsblutdruckmessungen und 24h-Blutdruckmessungen, Ernährungs- und Aktivitätsprotokolle, Blut- und Urinproben sowie anthropometrische Messungen wurden vor, während und fünf Wochen nach der Interventionsphase durchgeführt. Die Ergebnisse zeigen, dass in der Idealgruppe keine signifikante Blutdrucksenkung beobachtet werden konnte. Dies lässt sich durch die Tatsache erklären, dass die Lebens-mittel- und Nährstoffaufnahme der deutschen

  18. [Immunohistochemical Analysis of Krebs von den Lungen-6 (KL-6) Expression in Lung Tissue in Primary Lung Cancer Patients with High Serum KL-6 Levels].

    PubMed

    Yatsuyanagi, Eiji; Sato, Kazuhiro; Sato, Keisuke

    2015-09-01

    We investigated sialylated carbohydrate antigen( Krebs von den Lungen-6:KL-6) expression in lung tissue and correlation between the expression and serum KL-6 level in the patients with primary lung cancer. Thirty-four primary lung cancer patients with high serum KL-6 levels( >500 U/ml) were evaluated. A coexistence of interstitial pneumonia (IP) was histopathologically evaluated and an immunohistochemical staining using a mouse anti-human KL-6 antibody (mKL-6) was performed. A multiple regression analysis was also caluculated using a serum KL-6 level as a target variable and the histopathological and immunohistochemical factors (KL-6 expression in cancer tissue and IP tissue, coexistence of IP, tumor size, pathological staging) as descriptive variables. Twenty-two patients (64.7%) were histopathologically concomitant with IP. Cancer tissues were positively stained by mKL-6 in 32 patients (94.1%). Among them, 20 patients were concomitant with IP and all of their cancer tissues were more strongly stained by mKL-6 than IP tissues. Although considerable high rate of lung cancer patients might express the KL-6 in the cancer tissue, we could not reveal the relationship between the expression and serum KL-6 level by a multiple regression analysis. For revealing the mechanism of elevating serum KL-6 level in the patients with lung cancer, more detailed and powerful study is thought to be needed. PMID:26329623

  19. Early detection of colon cancer by increased serum level of Krebs von den Lungen-6 in a patient with dermatomyositis-associated interstitial pneumonia.

    PubMed

    Fukuhara, Naoko; Tanino, Yoshinori; Sato, Suguru; Fukuhara, Atsuro; Uematsu, Manabu; Nikaido, Takefumi; Misa, Kenichi; Sato, Yasuko; Saito, Junpei; Wang, Xintao; Munakata, Mitsuru

    2015-01-01

    Krebs von den Lungen-6 (KL-6) is a high-molecular-weight glycoprotein which is elevated in serum of patients with interstitial pneumonia (IP). Serum KL-6 level is clinically used for the diagnosis of IP as well as the evaluation of its disease activity. KL-6 is originally identified when exploring novel soluble antigens in patients with lung cancer, and is known to be elevated in patients with several malignant tumors. The risk of malignant tumors is high in IP patients with polymyositis and dermatomyositis (PM/DM), and follow-up of KL-6 levels may allow earlier detection of such tumors. However, to date, there are only a few reports showing the usefulness of following-up serum KL-6 levels for finding malignant tumors in IP patients with PM/DM. Here, we described the first patient in whom increased serum KL-6 led to the diagnosis of colon cancer during follow-up of DM-associated IP. PMID:26422573

  20. Differential predation by age and sex classes in blue wildebeest in Serengeti: study of a modern carnivore den in Olduvai Gorge (Tanzania).

    PubMed

    Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Martínez-Maza, Cayetana; Mabulla, Audax; Baquedano, Enrique

    2015-01-01

    Age and sex selection of prey is an aspect of predator ecology which has been extensively studied in both temperate and African ecosystems. This dimension, along with fecundity, survival rates of prey and mortality factors other than predation are important in laying down the population dynamics of prey and have important implications in the management of species. A carnivore den located in the short-grassland ecological unit of the Serengeti was studied. Sex- and age- class (using five age categories) of the wildebeest remains recovered were analyzed through horn morphology, biometrics of the bones and tooth wear patterns. We compared our results with previous studies from lion and hyaena kills through multivariate analyses. Seasonality of the accumulation was analyzed through tooth histology. PCA and CVA results show that age class selection by predators depends on season, habitat-type, and growth rate of the wildebeest population. Female-biased predation was found to contradict classical hypotheses based on territorial male behaviour. The lion and spotted hyaena showed strong selection on age classes, contrary to previous studies. Migratory wildebeest sex ratio is regulated through differential predation by seasons and female deaths in the wet season are a trade-off for population stability. These data are crucial for an effective management of the species and the new method created may be useful for different carnivore species and their prey. PMID:26017363

  1. Differential Predation by Age and Sex Classes in Blue Wildebeest in Serengeti: Study of a Modern Carnivore Den in Olduvai Gorge (Tanzania)

    PubMed Central

    Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Martínez-Maza, Cayetana; Mabulla, Audax; Baquedano, Enrique

    2015-01-01

    Age and sex selection of prey is an aspect of predator ecology which has been extensively studied in both temperate and African ecosystems. This dimension, along with fecundity, survival rates of prey and mortality factors other than predation are important in laying down the population dynamics of prey and have important implications in the management of species. A carnivore den located in the short-grassland ecological unit of the Serengeti was studied. Sex- and age- class (using five age categories) of the wildebeest remains recovered were analyzed through horn morphology, biometrics of the bones and tooth wear patterns. We compared our results with previous studies from lion and hyaena kills through multivariate analyses. Seasonality of the accumulation was analyzed through tooth histology. PCA and CVA results show that age class selection by predators depends on season, habitat-type, and growth rate of the wildebeest population. Female-biased predation was found to contradict classical hypotheses based on territorial male behaviour. The lion and spotted hyaena showed strong selection on age classes, contrary to previous studies. Migratory wildebeest sex ratio is regulated through differential predation by seasons and female deaths in the wet season are a trade-off for population stability. These data are crucial for an effective management of the species and the new method created may be useful for different carnivore species and their prey. PMID:26017363

  2. Effekt einer ad libitum verzehrten fettreduzierten Kost, reich an Obst, Gemüse und Milchprodukten auf den Blutdruck bei Borderline-Hypertonikern

    NASA Astrophysics Data System (ADS)

    Möseneder, Jutta M.

    2002-01-01

    In der randomisierten, multizentrischen DASH-Studie (Dietary Approaches to Stop Hy-pertension), die unter kontrollierten Bedingungen stattfand, führte eine fettreduzierte Mischkost, reich an Obst, Gemüse und Milchprodukten, bei Borderline-Hypertonikern zu einer signifikanten Blutdrucksenkung. Während der Studienphase wurden Körpermasse, Natrium-Aufnahme sowie Alkoholzufuhr aufgrund der bekannten Einflussnahme auf den Blutdruck konstant gehalten. In der eigenen Pilot-Studie sollte untersucht werden, ob das Ergebnis der DASH-Studie (i) mit deutschen Hypertonikern und (ii) unter habituellen Ernährungs- und Lebensbedingungen mit regelmäßig durchgeführter Ernährungsberatung und ad libitum Verzehr anstelle des streng kontrollierten Studienansatzes bestätigt werden kann. Eine Konstanz der Körpermasse, der Natrium-Urinausscheidung (unter diesem Studienansatz valider als die Aufnahme) und des Alkoholkonsums wurde vorausgesetzt. Die Studienpopulation setzte sich aus 53 übergewichtigen Probanden mit einer nicht medikamentös therapierten Borderline-Hypertonie und ohne Stoffwechselerkrankungen zusammen. Die Studienteilnehmer wurden randomisiert entweder der Idealgruppe mit einer fettarmen Kost reich an Milchprodukten, Obst und Gemüse (ähnlich der DASH-Idealgruppe) oder der Kontrollgruppe mit habitueller Ernährungsweise zugeteilt. Über einen Zeitraum von fünf Wochen wurde den Probanden etwa 50% ihres täglichen Lebensmittelbedarfes entsprechend ihrer Gruppenzugehörigkeit kostenfrei zur Verfügung gestellt. Gelegenheitsblutdruckmessungen und 24h-Blutdruckmessungen, Ernährungs- und Aktivitätsprotokolle, Blut- und Urinproben sowie anthropometrische Messungen wurden vor, während und fünf Wochen nach der Interventionsphase durchgeführt. Die Ergebnisse zeigen, dass in der Idealgruppe keine signifikante Blutdrucksenkung beobachtet werden konnte. Dies lässt sich durch die Tatsache erklären, dass die Lebens-mittel- und Nährstoffaufnahme der deutschen

  3. Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome

    PubMed Central

    Bedeschi, M.F.; Colombo, L.; Mari, F.; Hofmann, K.; Rauch, A.; Gentilin, B.; Renieri, A.; Clerici, D.

    2011-01-01

    Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation. PMID:22140376

  4. Auditory Function in Children with Charcot-Marie-Tooth Disease

    ERIC Educational Resources Information Center

    Rance, Gary; Ryan, Monique M.; Bayliss, Kristen; Gill, Kathryn; O'Sullivan, Caitlin; Whitechurch, Marny

    2012-01-01

    The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of…

  5. Genetics Home Reference: Charcot-Marie-Tooth disease

    MedlinePlus

    ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  6. Causes of Charcot-Marie-Tooth Disease (CMT)

    MedlinePlus

    ... The peripheral nerve fibers, called axons , extend from sensory nerve cells in the body's periphery back toward ... which explains why CMT mostly causes motor and sensory problems in the body’s extremities. Inheritance patterns in ...

  7. Data assimilative twin-experiment in a high-resolution Bay of Biscay configuration: 4DEnOI based on stochastic modeling of the wind forcing

    NASA Astrophysics Data System (ADS)

    Vervatis, V.; Testut, C. E.; De Mey, P.; Ayoub, N.; Chanut, J.; Quattrocchi, G.

    2016-04-01

    A twin-experiment is carried out introducing elements of an Ensemble Kalman Filter (EnKF), to assess and correct ocean uncertainties in a high-resolution Bay of Biscay configuration. Initially, an ensemble of 102 members is performed by applying stochastic modeling of the wind forcing. The target of this step is to simulate the envelope of possible realizations and to explore the robustness of the method at building ensemble covariances. Our second step includes the integration of the ensemble-based error estimates into a data assimilative system adopting a 4D Ensemble Optimal Interpolation (4DEnOI) approach. In the twin-experiment context, synthetic observations are simulated from a perturbed member not used in the subsequent analyses, satisfying the condition of an unbiased probability distribution function against the ensemble by performing a rank histogram. We evaluate the assimilation performance on short-term predictability focusing on the ensemble size, the observational network, and the enrichment of the ensemble by inexpensive time-lagged techniques. The results show that variations in performance are linked to intrinsic oceanic processes, such as the spring shoaling of the thermocline, in combination with external forcing modulated by river runoffs and time-variable wind patterns, constantly reshaping the error regimes. Ensemble covariances are able to capture high-frequency processes associated with coastal density fronts, slope currents and upwelling events near the Armorican and Galician shelf break. Further improvement is gained when enriching model covariances by including pattern phase errors, with the help of time-neighbor states augmenting the ensemble spread.

  8. Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

    SciTech Connect

    Al-Mamgani, Abrahim; Rooij, Peter van; Verduijn, Gerda M.; Meeuwis, Cees A.; Levendag, Peter C.

    2012-09-01

    Purpose: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Methods and Materials: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. Results: After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade {>=}2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Conclusions: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in

  9. Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum

    PubMed Central

    Brunger, Axel T.; Das, Debanu; Deacon, Ashley M.; Grant, Joanna; Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Levitt, Michael; Schröder, Gunnar F.

    2012-01-01

    Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence. PMID:22505259

  10. Patient-reported outcomes at hospital discharge from Heart Centres, a national cross-sectional survey with a register-based follow-up: the DenHeart study protocol

    PubMed Central

    Berg, Selina Kikkenborg; Svanholm, Jette; Lauberg, Astrid; Borregaard, Britt; Herning, Margrethe; Mygind, Anna; Christensen, Anne Vinggaard; Christensen, Anne Illemann; Ekholm, Ola; Juel, Knud; Thrysøe, Lars

    2014-01-01

    Introduction Patient reported health status, which includes symptom burden, functional status and quality of life, is an important measure of health. Differences in health status between diagnostic groups within cardiology have only been sparsely investigated. These outcomes may predict morbidity, mortality, labour market affiliation and healthcare utilisation in various diagnostic groups. A national survey aiming to include all cardiac diagnostic groups from a total Heart Centre population has been designed as the DenHeart survey. Methods and analysis DenHeart is designed as a cross-sectional survey with a register-based follow-up. All diagnostic groups at the five national Heart Centres are included during 1 year (15 April 2013 to 15 April 2014) and asked to fill out a questionnaire at hospital discharge. The total eligible population, both responders and non-responders, will be followed in national registers. The following instruments are used: SF-12, Hospital Anxiety and Depression Scale, EQ-5D, Brief Illness Perception Questionnaire (B-IPQ), HeartQoL and Edmonton Symptom Assessment Scale. The following variables are collected from national registers: action diagnosis, procedures, comorbidity, length of hospital stay, type of hospitalisation, visits to general practitioners and other agents in primary healthcare, dispensed prescription medication, vital status and cause of death. Labour market affiliation, sick leave, early retirement pension, educational degree and income will be collected from registers. Frequency distributions and multiple logistic regression analyses will be used to describe and assess differences in patient reported outcomes at hospital discharge between diagnostic groups and in-hospital predicting factors. Cox proportional hazards regression models with age as the time scale will be used to investigate associations between patient reported outcomes at baseline and morbidity/mortality, labour market affiliation and healthcare utilisation

  11. Erfahrungen mit den Pentax SDHF-Refraktoren.

    NASA Astrophysics Data System (ADS)

    de Lignie, J.

    1996-10-01

    Behandelt werden: die SDHF-Refraktoren, mechanische Eigenschaften und Verarbeitung, die Montierung MS-3n, Beobachtungen mit der SDHF-Optik und optische Qualität, der 75 SDHF, der 105 SDHF. Fotografischer Teil: die Pentax 645 als Astrokamera, fotografische Abbildung der Objektive zur Pentax 645 und der SDHF-Optik, Zubehör.

  12. Wasserversorgung in den schleswig-holsteinischen Marschengebieten

    NASA Astrophysics Data System (ADS)

    Coldewey, Wilhelm Georg; Meier, Dirk

    2015-03-01

    Archeological findings from the Roman Imperial era show that already in the first centuries A.D., people were actively searching for solutions for their water supply problems in the marshy regions of the North Sea coast. These problems were solved by using simple installations in the form of water pits as well as more complex structures such as dug wells with different inflows and outflows. The water supply system used on the North Frisian Halligen is particularly elaborate, consisting of well-like reservoirs. It was only with the flood disaster of 1962 that a radical change took place. Because the storm surge caused saltwater to penetrate into the historical supply installations, they could no longer be used for drinking water purposes and were replaced by fresh water pipes from the mainland. Only the water pits and the dew ponds have withstood the test of time and may potentially be used in the future.

  13. Articulating Breath: Writing Charcot's Hysteric with "Performance Writing"

    ERIC Educational Resources Information Center

    Worden, Jessica

    2014-01-01

    The overlap between the visual and textual in practice research provides an opportunity to explore ways of presenting knowledge through "performance writin". The purpose of this paper is to demonstrate how a performance writing practice can be incorporated into and shape research writing. This text uses descriptions of Jean-Martin…

  14. Chao Mung Den Dat My (Welcome to America).

    ERIC Educational Resources Information Center

    Los Angeles County Commission on Human Relations, CA.

    The purpose of this booklet is to introduce Southeast Asian refugees to some American attitudes and social styles. The complete English text is repeated in Khmer (Cambodian language) and Vietnamese. Topics discussed include: America as a very young country; America as a mixture of different people; that urban life is complex, fast-paced, and…

  15. Reflections on My Time in the Wolfe Den

    NASA Technical Reports Server (NTRS)

    Stahl, H. Philip

    2012-01-01

    The three and a half years I spent as a member of the Infrared Group were transitional. Bill Wolfe was the nexus. Bill played a role in getting me to Arizona and keeping me there. He helped me advance professionally and taught me how to think like a systems engineer. He played a central role in my effort to earn a PhD. And, he helped start me in SPIE. This paper contains my personal and honest reflections on the impact which Bill Wolfe has had on me.

  16. Ueber den Nachweis von Exoplaneten in der ASAS-3 Datenbank

    NASA Astrophysics Data System (ADS)

    Huemmerich, Stefan; Bernhard, Klaus

    2015-02-01

    Under favourable circumstances, transits of known exoplanets with large amplitudes like WASP-18 b can be observed in the ASAS-3 database. An attempt to search for exoplanets using ASAS-3 data is discussed.

  17. Osteitis in the dens of axis caused by Treponema pallidum

    PubMed Central

    2013-01-01

    Background Syphilis has been referred to as “the great imitator” due to its ability to imitate other diseases. Untreated syphilis becomes a systemic infection that can involve almost every organ systems. Treponema pallidum has a high affinity for bone tissue, but osteitis has mainly been described in late stages of the disease. Vertebral involvement is rare, and this is to our knowledge the first case describing syphilitic spondylitis in early acquired syphilis. Case presentation We here describe destructive osteitis in the vertebral column as the initial manifestation of early acquired syphilis in a 24-year-old caucasian homosexual male with HIV infection. The diagnosis was reached by universal bacterial PCR and DNA sequencing of the DNA product. It was confirmed by PCR specific for Treponema pallidum, immunohistochemistry and detection of increasing antibody titer. Conclusions As syphilis has re-emerged in Western countries and remains a worldwide common disease it is important to have in mind as a causative agent of skeletal symptoms, especially among HIV-infected individuals or men who have sex with men (MSM). PMID:23885957

  18. Historisches Rätsel Er hatte den Durchblick

    NASA Astrophysics Data System (ADS)

    Loos, Andreas

    2002-03-01

    Seine Jugend ist voller Schicksalsschläge: Mit zwölf Jahren wird er als elftes und jüngstes Kind eines Glasermeisters Vollwaise, mit vierzehn stürzt das Haus seines Pflegevaters und Lehrherren über ihm zusammen. Auch ist ihm kein langes Leben vergönnt: Mit gerade 39 Jahren ereilt ihn die Lungen- und Nervenschwindsucht.

  19. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  20. Learn About Neuromuscular Disease

    MedlinePlus

    ... Muscular Atrophy (Charcot-Marie-Tooth Disease) Phosphofructokinase Deficiency Phosphoglycerate Kinase Deficiency Phosphoglycerate Mutase Deficiency Phosphorylase Deficiency Phosphorylase Deficiency Polymyositis ( ...

  1. Changes of gait pattern in children with Charcot-Marie-Tooth disease type 1A: a 18 months follow-up study

    PubMed Central

    2013-01-01

    Background In a previous study we identified 3 different gait patterns in a group of children with CMT1A disease: Normal-like (NL), Foot-drop (FD), Foot-drop and Push-off Deficit (FD&POD). Goal of the present study was to perform a follow-up evaluation of the same group of patients to analyze possible changes of gait features in relation to disease progression or specific therapy. Methods Nineteen children with CMT1A were evaluated clinically (CMT-Examination Score and Overall Neuropathy Limitation Scale) and through gait analysis 18.2±1.5 months after a baseline evaluation. Meanwhile, 3 of them had foot surgery. Results Fifteen out of the 16 non-operated patients significantly changed at least one of the two parameters associated to primary signs (FD and/or POD). Eleven participants worsened at least one parameter and 9 improved one parameter. CMTES significantly worsened for the group of non-operated patients. However, there was no change in CMTES score in 4 patients and in ONLS score in 11. At subgroup level, participants originally belonging to NL group showed a trend towards a foot-drop deficit (−15%, ns); FD and FD&POD subgroups did not change their primary signs, although significant changes were identified individually. All 3 patients operated have improved push-off and proximal joint patterns during walking. Clinical scores did not change within any sub-group. Conclusions Subtle changes occurring in 1.5 year in gait features of CMT1A children can be instrumentally identified. Such changes show a large inter-subject variability, with some patients even improving their walking pattern. There is anecdotal evidence that foot surgery may improve the push-off phase of gait. PMID:23819439

  2. X-linked Charcot-Marie-Tooth (CMT) neuropathies (CMTX1, CMTX2, CMTX3) show different clinical phenotype and molecular genetics

    SciTech Connect

    Ionasescu, V.V.; Searby, C.C.; Ionasescu, R.

    1994-09-01

    The purpose of this study was to compare the X-linked dominant type CMTX1 (20 families) with X-linked recessive types CMTX2 and CMTX3 (2 families). The clinical phenotype was consistent with CMT peripheral neuropathy in all cases including distal weakness, atrophy and sensory loss, pes cavus and areflexia. Additional clinicial involvement of the central nervous system was present in one family with CMTX2 (mental retardation) and one family with CMTX3 (spastic paraparesis). Tight genetic linkage to Xq13.1 was present in 20 families with CMTX1 (Z=34.07 at {theta}=0) for the marker DXS453. Fifteen of the CMTX1 families showed point mutations of the connexin 32 coding region (5 nonsense mutations, 8 missense mutations, 2 deletions). Five CMTX1 neuropathy families showed no evidence of point mutations of the CX32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype in these families may be the result of promoter mutations, 3{prime}-untranslated region mutations or exon/intron splice site mutations or a mutation with a different type of connexin but which has close structural similarities to CX32. No mutations of the CX32 coding region were found in the CMTX2 or CMTX3 families. Linkage to Xq13.1 was excluded in both families. Genetic linkage to Xp22.2 was present in the CMTX2 family (Z=3.54 at {theta}=0) for the markers DXS987 and DXS999. Suggestion of linkage to Xq26 (Z=1.81 at {theta}=0) for the marker DXS86 was present in the CMTX3 family.

  3. Arbeitsmittel fur den Deutschunterricht an Auslander (Materials for German Instruction to Foreigners).

    ERIC Educational Resources Information Center

    Kaufmann, Gerhard, Comp.

    This annotated German bibliography of textbooks for use in language programs includes a wide variety of instructional media. Materials are classified under: (1) language texts, (2) teachers' texts, (3) language texts for foreigners, (4) exercise books and tapes, (5) testing materials, (6) radio courses, (7) instructional films, (8) vocational…

  4. Floral volatiles ofTanacetum vulgare L. attractive toLobesia botrana den. et schiff. females.

    PubMed

    Gabel, B; Thiéry, D; Suchy, V; Marion-Poll, F; Hradsky, P; Farkas, P

    1992-05-01

    The European grapevine moth (EGVM),Lobesia botrana, is a major pest of grapes in Europe. Females are attracted to a nonhost plant: tansy (Tanacetum vulgare L.), which is a common weed in Slovakian vineyards. A steam distillate extract of tansy flowers was analyzed by means of a GC-EAG technique to screen constituents detected by the olfactory receptors of EGVM females. From more than 200 GC peaks, nine peaks corresponding to monoterpenoids released an EAG response in more than 70% of the females (N=15):p-cymene,d-limonene,α-thujene,α-thujone,β-thujone, thujyl alcohol, terpinene-4-ol, (Z)-verbenol, and piperitone. The steam distillate of tansy as well as a synthetic blend of identified compounds released consistent attraction in a field cage. The use of nonhost plants and host plant odors in integrated pest management is discussed. PMID:24253963

  5. Eine photometrische Loesung f¸r den Doppelstern V381 Canis Majoris

    NASA Astrophysics Data System (ADS)

    Hauck, Norbert

    2015-04-01

    V381 CMa is known as a bright eclipsing binary system having an orbital period of 3.4 days. Modelling of old and new photometric data now revealed an annular eclipse in the primary minimum, i.e. a transit of a smaller and cooler companion in front of the A-type star primary component. By combining the obtained relative parameters of the components with stellar models a mass of about 2.76 Msun and a radius of 4.39 Rsun has been derived for the A-type star, and a mass of about 0.79 Msun and a radius of 0.72 Rsun for the secondary component having a Teff of about 4850 K. Apparently, the components of the binary can be classified as an A-type subgiant and a K-type dwarf. [The online version of this paper is written in German and English].

  6. First trace and body fossil evidence of a burrowing, denning dinosaur

    PubMed Central

    Varricchio, David J; Martin, Anthony J; Katsura, Yoshihiro

    2007-01-01

    A fossil discovery in the mid-Cretaceous Blackleaf Formation of southwest Montana, USA, has yielded the first trace and body fossil evidence of burrowing behaviour in a dinosaur. Skeletal remains of an adult and two juveniles of Oryctodromeus cubicularis gen. et sp. nov., a new species of hypsilophodont-grade dinosaur, were found in the expanded distal chamber of a sediment-filled burrow. Correspondence between burrow and adult dimensions supports Oryctodromeus as the burrow maker. Additionally, Oryctodromeus exhibits features of the snout, shoulder girdle and pelvis consistent with digging habits while retaining cursorial hindlimb proportions. Association of adult and young within a terminal chamber provides definitive evidence of extensive parental care in the Dinosauria. As with modern vertebrate cursors that dig, burrowing in Oryctodromeus may have been an important adaptation for the rearing of young. Burrowing also represents a mechanism by which small dinosaurs may have exploited the extreme environments of polar latitudes, deserts and high mountain areas. The ability among dinosaurs to find or make shelter may contradict some scenarios of the Cretaceous–Paleogene impact event. Burrowing habits expand the known range of nonavian dinosaur behaviours and suggest that the cursorial ancestry of dinosaurs did not fully preclude the evolution of different functional regimes, such as fossoriality. PMID:17374596

  7. Congenital anomaly of craniovertebral junction: atlas-dens fusion with C1 anterior arch cleft.

    PubMed

    Pérez-Vallina, José R; Riaño-Galán, Isolina; Cobo-Ruisánchez, Angeles; Orejas-Rodriguez-Arango, Gonzalo; López-Muñiz, Carlos; Fernández-Martínez, José M

    2002-02-01

    A rare case of congenital atlantoaxial block is reported. A 13-year-old boy had a fusion of a non-separated odontoid process with the anterior arch of the atlas, in association with an anterior midline C1 arch cleft. PMID:11891461

  8. Nay'nadeligha I'ghaan Dghat'aen'den (The War at Nay'nadeli).

    ERIC Educational Resources Information Center

    Peters, Henry

    This reader is intended for use in a bilingual education setting and is geared towards students who are competent speakers of Ahtna Athabaskan with knowledge of the writing system. It is an historical account of a battle and its aftermath from the Cantwell area. It includes an interlinear English translation and a free English translation. (AMH)

  9. Rear-Guard Actions against an "Impoverishing Delusion": Anmerkungen zur Situation der Auslandsgermanistik in den Americas

    ERIC Educational Resources Information Center

    McCarthy, John A.

    2010-01-01

    This contribution responds to the previous three articles by highlighting common concerns across the Americas. It also offers suggestions for how the field of German might want to move forward in an inclusive fashion. Key principles of orientation are EU language policy and transcultural education as a transformative experience in shaping…

  10. Pyritoxidationsprozesse im cretazischen Emschermergel infolge von aeroben Bedingungen durch den Emscherumbau

    NASA Astrophysics Data System (ADS)

    Droste, Björn; Wisotzky, Frank

    2015-09-01

    Due to the restoration of the Emscher river system, large amounts of the Emschermergel, a Cretaceous sediment containing significant amounts of carbonate and pyrite, will be released from its anoxic state. The oxidation of pyrite results in the release of protons, iron and sulfate. In order to evaluate the impact of the reaction products, extensive laboratory investigations were carried out. The methodology can detect pyrite content in the range of magnitude of the Rhenish lignite mining area (average 0.21 wt.% Pyritic-S). The formation of a naturally-occurring weathering horizon could also be detected. Under laboratory conditions, further oxidation of the weathered laboratory samples could be observed. Column experiments show significant release of sulfate at high concentrations. Hydrochemical modelling and acid-base accounting show neutralization of the free protons by the effective carbonate buffer in the sediment.

  11. VizieR Online Data Catalog: HST/ACS Coma Cluster Survey. X. (den Brok+, 2014)

    NASA Astrophysics Data System (ADS)

    den Brok, M.; Peletier, R. F.; Seth, A.; Balcells, M.; Dominguez, L.; Graham, A. W.; Carter, D.; Erwin, P.; Ferguson, H. C.; Goudfrooij, P.; Guzman, R.; Hoyos, C.; Jogee, S.; Lucey, J.; Phillipps, S.; Puzia, T.; Valentijn, E.; Kleijn, G. V.; Weinzirl, T.

    2015-05-01

    The Coma ACS Survey (Carter et al., 2008ApJS..176..424C) provides data in two passbands for 25 fields pointed at the core of the Coma cluster and at the outskirts. The exposure times in the two passbands, F814W and F475W (which are roughly equivalent to the IC and g band) were ~1400 and ~2600s. The original envisaged coverage of the cluster was much larger than 25 fields, but due to the ACS failure in 2008 January the survey was not completed. (2 data files).

  12. Identifizierung der Nitratabbauprozesse und Prognose des Nitratabbaupotenzials in den Sedimenten des Hessischen Rieds

    NASA Astrophysics Data System (ADS)

    Kludt, Christoph; Weber, Frank-Andreas; Bergmann, Axel; Knöller, Kay; Berthold, Georg; Schüth, Christoph

    2016-03-01

    Microbial denitrification contributes significantly to the mitigation of nitrate contamination in sedimentary aquifers by reducing nitrate coupled to the consumption of organic carbon (heterotrophic) and iron sulphides like pyrite (autotrophic). However, these phases are often only present in trace amounts and can become depleted, so that denitrification will eventually cease. In order to implement measures within the EC-Water Framework Directive, we investigated the denitrification potential and the denitrification processes in the sediments of the Hessian Ried. The reduction potential was quantified and characterized by solid-phase analyses of drill core samples. Depth-oriented investigations of hydrochemistry (i.e. stable isotopes, N2Excess) allowed determining nitrate input, reduction progress and average reduction kinetics upstream of selected wells. Despite low sulphide contents (max. 123 mg-S/kg), autotrophic denitrification was typically the dominant process. The results can be used to delineate risk areas, downstream of which denitrification can be expected to cease in the near future.

  13. Curriculare Schwerpunkte und Entwiklungstrends im Erziehungs und Gesellschaftswissenschaftlichen Studium fur Den Lehrerberuf in der Bundesrepublik Deutschland

    ERIC Educational Resources Information Center

    Bayer, Manfred; Kolbe, Manfred

    1975-01-01

    An empirical study on the curricular content of lectures offered to education students in the Federal Republic of Germany was designed to ascertain what knowledge and competency can be acquired by attending the available courses. In German; introduction in English. (MM)

  14. Progress in molecular diagnosis of Charcot-Marie-Tooth-disease type 1 (CMT 1, HMSN I) and hereditary neuropathy with liability to pressure palsies (HNPP) by fluorescence in situ hybridization (FISH)-detection of a potential genetic mosaicism

    SciTech Connect

    Bathke, K.; Liehr. T.; Ekici, A.

    1994-09-01

    We tested 20 CMT 1 patients characterized according to the criteria of the European CMT consortium by Southern hybridization of MspI restricted genomic DNA with probes pVAW409R1, pVAW412Hec and pEW401HE. In 11 of the 20 CMT 1 cases (55%), we observed a duplication in 17q11.2; one patient had a dinucleotide insertion in exon 6 of the PO-gene (5%). One HNPP case had a typical 17p11.2 deletion. Analysis of CA-repeats was performed with primers RM11GT and Mfd41; SSCP-analysis of the PO, PMP22 and Cx32-genes is in progress. FISH was carried out with probe pVAW409R1. 125 interphase nuclei were analyzed for each proband by counting the signals per nucleus. Normal cells show a characteristic distribution of signals: 1 signal in 5.9% of nuclei, 2 in 86.3% and 3 in 7.8%. A duplication is indicated by a shift to 3 signals in more than approximately 60% and 2 in less than 25% of the nuclei. In contrast, the 17p11.2 deletion of the HNPP patient shifts to 82.4% of nuclei with a single hybridization signal versus 14.4% with 2 signals. We detected one case with significantly abnormal distribution of interphase nuclei hybridization signals compared to cultures of normal cells and to those with 17p11.2 duplication or deletion: 3.2% nuclei revealed 1 signal, 48.0% two signals and 48.8% 3 signals, indicating a pathogenic but moderate dosis increase compared to the throughout duplicated cases. FISH with probe pVAW409R1 is a versatile tool to detect the HNPP deletion both in interphase nuclei and in metaphase chromosomes. In CMT 1 disease interphase nuclei are required for FISH analysis due to the small duplication of 1.5 Mbp. In contrast to Southern techniques, FISH is able to detect genetic mosaicism.

  15. Versuch einer Ubungstypologie fur den fachbezogenen Fremdsprachenunterricht (A Trial Typology of Exercises for Career-Oriented Foreign Language Instruction)

    ERIC Educational Resources Information Center

    Becker, Norbert

    1973-01-01

    Examples of exercises derived from the text Fachdeutsch fur spanischsprachige Naturwissenschaftler: Mathematiker, Physiker, Chemiker'' (Technical German for Spanish-Speaking Scientists: Mathematicians, Physicists, Chemists) soon to be published by the Max Hueber Verlag, Munich, West Germany. (RS)

  16. Fernsehkurs staerker in den Russischunterricht integrieren (Integrating the Television Course More Firmly into the Teaching of Russian)

    ERIC Educational Resources Information Center

    Sattler, Gerda

    1975-01-01

    Reports on experiences covering two years of use of a Russian television course for Grade 9. The course is seen as particularly useful in reinforcing knowledge of vocabulary of past lessons. Several practical hints to the teacher, e.g., preparation for the television lesson, are offered. (Text is in German.) (IfS/WGA)

  17. Bericht uber den 2. Internationalen Kongress fur Angewandte Linguistik (Report on the Second International Congress for Applied Linguistics).

    ERIC Educational Resources Information Center

    Mohr, Peter

    This report of the 1969 Second International Congress for Applied Linguistics contains summaries of papers and speeches on the following topics: (1) linguistics applied to literary texts, (2) computer analysis of texts, (3) research in the psychology of first language learning, (4) research in the psychology of second language learning, (5) speech…

  18. In the footsteps of astronomers in Bremen and Lilienthal. (German Title: Auf den Spuren von Astronomen in Bremen und Lilienthal)

    NASA Astrophysics Data System (ADS)

    Langkavel, Arno

    When Bremen and Lilienthal are mentioned, people interested in the history of astronomy will first of all remember Wilhelm Olbers (1785-1840) and Johann Hieronymus Schroeter (1745-1816). In addition to them, Friedrich Wilhelm Bessel (1784-1846) and Carl Friedrich Gauß (1777-1855) have also left their traces. Two walks describe the main memorial sites, which are all outdoors and easily accessible to the general public.

  19. VizieR Online Data Catalog: FeI radiative lifetime and branching fractions (Den Hartog+, 2014)

    NASA Astrophysics Data System (ADS)

    Den Hartog, E. A.; Ruffoni, M. P.; Lawler, J. E.; Pickering, J. C.; Lind, K.; Brewer, N. R.

    2015-02-01

    From our recent work for the APOGEE and Gaia-ESO surveys (Ruffoni et al. 2013ApJ...779...17R; 2014, J/MNRAS/441/3127), we have assembled a catalog of high-resolution, intensity calibrated FeI line spectra, measured in emission by Fourier transform (FT) spectroscopy in overlapping regions from 1800/cm to 35500/cm. From this catalog, we have used the two spectra shown in Table 2 to measure branching fractions (BFs) for lines linked to many of the levels listed in Table 1. (2 data files).

  20. Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits.

    PubMed

    Johnson, Barbara W; Goodman, Christin H; Jee, Youngmee; Featherstone, David A

    2016-04-01

    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JEDetect™ MAC-ELISA (JEDetect), a differential testing algorithm was developed in which samples tested by JEDetect with positive results were subsequently tested by the DENDetect™ MAC-ELISA (DENDetect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JEDetect and DENDetect and were classified as JE- (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JEDetect and DENDetect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID:26856911

  1. Die Sprache der Hande zu den Handen sprechen (Talking the Language of the Hands to the Hands). DB-LINK.

    ERIC Educational Resources Information Center

    Miles, Barbara

    This paper examines the importance of hands for the person who is deafblind, reviews hand development, and identifies specific teaching skills that facilitate hand development and expressiveness in persons who are deafblind. It notes that the hands of a deafblind individual serve not only as tools but also as sense organs (to compensate for their…

  2. Gene Expression Analysis Indicates Divergent Mechanisms in DEN-Induced Carcinogenesis in Wild Type and Bid-Deficient Livers.

    PubMed

    Yu, Changshun; Yan, Shengmin; Khambu, Bilon; Chen, Xiaoyun; Dong, Zheng; Luo, Jianhua; Michalopoulos, George K; Wu, Shangwei; Yin, Xiao-Ming

    2016-01-01

    Bid is a Bcl-2 family protein. In addition to its pro-apoptosis function, Bid can also promote cell proliferation, maintain S phase checkpoint, and facilitate inflammasome activation. Bid plays important roles in tissue injury and regeneration, hematopoietic homeostasis, and tumorigenesis. Bid participates in hepatic carcinogenesis but the mechanism is not fully understood. Deletion of Bid resulted in diminished tumor burden and delayed tumor progression in a liver cancer model. In order to better understand the Bid-regulated events during hepatic carcinogenesis we performed gene expression analysis in wild type and bid-deficient mice treated with a hepatic carcinogen, diethylnitrosamine. We found that deletion of Bid caused significantly fewer alterations in gene expression in terms of the number of genes affected and the number of pathways affected. In addition, the expression profiles were remarkably different. In the wild type mice, there was a significant increase in the expression of growth regulation-related and immune/inflammation response-related genes, and a significant decrease in the expression of metabolism-related genes, both of which were diminished in bid-deficient livers. These data suggest that Bid could promote hepatic carcinogenesis via growth control and inflammation-mediated events. PMID:27196317

  3. Gene Expression Analysis Indicates Divergent Mechanisms in DEN-Induced Carcinogenesis in Wild Type and Bid-Deficient Livers

    PubMed Central

    Yu, Changshun; Yan, Shengmin; Khambu, Bilon; Chen, Xiaoyun; Dong, Zheng; Luo, Jianhua; Michalopoulos, George K.; Wu, Shangwei; Yin, Xiao-Ming

    2016-01-01

    Bid is a Bcl-2 family protein. In addition to its pro-apoptosis function, Bid can also promote cell proliferation, maintain S phase checkpoint, and facilitate inflammasome activation. Bid plays important roles in tissue injury and regeneration, hematopoietic homeostasis, and tumorigenesis. Bid participates in hepatic carcinogenesis but the mechanism is not fully understood. Deletion of Bid resulted in diminished tumor burden and delayed tumor progression in a liver cancer model. In order to better understand the Bid-regulated events during hepatic carcinogenesis we performed gene expression analysis in wild type and bid-deficient mice treated with a hepatic carcinogen, diethylnitrosamine. We found that deletion of Bid caused significantly fewer alterations in gene expression in terms of the number of genes affected and the number of pathways affected. In addition, the expression profiles were remarkably different. In the wild type mice, there was a significant increase in the expression of growth regulation-related and immune/inflammation response-related genes, and a significant decrease in the expression of metabolism-related genes, both of which were diminished in bid-deficient livers. These data suggest that Bid could promote hepatic carcinogenesis via growth control and inflammation-mediated events. PMID:27196317

  4. Nitrogen input into the soil by N{sub 2} fixing plants; Stickstoffeintrag in den boden durch stickstoffixierende pflanzen

    SciTech Connect

    Haunold, E.

    1992-04-01

    Only prokaryontic organisms are able to fix nitrogen. These are about 200 species of bacteria and blue green algae. Of their biochemical efficiency about 500,000 eukaryontic plants (thereof about 340,000 species of flowering plants and more than 100,000 species of fungi) and over 1,000,000 species of animals profit. On a global scale about 200 Mio t/a of nitrogen is being fixed by the prokaryonts. Air nitrogen in legumes varies between 50 and 90% and depends upon the relationship between host and microbe, nutrient status of the soil, water and climatic conditions etc.

  5. Fishers' knowledge as a source of information about the estuarine dolphin (Sotalia guianensis, van Bénéden, 1864).

    PubMed

    Manzan, Maíra Fontes; Lopes, Priscila F M

    2015-01-01

    Fishers' local ecological knowledge (LEK) is an additional tool to obtain information about cetaceans, regarding their local particularities, fishing interactions, and behavior. However, this knowledge could vary in depth of detail according to the level of interaction that fishers have with a specific species. This study investigated differences in small-scale fishers' LEK regarding the estuarine dolphin (Sotalia guianensis) in three Brazilian northeast coastal communities where fishing is practiced in estuarine lagoons and/or coastal waters and where dolphin-watching tourism varies from incipient to important. The fishers (N = 116) were asked about general characteristics of S. guianensis and their interactions with this dolphin during fishing activities. Compared to lagoon fishers, coastal fishers showed greater knowledge about the species but had more negative interactions with the dolphin during fishing activities. Coastal fishing not only offered the opportunity for fishers to observe a wider variety of the dolphin's behavior, but also implied direct contact with the dolphins, as they are bycaught in coastal gillnets. Besides complementing information that could be used for the management of cetaceans, this study shows that the type of environment most used by fishers also affects the accuracy of the information they provide. When designing studies to gather information on species and/or populations with the support of fishers, special consideration should be given to local particularities such as gear and habitats used within the fishing community. PMID:25399120

  6. [Babinski and hysteria].

    PubMed

    Allilaire, Jean-François

    2007-10-01

    Babinski made important contributions to both psychiatry and neurology. He disagreed with Charcot's theatrical interpretation of hysteria and made a subtle distinction between Suggestion and Persuasion, thereby differentiating Hysteria from Pithiatism. This paper examines Charcot's concepts and the way in which Babinski refined and honed his master's theories. PMID:18447055

  7. CMT1

    MedlinePlus

    ... 1 is the most common subtype of CMT, accounting for roughly two-thirds of all cases. CMT1 ... CMT Signs and Symptoms Diagnosis Causes/Inheritance Medical Management Research Living With Charcot-Marie-Tooth Disease (CMT) ...

  8. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    ClinicalTrials.gov

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  9. Qualitative Data Collection and Interpretation: A Turkish Social Studies Lesson=Nitel Veri Toplama ve Yorumlama: Türkiye' den bir Sosyal Bilgiler Dersi

    ERIC Educational Resources Information Center

    Grammes, Tilman; Açikalin, Mehmet

    2016-01-01

    The classroom with its teaching-learning dynamics creates a kind of "embryonic society" in which the micro-policies of collective social knowledge construction and meaning can be re-constructed; therefore, it can be considered as a kind of "mirror" of political culture. Thus, comparative lesson research, which requires in-depth…

  10. Die Religiose Konstante. Uber den padagogischen Umgang mit naturwissenshcaftlichen Hypothesen (The Religious Constant--The Interpretation of Hypotheses of the Natural Sciences in Educational Theory).

    ERIC Educational Resources Information Center

    Neumann, Dieter

    1999-01-01

    Shows how evolution-theoretical behavioral research may serve to influence the theory production of pedagogics. Questions which truths and securities are required by educational practice and which consequences can be drawn for the level of theoretical cognition of the respective discipline. An analysis of the relation between religion in its…

  11. Phylogenetic relationships among members of the Comamonadaceae, and description of Delftia acidovorans (den Dooren de Jong 1926 and Tamaoka et al. 1987) gen. nov., comb. nov.

    PubMed

    Wen, A; Fegan, M; Hayward, C; Chakraborty, S; Sly, L I

    1999-04-01

    The phylogenetic relationships among members of the family Comamonadaceae and several unclassified strains were studied by direct sequencing of their PCR-amplified 16S rRNA genes. Based on the 16S rRNA gene sequence analysis, members of the family formed a coherent group. The closest relatives are species of the Rubrivivax sub-group: Leptothrix discophora, Ideonella dechloratans and Rubrivivax gelatinosus. The genus Hydrogenophaga formed two subclusters, as did the species of Acidovorax, whereas the five species of the genus [Aquaspirillum] were polyphyletic. Comamonas acidovorans was phylogenetically distant from the type species of Comamonas, Comamonas terrigena. On the basis of this work and previous studies, Comamonas acidovorans is removed from the genus Comamonas and renamed as Delftia acidovorans gen. nov., comb. nov. Descriptions of the new genus Delftia and of the type species Delftia acidovorans, for which the type strain is ATCC 15668T, are presented. PMID:10319477

  12. Grüne Infrastruktur in den Städten Nordrhein-Westfalens - Bedeutung als Standortfaktor und Einfluss auf das Standortmarketing

    NASA Astrophysics Data System (ADS)

    Schäffer, Ina

    2016-05-01

    Hardly any other city in North Rhine-Westphalia has such a green image as the city of Münster. It embodies the image of a livable city in Germany. Other North Rhine-Westphalian cities also work on their external perception and are approaching the task of getting a greener image for themselves in many ways. A central question is how it is done precisely and whether urban green infrastructure can be a locational factor to affect location-based marketing. This article deals with the strategies of various cities in North Rhine-Westphalia.

  13. Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation.

    PubMed

    Gassas, Adam; Schechter, Tal; Krueger, Joerg; Craig-Barnes, Hayley; Sung, Lillian; Ali, Muhammad; Dell, Sharon; Egeler, R Maarten; Zaidman, Irina; Palaniyar, Nades

    2015-08-01

    Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage. PMID:25963919

  14. Grüne Infrastruktur -. Konzepte und Strategien zur Förderung eines Bewusstseins für den Wert von Stadtgrün

    NASA Astrophysics Data System (ADS)

    Menke, Peter

    2016-06-01

    Due to climate change, but also because of the demographic change and financial constraints in many municipalities, the future of cities is a currently much-discussed topic. Conflicts over land-use are inevitable: As densification is an essential principle in growing cities, the pressure on open (green) spaces rises. Climate Change and water-management as well as mobility-issues and air-quality confront municipalities with new challenges, in terms of open space planning and greenery in the city. It is necessary to save the existing green in these days of budget-shortage and other priorities in communities. Municipalities have to raise new strategies to strengthen the awareness of the value of green in public and in the local business.

  15. Drei Wochen bei den Internationalen Sommerkursen in Erfurt, 22. Juli-11. August 1968 (Three Weeks at the International Summer Courses in Erfurt).

    ERIC Educational Resources Information Center

    Mayer, Elizabeth M.

    This paper discusses life in East Germany as observed by the author during a three-week program of summer courses in Erfurt. Background information includes a description of Erfurt, a brief review of its history, and analysis of the daily life of East Germans--their attitudes towards the state, physical appearance, salary structure, and…

  16. Grüne Infrastruktur in den Städten Nordrhein-Westfalens. Bedeutung als Standortfaktor und Einfluss auf das Standortmarketing

    NASA Astrophysics Data System (ADS)

    Schäffer, Ina

    2016-06-01

    Hardly any other city in North Rhine-Westphalia has such a green image as the city of Münster. It embodies the image of a livable city in Germany. Other North Rhine-Westphalian cities also work on their external perception and are approaching the task of getting a greener image for themselves in many ways. A central question is how it is done precisely and whether urban green infrastructure can be a locational factor to affect location-based marketing. This article deals with the strategies of various cities in North Rhine-Westphalia.

  17. Light and scanning electron microscopic study of the tongue in the estuarine dolphin (Sotalia guianensis van Bénéden, 1864).

    PubMed

    Guimarães, Juliana Plácido; Mari, Renata de Britto; Marigo, Juliana; Rosas, Fernando César Weber; Watanabe, Ii-Sei

    2011-08-01

    The importance of the tongue during feeding, and the limited information on the tongue of most aquatic mammals led us to investigate its morphological aspects in sexually immature and mature Sotalia guianensis. Six tongues were measured and photo-documented after their removal from the oral cavity. The samples were divided into rostral, middle, and caudal regions, and examined using light microscopy and scanning electron microscopy (S.E.M.). Sotalia guianensis tongue presented lateral grooves from the apex to the middle portion, while the anterolateral region presented marginal papillae. Histological characteristics revealed the presence of a keratinized stratified epithelium, salivary glands in the middle and caudal portions of the tongue, and filiform papillae in the caudal region. S.E.M. images revealed the presence of filiform papillae and ducts of salivary glands in the middle and caudal portions of the tongue. We can conclude that the characteristics found in this study may reflect an adaptation to changes in diet after weaning. PMID:21801004

  18. Han Hoan Chao Ban Den Hoa Ky. Sach Chi Dan Danh Cho Nguoi Ti Nan. (Welcome to the United States. A Guidebook for Refugees).

    ERIC Educational Resources Information Center

    Center for Applied Linguistics, Washington, DC. Refugee Service Center.

    This guidebook provides Vietnamese-speaking refugees being resettled in the United States with general information about what they will encounter and the services they can receive in their first months in the country. The book is distributed to overseas processing agencies, refugees overseas who have been approved for U.S. admission, and service…

  19. Feeding associations between Guiana dolphins, Sotalia guianensis (Van Bénèden, 1864) and seabirds in the Lagamar estuary, Brazil.

    PubMed

    Santos, M C O; Oshima, J E F; Pacífico, E S; Silva, E

    2010-02-01

    The main objective of the present study was to describe the characteristics regarding interactions between Guiana dolphins, Sotalia guianensis and seabirds in feeding associations in two distinct areas of the Lagamar estuary, Brazil. Boat-based surveys directed towards photo-identification studies of S. guianensis were conducted in the Cananéia Estuary (CE) (25 degrees 01' S and 47 degrees 55' W) from July 2004 to March 2008, as well as in the Paranaguá Estuarine Complex (PEC) (25 degrees 24' S and 48 degrees 24' W) from April 2006 to February 2008. On all occasions when seabirds were observed engaging in multi-species feeding associations with S. guianensis, data on species involved and their numbers were gathered. From 435 observed groups of S. guianensis in the CE, 38 (8.7%) involved interactions with seabirds. In the PEC, from the 286 observed groups, 32 (11.2%) involved the mentioned interactions. The following seabirds were observed in feeding associations with S. guianensis: Fregata magnificens, Sula leucogaster, Phalacrocorax brasilianus, and Sterna sp. In the CE, S. leucogaster was more commonly observed in feeding associations with Guiana dolphins (chi2 = 22.84; d.f. = 3, p < 0.05), while in the PEC no differences were reported when comparing seabird species (chi2 = 5.78; d.f.=3, p = 0.1223). In the CE, feeding associations were significantly more frequent in inner waters (subset A0; chi2 = 9.52; d.f. = 2, p < 0.05), and in winter (chi2 = 12.46; d.f. = 1, p < 0.05). Within these events, 44.7% of the association groups were composed by more than one seabird species. Seasonality in feeding associations was also observed in the PEC (chi2 = 4.76; d.f. = 1, p < 0.05), with same patterns observed in the CE. Interactions were more frequent in inner waters of the Laranjeiras bay, PEC (chi2 = 11.65; d.f. = 2, p < 0.05). Within these events, 74.2% of the association groups were composed by more than one seabird species. Water transparency, prey and seabird abundance and distribution, cetacean group size, and the life cycle of prey and seabirds are listed as the main factors addressing multi-species feeding associations in the Lagamar estuary. PMID:20231955

  20. Behaviour of Sotalia guianensis (van Bénéden, 1864) (Cetacea, Delphinidae) and ethnoecological knowledge of artisanal fishermen from Canavieiras, Bahia, Brazil

    PubMed Central

    2012-01-01

    Artisanal fishermen, because of their direct and frequent contact with the aquatic environment, possess a wealth of knowledge about the natural history of the fauna of the region in which they live. This knowledge, both practical and theoretical, has been frequently utilized and integrated into academic research. Taking this into consideration, this study discusses the ethnoecological knowledge of artisanal fishermen from a community in Canavieiras, state of Bahia, Brazil regarding the Guiana dolphin (Sotalia guianensis), a typically costal member of the family Delphinidae that is little studied in this region. To this end, the behaviour of S. guianensis in Canavieiras was recorded over one year and the data obtained were compared with fishermen’s reports. A total of 609 hours of behavioural observations of S. guianensis was conducted from a fixed point in alternate morning and afternoon sessions between October 2009 and September 2010. Observations were conducted from a pier (15°40’59”S and 38°56’38”W) situated on the banks of the Pardo River estuary - the region’s main river - at 5.5 m above water level. For ethnoecological data collection, semi-structured interviews were carried out with 26 fishermen in May, June and September 2010 and January 2011 in the fishing community of Atalaia. Occasional boat expeditions were made with the fishermen to compare their reports with direct observations of the behaviour of S. guianensis. The results demonstrate that fishermen possess a body of knowledge about S. guianensis that describes in detail the main behavioural aspects of the species. They reported the presence of S. guianensis in the Pardo River estuary throughout the year and its gregarious behaviour. They cited a relationship between the movement of dolphins and tidal cycles, and their presence in the estuary associated with the search for food. In addition, the fishermen reported that numbers of infants in groups were proportional to group size. Behaviours described were compatible with the observations made in situ and with data found in the scientific literature, confirming the importance of traditional knowledge in complementing scientific data. One behaviour mentioned by the fishermen that had no equivalence in the scientific literature was confirmed in situ and, therefore, constitutes the first record for this species. PMID:22584063

  1. Materialien und Modelle fuer den Franzoesischunterricht in der Sekundarstufe Zwei (Materials and Models for Teaching French in Grades 11-13)

    ERIC Educational Resources Information Center

    Frei, Alfons

    1978-01-01

    Texts available for French courses in the highest grades are listed according to topics, which include: position of women, today's youth, the language of advertising, French colonialism, holidays and tourism, modern city living, criminality, French politics. Hints for the teacher are included. (Text is in German.) (IFS/WGA)

  2. Grüne Infrastruktur - - Konzepte und Strategien zur Förderung eines Bewusstseins für den Wert von Stadtgrün

    NASA Astrophysics Data System (ADS)

    Menke, Peter

    2016-05-01

    Due to climate change, but also because of the demographic change and financial constraints in many municipalities, the future of cities is a currently much-discussed topic. Conflicts over land-use are inevitable: As densification is an essential principle in growing cities, the pressure on open (green) spaces rises. Climate Change and water-management as well as mobility-issues and air-quality confront municipalities with new challenges, in terms of open space planning and greenery in the city. It is necessary to save the existing green in these days of budget-shortage and other priorities in communities. Municipalities have to raise new strategies to strengthen the awareness of the value of green in public and in the local business.

  3. Characteristics of Patients Who Admitted to the Emergency Department Because of Burns Due to Dens Liquids Such as Hot Milk/Oil

    PubMed Central

    Bayramoglu, Atif; Sener, M. Talip; Cakir, Zeynep; Aslan, Sahin; Emet, Mucahit; Akoz, Ayhan

    2016-01-01

    Objective: Burn is the tissue damage on body caused due to various reasons. Although all burns caused by hot liquids are investigated as scalding burns, dense liquid burns (DLB) caused by such as milk and oil are different from other burns. The aim of this study was to report the properties of DLB. Materials and Methods: Patients admitted to the Emergency Service of Atatürk University Hospital, with DLB from June 2003 to December 2008, were examined retrospectively. Results: During the study, 28 DLB patients were admitted to the emergency service. The most common admission were found in autumn 28.6% (n=8), and in May and June, 17.9% (n=5). The frequency of burns on the right upper extremity was seen in 50% (n=14) of the patients. The burn degree of all patients was determined as 2nd degree. Seventy-five percent (n=21) of the patients were discharged, 14.3% (n=4) were hospitalized. None of the patients died. Conclusion: Dense liquid burns is a burn type that is commonly seen in women, absolutely causing 2nd degree burns, frequently reported in upper extremity and head/neck regions, and in contrast to other studies, in our region it is completely seen in patients living in city centre. PMID:27026759

  4. Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dengue is an arthropod-borne viral infection mainly vectored through the bite of Aedes mosquitoes. Recently, its transmission has strongly increased in urban and semi-urban areas of tropical and sub-tropical regions worldwide, becoming a major international public health concern. There is no specifi...

  5. Evolution of the passive and active microwave signatures of a large sea ice feature during its 21<den>2den>-year drift through the Arctic Ocean

    NASA Astrophysics Data System (ADS)

    Gohin, Francis; Cavanié, Alain; Ezraty, Robert

    1998-04-01

    Although estimation of the total ice concentration from special sensor microwave imagers (SSM/I) has proven to be successful, none of the various algorithms developed to discriminate new and older ice provide satisfying results. While the strong contrast between the emissivity of sea ice and that of open water can be utilized to provide reliable estimators of the total ice concentration, passive microwave characteristics of second-year and multiyear ice may locally evolve in different ways, even during the cold season. Scatterometers, as the active microwave instrument in wind mode (AMI-wind) on board the European Remote Sensing Satellites (ERS), provide backscatter data which have a higher sensitivity to the surface topography of ice and a better stability in time, at a resolution compatible with the SSM/I measurements. Here we present the evolutions of the microwave properties of an ice feature appearing along the shores of Novosibirskiye Ostrova (New Siberian Islands) at the end of July 1992 as the ice ages during its 3-year drift toward the Fram Strait. The track of this well-defined ice surface is easily followed on the maps of the backscatter coefficient provided by the AMI-wind during the cold season. In summer, because of melting, the ice undergoes critical changes which alter its microwave signatures and hamper automatic tracking. Moreover, on approaching the Fram Strait the resolution of the scatterometer is not sufficient to capture the complex and rapid transformations of the ice cover. To compensate for this, buoy data obtained from the International Arctic Buoy Program are used, alone during summers or together with satellite data, to build basin-wide ice displacement fields. These displacement fields, successively applied to each pixel of the ice feature selected, provide a series of Lagrangian observations. During the drift, which ends in May 1995, the active and passive signatures evolve coherently, except for the cold season 1992-1993 when unrealistic multiyear ice concentrations are deduced from the brightness temperatures, which, at that time, are much less stable than the backscatter coefficient over the ice surface tracked, identified as second-year ice.

  6. Les Differences dans l'emploi de la construction possessive "N1"+"DE"+"N2" entre le XIX et le XX s. dans la prose litteraire francaise (Differences in the Use of the Possessive Construction "N1"+"de"+"N2" between 19th and 20th Century French Literature).

    ERIC Educational Resources Information Center

    Roglic, Vera

    1991-01-01

    Study looks at frequency of noun1 + de + noun2 possessive in French prose. Researchers used chi-square and Pearson test to analyze results of syntagmatic possessive construction in works by Hugo, Stendahl, Balzac, Zola, Gide, Malraux, St. Exupery, and Sartre. Findings indicate that syntagmatic genitive possessive is more commonly found in…

  7. William Shakespeare's neurology.

    PubMed

    Paciaroni, Maurizio; Bogousslavsky, Julien

    2013-01-01

    Many of Shakespeare's plays contain characters who appear to be afflicted by neurological or psychiatric disorders. Shakespeare, in his descriptive analysis of his protagonists, was contributing to the understanding of these disorders. In fact, Charcot frequently used Shakespearean references in his neurological teaching sessions, stressing how acute objective insight is essential to achieving expert clinical diagnosis. Charcot found in Shakespeare the same rigorous observational techniques for which he himself became famous. This chapter describes many of Shakespearean characters suffering from varied neurological disorders, including Parkinsonism, epilepsy, sleeping disturbances, dementia, headache, prion disease, and paralyses. PMID:24290473

  8. In the land of giants: the legacy of José Dantas de Souza Leite.

    PubMed

    Teive, Hélio A G; Lima, Plínio M; Germiniani, Francisco M B; Boguszewski, César L

    2015-07-01

    The authors describe the extraordinary contribution to science made by José Dantas de Souza Leite, who graduated from the Bahia School of Medicine and trained in Prof. Charcot's Neurology Service under the supervision of Charcot's most able pupil, Dr. Pierre Marie. Souza Leite presented his doctoral thesis on acromegaly, in Paris in 1890, and in the following year both him and Pierre Marie published a book on the subject, "Essays on Acromegaly". This exceptional work established Souza Leite internationally as an important researcher, and the first Brazilian physician to contribute to the development of neuroendocrinology in an innovative way. PMID:26200060

  9. Zwischen den Stuhlen: Untersuchungen zur Situation der Korrektoren an der Fernuniversitat 1980, (In between Chairs: The Situation of Tutors (Correctors) at the FernUniversitat in 1980). ZIFF Papiere 34.

    ERIC Educational Resources Information Center

    Fritsch, Helmut; And Others

    An empirical study of tutors responsible for evaluating students' assignments at the Fernuniversitat in 1980 employed an 18-item questionnaire, analysis of open-ended responses, analysis of graders' comments on more than 1,000 assignments, and interviews with staff. The process of evaluating students' work was shown to be inefficient, with minimal…

  10. Five letters by Tycho Brahe to the Görlitz astronomer Bartholomäus Scultetus. (German Title: Fünf Briefe Tycho Brahes an den Görlitzer Astronomen Bartholomäus Scultetus (1540-1614))

    NASA Astrophysics Data System (ADS)

    Helfricht, Juergen

    The five letters by the Danish astronomer Tycho Brahe to the Görlitz astronomer, mayor, and reformer of the calendar Bartholomäus Scultetus are for the first time translated from Latin into German with comments. The letters of October 12, 1581, August 17, 1588, December 8, 1590, March 12, 1592, and Januar 7, 1600, which are to a certain extent very personal letters, deal with, among other items, Scultetus's manuscript on the comet of 1577 and offer interesting details regarding Brahe's observatories on the island Hveen and near Prague. In addition, they provide information on his projects of books, problems with paper and print, his pupil Paul Wittich, currently largely unknown correspondents and his friends in Saxony and Silesia. The author prefaces the letters with biographical information on the 16th century Görlitz astronomer.

  11. Bericht uber den 2. Internationalen Kongress fur Angewandte Linguistik. Cambridge 8.-12. IX. 1969. [Report on the Second International Congress for Applied Linguistics, Cambridge, Dec. 8-12, 1969.

    ERIC Educational Resources Information Center

    Mohr, Peter

    This paper is a summary report on the Second International Congress of Applied Linguistics held in Cambridge, England in September 1969. Because of the large number of papers delivered, only a selection of the papers delivered in any one section of the Congress are considered, and the author attempts to identify current interests and trends in…

  12. Das Licht am Ende des Tunnels: Motivationsstrukturen fur den Deutschunterricht Reflexionen uber ein altes und stets neues Problem (The Light at the End of the Tunnel: Structures for Motivating German Teaching. Reflections on an Old and Continually New Problem).

    ERIC Educational Resources Information Center

    Classen, Albrecht

    2001-01-01

    Argues that despite the decline in enrollments in German at elementary and secondary schools and colleges and universities, there is reason to hope that interest can be invigorated. Suggests that there are easy instructional methods and materials for developing a new motivation in learning the language. (Author/VWL)

  13. Dreissig Jahre Volksrepublik Polen. Aus den Thesen des Zentralkomitees der Polnischen Vereinigten Arbeiterpartei (Thirty years of the People's Republic of Poland. From the Theses of the Central Committee of the Polish United Workers' Party)

    ERIC Educational Resources Information Center

    Fremdsprachenunterricht, 1974

    1974-01-01

    Offers an overview of the development of the teaching of Russian in the People's Republic of Poland since its introduction in 1945 and the support of the periodical "Jezyk Rosyjski" (Russian Language) in the attainment of the goals set by the Ministry of Popular Education of the People's Republic of Poland. (Text is in German.) (IFS/WGA)

  14. Nanoparticles in the fight against mosquito-borne diseases: bioactivity of Bruguiera cylindrica-synthesized nanoparticles against dengue virus DEN-2 (in vitro) and its mosquito vector Aedes aegypti (Diptera: Culicidae).

    PubMed

    Murugan, Kadarkarai; Dinesh, Devakumar; Paulpandi, Manickam; Althbyani, Abdulaziz Dakhellah Meqbel; Subramaniam, Jayapal; Madhiyazhagan, Pari; Wang, Lan; Suresh, Udaiyan; Kumar, Palanisamy Mahesh; Mohan, Jagathish; Rajaganesh, Rajapandian; Wei, Hui; Kalimuthu, Kandasamy; Parajulee, Megha N; Mehlhorn, Heinz; Benelli, Giovanni

    2015-12-01

    Mosquitoes are blood-feeding insects serving as the most important vectors for spreading human pathogens and parasites. Dengue is a viral disease mainly vectored through the bite of Aedes mosquitoes. Its transmission has recently increased in urban and semi-urban areas of tropical and subtropical regions worldwide, becoming a major international public health concern. There is no specific treatment for dengue. Its prevention and control solely depend on effective vector control measures. Mangrove plants have been used in Indian traditional medicine for a wide array of purposes. In this research, we proposed a method for biosynthesis of antiviral and mosquitocidal silver nanoparticles (AgNP) using the aqueous extract of Bruguiera cylindrica leaves. AgNP were characterized using a variety of biophysical analyses, including UV-visible spectrophotometry, Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Bruguiera cilyndrica aqueous extract and green-synthesized AgNP were tested against the primary dengue vector Aedes aegypti. AgNP were the most effective. LC50 values ranged from 8.93 ppm (larva I) to 30.69 ppm (pupa). In vitro experiments showed that 30 μg/ml of AgNP significantly inhibited the production of dengue viral envelope (E) protein in vero cells and downregulated the expression of dengue viral E gene. Concerning nontarget effects, we observed that the predation efficiency of Carassius auratus against A. aegypti was not affected by exposure at sublethal doses of AgNP. Predation in the control was 71.81 % (larva II) and 50.43 % (larva III), while in an AgNP-treated environment, predation was boosted to 90.25 and 76.81 %, respectively. Overall, this study highlights the concrete potential of green-synthesized AgNP in the fight against dengue virus. Furthermore, B. cylindrica-synthesized AgNP can be employed at low doses to reduce larval and pupal population of A. aegypti, without detrimental effects of predation rates of mosquito predators, such as C. auratus. PMID:26290219

  15. Can Break-Dance Break Your Neck? C1/C2 Luxation with a Combined Dens Fracture Without Neurological Deficits in an 11-Year Old Boy After a Break-Dance Performance.

    PubMed

    Petridis, Athanasios K; Kinzel, Adrian; Blaeser, Klaus; Thissen, Joost; Maslehaty, Homajoun; Scholz, Martin

    2015-09-28

    Atlantoaxial dislocation in children is a very rare condition. We present the case of a dislocation happened during a break-dance maneuver. The purpose of this report is describing dangers of break-dancing and discussing the treatment we chose. The patient was followed up until 12 months after surgery. Magnetic resonance imaging and computed tomography of the cervical spine were evaluated. Translaminar fixation of C1/C2 had been performed after manual reposition under X-ray illumination. After a 12-month follow-up, the patient shows a stable condition without neurological dysfunction. He is not allowed to perform any extreme sports. PMID:26664716

  16. PROPOSED MEASURES OF CONTROL MANAGEMENT OF THE GRAPE MOTH, LOBESIA BOTRANA DEN AND SCHIFF (LEPIDOPTERA: TORTRICIDAE), IN REFERENCE TO INFESTATION PERCENTAGES, YIELD LOSS AND ECONOMICS OF CONTROL IN EGYPT.

    PubMed

    Kordy, A M; Zaghloul, O A; Mourad, A K

    2014-01-01

    This study aims to evaluate the efficacy of five measures; including the release of two strains of Trichogramma, Bacillus thuringiensis (B.t.). Sweetened B.t. and the environmentally friend insecticide (Tracer®), to manage the grape moth, Lobesia botrana that infested the grape vines c.v. "Thompson seedless " in Egypt severely during the two successive years of 2011 and 2012. In concern to the release of the worldwide, Trichogramma evanescens Westwood., the mean total grape yield ranged from 8.00 to 14.00 ton/fed and from 6.90 to 11.9, in respect to the two seasons and the mean infestation percentages fluctuated between 50.00 and 16.14; 43.48 and 21.01 in sequence for the same years. The corresponding grape bunches loss percentages averaged from 21.43 to 6.91; 18.63 to 9.00,respectively for the same periods of this study. Whereas, it was noticed that in releasing the indigenous T. bourarchae was more effective than T. evanescens in reducing all the above mentioned grape yield particularly. Applying Bacillus thuringiensis (B.t.) and/or adding sugar as a stimulant to improve yields reduced the infestation and the crop loss percentage. However, Bacillus thuringiensis mixed with sugar which overweighed the use of Bacillus thuringiensis alone. Although Tracer® provided good harvest in both years, but unfortunately it affected the grape berries components rather than the other treatments. Control plots indicated 48 and 50% infestation, with very low yield compared with the other five trials to manage the assigned insect pest. For the first time worldwide economics and profits were computed taking into account the whole market sale, the total control costs and the gross income to decide the most profitable treatment for the table grape growers under the Egyptian conditions. It was found that the mean (L.E.) profits/fed were arranged in a descending order as follows: 470.95, 513.28, 504.78, 500.82, 397.25 and 0.00 for Bacillus thuringiensis + sugar, Trichogramma bourarchae, Trichogramma evanescens Westwood, Dipel-2x®, Tracer® and control in respect in 2011. The corresponding values in the year 2012 were 453.85, 445.58, 427.18, 377.00, 349.18 and 0.00 for Trichogramma bourarchae, Bacillus thuringiensis + sugar, Dipel-2x®, Trichogramma evanescens Westwood, Tracer® and control in respect. The obtained results were analysed and discussed in the text. PMID:26084105

  17. Diglossische Prozesse (Zwischen Deutsch und Spanisch) unter den Spanischen Emigranten der 2. Generation in Deutschland: Eine Soziolinguistische Studie (Diglossia Processes (Between German and Spanish) Among Second Generation Spanish Immigrants in Germany: A Sociolinguistic Study).

    ERIC Educational Resources Information Center

    Sanchez, Karin Vilar

    1998-01-01

    Presents a sociolinguistic study of second-generation Spanish immigrants in Germany. Specific focus is on "diglossia processes," or how Spanish and German are used for different sociolinguistic situations. (Author/VL)

  18. Corporate Regional Responsibility - Warum engagieren sich Unternehmen gemeinsam für ihre Region?. Motive der kollektiven regionalen Verantwortungsübernahme von Unternehmen an den Beispielen des Initiativkreises Ruhr und der Wirtschaftsinitiative FrankfurtRheinMain

    NASA Astrophysics Data System (ADS)

    Schiek, Meike

    2016-03-01

    Companies can voluntarily participate in matters of regional developments, thereby accepting responsibility on a regional level. Referring to the concept of Corporate Social Responsibility (CSR), the term Corporate Regional Responsibility (CRR) is used to describe this behavior. Moreover, companies can form a CRR-corporation with other companies in order to take over a collective CRR. So far, the motives of companies for exercising collective CRR are unknown, thus, corporate resources can not be mobilized and utilized efficiently for regional developments. This article explores the subject of collective CRR and illustrates CRR motives using the example of the two CRR-cooperations Initiativkreis Ruhr and Wirtschaftsinitiative FrankfurtRheinMain.

  19. Great careers: Cornil, Bouchard, Bourneville and Proust.

    PubMed

    Paciaroni, Maurizio; Cittadini, Elisabetta; Bogousslavsky, Julien

    2011-01-01

    Several French physicians of the 19th century are considered to be the pioneers of modern neurology, especially Jean-Martin Charcot. Later, the pupils of Charcot--interns at La Salpêtrière Hospital in Paris, including Cornil, Bouchard and Bourneville--went on to make great contributions to the field of neurology with their own discoveries. Specifically, with their mentor, they made the following contributions: Bouchard is responsible for first-ever description of cerebral hemorrhage pathogenesis; Bourneville arranged for the publication of Charcot's works; Cornil demonstrated histological evidence that supported Guillaume Duchenne's hypothesis regarding the cause of paralysis in poliomyelitis and he made the first diagnosis of chronic childhood arthritis. Besides these physicians, Adrien Proust, the father of the novelist Marcel, who had met Charcot at the Salpêtrière during the early part of his career, was a renowned physician, who also contributed greatly to research through his published works on stroke, aphasia, hysteria and neurasthenia. PMID:20938147

  20. Fly model causes neurological rethink

    PubMed Central

    Sadanandappa, Madhumala K

    2013-01-01

    A Drosophila model for a neurological disorder called type 2B Charcot-Marie-Tooth disease reveals that it has its origins in a partial loss of function, rather than a gain of function, which points to the need for a new therapeutic approach. PMID:24336781

  1. Paul Sollier: the first clinical neuropsychologist.

    PubMed

    Bogousslavsky, Julien; Walusinski, Olivier

    2011-01-01

    Paul Sollier (1861-1933) is perhaps the most unjustly forgotten follower of Jean-Martin Charcot. He studied with Désiré Bourneville, Charcot's second interne, and was considered by Léon Daudet as the cleverest collaborator of Charcot, along with Joseph Babinski. Charcot assigned him the task of summarizing the theories on memory, which led to two major books, in 1892 and 1900, that anticipated several contemporary concepts by several decades. In 1905-1906, the novelist Marcel Proust spent 6 weeks with Sollier in his sanatorium at Boulogne-Billancourt, and it is now obvious that several of Proust's ideas on involuntary memories which appear inside In Search of Lost Time (published 8 years later) had been inspired by Sollier's theories on the 'surge of reminiscences'. Sollier also designed the framework which led to the intellectual quotient (IQ) and made interesting studies on hysteria and behavioral issues in neurological diseases, activities that may make him the first modern clinical neuro psychologist. Sollier was also the first to correlate clinical findings with neurophysiological concepts, which makes him a precursor of our current approach to neurology and psychiatry. PMID:20938150

  2. Anglo-French contributions to the recognition of rheumatoid arthritis

    PubMed Central

    Fraser, Kevin J.

    1982-01-01

    Early descriptions of rheumatoid arthritis in the English and French literature are reviewed. Charcot pointed out that the disease was recognised as distinct from gout in eighteenth century England, and pictorial evidence for this is presented. His own work on arthritis led to a series of noteworthy interactions with Alfred Baring Garrod, which are discussed. Images PMID:7051988

  3. Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.

    PubMed

    Sanmaneechai, Oranee; Feely, Shawna; Scherer, Steven S; Herrmann, David N; Burns, Joshua; Muntoni, Francesco; Li, Jun; Siskind, Carly E; Day, John W; Laura, Matilde; Sumner, Charlotte J; Lloyd, Thomas E; Ramchandren, Sindhu; Shy, Rosemary R; Grider, Tiffany; Bacon, Chelsea; Finkel, Richard S; Yum, Sabrina W; Moroni, Isabella; Piscosquito, Giuseppe; Pareyson, Davide; Reilly, Mary M; Shy, Michael E

    2015-11-01

    We aimed to characterize genotype-phenotype correlations and establish baseline clinical data for peripheral neuropathies caused by mutations in the myelin protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot-Marie-Tooth disease type 1. Recent research makes clinical trials for patients with MPZ mutations a realistic possibility. However, the clinical severity varies with different mutations and natural history data on progression is sparse. We present cross-sectional data to begin to define the phenotypic spectrum and clinical baseline of patients with these mutations. A cohort of patients with MPZ gene mutations was identified in 13 centres of the Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009 and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments. Genetic testing was performed in all patients and/or in first- or second-degree relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie-Tooth disease type 1B. There were 103 patients from 71 families with 47 different MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and mutations were separated into infantile, childhood and adult-onset groups. The infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and slower nerve conductions than the other groups, and severity increased with age. Twenty-three patients had no family history of Charcot-Marie-Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking assistance or support, and 10 required wheelchairs. There was hearing loss in 21 and scoliosis in 17. Forty-two patients did not begin walking until after 15 months of age. Half of the infantile onset patients then required ambulation aids or wheelchairs for

  4. Serotype and genotype analysis of dengue virus by sequencing followed by phylogenetic analysis using samples from three mini outbreaks-2007-2009 in Pakistan

    PubMed Central

    2011-01-01

    Background Since the first reported outbreak of dengue hemorrhagic fever in Pakistan, several mini outbreaks have erupted in the region. Dengue virus serotype 3 (DEN-3) was first documented in 2005 outbreak in Karachi. Reports show that serotype 3 is prevalent in Lahore since 2008. Serotype 2 (DEN-2) is the major circulating serotype in Pakistan as it is documented since 1994. We have conducted a detailed study of three outbreaks of dengue virus infection that occurred in years 2007, 2008 and 2009 in Lahore by using molecular techniques such as PCR and nucleotide sequencing of the C-prM gene junction of Dengue virus. Results Through the analysis of 114 serum samples collected over the period of three years (2007-2009), total 20 patients were found to be infected with dengue virus. In year 2007, four were positive for serotype 2 and one sample was positive for serotype DEN-3. In 2008, five samples had concurrent infection with serotypes DEN-2 and DEN-3 while three samples were infected only with serotype DEN-2. In year 2009, one sample had concurrent infection with serotypes DEN-2 and DEN-3 while six were positive for serotype DEN-2 only. Conclusions Our study showed that serotype DEN-2 was dominant in positive samples of dengue virus infection collected during the period of three years (2007-2009). The other serotype present was serotype DEN-3. Genotypes of serotype DEN-2 and serotype DEN-3 were subtype IV and subtype III, respectively. PMID:21906394

  5. 36 CFR 13.920 - Wildlife distance conditions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., an active raptor nest, or occupied den site; or (2) Engaging in photography within 25 yards of a moose, caribou, Dall sheep, wolf, an active raptor nest, or occupied den site. (c) Prohibitions....

  6. 36 CFR 13.920 - Wildlife distance conditions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., an active raptor nest, or occupied den site; or (2) Engaging in photography within 25 yards of a moose, caribou, Dall sheep, wolf, an active raptor nest, or occupied den site. (c) Prohibitions....

  7. 36 CFR 13.920 - Wildlife distance conditions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., an active raptor nest, or occupied den site; or (2) Engaging in photography within 25 yards of a moose, caribou, Dall sheep, wolf, an active raptor nest, or occupied den site. (c) Prohibitions....

  8. 36 CFR 13.920 - Wildlife distance conditions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., an active raptor nest, or occupied den site; or (2) Engaging in photography within 25 yards of a moose, caribou, Dall sheep, wolf, an active raptor nest, or occupied den site. (c) Prohibitions....

  9. 36 CFR 13.920 - Wildlife distance conditions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., an active raptor nest, or occupied den site; or (2) Engaging in photography within 25 yards of a moose, caribou, Dall sheep, wolf, an active raptor nest, or occupied den site. (c) Prohibitions....

  10. Futuristic Airframe Concepts & Technology (FACT)

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The distributed exhaust nozzle (DEN) components: view of the DEN nozzle from upstream looking downstream (looking out of the exit of the nozzle). Photographed in building 1221B, room 116, Jet Noise Lab.

  11. Development of DENVax: A chimeric dengue-2 PDK-53-based tetravalent vaccine for protection against dengue fever

    PubMed Central

    Osorio, Jorge E.; Huang, Claire Y.-H.; Kinney, Richard M.; Stinchcomb, Dan T.

    2015-01-01

    Dengue. virus infection is the leading arboviral cause of disease worldwide. A vaccine is being developed based on the attenuated DEN-2 virus, DEN-2 PDK-53. In this review, we summarize the characteristics of the parent DEN-2 PDK-53 strain as well as the chimeric viruses containing the prM and E genes of DEN-1, DEN-3 or DEN-4 virus in the genetic backbone of the DEN-2 PDK-53 virus (termed DENVax). Tetravalent DENVax formulations containing cloned, fully sequenced isolates of the DEN-2 PDK-53 virus and the three chimeras have been evaluated for safety and efficacy in preclinical animal models. Based on the safety, immunogenicity and efficacy in preclinical studies, Phase 1 clinical testing of DENVax has been initiated. PMID:21777638

  12. Evolution: Treibende Kräfte in Natur und Kultur

    NASA Astrophysics Data System (ADS)

    Wuketits, Franz M.

    Vorbemerkung Der vorliegende Text ist sozusagen die Nachschrift meines im Dezember 2007 in Dresden gehaltenen Vortrags. Ich hielt den Vortrag im Wesentlichen in freier Rede, nur auf der Basis einiger Notizen, und schrieb den vollen Text danach. Dabei habe ich den Vortragsstil beibehalten. Allerdings habe ich nachträglich manches hinzugefügt, den Beitrag mit ein paar Anmerkungen versehen und einiges an zwischenzeitlich erschienener Literatur berücksichtigt.

  13. Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression.

    PubMed

    Chem, Y K; Chua, K B; Malik, Y; Voon, K

    2015-06-01

    Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were (Ser)[326](Leu), (Ser)[340](Leu) at the deduced E protein, (Ile)[250](Thr) at NS1 protein, and (Thr)[41](Ser) at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection. PMID:26691263

  14. Matthias Falter und die frühe Halbleitertechnik in der DDR

    NASA Astrophysics Data System (ADS)

    Dittmann, Frank

    Nach einer ganzen Reihe von Vorarbeiten weltweit1 konnten im Dezember 1947 die amerikanischen Physiker Walter H. Brattain, John Bardeen und William Shockley in den Bell Laboratories den Transistoreffekt demonstrieren. Damit legten sie den Grundstein für die Mikroelektronik als Basistechnologie des Informationszeitalters.

  15. Glial cells in ALS: the missing link?

    PubMed

    Raibon, Elsa; Todd, Lisa Marie; Möller, Thomas

    2008-08-01

    Amyotrophic lateral sclerosis (ALS) was initially known as Charcot's sclerosis, named after the French neurobiologist and physician Jean-Martin Charcot who first described this type of muscular atrophy in the early nineteenth century. In the United States, ALS became widely known as Lou Gehrig's disease after the famous baseball player who succumbed to the disease in the late 1930s. Currently, ALS is the most common motor neuron disease, with a worldwide incidence of 8 cases per 100,000 population per year. Familial forms constitute approximately 5% to 10% of all cases. Onset increases with age, with a peak in the seventh decade and a slight preponderance (relative risk, 1.3-1.5) among men compared with women. Rapid progression of motor neuron loss leads to death an average of 3 to 5 years after symptom onset. The cause of ALS remains unknown and there is still no curative therapy. PMID:18625409

  16. The girls of La Salpêtrière.

    PubMed

    Walusinski, Olivier

    2014-01-01

    It was only by chance that French hospital authorities assigned Jean-Martin Charcot to the care of hysterics and epileptics, starting in 1870, at La Salpêtrière Hospital. The famous clinical work that resulted has been the subject of much discussion and, in many cases, misinterpretation. By referring to original sources, i.e., the medical observations written at the time by the department's staff, our aim is to bring the hospitalized patients to life. Many of these observations contain intimate details and reveal the painful experiences that led these young women to La Salpêtrière. To understand the gradual, 20-year evolution of Charcot's neurological thinking about hysteria, from organicity to psychology, in both clinical and therapeutic terms, it is more revealing to analyze all the physical and psychological miseries that make up this forgotten 'human material' than it is to examine the neurologist's famous lessons. PMID:25273490

  17. Where is Gilles? Or, the little mistake in a copy of Brouillet's painting: "a clinical lesson at the Salpêtrière".

    PubMed

    Germiniani, Francisco M B; Moro, Adriana; Munhoz, Renato P; Teive, Hélio A G

    2013-05-01

    Professor Jean-Martin Charcot is considered the most important professor of Neurology and also the head of the Salpêtrière School of Neurology. In a famous picture painted by André Brouillet and presented at the Salon of 1887, under the title "A clinical lesson at the Salpêtrière", Professor Charcot presents a case of hysteria to a large audience of physicians and renowned intellectuals. Copies of this guided picture are also available for sale at the shop of the Museum of the School of Medicine of Paris and are frequently used in lectures by neurologists worldwide. However, in these reproductions, Gilles de la Tourette's and Charles Féré's positions are inverted. This historical note sheds some light on this little mistake in some of the reproductions of Brouillet's famous painting, so that further confusion can be avoided. PMID:23689411

  18. Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A

    PubMed Central

    Swetha, Rayapadi G.

    2014-01-01

    The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures. PMID:25400662

  19. [Diabetic foot syndrome and diabetic neuropathic osteoarthropathy (DNOAP): an update of conservative and surgical therapy methods].

    PubMed

    Hofstaetter, S G; Trieb, K

    2014-10-01

    A diabetic foot or Charcot foot diagnosed in time can reduce a lot of problems for the patient, lessen high medical expense, and last but not least prevent an amputation. Good treatment options of the diabetic foot result from new technologies in wound management, angioplastic vessel improvement and optimised orthopaedic aids. Nevertheless it stays a challenging issue for practitioners and medical and health care as well as hospital owners to master this problem which will be even growing in the long run. This article intends to raise the awareness for the diabetic foot and the neuropathic osteoarthropathy, and furthermore illustrate diagnostic steps and offer therapeutic options. After distinguishing the diabetic foot from the Charcot foot a selective therapy for each entity has to be initiated. An interdisciplinary approach of specialists in dermatology, radiology, orthopaedic and internal medicine, plastic surgery and orthopaedic shoemaking is essential for a good therapeutic monitoring in order to avoid the amputation of the lower leg. PMID:25313707

  20. What's New in Severe Deformity Correction: The German Perspective.

    PubMed

    Schmitt, Sebastian; Peak, Anna C; Berrsche, Gregor; Wenz, Wolfram

    2016-06-01

    Foot deformities are found in several neurologic conditions, most typically, but not exclusively, Charcot-Marie-Tooth disease. Posttraumatic deformities and undercorrection or overcorrection of congenital talipes equinovarus are also encountered. A severely deformed foot that cannot fit into normal shoes presents a significant day-to-day challenge to the young and active patient. This article presents some basic principles for evaluating the deformity and a toolkit of procedures to deal with these complex cases. PMID:27261803