Sample records for gm1 gangliosidosis patients

  1. Brain Proton Magnetic Resonance Spectroscopy and Neuromuscular Pathology in a Patient With GM1 Gangliosidosis

    Microsoft Academic Search

    Nicola Brunetti-Pierri; Meenakshi B. Bhattacharjee; Zhiyue J. Wang; Zili Chu; David A. Wenger; Lorraine Potocki; Jill Hunter; Fernando Scaglia

    2008-01-01

    The authors report the clinical, neuroradiologic, and neuromuscular pathological findings in a patient with GM1 gangliosidosis. The proton magnetic resonance spectroscopy, previously reported in a single patient with GM1 gangliosidosis, detected a mild reduction of N-acetylaspartate, consistent with relative paucity of axons and neurons and increased levels of myoinositol suggestive of gliotic white matter changes along with the accumulation of

  2. Neuroimaging findings in infantile GM1 gangliosidosis

    Microsoft Academic Search

    Ilknur Erol; Füsun Alehan; M. Ali Pourbagher; Oguz Canan; S. Vefa Yildirim

    2006-01-01

    GM1 gangliosidosis is an autosomal recessive glycosphingolipid storage disease caused by defects in the enzyme ?-galactosidase. Three clinical forms (infantile-, juvenile-, and adult-onset) of the disease are recognized. Patients with infantile GM1 gangliosidosis present at birth or shortly thereafter with somatic and bony changes, followed by severe neurological deterioration ultimately leading to death within the first 2 years of life.

  3. Genotypic and phenotypic characterization of Brazilian patients with GM1 gangliosidosis.

    PubMed

    Sperb, Fernanda; Vairo, Filippo; Burin, Maira; Mayer, Fabiana Quoos; Matte, Ursula; Giugliani, Roberto

    2013-01-01

    GM1 gangliosidosis is a lysosomal disorder caused by ?-galactosidase deficiency due to mutations in the GLB1 gene. It is a rare neurodegenerative disorder with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we review GLB1 mutations and clinical features from 65 Brazilian GM1 gangliosidosis patients. Molecular analysis showed 17 different mutations and c.1622-1627insG was the most frequent, accounting for 50% of the alleles. Cognitive impairment was the main clinical sign, observed in 82% of patients, followed by hepatosplenomegaly observed in 56% of patients. It was possible to establish a significant correlation between age at onset of symptoms preceding the first year of life and the presence of the mutation c.1622-1627insG (p=0.03). Overall our findings differ from literature and represent the exclusive genotypic profile found in Brazilian GM1 gangliosidosis patients. PMID:23046582

  4. Chemical chaperone therapy for GM1-gangliosidosis.

    PubMed

    Suzuki, Y

    2008-02-01

    We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound N-octyl-4-epi-beta-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced beta-galactosidase activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone therapy will prove useful for some patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement. PMID:18202827

  5. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations

    Microsoft Academic Search

    D. Hofer; K. Paul; K. Fantur; M. Beck; A. Roubergue; A. Vellodi; B. J. Poorthuis; H. Michelakakis; B. Plecko; E. Paschke

    2010-01-01

    GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid ?-galactosidase (GLB1). In addition allelic variants of this gene can result in Morquio B disease, a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1

  6. GM1 gangliosidosis type 1 in twins

    Microsoft Academic Search

    C M Ginsburg; C G Long

    1977-01-01

    This report describes 7-month-old monozygotic twin female infants with GM1 gangliosidosis type I. In addition to the usual clinical and biochemical abnormalities generalized intracutaneous telangiectasis were present in both infants.

  7. Genetic heterogeneity in GM1-gangliosidosis

    Microsoft Academic Search

    H. Galjaard; A. Hoogeveen; W. Keijzer; H. A. de Wit-Verbeek; A. J. J. Reuser; MAE WAN HO; D. ROBINSON

    1975-01-01

    GM1-GANGLIOSIDOSIS is an inherited lysosomal storage disease which is due to a deficiency of the acid hydrolase GM1-beta-galactosidase1. During the past few years several clinical variants have been described2-6 that differ in time of onset of symptoms, involvement of visceral organs or skeletal tissue and in the degree of neuronal and mental deterioration. Some of these variants have been related

  8. GM1-generalized gangliosidosis variant with cardiomegaly

    Microsoft Academic Search

    P. F. Benson; S. P. Brown; A. Babarik; T. P. Mann

    1976-01-01

    A female infant with generalized GM1-gangliosidosis differing in several aspects from previously reported cases is described. Clinically she is the first case to have cardiomegaly, unilateral congenitial dislocation of the hip and normal facial appearance. She had a higher residual leucocyte ?-galactosidase activity towards two synthetic substrates, namely p-nitrophenyl-?-D-galactoside (PNP-?-gal) and 4-methylumbelliferyl-?-D-galactoside (MU-?-gal) than in previously reported cases. Total ?-hexosaminidase

  9. A homozygous missense arginine to histidine substitution at position 482 of the ?-galactosidase in an Italian infantile GM1-gangliosidosis patient

    Microsoft Academic Search

    G. Mosna; S. Fattore; G. Tubiello; S. Brocca; M. Trubia; E. Gianazza; R. Gatti; C. Danesino; A. Minelli; M. Piantanida

    1992-01-01

    We have studied, by the polymerase chain reaction, the ß-galactosidase cDNA from several Italian patients with infantile GM1-gangliosidosis. One homozygote for a previously undiscovered G > A mutation at position 1479, causing an arginine to histidine change, was detected. The same mutation, in heterozygosis, was identified in 6 unrelated patients, but not in 100 normal chromosomes.

  10. Expression and characterization of 14 GLB1 mutant alleles found in GM1-gangliosidosis and Morquio B patients

    Microsoft Academic Search

    Raul Santamaria; Amparo Chabas; John W. Callahan; Daniel Grinberg; L. Vilageliu

    2007-01-01

    GM1-gangliosidosis and Morquio B disease are lysosomal storage disorders caused by b-galactosidase de- ficiency attributable to mutations in the GLB1 gene. On reaching the endosomal-lysosomal compartment, the b- galactosidase protein associates with the protective protein\\/ cathepsin A (PPCA) and neuraminidase proteins to form the lysosomal multienzyme complex (LMC). The correct inter- action of these proteins in the complex is essential

  11. Modulating action of the new polymorphism L436F detected in the GLB1 gene of a type-II GM1 gangliosidosis patient

    Microsoft Academic Search

    Anna Caciotti; Tiziana Bardelli; John Cunningham; Alessandra D'Azzo; Enrico Zammarchi; Amelia Morrone

    2003-01-01

    We report the modulating action of the L436F new polymorphism identified in the GLB1 gene of a patient affected by GM1 gangliosidosis with onset at 17 months and rapidly progressive psychomotor deterioration. Sequencing analysis and familial restriction studies revealed that the maternal allele of this patient carried the L436F polymorphism in cis with the known R201C mutation. The new mutation R68W

  12. GM1 gangliosidosis and Morquio B disease: An update on genetic alterations and clinical findings

    Microsoft Academic Search

    Anna Caciotti; Scott C. Garman; Yadilette Rivera-Colón; Elena Procopio; Serena Catarzi; Lorenzo Ferri; Carmen Guido; Paola Martelli; Rossella Parini; Daniela Antuzzi; Roberta Battini; Michela Sibilio; Alessandro Simonati; Elena Fontana; Alessandro Salviati; Gulcin Akinci; Cristina Cereda; Carlo Dionisi-Vici; Francesca Deodato; Adele d'Amico; Alessandra d'Azzo; Enrico Bertini; Mirella Filocamo; Maurizio Scarpa; Maja di Rocco; Cynthia J. Tifft; Federica Ciani; Serena Gasperini; Elisabetta Pasquini; Renzo Guerrini; Maria Alice Donati; Amelia Morrone

    2011-01-01

    GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000–1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected

  13. Chemical chaperone therapy for brain pathology in GM1-gangliosidosis

    PubMed Central

    Matsuda, Junichiro; Suzuki, Osamu; Oshima, Akihiro; Yamamoto, Yoshie; Noguchi, Akira; Takimoto, Kazuhiro; Itoh, Masayuki; Matsuzaki, Yuji; Yasuda, Yosuke; Ogawa, Seiichiro; Sakata, Yuko; Nanba, Eiji; Higaki, Katsumi; Ogawa, Yoshimi; Tominaga, Lika; Ohno, Kousaku; Iwasaki, Hiroyuki; Watanabe, Hiroshi; Brady, Roscoe O.; Suzuki, Yoshiyuki

    2003-01-01

    We synthesized a galactose derivative, N-octyl-4-epi-?-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, ?-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal ?-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with ?-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement. PMID:14676316

  14. GM 1 gangliosidosis: Clinical and laboratory findings in eight families

    Microsoft Academic Search

    Roberto Giugliani; Janice Coelho Dutra; Maria Luiza Saraiva Pereira; Newra Rotta; Maria de Lourdes Drachler; Ligia Ohlweiller; Joăo Monteiro Pina Neto; Carlos Eduardo Pinheiro; Dinis José Breda

    1985-01-01

    GM1 Gangliosidosis is an autosomal recessive genetic disorder due to deficiency of the lysosome enzyme beta-galactosidase, with consequent tissue accumulation of glycolipids, oligosaccharides, and especially GM1 ganglioside. In the present paper we report the clinical and laboratory findings obtained for eight families starting from eight index cases exhibiting the childhood form of the disease. The total number of cases in

  15. GM 1 gangliosidosis: Review of clinical, molecular, and therapeutic aspects

    Microsoft Academic Search

    Nicola Brunetti-Pierri; Fernando Scaglia

    2008-01-01

    GM1 gangliosidosis is a lysosomal storage disorder due to deficiency of the ?-galactosidase enzyme. This deficiency results in accumulation of GM1 gangliosides and related glycoconjugates in the lysosomes leading to lysosomal swelling, cellular damage, and organ dysfunction. The disease is lethal in the infantile and juvenile forms. To date, up to 102 mutations distributed along the ?-galactosidase gene (GLB1) have

  16. Structural bases of GM1 gangliosidosis and Morquio B disease

    Microsoft Academic Search

    Mizuki Morita; Seiji Saito; Kazuyoshi Ikeda; Kazuki Ohno; Kanako Sugawara; Toshihiro Suzuki; Tadayasu Togawa; Hitoshi Sakuraba

    2009-01-01

    Allelic mutations of the lysosomal ?-galactosidase gene cause heterogeneous clinical phenotypes, such as GM1 gangliosidosis and Morquio B disease, the former being further classified into three variants, namely infantile, juvenile and adult forms; and heterogeneous biochemical phenotypes were shown in these forms. We tried to elucidate the bases of these diseases from a structural viewpoint. We first constructed a three-dimensional

  17. Rapid prenatal diagnosis of GM 1 -gangliosidosis using microchemical methods

    Microsoft Academic Search

    W. J. Kleijer; E. Van der Veer; M. F. Niermeijer

    1976-01-01

    Prenatal diagnoses were established in 3 pregnancies at risk for GM1-gangliosidosis at 9, 10, and 12 days after amniocentesis. ß-galactosidase activities in cultured amniotic fluid cells were determined by microchemical assays in cell homogenates and in isolated groups of 10–30 freeze-dried cells. The latter method requires only a few hundred cells growing in one or more clones and will usually

  18. The leukoencephalopathy of infantile GM1 gangliosidosis: oligodendrocytic loss and axonal dysfunction

    Microsoft Academic Search

    J. Patrick van der Voorn; Wout Kamphorst; Marjo S. van der Knaap; James M. Powers

    2004-01-01

    A myelin deficit in the cerebral white matter in infantile GM1 gangliosidosis is well established. Some have proposed this deficit to be secondary to axonal loss, while others argue for delayed or arrested myelination. We compared the frontal white and gray matter of two infants with GM1 gangliosidosis with four age-matched controls, using light microscopy with a quantitative analysis, immunohistochemistry,

  19. Candidate molecules for chemical chaperone therapy of GM1-gangliosidosis.

    PubMed

    Higaki, Katsumi; Ninomiya, Haruaki; Suzuki, Yoshiyuki; Nanba, Eiji

    2013-09-01

    A growing body of evidence suggests that misfolding of a mutant protein followed by its aggregation or premature degradation in the endoplasmic reticulum is one of the main mechanisms that underlie inherited neurodegenerative diseases, including lysosomal storage diseases. Chemical or pharmacological chaperones are small molecules that bind to and stabilize mutant lysosomal enzyme proteins in the endoplasmic reticulum. A number of chaperone compounds for lysosomal hydrolases have been identified in the last decade. They have gained attention because they can be orally administrated, and also because they can penetrate the blood-brain barrier. In this article, we describe two chaperone candidates for the treatment of GM1-gangliosidosis. We also discuss the future direction of this strategy targeting other lysosomal storage diseases as well as protein misfolding diseases in general. PMID:24024947

  20. Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis.

    PubMed

    Matsuda, Junichiro; Suzuki, Osamu; Oshima, Akihiro; Yamamoto, Yoshie; Noguchi, Akira; Takimoto, Kazuhiro; Itoh, Masayuki; Matsuzaki, Yuji; Yasuda, Yosuke; Ogawa, Seiichiro; Sakata, Yuko; Nanba, Eiji; Higaki, Katsumi; Ogawa, Yoshimi; Tominaga, Lika; Ohno, Kousaku; Iwasaki, Hiroyuki; Watanabe, Hiroshi; Brady, Roscoe O; Suzuki, Yoshiyuki

    2003-12-23

    We synthesized a galactose derivative, N-octyl-4-epi-beta-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, beta-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal beta-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with beta-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement. PMID:14676316

  1. Chaperone therapy update: Fabry disease, GM1-gangliosidosis and Gaucher disease.

    PubMed

    Suzuki, Yoshiyuki

    2013-06-01

    Chaperone therapy is a newly developed molecular therapeutic approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. Based on early molecular studies during the last decade of the 20th century and early years of the 21st century, mainly on Fabry disease and GM1-gangliosidosis, we found some mutant enzyme proteins were unstable in the cell, and unable to express catalytic activities. Subsequently galactose and other active-site binding substrate analogs were found stabilized and enhance the mutant enzyme activity in culture cells. We concluded that the mutant misfolding enzyme protein and substrate analog competitive inhibitor (chemical chaperone) form a stable complex to be transported to the lysosome, to restore the catalytic activity of mutant enzyme after spontaneous dissociation under the acidic condition. This gene mutation-specific molecular interaction is a paradoxical phenomenon that an enzyme inhibitor in vitro serves as an enzyme stabilizer in situ. First we developed a commercially available compound 1-deoxygalactonojirimycin (DGJ) for Fabry disease, and confirmed the above molecular phenomenon. Currently DGJ has become a new candidate of oral medicine for Fabry disease, generalized vasculopathy involving the kidneys, heart and central nervous system in the middle age. This drug development has reached the phase 3 of human clinical study. Then we found two valienamine derivatives, N-octyl-4-epi-?-valienamine (NOEV) and N-octyl-?-valienamine (NOV), as promising therapeutic agents for human ?-galactosidase deficiency disorders (GM1-gangliosidosis and Morquio B disease) and ?-glucosidase deficiency disorders (phenotypic variations of Gaucher disease), respectively. Originally NOEV and NOV had been discovered as competitive inhibitors, and then their paradoxical bioactivities as chaperones were confirmed in cultured fibroblasts from patients with these disorders. Subsequently GM1-gangliosidosis model mice have been used for confirmation of clinical effectiveness, adverse effects and pharmacokinetic studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced ?-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Computational analysis revealed pH-dependent enzyme-chaperone interactions. Our recent study indicated chaperone activity of a new DGJ derivative, MTD118, for ?-galactosidase complementary to NOEV. NOV also showed the chaperone effect toward several ?-glucosidase gene mutants in Gaucher disease. Furthermore a commercial expectorant drug ambroxol was found to be a chaperone for ?-glucosidase. A few Gaucher patients responded to this drug with remarkable improvement of oculomotor dysfunction and myoclonus. We hope chaperone therapy will become available for some patients with Fabry disease, GM1-gangliosidosis, Gaucher disease, and other lysosomal storage diseases particularly with central nervous system involvement. PMID:23290321

  2. N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis

    Microsoft Academic Search

    Julie L. Kasperzyk; Mohga M. El-Abbadi; Eric C. Hauser; Alessandra d'Azzo; Frances M. Platt; Thomas N. Seyfried

    2004-01-01

    GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid b-galactosidase (b-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired

  3. 698. Gene Therapy of Murine GM1 Gangliosidosis by Genetically Modified Bone Marrow Hematopoietic Progenitor Cells

    Microsoft Academic Search

    Renata Sano; Alessandra Tessitore; Angela Ingrassia; Alessandra d'Azzo

    2004-01-01

    b-galactosidase (b-gal), a lysosomal enzyme involved in the removal of b-linked terminal galactosyl residues of many glycoconjugates, is deficient in the neurodegenerative lysosomal disorder GM1-gangliosidosis (GM1). GM1-\\/-mice closely mimic the most fundamental aspects of the neuropathological and neurochemical abnormalities of the human disorder. Bone marrow progenitor cells have been used as a source of corrective protein because of their ability

  4. Maternal uniparental isodisomy causing autosomal recessive GM1 gangliosidosis: a clinical report.

    PubMed

    King, Jessica E; Dexter, Amy; Gadi, Inder; Zvereff, Val; Martin, Meaghan; Bloom, Miriam; Vanderver, Adeline; Pizzino, Amy; Schmidt, Johanna L

    2014-10-01

    Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase. Subsequently, homozygous missense mutations in the galactosidase, beta 1 (GLB1) gene on chromosome 3 were found. Parental testing confirmed inheritance of two copies of the same mutated maternal GLB1 gene, and no paternal copy. SNP analysis was also done to confirm paternity. The patient was ultimately diagnosed with autosomal recessive GM1 gangliosidosis caused by maternal uniparental isodisomy. We provide a review of this patient and others in which uniparental disomy (UPD) of a non-imprinted chromosome unexpectedly caused an autosomal recessive condition. This is the first case of GM1 gangliosidosis reported in the literature to have been caused by UPD. It is important for genetic counselors and other health care providers to be aware of the possibility of autosomal recessive disease caused by UPD. UPD as a cause of autosomal recessive disease drastically changes the recurrence risk for families, and discussions surrounding UPD can be complex. Working with families to understand UPD when it occurs requires a secure and trusting counselor-family relationship. PMID:24777551

  5. Mutation analysis of GM1 gangliosidosis in a Siamese cat from Japan in the 1960s.

    PubMed

    Uddin, Mohammad M; Tanimoto, Takeshi; Yabuki, Akira; Kotani, Takao; Kuwamura, Mitsuru; Chang, Hye-Sook; Yamato, Osamu

    2012-12-01

    GM1 gangliosidosis is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the ?-galactosidase (GLB1) gene. In feline GM1 gangliosidosis, a pathogenic mutation (c.1448G>C) of the feline GLB1 gene was identified in Siamese and Korat cats previously diagnosed with the disease in the USA and Italy, respectively. The present study demonstrated the same mutation in a Siamese cat that had been diagnosed with GM1 gangliosidosis in Japan in the 1960s. The mutation was confirmed using DNA extracted from stored paraffin-embedded brain tissue by a direct sequencing method and a polymerase chain reaction-restriction fragment length polymorphism assay. This pathogenic mutation seems to have been distributed around the world. PMID:22772479

  6. Therapeutic chaperone effect of N-octyl 4-epi-?-valienamine on murine G(M1)-gangliosidosis.

    PubMed

    Suzuki, Yoshiyuki; Ichinomiya, Satoshi; Kurosawa, Mieko; Matsuda, Junichiro; Ogawa, Seiichiro; Iida, Masami; Kubo, Takatoshi; Tabe, Miho; Itoh, Masayuki; Higaki, Katsumi; Nanba, Eiji; Ohno, Kousaku

    2012-05-01

    Therapeutic chaperone effect of a valienamine derivative N-octyl 4-epi-?-valienamine (NOEV) was studied in G(M1)-gangliosidosis model mice. Phamacokinetic analysis revealed rapid intestinal absorption and renal excretion after oral administration. Intracellular accumulation was not observed after continuous treatment. NOEV was delivered to the central nervous system through the blood-brain barrier to induce high expression of the apparently deficient ?-galactosidase activity. NOEV treatment starting at the early stage of disease resulted in remarkable arrest of neurological progression within a few months. Survival time was significantly prolonged. This result suggests that NOEV chaperone therapy will be clinically effective for prevention of neuronal damage if started early in life hopefully also in human patients with G(M1)-gangliosidosis. PMID:22436580

  7. Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis

    Microsoft Academic Search

    Elena Elliot-Smith; Anneliese O. Speak; Emyr Lloyd-Evans; David A. Smith; Aarnoud C. van der Spoel; Mylvaganam Jeyakumar; Terry D. Butters; Raymond A. Dwek; Alessandra d’Azzo; Frances M. Platt

    2008-01-01

    GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal ?-galactosidase deficiency, resulting in the storage of GM1 and GA1, primarily in the central nervous system. This disease typically afflicts infants and young children and there is currently no effective therapy. Substrate reduction therapy (SRT) could be of potential benefit.The imino sugars N-butyldeoxynojirimycin (NB-DNJ, miglustat, Zavesca™) and N-butyldeoxygalactonojirimycin (NB-DGJ) used

  8. Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis.

    PubMed

    Aguilar-Moncayo, M; Takai, T; Higaki, K; Mena-Barragán, T; Hirano, Y; Yura, K; Li, L; Yu, Y; Ninomiya, H; García-Moreno, M I; Ishii, S; Sakakibara, Y; Ohno, K; Nanba, E; Ortiz Mellet, C; García Fernández, J M; Suzuki, Y

    2012-07-01

    Competitive inhibitors of either ?-galactosidase (?-Gal) or ?-galactosidase (?-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp(2)-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal ?- and ?-Gal associated with Fabry disease and GM(1) gangliosidosis. PMID:22618082

  9. Magnetic Resonance Imaging Findings and Novel Mutations in GM1 Gangliosidosis

    Microsoft Academic Search

    Aithala Gururaj; László Sztriha; Josef Hertecant; Johan G. Johansen; Theodoros Georgiou; Yvan Campos; Anthi Drousiotou; Alessandra dAzzo

    2005-01-01

    Two unrelated children and their siblings of Arab origin were diagnosed as having GM1 gangliosidosis on the basis of clinical features and markedly low levels of ?-galactosidase. The T2-weighted magnetic resonance images of the brain revealed certain characteristic features, including delayed myelination and abnormal appearance of the subcortical white matter, internal capsule, and basal ganglia. Their mutation analysis showed two

  10. Chemical chaperone therapy: clinical effect in murine G(M1)-gangliosidosis.

    PubMed

    Suzuki, Yoshiyuki; Ichinomiya, Satoshi; Kurosawa, Mieko; Ohkubo, Masato; Watanabe, Hiroshi; Iwasaki, Hiroyuki; Matsuda, Junichiro; Noguchi, Yoko; Takimoto, Kazuhiro; Itoh, Masayuki; Tabe, Miho; Iida, Masami; Kubo, Takatoshi; Ogawa, Seiichiro; Nanba, Eiji; Higaki, Katsumi; Ohno, Kousaku; Brady, Roscoe O

    2007-12-01

    Certain low-molecular-weight substrate analogs act both as in vitro competitive inhibitors of lysosomal hydrolases and as intracellular enhancers (chemical chaperones) by stabilization of mutant proteins. In this study, we performed oral administration of a chaperone compound N-octyl-4-epi-beta-valienamine to G(M1)-gangliosidosis model mice expressing R201C mutant human beta-galactosidase. A newly developed neurological scoring system was used for clinical assessment. N-Octyl-4-epi-beta-valienamine was delivered rapidly to the brain, increased beta-galactosidase activity, decreased ganglioside G(M1), and prevented neurological deterioration within a few months. No adverse effect was observed during this experiment. N-Octyl-4-epi-beta-valienamine will be useful for chemical chaperone therapy of human G(M1)-gangliosidosis. PMID:17994547

  11. Founder mutation causing infantile GM1-gangliosidosis in the Gypsy population

    Microsoft Academic Search

    Ivanka Sinigerska; David Chandler; Vijesh Vaghjiani; Irfet Hassanova; Rebecca Gooding; Amelia Morrone; Ivo Kremensky; Luba Kalaydjieva

    2006-01-01

    The Gypsies are a trans-national founder population of Asian descent, whose genetic heritage is still incompletely characterized. Here, we describe the first founder mutation leading to a lysosomal storage disorder in this population: R59H in GLB1, which causes infantile GM1-gangliosidosis. The R59H carrier rate is ?2% in the general Gypsy population and ?10% in the Rudari sub-isolate. Haplotype analysis suggests

  12. Myelin abnormalities in the optic and sciatic nerves in mice with GM1-gangliosidosis.

    PubMed

    Heinecke, Karie A; Luoma, Adrienne; d'Azzo, Alessandra; Kirschner, Daniel A; Seyfried, Thomas N

    2015-01-01

    GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old ?-galactosidase (?-gal) +/? and ?-gal -/- mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the ?-gal -/- mice than in unaffected ?-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the ?-gal -/- mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of ?-gal -/- mice than in ?-gal +/? mice; however, cholesteryl esters were enriched in the ?-gal -/- mice. No major abnormalities in these lipids were detected in the sciatic nerve of the ?-gal -/- mice. The abnormalities in GM1 and myelin lipids in optic nerve of ?-gal -/- mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and ?-gal -/- mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of ?-gal -/- mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

  13. Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis

    PubMed Central

    Heinecke, Karie A.; Luoma, Adrienne; d’Azzo, Alessandra; Kirschner, Daniel A.

    2015-01-01

    GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old ?-galactosidase (?-gal) +/? and ?-gal ?/? mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the ?-gal ?/? mice than in unaffected ?-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the ?-gal ?/? mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of ?-gal ?/? mice than in ?-gal +/? mice; however, cholesteryl esters were enriched in the ?-gal ?/? mice. No major abnormalities in these lipids were detected in the sciatic nerve of the ?-gal ?/? mice. The abnormalities in GM1 and myelin lipids in optic nerve of ?-gal ?/? mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and ?-gal ?/? mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of ?-gal ?/? mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

  14. A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis.

    PubMed

    Takai, Tomoko; Higaki, Katsumi; Aguilar-Moncayo, Matilde; Mena-Barragán, Teresa; Hirano, Yuki; Yura, Kei; Yu, Liang; Ninomiya, Haruaki; García-Moreno, M Isabel; Sakakibara, Yasubumi; Ohno, Kousaku; Nanba, Eiji; Ortiz Mellet, Carmen; García Fernández, José M; Suzuki, Yoshiyuki

    2013-03-01

    Lysosomal ?-galactosidase (?-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of ?-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp(2)-iminosugar type, namely 5N,6S-(N'-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant ?-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human ?-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N'-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 ?-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of ?-Gal mutants. PMID:23337983

  15. A Bicyclic 1-Deoxygalactonojirimycin Derivative as a Novel Pharmacological Chaperone for GM1 Gangliosidosis

    PubMed Central

    Takai, Tomoko; Higaki, Katsumi; Aguilar-Moncayo, Matilde; Mena-Barragán, Teresa; Hirano, Yuki; Yura, Kei; Yu, Liang; Ninomiya, Haruaki; García-Moreno, M. Isabel; Sakakibara, Yasubumi; Ohno, Kousaku; Nanba, Eiji; Ortiz Mellet, Carmen; García Fernández, José M.; Suzuki, Yoshiyuki

    2013-01-01

    Lysosomal ?-galactosidase (?-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of ?-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp2-iminosugar type, namely 5N,6S-(N?-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant ?-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human ?-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N?-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 ?-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of ?-Gal mutants. PMID:23337983

  16. Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1-gangliosidosis

    PubMed Central

    Adams, David A.; Markello, Thomas; Golas, Gretchen; Yang, Sandra; Sincan, Murat; Simeonov, Dimitre R.; Fuentes Fajardo, Karin; Hansen, Nancy F.; Cherukuri, Praveen F.; Cruz, Pedro; Teer, Jamie K.; Mullikin, James C.; Boerkoel, Cornelius F.; Gahl, William A.; Tifft, Cynthia J.

    2012-01-01

    Objective: To utilize high-throughput sequencing to determine the etiology of juvenile-onset neurodegeneration in a 19-year-old woman with progressive motor and cognitive decline. Methods: Exome sequencing identified an initial list of 133,555 variants in the proband's family, which were filtered using segregation analysis, presence in dbSNP, and an empirically derived gene exclusion list. The filtered list comprised 52 genes: 21 homozygous variants and 31 compound heterozygous variants. These variants were subsequently scrutinized with predicted pathogenicity programs and for association with appropriate clinical syndromes. Results: Exome sequencing data identified 2 GLB1 variants (c.602G>A, p.R201H; c.785G>T, p.G262V). ?-Galactosidase enzyme analysis prior to our evaluation was reported as normal; however, subsequent testing was consistent with juvenile-onset GM1-gangliosidosis. Urine oligosaccharide analysis was positive for multiple oligosaccharides with terminal galactose residues. Conclusions: We describe a patient with juvenile-onset neurodegeneration that had eluded diagnosis for over a decade. GM1-gangliosidosis had previously been excluded from consideration, but was subsequently identified as the correct diagnosis using exome sequencing. Exome sequencing can evaluate genes not previously associated with neurodegeneration, as well as most known neurodegeneration-associated genes. Our results demonstrate the utility of “agnostic” exome sequencing to evaluate patients with undiagnosed disorders, without prejudice from prior testing results. PMID:22675082

  17. Founder mutation causing infantile GM1-gangliosidosis in the Gypsy population.

    PubMed

    Sinigerska, Ivanka; Chandler, David; Vaghjiani, Vijesh; Hassanova, Irfet; Gooding, Rebecca; Morrone, Amelia; Kremensky, Ivo; Kalaydjieva, Luba

    2006-05-01

    The Gypsies are a trans-national founder population of Asian descent, whose genetic heritage is still incompletely characterized. Here, we describe the first founder mutation leading to a lysosomal storage disorder in this population: R59H in GLB1, which causes infantile GM1-gangliosidosis. The R59H carrier rate is approximately 2% in the general Gypsy population and approximately 10% in the Rudari sub-isolate. Haplotype analysis suggests that the Gypsy diaspora may have contributed to the spread of this mutation to South America. PMID:16466959

  18. Case series of two siblings suffering from GM1 gangliosidosis resulting in early multiple joint arthroplasties

    Microsoft Academic Search

    Yasmeen Khan

    2010-01-01

    Introduction  GM1 gangliosidosis is a rare autosomal recessive lysosomal storage disorder leading to accumulation of substrates of gangliosides\\u000a in lysosomes (Okada and O'Brien, Science 160:1002–1004, 1968; Brunetti-Pierri and Scaglia, Mol Genet Metab 94:391–396, 2008). The disease is diagnosed by a deficiency of beta-galactosidase enzyme (Brunetti-Pierri and Scaglia, Mol Genet Metab 94:391–396,\\u000a 2008). Animal studies and in vitro models have shown an

  19. Crystal structure of human ?-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases.

    PubMed

    Ohto, Umeharu; Usui, Kimihito; Ochi, Toshinari; Yuki, Kenjiro; Satow, Yoshinori; Shimizu, Toshiyuki

    2012-01-13

    G(M1) gangliosidosis and Morquio B are autosomal recessive lysosomal storage diseases associated with a neurodegenerative disorder or dwarfism and skeletal abnormalities, respectively. These diseases are caused by deficiencies in the lysosomal enzyme ?-d-galactosidase (?-Gal), which lead to accumulations of the ?-Gal substrates, G(M1) ganglioside, and keratan sulfate. ?-Gal is an exoglycosidase that catalyzes the hydrolysis of terminal ?-linked galactose residues. This study shows the crystal structures of human ?-Gal in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. Human ?-Gal is composed of a catalytic TIM barrel domain followed by ?-domain 1 and ?-domain 2. To gain structural insight into the molecular defects of ?-Gal in the above diseases, the disease-causing mutations were mapped onto the three-dimensional structure. Finally, the possible causes of the diseases are discussed. PMID:22128166

  20. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan.

    PubMed

    Weismann, Cara M; Ferreira, Jennifer; Keeler, Allison M; Su, Qin; Qui, Linghua; Shaffer, Scott A; Xu, Zuoshang; Gao, Guangping; Sena-Esteves, Miguel

    2015-08-01

    GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease where GLB1 gene mutations result in a reduction or absence of lysosomal acid ?-galactosidase (?gal) activity. ?gal deficiency leads to accumulation of GM1-ganglioside in the central nervous system (CNS). GM1 is characterized by progressive neurological decline resulting in generalized paralysis, extreme emaciation and death. In this study, we assessed the therapeutic efficacy of an adeno-associated virus (AAV) 9-m?gal vector infused systemically in adult GM1 mice (?Gal(-/-)) at 1 × 10(11) or 3 × 10(11) vector genomes (vg). Biochemical analysis of AAV9-treated GM1 mice showed high ?Gal activity in liver and serum. Moderate ?Gal levels throughout CNS resulted in a 36-76% reduction in GM1-ganglioside content in the brain and 75-86% in the spinal cord. Histological analyses of the CNS of animals treated with 3 × 10(11) vg dose revealed increased presence of ?gal and clearance of lysosomal storage throughout cortex, hippocampus, brainstem and spinal cord. Storage reduction in these regions was accompanied by a marked decrease in astrogliosis. AAV9 treatment resulted in improved performance in multiple tests of motor function and behavior. Also the majority of GM1 mice in the 3 × 10(11) vg cohort retained ambulation and rearing despite reaching the humane endpoint due to weight loss. Importantly, the median survival of AAV9 treatment groups (316-576 days) was significantly increased over controls (250-264 days). This study shows that moderate widespread expression of ?gal in the CNS of GM1 gangliosidosis mice is sufficient to achieve significant biochemical impact with phenotypic amelioration and extension in lifespan. PMID:25964428

  1. A Duplication in the Canine ?-Galactosidase Gene GLB1 Causes Exon Skipping and GM1-Gangliosidosis in Alaskan Huskies

    PubMed Central

    Kreutzer, Robert; Leeb, Tosso; Müller, Gundi; Moritz, Andreas; Baumgärtner, Wolfgang

    2005-01-01

    GM1-gangliosidosis is a lysosomal storage disease that is inherited as an autosomal recessive disorder, predominantly caused by structural defects in the ?-galactosidase gene (GLB1). The molecular cause of GM1-gangliosidosis in Alaskan huskies was investigated and a novel 19-bp duplication in exon 15 of the GLB1 gene was identified. The duplication comprised positions +1688–+1706 of the GLB1 cDNA. It partially disrupted a potential exon splicing enhancer (ESE), leading to exon skipping in a fraction of the transcripts. Thus, the mutation caused the expression of two different mRNAs from the mutant allele. One transcript contained the complete exon 15 with the 19-bp duplication, while the other transcript lacked exon 15. In the transcript containing exon 15 with the 19-bp duplication a premature termination codon (PTC) appeared, but due to its localization in the last exon of canine GLB1, nonsense-mediated RNA decay (NMD) did not occur. As a consequence of these molecular events two different truncated GLB1 proteins are predicted to be expressed from the mutant GLB1 allele. In heterozygous carrier animals the wild-type allele produces sufficient amounts of the active enzyme to prevent clinical signs of disease. In affected homozygous dogs no functional GLB1 is synthesized and GM1-gangliosidosis occurs. PMID:15944348

  2. Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the c.1448G>C mutation of the feline GLB1 gene: case study.

    PubMed

    Uddin, Mohammad Mejbah; Hossain, Mohammad Alamgir; Rahman, Mohammad Mahbubur; Chowdhury, Morshedul Alam; Tanimoto, Takeshi; Yabuki, Akira; Mizukami, Keijiro; Chang, Hye-Sook; Yamato, Osamu

    2013-01-01

    GM1 gangliosidosis is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations in the ?-galactosidase (GLB1) gene. In feline GM1 gangliosidosis, a pathogenic mutation (c.1448G>C) in the feline GLB1 gene was identified in Siamese cats in the United States and Japan and in Korat cats in Western countries. The present study found the homozygous c.1448G>C mutation in 2 apparent littermate native kittens in Bangladesh that were exhibiting neurological signs. This is the first identification of GM1 gangliosidosis in native domestic cats in Southeast Asia. This pathogenic mutation seems to have been present in the domestic cat population in the Siamese region and may have been transferred to pure breeds such as Siamese and Korat cats originating in this region. PMID:23123943

  3. Evaluation of N-nonyl-deoxygalactonojirimycin as a pharmacological chaperone for human GM1 gangliosidosis leads to identification of a feline model suitable for testing enzyme enhancement therapy.

    PubMed

    Rigat, Brigitte A; Tropak, Michael B; Buttner, Justin; Crushell, Ellen; Benedict, Daphne; Callahan, John W; Martin, Douglas R; Mahuran, Don J

    2012-09-01

    Deficiencies of lysosomal ?-D-galactosidase can result in GM1 gangliosidosis, a severe neurodegenerative disease characterized by massive neuronal storage of GM1 ganglioside in the brain. Currently there are no available therapies that can even slow the progression of this disease. Enzyme enhancement therapy utilizes small molecules that can often cross the blood brain barrier, but are also often competitive inhibitors of their target enzyme. It is a promising new approach for treating diseases, often caused by missense mutations, associated with dramatically reduced levels of functionally folded enzyme. Despite a number of positive reports based on assays performed with patient cells, skepticism persists that an inhibitor-based treatment can increase mutant enzyme activity in vivo. To date no appropriate animal model, i.e., one that recapitulates a responsive human genotype and clinical phenotype, has been reported that could be used to validate enzyme enhancement therapy. In this report, we identify a novel enzyme enhancement-agent, N-nonyl-deoxygalactonojirimycin, that enhances the mutant ?-galactosidase activity in the lysosomes of a number of patient cell lines containing a variety of missense mutations. We then demonstrate that treatment of cells from a previously described, naturally occurring feline model (that biochemically, clinically and molecularly closely mimics GM1 gangliosidosis in humans) with this molecule, results in a robust enhancement of their mutant lysosomal ?-galactosidase activity. These data indicate that the feline model could be used to validate this therapeutic approach and determine the relationship between the disease stage at which this therapy is initiated and the maximum clinical benefits obtainable. PMID:22784478

  4. Evaluation of N-nonyl-deoxygalactonojirimycin as a pharmacological chaperone for human GM1 gangliosidosis leads to identification of a feline model suitable for testing enzyme enhancement therapy

    PubMed Central

    Rigat, Brigitte A.; Tropak, Michael B.; Buttner, Justin; Crushell, Ellen; Benedict, Daphne; Callahan, John W.; Martin, Douglas R.; Mahuran, Don J.

    2012-01-01

    Deficiencies of lysosomal ?-D-galactosidase can result in GM1 gangliosidosis, a severe neurodegenerative disease characterized by massive neuronal storage of GM1 ganglioside in the brain. Currently there are no available therapies that can even slow the progression of this disease. Enzyme enhancement therapy utilizes small molecules that can often cross the blood brain barrier, but are also often competitive inhibitors of their target enzyme. It is a promising new approach for treating diseases, often caused by missense mutations, associated with dramatically reduced levels of functionally folded enzyme. Despite a number of positive reports based on assays performed with patient cells, skepticism persists that an inhibitor-based treatment can increase mutant enzyme activity in vivo. To date no appropriate animal model, i.e., one that recapitulates a responsive human genotype and clinical phenotype, has been reported that could be used to validate enzyme enhancement therapy. In this report, we identify a novel enzyme enhancement-agent, N-nonyl-deoxygalactonojirimycin, that enhances the mutant ?-galactosidase activity in the lysosomes of a number of patient cell lines containing a variety of missense mutations. We then demonstrate that treatment of cells from a previously described, naturally occurring feline model (that biochemically, clinically and molecularly closely mimics GM1 gangliosidosis in humans) with this molecule, results in a robust enhancement of their mutant lysosomal ?-galactosidase activity. These data indicate that the feline model could be used to validate this therapeutic approach and determine the relationship between the disease stage at which this therapy is initiated and the maximum clinical benefits obtainable. PMID:22784478

  5. Fluorous iminoalditols act as effective pharmacological chaperones against gene products from GLB? alleles causing GM1-gangliosidosis and Morquio B disease.

    PubMed

    Fantur, Katrin M; Wrodnigg, Tanja M; Stütz, Arnold E; Pabst, Bettina M; Paschke, Eduard

    2012-05-01

    Unlike replacement therapy by infusion of exogenous recombinant lysosomal enzymes, pharmacological chaperones aim at a gain of function of endogenous gene products. Deficits resulting from missense mutations may become treatable by small, competitive inhibitors binding to the catalytical site and thus correcting the erroneous conformation of mutant enzymes. This may prevent their premature degradation and normalize intracellular trafficking as well as biological half-life. A major limitation currently arises from the huge number of individual missense mutations and the lack of knowledge on the structural requirements for specific interaction with mutant protein domains. Our previous work on mutations of the ?-galactosidase (?-gal) gene, causing GM1 gangliosidosis (GM1) and Morquio B disease (MBD), respectively, characterized clinical phenotypes as well as biosynthesis, intracellular transport and subcellular localization of mutants. We recently identified an effective chaperone, DL-HexDGJ (Methyl 6-{[N(2)-(dansyl)-N(6)-(1,5-dideoxy-D-galactitol-1,5-diyl)- L-lysyl]amino} hexanoate), among a series of N-modified 1-deoxygalactonojirimycin derivatives carrying a dansyl group in its N-acyl moiety. Using novel and flexible synthetic routes, we now report on the effects of two oligofluoroalkyl-derivatives of 1-deoxygalactonojirimycin, Ph(TFM)(2)OHex-DGJ (N-(?,?-di-trifluoromethyl) benzyloxyhexyl-1,5-dideoxy-1,5-imino-D: -galactitol) and (TFM)(3)OHex-DGJ (N-(Nonafluoro-tert-butyloxy)hexyl-1,5-dideoxy-1,5-imino-D: -galactitol) on the ?-gal activity of GM1 and MBD fibroblasts. Both compounds are competitive inhibitors and increase the residual enzyme activities up to tenfold over base line activity in GM1 fibroblasts with chaperone-sensitive mutations. Western blots showed that this was due to a normalization of protein transport and intralysosomal maturation. The fact that the novel compounds were effective at very low concentrations (0.5-10 ?M) in the cell culture medium as well as their novel chemical character suggest future testing in animal models. This may contribute to new aspects for efficient and personalized small molecule treatment of lysosomal storage diseases. PMID:22033734

  6. IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls.

    PubMed Central

    Bansal, A S; Abdul-Karim, B; Malik, R A; Goulding, P; Pumphrey, R S; Boulton, A J; Holt, P L; Wilson, P B

    1994-01-01

    AIMS--To compare the titre of anti-ganglioside antibodies (AGA) to GM1 ganglioside in patients with central and peripheral neurological disease and pure motor and sensorimotor neuropathy, in patients with classic autoimmune diseases, and controls. METHODS--AGA to GM1 were measured using an enzyme linked immunosorbent assay (ELISA) technique, highly purified bovine GM1 ganglioside, and sequential dilution of control and test sera. Antibody titre was calculated using the optical density readings of three consecutive serum dilutions multiplied by the dilution factor. RESULTS--A considerable overlap was evident in the titre of AGA to GM1 in control and test sera. High antibody titres were most frequent in patients with multifocal motor neuropathy with conduction block (MMNCB). Low AGA titre were observed in several patient groups. Compared with the controls, the median titre of AGA to GM1 was significantly higher in patients with multiple sclerosis, rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus. In contrast, the median titre in patients with diabetic peripheral neuropathy, motor neurone disease, sensorimotor neuropathy and chronic inflammatory demyelinating polyneuropathy was no different from that in normal control subjects. CONCLUSIONS--Estimation of AGA to GM1 may be helpful in the diagnosis of MMNCB in patients with a pure motor neuropathy but in few other conditions. Low titre AGA to GM1 are evident in several autoimmune conditions. The pathogenetic importance of AGA to GM1 in patients with neuropathy is not clear. PMID:8027366

  7. G M1 -gangliosidosis: Accumulation of ganglioside G M1 in cultured skin fibroblasts and correlation with clinical types

    Microsoft Academic Search

    Yoshiyuki Suzuki; Norimasa Nakamura; Kazuko Fukuoka

    1978-01-01

    Uptake of radioactivity from 14C-galactose into gangliosides by cultured skin fibroblasts was studied. GM3 was the major ganglioside in control human fibroblasts. An increase of GM1 was demonstrated in GM1-gangliosidosis fibroblasts. The degree of GM1 accumulation was correlated with the clinical types of this disease. The fibroblasts from an infantile-type patient showed a marked increase of GM1. In late-onset types

  8. Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology

    Microsoft Academic Search

    Renata Sano; Alessandra Tessitore; Angela Ingrassia; Alessandra d'Azzo

    2005-01-01

    Bone marrow cells (BMCs) could correct some pathologic conditions of the central nervous system (CNS) if these cells would effectively repopulate the brain. One such condition is GM1-gangliosido- sis, a neurodegenerative glycosphingo- lipidosis due to deficiency of lysosomal -galactosidase (-gal). In this disease, abnormal build up of GM1-ganglioside in the endoplasmic reticulum of brain cells results in calcium imbalance, induction

  9. Mutations in acid [beta]-galactosidase cause GM[sub 1]-gangliosidosis in American patients

    Microsoft Academic Search

    R. M. Boustany; W. H. Qian; K. Suzuki

    1993-01-01

    The authors describe four new mutations in the [beta]-galactosidase gene. These are the first mutations causing infantile and juvenile GM[sub 1]-gangliosidosis to be described in American patients. Cell lines from two patients with juvenile and from six patients with infantile GM[sub 1]-gangliosidosis were analyzed. Northern blot analysis showed the acid [beta]-galactosidase message to be of normal size and quantity in

  10. Newly observed thalamic involvement and mutations of the HEXA gene in a Korean patient with juvenile GM2 gangliosidosis

    Microsoft Academic Search

    Soon Min Lee; Min Jung Lee; Joon Soo Lee; Heung Dong Kim; Jin Sung Lee; Jinna Kim; Seung Koo Lee; Young Mock Lee

    2008-01-01

    Neuroimaging studies of patients with GM2 gangliosidosis are rare. The thalamus and basal ganglia are principally involved\\u000a in patients affected by the infantile form of GM2 gangliosidosis. Unlike in the infantile form, in juvenile or adult type\\u000a GM2 gangliosidosis, progressive cortical and cerebellar atrophy is the main abnormality seen on conventional magnetic resonance\\u000a imaging (MRI); no basal ganglial or thalamic

  11. Serum anti-GM1 and anti-GD1a antibodies in patients with motor neuron disease.

    PubMed

    Voumvourakis, C; Rombos, A; Konstantoulakis, M M; Segditsa, I; Papageorgiou, C

    1992-12-01

    Using an enzyme-linked immunosorbent assay (ELISA) sera from 100 individuals, 20 with motor neuron disease (MND), 25 with peripheral neuropathy (PN), 15 with degenerative dementia and 40 controls, were examined in order to detect serum IgM and IgG anti-GM1 and anti-GD1a antibodies. Patients with MND showed statistically significant higher levels of IgM anti-GM1 antibody compared to the control group. Three patients with peripheral neuropathy had very high levels of anti-GM1 and anti-GD1a antibodies. Antibody levels in patients with degenerative dementia showed no difference compared to the controls. These results suggest that a further inquiry into the role of serum anti-GM1 and anti-GD1a activity in motor neuron disease and peripheral neuropathy is necessary. PMID:1481647

  12. Genetics Home Reference: GM1 gangliosidosis

    MedlinePLUS

    ... retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an ... experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. ...

  13. Pharmacokinetics, safety and tolerability of miglustat in the treatment of pediatric patients with GM2 gangliosidosis

    Microsoft Academic Search

    Gustavo H. B. Maegawa; Paul L. M. van Giersbergen; Sandra Yang; Brenda Banwell; Christopher P. Morgan; Jasper Dingemanse; Cynthia J. Tifft; Joe T. R. Clarke

    2009-01-01

    GM2 gangliosidosis (GM2g) is an inherited neurodegenerative disorder caused by deficiency of lysosomal ?-hexosaminidase A, resulting in accumulation of GM2 ganglioside, principally in the brain. Substrate reduction therapy is currently under investigation as a treatment. The study investigated the pharmacokinetics and safety of miglustat given as single and multiple doses in infantile and juvenile GM2g patients for 6- and 24-months,

  14. Mutations in the lysosomal [beta]-galactosidase gene that cause the adult form of GMI gangliosidosis

    Microsoft Academic Search

    S. Chakraborty; M. A. Rafi; D. A. Wenger

    1994-01-01

    Three adult patients with acid-galactosidase deficiency\\/GM1 gangliosidosis who were from two unrelated families of Scandinavian descent were found to share a common point mutation in the coding region of the corresponding gene. The patients share common clinical features, including early dysarthria, mild ataxia, and bone abnormalities. When cDNA from the two patients in family 1 was PCR amplified and sequenced,

  15. Mutations in acid [beta]-galactosidase cause GM[sub 1]-gangliosidosis in American patients

    SciTech Connect

    Boustany, R.M.; Qian, W.H. (Duke Univ., Durham, NC (United States)); Suzuki, K. (Univ. of North Carolina, Chapel Hill, NC (United States))

    1993-10-01

    The authors describe four new mutations in the [beta]-galactosidase gene. These are the first mutations causing infantile and juvenile GM[sub 1]-gangliosidosis to be described in American patients. Cell lines from two patients with juvenile and from six patients with infantile GM[sub 1]-gangliosidosis were analyzed. Northern blot analysis showed the acid [beta]-galactosidase message to be of normal size and quantity in two juvenile and four infantile cases and of normal size but reduced quantity in two infantile cases. The mutations are distinct from the Japanese mutations. All are point mutations leading to amino acid substitutions: Lys[sup 577] [yields] Arg, Arg[sup 590] [yields] His, and Glu[sup 632] [yields] Gly. The fourth mutation, Arg[sup 208] [yields] Cys, accounts for 10 of 16 possible alleles. Two infantile cases from Puerto Rico of Spanish ancestry are homozygous for this mutation, suggesting that this allele may have come to South America and North America via Puerto Rico. That these mutations cause clinical disease was confirmed by marked reduction in catalytic activity of the mutant proteins in the Cos-1 cell expression system. 12 refs., 5 figs., 2 tabs.

  16. Molecular consequences of the pathogenic mutation in feline G M1 gangliosidosis

    Microsoft Academic Search

    Douglas R. Martin; Brigitte A. Rigat; Polly Foureman; G. S. Varadarajan; Misako Hwang; Barbara K. Krum; Bruce F. Smith; John W. Callahan; Don J. Mahuran; Henry J. Baker

    2008-01-01

    GM1 gangliosidosis is an inherited, fatal neurodegenerative disease caused by deficiency of lysosomal ?-d-galactosidase (EC 3.2.1.23) and consequent storage of undegraded GM1 ganglioside. To characterize the genetic mutation responsible for feline GM1 gangliosidosis, the normal sequence of feline ?-galactosidase cDNA first was defined. The feline ?-galactosidase open reading frame is 2010 base pairs, producing a protein of 669 amino acids.

  17. Neuroradiological findings in GM2 gangliosidosis variant B1

    PubMed Central

    Bano, Shahina; Prasad, Akhila; Yadav, Sachchida Nand; Chaudhary, Vikas; Garga, Umesh Chandra

    2011-01-01

    GM2 gangliosidosis variant B1 is a very rare lysosomal disorder. As per our knowledge, to date, only one article depicting the magnetic resonance imaging (MRI) findings of GM2 gangliosidosis variant B1 is available in the literature. We are the first to describe the neuroradiological findings in an Indian patient diagnosed with GM2 gangliosidosis variant B1. PMID:22408656

  18. G M1 -gangliosidosis: Chromosome 3 assignment of the ? -galactosidase-A gene ( ? GAL A )

    Microsoft Academic Search

    Thomas B. Shows; Linda R. Scrafford-Wolff; Judith A. Brown; Miriam H. Meisler

    1979-01-01

    The structural gene (ßGALA) coding for lysosomal ß-galactosidase- A (EC 3.2.1.23) has been assigned to human chromosome 3 using man-mouse somatic cell hybrids. Human ß-galactosidase-A was identified in cell hybrids with a species-specific antiserum to human liver ß-galactosidase-A. The antiserum precipitates ß-galactosidase-A from human tissues, cultured cells, and cell hybrids, and recognizes cross-reacting material from a patient with GM1 gangliosidosis.

  19. Generalized CNS disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid ?-galactosidase

    Microsoft Academic Search

    Christopher N. Hahn; Maria del Pilar Martin; Maria Schröder; Marie T. Vanier; Yoji Hara; Kinuko Suzuki; Kunihiko Suzuki; Alessandra d'Azzo

    Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid ?-galactosidase (?-gal). The disease manifests itself either as an infantile, juvenile or adult form and is primarily a neurological disorder with progressive brain dysfunction. A mouse model lacking a functional ?-gal gene has been generated by homologous recombination and embryonic stem cell technology. Tissues from affected mice are devoid

  20. DLHex-DGJ, a novel derivative of 1-deoxygalactonojirimycin with pharmacological chaperone activity in human G M1-gangliosidosis fibroblasts

    Microsoft Academic Search

    Katrin Fantur; Doris Hofer; Georg Schitter; Andreas J. Steiner; Bettina M. Pabst; Tanja M. Wrodnigg; Arnold E. Stütz; Eduard Paschke

    2010-01-01

    GM1-gangliosidosis (GM1) and Morquio B disease (MBD) are rare lysosomal storage disorders caused by mutations in the gene GLB1. Its main gene product, human acid ?-galactosidase (?-Gal) degrades two functionally important molecules, GM1-ganglioside and keratan sulfate in brain and connective tissues, respectively. While GM1 is a severe, phenotypically heterogenous neurodegenerative disorder, MBD is a systemic bone disease without effects on

  1. GM2 gangliosidosis variant B1

    Microsoft Academic Search

    Salvatore Grosso; Maria Angela Farnetani; Rosario Berardi; Maria Margollicci; Paolo Galluzzi; Rossella Vivarelli; Guido Morgese; Paolo Ballestri

    2003-01-01

    .   Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to\\u000a juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis\\u000a variant B1, two presenting with the infantile form and one with the juvenile form. The MRI appearances of the two patients

  2. Mutation analyses in 17 patients with deficiency in acid ß-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B

    Microsoft Academic Search

    Eduard Paschke; Ivica Milos; Heidemarie Kreimer-Erlacher; Gerald Hoefler; Michael Beck; Maria Hoeltzenbein; Wim Kleijer; Thierry Levade; Helen Michelakakis; B. Radeva

    2001-01-01

    An inherited deficiency in #-galactosidase can result in GM1 gangliosidosis, with several phenotypes of generalized or chronic psychomotor deterioration, as well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of neurological symptoms. We performed mutation analyses in 17 juvenile and adult patients from various European regions with a deficiency in #-galactosidase and skeletal abnormalities. Fifteen of these had

  3. Chemical chaperone therapy for G M1 -gangliosidosis

    Microsoft Academic Search

    Y. Suzuki

    2008-01-01

    .  We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous\\u000a competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as\\u000a a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound\\u000a N-octyl-4-epi-?-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV

  4. High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts

    Microsoft Academic Search

    V. S. Akhunov; T. V. Mirenburg; X. D. Krasnopolskaya

    1994-01-01

    GM1- and GM2-gangliosides were isolated from brain and radio-labelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM1- and GM2-gangliosidoses as well as the identification of B, O and AB types of GM2-gangliosidosis.

  5. Prenatal diagnosis of G M1 -gangliosidosis: Biochemical manifestations in fetal tissues

    Microsoft Academic Search

    T. Kudoh; K. Kikuchi; F. Nakamura; S. Yokoyama; K. Karube; S. Tsugawa; R. Minami; T. Nakao

    1978-01-01

    A prenatal diagnosis of GM1-gangliosidosis was made in a pregnancy at risk, on the basis of a deficiency of ß-galactosidase activity demonstrated in cultured aminiotic fluid cells. Biochemical analyses were performed in the aborted fetus. GM1-ganglioside ß-galactosidase activity was reduced to 1% of the control value in both the brain and liver of the affected fetus. Lamellar bodies suggestive of

  6. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant

    SciTech Connect

    Schepers, U.; Glombitza, G.; Lemm, T. [Institut fuer Organische Chemie und Biochemie der Universitaet, Bonn (Germany)] [and others

    1996-11-01

    Lysosomal degradation of ganglioside GM2 by {beta}-hexosaminidase A (hex A) requires the presence of the GM2 activator protein (GM2AP) as an essential cofactor. A deficiency of the GM2 activator causes the AB variant of GM2 gangliosidosis, a recessively inherited disorder characterized by excessive neuronal accumulation of GM2 and related glycolipids. Two novel mutations in the GM2 activator gene (GM2A) have been identified by the reverse-transcriptase-PCR method - a three-base deletion, AAG{sup 262-264}, resulting in a deletion of Lys{sup 88}, and a single-base deletion, A{sup 410}, that causes a frameshift. The latter results in substitution of 33 amino acids and the loss of another 24 amino acid residues. Both patients are homoallelic for their respective mutations inherited from their parents, who are heteroallelic at the GM2A locus. Although the cultured fibroblasts of both patients produce normal levels of activator mRNA, they lack a lysosomal form of GM2AP. Pulse/chase labeling of cultured fibroblasts of the patients, in presence and absence of brefeldin A, indicates a premature degradation of both-mutant and truncated-GM2APs in the endoplasmic reticulum or Golgi. These results were supported by in vitro translation experiments and expression of the mutated proteins. When the mutated GM2APs were expressed in Escherichia coli, both mature GM2AP forms turned proved to exhibit only residual activities in an in vitro assay. 26 refs., 7 figs.

  7. Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form

    Microsoft Academic Search

    Akemi Tanaka; LanThiNgcok Hoang; Yasuaki Nishi; Satoshi Maniwa; Makio Oka; Tsunekazu Yamano

    2003-01-01

    Eight mutations of the a subunit of ß-hexosaminidase A gene ( HEXA) were identified in eight patients with GM2 gangliosidosis variant B. They were five missense mutations, two splice-site mutations, and one two-base deletion. Five of them, R252L (CGT?CTT), N295S (AAT?AAC), W420C (TGG?TGT), IVS 13, +2A?C, and del 265–266AC (exon 2), were novel mutations responsible for infantile acute form of

  8. Motor and reflex testing in G M1-gangliosidosis model mice

    Microsoft Academic Search

    Satoshi Ichinomiya; Hiroshi Watanabe; Kimiko Maruyama; Hiroko Toda; Hiroyuki Iwasaki; Mieko Kurosawa; Junichiro Matsuda; Yoshiyuki Suzuki

    2007-01-01

    A large number of genetic disease model mice have been produced by genetic engineering. However, phenotypic analysis is not sufficient, particularly for brain dysfunction in neurogenetic diseases. We tried to develop a new assessment system mainly for motor and reflex functions in GM1-gangliosidosis model mice. Two genetically engineered model mouse strains were used for this study: the ?-galactosidase-deficient knockout mouse

  9. Two new human {beta}-galactosidase gene mutations in American patients with slowly progressive G{sub M1} gangliosidosis

    SciTech Connect

    Shalish, C.; Breakefield, X.O. [Massachusetts General Hospital, Boston, MA (United States); Kaye, E.M. [Tufts Univ. School of Medicine, Boston, MA (United States)] [and others

    1994-09-01

    Two cases with slowly progressive forms of G{sub M1} gangliosidosis were each found to have a novel mutation for the {beta}-galactosidase gene. AS (died at 4 yr) began with symptoms at 8 months ({beta}-galactosidase activity 10% normal) and HS (59 yr) developed dystronic hand movements at age 3 yr ({beta}-galactosidase activity < 2% of normal controls). The entire 2.4 coding region was sequenced in both directions for each patient using RT-PCR. First strand cDNA was synthesized from fibroblast RNA and double stranded PCR fragments spanning the coding region were made with oligonucleotide primers. Sequencing was performed using asymmetric PCR products made from each double stranded product. Case AS was found to have a nine base-pair insertion [CAGAATTTT] on one allele beginning at nucleotide position 730, which did not result in a frameshift and is predicted to cause the insertion of three amino acids (Glu-Phe-Ser) between amino acids 44-45. No other mutations in the coding region were identified on this or the other allele in this individual. Case HS had a unique point mutation identified in one allele. This mutation was an A{r_arrow}G transition at nucleotide 797 which results in a Asn{r_arrow}Ser amino acid substitution in codon 266 (mutation N266S) with no other mutations found in the expressed RNA sequences. SSCP was performed on a 200 bp region surrounding codon 266 using genomic DNA from over 50 controls to look for changes in nucleotide sequence. Only case HS demonstrated a shift indicating that the base pair change did not represent a normal polymorphism.

  10. Infantile G M1 Gangliosidosis: Complete Morphology and Histochemistry of Two Autopsy Cases, with Particular Reference to Delayed Central Nervous System Myelination

    Microsoft Academic Search

    Rebecca D. Folkerth; Joseph Alroy; Ina Bhan; Edward M. Kaye

    2000-01-01

    Inborn metabolic errors causing lysosomal storage, such as ?-galactosidase deficiency (GM1 gangliosidosis [GM1]), have well-recognized effects on cellular function and morphology. In some classically “neuronal” storage diseases, including\\u000a GM1, neuroradiologic observations of infants have suggested a delay in myelination on the basis of persistently “immature” signal\\u000a intensities monitored over time. We sought to evaluate in a semiquantitative fashion the pattern

  11. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant

    Microsoft Academic Search

    U. Schepers; G. Glombitza; T. Lemm

    1996-01-01

    Lysosomal degradation of ganglioside GM2 by β-hexosaminidase A (hex A) requires the presence of the GM2 activator protein (GM2AP) as an essential cofactor. A deficiency of the GM2 activator causes the AB variant of GM2 gangliosidosis, a recessively inherited disorder characterized by excessive neuronal accumulation of GM2 and related glycolipids. Two novel mutations in the GM2 activator gene (GM2A) have

  12. Two new human β-galactosidase gene mutations in American patients with slowly progressive G{sub M1} gangliosidosis

    Microsoft Academic Search

    C. Shalish; X. O. Breakefield; E. M. Kaye

    1994-01-01

    Two cases with slowly progressive forms of G{sub M1} gangliosidosis were each found to have a novel mutation for the β-galactosidase gene. AS (died at 4 yr) began with symptoms at 8 months (β-galactosidase activity 10% normal) and HS (59 yr) developed dystronic hand movements at age 3 yr (β-galactosidase activity < 2% of normal controls). The entire 2.4 coding

  13. Biochemical and molecular characterization of novel mutations in GLB1 and NEU1 in patient cells with lysosomal storage disorders.

    PubMed

    Kwak, Jae Eun; Son, Mi-Young; Son, Ye Seul; Son, Myung Jin; Cho, Yee Sook

    2015-02-20

    Lysosomes are cytoplasmic compartments that contain many acid hydrolases and play critical roles in the metabolism of a wide range of macromolecules. Deficiencies in lysosomal enzyme activities cause genetic diseases, called lysosomal storage disorders (LSDs). Many mutations have been identified in the genes responsible for LSDs, and the identification of mutations is required for the accurate molecular diagnoses. Here, we analyzed cell lines that were derived from two different LSDs, GM1 gangliosidosis and sialidosis. GM1 gangliosidosis is caused by mutations in the GLB1 gene that encodes ?-galactosidase. A lack of ?-galactosidase activity leads to the massive accumulation of GM1 ganglioside, which results in neurodegenerative pathology. Mutations in the NEU1 gene that encodes lysosomal sialidase cause sialidosis. Insufficient activity of lysosomal sialidase progressively increases the accumulation of sialylated molecules, and various clinical symptoms, including mental retardation, appear. We sequenced the entire coding regions of GLB1 and NEU1 in GM1 gangliosidosis and sialidosis patient cells, respectively. We found the novel mutations p.E186A in GLB1 and p.R347Q in NEU1, as well as many other mutations that have been previously reported. We also demonstrated that patient cells containing the novel mutations showed the molecular phenotypes of the corresponding disease. Further structural analysis suggested that these novel mutation sites are highly conserved and important for enzyme activity. PMID:25600812

  14. Lysosomal accumulation of Trk protein in brain of GM? -gangliosidosis mouse and its restoration by chemical chaperone.

    PubMed

    Takamura, Ayumi; Higaki, Katsumi; Ninomiya, Haruaki; Takai, Tomoko; Matsuda, Junichiro; Iida, Masami; Ohno, Kousaku; Suzuki, Yoshiyuki; Nanba, Eiji

    2011-08-01

    G(M1) -gangliosidosis is a fatal neurodegenerative disorder caused by deficiency of lysosomal acid ?-galactosidase (?-gal). Accumulation of its substrate ganglioside G(M1) (G(M1) ) in lysosomes and other parts of the cell leads to progressive neurodegeneration, but underlying mechanisms remain unclear. Previous studies demonstrated an essential role for interaction of G(M1) with tropomyosin receptor kinase (Trk) receptors in neuronal growth, survival and differentiation. In this study we demonstrate accumulation of G(M1) in the cell-surface rafts and lysosomes of the ?-gal knockout (?-gal-/-) mouse brain association with accumulation of Trk receptors and enhancement of its downstream signaling. Immunofluorescence and subcellular fractionation analysis revealed accumulation of Trk receptors in the late endosomes/lysosomes of the ?-gal-/- mouse brain and their association with ubiquitin and p62. Administration of a chemical chaperone to ?-gal-/- mouse expressing human mutant R201C protein resulted in a marked reduction of intracellular storage of G(M1) and phosphorylated Trk. These findings indicate that G(M1) accumulation in rafts causes activation of Trk signaling, which may participate in the pathogenesis of G(M1) -gangliosidosis. PMID:21574998

  15. An open-label Phase I\\/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay–Sachs or Sandhoff variants)

    Microsoft Academic Search

    Joe T. R. Clarke; Don J. Mahuran; Swati Sathe; Edwin H. Kolodny; Brigitte A. Rigat; Julian A. Raiman; Michael B. Tropak

    2011-01-01

    Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay–Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for

  16. Antibodies to GM1(NeuGc) in Guillain–Barré syndrome after ganglioside therapy

    Microsoft Academic Search

    Masaaki Odaka; Nobuhiro Yuki; Eduardo Nobile-Orazio; Marinella Carpo; Koich Hirata

    2000-01-01

    N-Glycolylneuraminic acid-containing GM1 [GM1(Gc)] is a molecule for serum antibodies in patients with Guillain–Barré syndrome (GBS). To clarify the pathogenesis of GBS after treatment with bovine brain ganglioside, we investigated the presence of anti-GM1(Gc) antibody in patients who developed GBS after ganglioside injection. Serum samples were taken from nine Italian patients with GBS after ganglioside therapy as well as from

  17. Lysosomal acid hydrolases in established lymphoblastoid cell lines, transformed by Epstein-Barr virus, from patients with genetic lysosomal storage diseases

    Microsoft Academic Search

    R. Minami; Y. Watanabe; T. Kudoh; M. Suzuki; K. Oyanagi; T. Orii; T. Nakao

    1978-01-01

    Lysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases—Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease—and from obligate heterozygotes for these diseases.

  18. An autopsy case of infantile GM1 gangliosidosis with adrenal calcification

    Microsoft Academic Search

    Ritambhra Nada; Kirti Gupta; Sadhna Bhasin Lal; Rakesh Kumar Vasishta

    We describe an autopsy case of a 1-year-old male baby presenting with failure to gain milestones, floppiness, and reddish\\u000a skin lesions since birth. Fundoscopic examination revealed bilateral cherry-red spots in the macula. The baby died of respiratory\\u000a failure and autopsy revealed numerous ballooned neurons and astrocytes with cytoplasmic storage material seen throughout central\\u000a white matter, basal ganglia, cerebellum, choroid plexus,

  19. Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells

    Microsoft Academic Search

    Maria Schrtider; Doris Schnabel; Robert Hurwitz; Elisabeth Young; Kunihiko Suzuki; Konrad Sandhoff

    1993-01-01

    The GM2 activator is a hexosaminidase A-specific glycolipid-binding protein required for the lysosomal degradation of ganglioside GM2. Genetic deficiency of GM2 activator leads to a neurological disorder, an atypical form of Tay-Sachs disease (GM2 gangliosidosis variant AB). Here, we describe a G506 to C transversion (Arg169 to Pro) in the mRNA of an infantile patient suffering from GM2-gangliosidosis variant AB.

  20. Gene Transfer to Human Cells: Transducing Phage lambda plac Gene Expression in GMI-gangliosidosis Fibroblasts

    Microsoft Academic Search

    Jurgen Horst; Friedrich Kluge; Konrad Beyreuther; Wolfgang Gerok

    1975-01-01

    Genetic information from the bacterium Escherichia coli was transferred to human cells by means of the specialized transducing phage lambda plac carrying the bacterial z gene for the enzyme beta -galactosidase (beta -D-galactoside galactohydrolase, EC 3.2.1.23). As recipient cells, cultured skin fibroblasts from a patient with generalized gangliosidosis (GMI-gangliosidosis Type I) characterized by a severe deficiency of beta -galactosidase activity

  1. Mutations in the lysosomal [beta]-galactosidase gene that cause the adult form of GMI gangliosidosis

    SciTech Connect

    Chakraborty, S.; Rafi, M.A.; Wenger, D.A. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1994-06-01

    Three adult patients with acid-galactosidase deficiency/GM1 gangliosidosis who were from two unrelated families of Scandinavian descent were found to share a common point mutation in the coding region of the corresponding gene. The patients share common clinical features, including early dysarthria, mild ataxia, and bone abnormalities. When cDNA from the two patients in family 1 was PCR amplified and sequenced, most (39/41) of the clones showed a C-to-T transition (C[yields]T) at nucleotide 245 (counting from the initiation codon). This mutation changes the codon for the Thr(ACG) to Met(ATG). Mutant and normal sequences were also found in that position in genomic DNA, indicating the presence of another mutant allele. Genomic DNA from the patient in family 2 revealed the same point mutation in one allele. It was determined that in each family only the father carried the C[yields]T mutation. Expression studies showed that this mutation produced 3%-4% of [beta]-galactosidase activity, confirming its deleterious effects. The cDNA clones from the patients in family 1 that did not contain the C[yields]T revealed a 20-bp insertion of intronic sequence between nucleotides 75 and 76, the location of the first intron. Further analysis showed the insertion of a T near the 5[prime] splice donor site which led to the use of a cryptic splice site. It appears that the C[yields]T mutation results in enough functional enzyme to produce a mild adult form of the disease, even in the presence of a second mutation that likely produces nonfunctional enzyme. 31 refs., 7 figs., 1 tab.

  2. Passive transfer of IgG anti-GM1 antibodies impairs peripheral nerve repair

    PubMed Central

    Lopez, Pablo H.; Zhang, Gang; Zhang, Jiangyang; Lehmann, Helmar C.; Griffin, John W.; Schnaar, Ronald L.; Sheikh, Kazim A.

    2010-01-01

    Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin ? subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS. PMID:20631181

  3. GM1 antibodies in post-polio syndrome and previous paralytic polio

    Microsoft Academic Search

    E. Farbu; T. Rekand; O.-B. Tysnes; J. A. Aarli; N. E. Gilhus; C. A. Vedeler

    2003-01-01

    We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM,

  4. Substrate reduction therapy in juvenile GM2 gangliosidosis

    Microsoft Academic Search

    Gustavo H. B. Maegawa; Brenda L. Banwell; Susan Blaser; Geoffrey Sorge; Maggie Toplak; Cameron Ackerley; Cynthia Hawkins; Jason Hayes; Joe T. R. Clarke

    2009-01-01

    Substrate reduction therapy (SRT) is considered to be a potential therapeutic option for juvenile GM2 gangliosidosis (jGM2g). We evaluated the efficacy of SRT in jGM2g, assessing neurological, neuropsychological and brain magnetic resonance imaging (MRI) outcomes over a 24-month period of treatment. In an open-label and single-center study, five jGM2g patients (mean age 14.6±4.5years) received oral miglustat at doses of 100–200mg

  5. 889. Adeno-Associated Virus Gene Therapy of Feline Gangliosidosis

    Microsoft Academic Search

    Douglas R. Martin; Begona Cachon-Gonzalez; Miguel Sena-Esteves; Misako Hwang; Atoska S. Gentry; Nancy E. Morrison; Nancy R. Cox; Timothy M. Cox; Henry J. Baker

    2006-01-01

    Feline ganglioside storage diseases are authentic models of the human conditions and are valuable for development of gene therapy strategies for human patients. Deficiency of the lysosomal enzymes ?-galactosidase or ?-N-acetylhexosaminidase causes continuous cumulation of GM1 or GM2 ganglioside, respectively, resulting in disease manifestations nd death. There is no reliable treatment for human gangliosidoses, although knockout mouse models have been

  6. GM1 and GM2 gangliosides: recent developments.

    PubMed

    Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

    2014-03-01

    GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction. PMID:25372744

  7. GDNF signaling implemented by GM1 ganglioside; failure in Parkinson's disease and GM1-deficient murine model.

    PubMed

    Hadaczek, Piotr; Wu, Gusheng; Sharma, Nitasha; Ciesielska, Agnieszka; Bankiewicz, Krystof; Davidow, Amy L; Lu, Zi-Hua; Forsayeth, John; Ledeen, Robert W

    2015-01-01

    GDNF is indispensible for adult catecholaminergic neuron survival, and failure of GDNF signaling has been linked to loss of dopaminergic neurons in Parkinson's disease (PD). This study demonstrates attenuated GDNF signaling in neurons deficient in ganglio-series gangliosides, and restoration of such signaling with LIGA20, a membrane permeable analog of GM1. GM1 is shown to associate in situ with GFR?1 and RET, the protein components of the GDNF receptor, this being necessary for assembly of the tripartite receptor complex. Mice wholly or partially deficient in GM1 due to disruption of the B4galnt1 gene developed PD symptoms based on behavioral and neuropathological criteria which were largely ameliorated by gene therapy with AAV2-GDNF and also with LIGA20 treatment. The nigral neurons of PD subjects that were severely deficient in GM1 showed subnormal levels of tyrosine phosphorylated RET. Also in PD brain, GM1 levels in the occipital cortex, a region of limited PD pathology, were significantly below age-matched controls, suggesting the possibility of systemic GM1 deficiency as a risk factor in PD. This would accord with our finding that mice with partial GM1 deficiency represent a faithful recapitulation of the human disease. Together with the previously demonstrated age-related decline of GM1 in human brain, this points to gradual development of subthreshold levels of GM1 in the brain of PD subjects below that required for effective GDNF signaling. This hypothesis offers a dramatically different explanation for the etiology of sporadic PD as a manifestation of acquired resistance to GDNF. PMID:25448159

  8. MR Imaging and Proton Spectroscopy of Neuronal Injury in Late-Onset GM2 Gangliosidosis

    Microsoft Academic Search

    Matilde Inglese; Annette O. Nusbaum; Gregory M. Pastores; John Gianutsos; Edwin H. Kolodny; Oded Gonen

    BACKGROUND AND PURPOSE: Despite the ubiquity of GM2 gangliosides accumulation in patients with late-onset GM2 gangliosidosis (GM2G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. METHODS: During

  9. Hyperreflexia in Guillain-Barré syndrome: relation with acute motor axonal neuropathy and anti-GM1 antibody

    PubMed Central

    Kuwabara, S.; Ogawara, K.; Koga, M.; Mori, M.; Hattori, T.; Yuki, N.

    1999-01-01

    OBJECTIVES—To investigate the incidence of hyperreflexia in patients with Guillain-Barré syndrome (GBS), and its relation with electrodiagnosis of acute motor axonal neuropathy (AMAN), antiganglioside GM1 antibody, and Campylobacter jejuni infection. It was reported that patients with AMAN in northern China often had hyperreflexia in the recovery phase.?METHODS—In 54 consecutive Japanese patients with GBS, sequential findings of tendon reflexes were reviewed. By electrodiagnostic criteria, patients were classified as having AMAN or acute inflammatory demyelinating polyneuropathy (AIDP). Anti-GM1 and anti-C jejuni antibodies were measured by enzyme linked immunosorbent assays.?RESULTS—Seven (13%) patients developed hyperreflexia with the spread of the myotatic reflex to other segments in the early recovery phase, one of whom already had hyperreflexia in the acute progressive phase. Of the seven patients, six had AMAN and all seven had anti-GM1 antibodies, whereas only two had anti-C jejuni antibodies. Hyperreflexia was more often found in patients with AMAN than AIDP (6/23 v 1/18, p=0.002), and in patients with anti-GM1 antibodies than without them (7/26 v 0/28, p=0.01). Hyperreflexic patients had milder peak disabilities than patients without hyperreflexia (p=0.03). Increased motor neuron excitability in the hyperreflexic patients was supported by increased soleus H-reflex amplitudes and the appearance of H-reflexes in the small hand or foot muscles.?CONCLUSIONS—Hyperreflexia often occurs in patients with GBS especially with AMAN, anti-GM1 antibodies, and milder disease. Increased motor neuron excitability further characterises the subgroup of patients with GBS with AMAN and anti-GM1 antibodies.?? PMID:10406985

  10. Genetics Home Reference: GM2-gangliosidosis, AB variant

    MedlinePLUS

    ... if I still have specific questions about GM2-gangliosidosis, AB variant? Ask the Genetic and Rare Diseases Information Center . Where can I ... Professionals What glossary definitions help with understanding GM2-gangliosidosis, AB ... Home Reference Glossary . See also Understanding Medical Terminology . ...

  11. A Korean patient with Morquio B disease with a novel c.13_14insA mutation in the GLB1 gene.

    PubMed

    Sohn, Young Bae; Park, Hyung-Doo; Park, Sung Won; Kim, Se-Hwa; Cho, Sung-Yoon; Ko, Ah-Ra; Ki, Chang-Seok; Yeau, Sunghee; Jin, Dong-Kyu

    2012-01-01

    Mutations in the GLB1 gene, which encodes acid ?-galactosidase, can result in two disease phenotypes: GM1-gangliosidosis (MIM #230500) and Morquio B disease (Mucopolysaccharidosis type IVB, MIM #253010). Morquio B disease occurs much more infrequently than GM1-gangliodosis and is characterized by severe skeletal manifestations (dysostosis multiplex) without central nervous system involvement. Here, we report the first known Korean patient with Morquio B disease. A 7-year-old boy presented with severe progressive skeletal dysplasia including scoliosis, contractures of the elbows, xenu valgum, funnel chest, and trigger thumb requiring surgical intervention. The patient had normal neurological functions and mental status when evaluated by pediatric neurologists. The patient's urinary glycosaminoglycans, measured by the cetylpyridinium chloride (CPC) precipitation test, were 252.8 CPC unit/g creatinine (reference range < 175). Thin layer chromatography of urine showed a keratan sulfate band. Enzyme activity of ?-galactosidase in leukocytes was 1.15 nmol/hr/mg protein (reference range 78.1-117.7; 1-1.5% of normal). The patient had compound heterozygous mutations of the GLB1 gene: c.13_14insA (p.L5HfsX29), which was reported in a patient with infantile GM1 gangliosidosis with the near-complete absence of enzyme activity, and c.367G>A (p.G123R), which is a novel frame-shift mutation. In summary, we report the first known Korean patient with Morquio B disease and a novel mutation (c.13_14insA of GLB1). PMID:22371915

  12. Conformational analysis of GM1 oligosaccharide in water solution

    NASA Astrophysics Data System (ADS)

    Bernardi, Anna; Raimondi, Laura

    1995-04-01

    An unconstrained Monte Carlo/Energy Minimization conformational search was performed on ganglioside GM1 oligosaccharide, and results were compared to the known solution conformation of this molecule. The search was performed using the continuum water solvent model as implemented in MacroModel/Batchmin, and the force field AMBER*. The latter had to be modified by including new parameters for the NeuAc residue contained in GM1. The parameters were developed on the basis of molecular orbital calculations on simple model systems (and therefore should have general validity for molecular mechanics calculations on sialyl oligosaccharides). A nice agreement was reached between the computed structure and the available NMR data.

  13. Galleria mellonella native and analogue peptides Gm1 and ?Gm1. II) anti-bacterial and anti-endotoxic effects.

    PubMed

    Correa, Wilmar; Manrique-Moreno, Marcela; Behrends, Jochen; Patińo, Edwin; Marella, Chakravarthy; Peláez-Jaramillo, Carlos; Garidel, Patrick; Gutsmann, Thomas; Brandenburg, Klaus; Heinbockel, Lena

    2014-10-01

    Antimicrobial peptides (AMPs) are important components of the innate immune system of animals, plants, fungi and bacteria and are recently under discussion as promising alternatives to conventional antibiotics. We have investigated two cecropin-like synthetic peptides, Gm1, which corresponds to the natural overall uncharged Galleria mellonella native peptide and ?Gm1, a modified overall positively charged Gm1 variant. We have analysed these peptides for their potential to inhibit the endotoxin-induced secretion of tumour necrosis factor-? (TNF-?) from human mononuclear cells. Furthermore, in a conventional microbiological assay, the ability of these peptides to inhibit the growth of the rough mutant bacteria Salmonella enterica Minnesota R60 and the polymyxin B-resistant Proteus mirabilis R45 was investigated and atomic force microscopy (AFM) measurements were performed to characterize the morphology of the bacteria treated by the two peptides. We have also studied their cytotoxic properties in a haemolysis assay to clarify potential toxic effects. Our data revealed for both peptides minor anti-inflammatory (anti-endotoxin) activity, but demonstrated antimicrobial activity with differences depending on the endotoxin composition of the respective bacteria. In accordance with the antimicrobial assay, AFM data revealed a stronger morphology change of the R45 bacteria than for the R60. Furthermore, Gm1 had a stronger effect on the bacteria than ?Gm1, leading to a different morphology regarding indentations and coalescing of bacterial structures. The findings verify the biophysical measurements with the peptides on model systems. Both peptides lack any haemolytic activity up to an amount of 100?g/ml, making them suitable as new anti-infective agents. PMID:25016054

  14. Hyperreflexia in Guillain-Barré syndrome: relation with acute motor axonal neuropathy and anti-GM1 antibody

    Microsoft Academic Search

    Satoshi Kuwabara; Kazue Ogawara; Michiaki Koga; Masahiro Mori; Takamichi Hattori; Nobuhiro Yuki

    1999-01-01

    OBJECTIVESTo investigate the incidence of hyperreflexia in patients with Guillain-Barré syndrome (GBS), and its relation with electrodiagnosis of acute motor axonal neuropathy (AMAN), antiganglioside GM1 antibody, and Campylobacter jejuni infection. It was reported that patients with AMAN in northern China often had hyperreflexia in the recovery phase.METHODSIn 54 consecutive Japanese patients with GBS, sequential findings of tendon reflexes were reviewed.

  15. Clustering effects of GM1 and formation mechanisms of interdigitated liquid disordered domains in GM1/SM/CHOL-supported planar bilayers on mica surfaces

    NASA Astrophysics Data System (ADS)

    Shang, Zhiguo; Mao, Yanli; Tero, Ryugo; Liu, Xinli; Hoshino, Tyuji; Tanaka, Motohiko; Urisu, Tsuneo

    2010-09-01

    We have observed by atomic force microscopy that an interdigitated liquid disordered domain (ILDD) is formed in the ganglioside (GM1)/sphingomyelin (SM)/cholesterol (CHOL) bilayers on a mica surface and accelerates the formation of fibriller A? agglomerates. By studies of the mechanisms using molecular dynamics simulations, we conclude that the ILDD structure is formed as a result of the phase separation to SM- and GM1-rich domains on the mica surface induced by the effects of GM1 clustering and the interaction between the GM1 head group and the water layer adsorbed in the ditrigonal cavity on the mica surface.

  16. IgG anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in Guillain-Barré syndrome.

    PubMed

    Kuwabara, S; Yuki, N; Koga, M; Hattori, T; Matsuura, D; Miyake, M; Noda, M

    1998-08-01

    To investigate the pathophysiological role of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor or acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patients), or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathophysiological mechanisms in IgG anti-GM1-positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers. PMID:9708542

  17. Heat-Labile Enterotoxin: Beyond GM1 Binding

    PubMed Central

    Mudrak, Benjamin; Kuehn, Meta J.

    2010-01-01

    Enterotoxigenic Escherichia coli (ETEC) is a significant source of morbidity and mortality worldwide. One major virulence factor released by ETEC is the heat-labile enterotoxin LT, which is structurally and functionally similar to cholera toxin. LT consists of five B subunits carrying a single catalytically active A subunit. LTB binds the monosialoganglioside GM1, the toxin’s host receptor, but interactions with A-type blood sugars and E. coli lipopolysaccharide have also been identified within the past decade. Here, we review the regulation, assembly, and binding properties of the LT B-subunit pentamer and discuss the possible roles of its numerous molecular interactions. PMID:22069646

  18. GM2 gangliosidosis in British Jacob sheep.

    PubMed

    Wessels, M E; Holmes, J P; Jeffrey, M; Jackson, M; Mackintosh, A; Kolodny, E H; Zeng, B J; Wang, C B; Scholes, S F E

    2014-01-01

    GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock. PMID:24309906

  19. Clinical, enzymatic, and molecular characterisation of a Portuguese family with a chronic form of GM2-gangliosidosis B1 variant

    Microsoft Academic Search

    M G Ribeiro; T Sonin; R A Pinto; A Fontes; H Ribeiro; E Pinto; M M Palmeira; M C Sá Miranda

    1996-01-01

    Mutations in the hexosaminidase A gene (HEXA) causing the B1 variant of GM2-gangliosidosis result in the presence of a mutant enzyme protein with a catalytically defective alpha subunit. A rare and panethnically distributed mutation, transition G533A (Arg178His), is known to be a common allele among Portuguese patients with the subacute phenotype. We now report the presence of an Arg178His allele

  20. Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene.

    PubMed

    Garcia-Hartjes, Jaime; Bernardi, Silvia; Weijers, Carel A G M; Wennekes, Tom; Gilbert, Michel; Sansone, Francesco; Casnati, Alessandro; Zuilhof, Han

    2013-07-14

    Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100,000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent known CTB inhibitors. PMID:23689250

  1. On multivalent receptor activity of GM1 in cholesterol containing membranes.

    PubMed

    Šachl, Radek; Amaro, Mariana; Aydogan, Gokcan; Koukalová, Alena; Mikhalyov, Ilya I; Boldyrev, Ivan A; Humpolí?ková, Jana; Hof, Martin

    2015-04-01

    Gangliosides located at the outer leaflet of plasma membrane are molecules that either participate in recognizing of exogenous ligand molecules or exhibit their own receptor activity, which are both essential phenomena for cell communication and signaling as well as for virus and toxin entry. Regulatory mechanisms of lipid-mediated recognition are primarily subjected to the physical status of the membrane in close vicinity of the receptor. Concerning the multivalent receptor activity of the ganglioside GM1, several regulatory strategies dealing with GM1 clustering and cholesterol involvement have been proposed. So far however, merely the isolated issues were addressed and no interplay between them investigated. In this work, several advanced fluorescence techniques such as Z-scan fluorescence correlation spectroscopy, Förster resonance energy transfer combined with Monte Carlo simulations, and a newly developed fluorescence antibunching assay were employed to give a more complex portrait of clustering and cholesterol involvement in multivalent ligand recognition of GM1. Our results indicate that membrane properties have an impact on a fraction of GM1 molecules that is not available for the ligand binding. While at low GM1 densities (~1 %) it is the cholesterol that turns GM1 headgroups invisible, at higher GM1 level (~4 %) it is purely the local density of GM1 molecules that inhibits the recognition. At medium GM1 content, cooperation of the two phenomena occurs. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. PMID:25101973

  2. Variability of bacterial gene-directed enzyme production in human genetically deficient cells

    Microsoft Academic Search

    Jfirgen Horst; Friedrich Kluge; Wolfgang Gerok

    1979-01-01

    Human ß-galactosidase-deficient skin fibroblasts from a patient with generalized gangliosidosis (GM1-gangliosidosis type I) were treated with phage ? plac DNA, coding for Escherichia coli ß-galactosidase (ß-D-galactoside galactohydrolase, EC 3.2.1.23). New ß-galactosidase activity detected in cell extracts of phage DNA-treated GM1-gangliosidosis fibroblasts continued to vary considerably from one experiment to another. It behaved like the E. coliz-gene product upon immunochemical and

  3. Spontaneous curvature of ganglioside GM1 Effect of cross-linking Lucyna Mrwczyn ska a,

    E-print Network

    Iglic, Ales

    23 May 2012 Keywords: Ganglioside GM1 Intrinsic molecular shape Membrane curvature Cholera toxin-tagged cholera toxin subunit B (CTB) plus anti- CTB was analysed in cell membranes by fluorescence microscopy microdomains (rafts) [1,2]. GM1 is the natural receptor of cholera toxin [3]. Fluo- rophore-conjugated cholera

  4. Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment

    NASA Astrophysics Data System (ADS)

    Schneider, J. S.; Pope, Anne; Simpson, Kimberly; Taggart, James; Smith, M. G.; Distefano, L.

    1992-05-01

    A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

  5. Structural basis of the GM2 gangliosidosis B variant

    Microsoft Academic Search

    Fumiko Matsuzawa; Sei-ichi Aikawa; Hitoshi Sakuraba; HoangThiNgoc Lan; Akemi Tanaka; Kousaku Ohno; Yuko Sugimoto; Haruaki Ninomiya; Hirofumi Doi

    2003-01-01

    To study the structural basis of the GM2 gangliosidosis B variant, we constructed the three-dimensional structures of the human ß-hexosaminidase a-subunit and the heterodimer of the a- and ß-subunits, Hex A, by homology modeling. The a-subunit is composed of two domains, domains I and II. Nine mutant models due to specific missense mutations were constructed as well and compared with

  6. Ganglioside G M1 metabolism in living human fibroblasts with ?-galactosidase deficiency

    Microsoft Academic Search

    G. M. S. Mancini; A. T. Hoogeveen; H. Galjaard; J. E. Mansson; L. Svennerholm

    1986-01-01

    The uptake and catabolism of [3H-ceramide]-GM1 was followed in living fibroblasts from patient with different forms of ß-galactosidase deficiency. Gangliosides are identified according to the nomenclature of Svennerholm (1963). A total inability to metabolize the ingested substrate was found in infantile GM1-gangliosidosis whereas cells from an adult GM1-gangliosidosis variant showed a slower rate of degradation, compared with controls. Morquio B

  7. Diagnosis of infantile and juvenile forms of G M2 gangliosidosis variant 0. residual activities toward natural and different synthetic substrates

    Microsoft Academic Search

    H.-J. Kytzia; U. Hinrichs; K. Sandhoff

    1984-01-01

    p-Nitrophenyl-6-sulfo-2-acetamido-2-deoxy-ß-d-glucopyranoside, which is known to be a specific substrate for human hexosaminidase A, has recently been used successfully for diagnosis of variants B and B1 of GM2-gangliosidosis (Fuchs et al. 1983; Kytzia et al. 1983; Li et al. 1983). However, it is hydrolyzed by hexosaminidase S as well and is therefore not suitable for detection of patients with variant 0,

  8. Juvenile GM2 Gangliosidosis Caused by Substitution of Histidine for Arginine at Position 499 or 504 of the a-Subunit of &Hexosaminidase

    Microsoft Academic Search

    Elizabeth F. NeufeldQ

    1990-01-01

    Juvenile GM2 gangliosidosis is a rare neurodegener- ative disorder closely related to Tay-Sachs disease but of later onset and more protracted course. The bio- chemical defect lies in the a-subunit of the lysosomal enzyme &hexosaminidase. Cultured fibroblasts de- rived from patient A synthesized an a-subunit which could acquire mannose 6-phosphate and be secreted, but which failed to associate with the

  9. GM1 reduces injury-induced metabolic deficits and degeneration in the rat optic nerve.

    PubMed

    Yoles, E; Zalish, M; Lavie, V; Duvdevani, R; Ben-Bassat, S; Schwartz, M

    1992-12-01

    This study demonstrates the earliest reported effects of GM1 treatment on crush-injured axons of the mammalian optic nerve. GM1, administered intraperitoneally immediately after injury, was found to reduce the injury-induced metabolic deficit in nerve activity within 2 hr of injury, as measured by changes in the nicotine-amine adenine dinucleotide redox state. After 4 wk, transmission electron microscopy 1 mm distal to the site of injury revealed a sevenfold increase in axonal survival in GM1-treated compared to untreated injured nerves. These results emphasize the beneficial effect of GM1 on injured optic nerves as well as the correlation between immediate and long-term consequences of the injury. Thus, these results have implications for treating damaged optic nerves. PMID:1464504

  10. Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment

    Microsoft Academic Search

    J. S. Schneider; Anne Pope; Kimberly Simpson; James Taggart; M. G. Smith; L. Distefano

    1992-01-01

    A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of

  11. MECHANISMS UNDERLYING THE MICRON-SCALE SEGREGATION OF STEROLS AND GM1 IN LIVE MAMMALIAN SPERM

    PubMed Central

    Selvaraj, Vimal; Asano, Atsushi; Buttke, Danielle E.; Sengupta, Prabuddha; Weiss, Robert S.; Travis, Alexander J.

    2009-01-01

    We demonstrate for the first time that a stable, micron-scale segregation of focal enrichments of sterols exists at physiological temperature in the plasma membrane of live murine and human sperm. These enrichments of sterols represent microheterogeneities within this membrane domain overlying the acrosome. Previously, we showed that cholera toxin subunit B (CTB), which binds the glycosphingolipid, GM1, localizes to this same domain in live sperm. Interestingly, the GM1 undergoes an unexplained redistribution upon cell death. We now demonstrate that GM1 is also enriched in the acrosome, an exocytotic vesicle. Transfer of lipids between this and the plasma membrane occurs at cell death, increasing GM1 in the plasma membrane without apparent release of acrosomal contents. This finding provides corroborative support for an emerging model of regulated exocytosis in which membrane communications might occur without triggering the “acrosome reaction.” Comparison of the dynamics of CTB-bound endogenous GM1 and exogenous BODIPY-GM1 in live murine sperm demonstrate that the sub-acrosomal ring functions as a specialized diffusion barrier segregating specific lipids within the sperm head plasma membrane. Our data show significant differences between endogenous lipids and exogenous lipid probes in terms of lateral diffusion. Based on these studies, we propose a hierarchical model to explain the segregation of this sterol- and GM1-enriched domain in live sperm, which is positioned to regulate sperm fertilization competence and mediate interactions with the oocyte. Moreover, our data suggest potential origins of sub-types of membrane raft microdomains enriched in sterols and/or GM1 that can be separated biochemically. PMID:19012288

  12. Immunohistochemical detection of hepatic GM1 and GM2 gangliosides in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Adela V. Abregú; Susana B. Genta; Alicia N. Sánchez Riera; Sara S. Sánchez

    2002-01-01

    This study was undertaken to investigate the consequences of diabetes on the expression of GM1 and GM2 gangliosides in rat liver. Experimental diabetes was induced by treatment with Streptozotocin (STZ) in adult male Sprague–Dawley rats. Two-dimensional thin-layer chromatography of total ganglioside preparations of liver tissues from STZ-induced diabetic rats showed an increased amount of GM1, while GM2 could not be

  13. Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice.

    PubMed

    Silva, R H; Felicio, L F; Frussa-Filho, R

    1999-01-01

    Some experimental evidence suggests that the beneficial effects of monosialoganglioside GM1 on learning and memory could be related to an improving effect in central cholinergic function. The present study investigates the effects of GM1 on the memory impairment induced by scopolamine in rats or mice tested in passive (PA) and discriminative avoidance (DA) tasks, respectively. Wistar EPM-1 male rats and Swiss EPM-M1 male mice were treated daily IP with 50 mg/kg GM1 or saline for 7 or 14 days, respectively. Twenty-four hours after the last injection, GM1-treated animals received 1 mg/kg scopolamine (GM1-SCO) and saline-treated animals received 1 mg/kg scopolamine (SAL-SCO) or saline (SAL-SAL) IP. Twenty minutes later, the animals were submitted to PA or DA conditioning, and tests were performed 24 h later. The latency in entering the dark chamber of the PA apparatus (LD) presented by SAL-SCO rats was significantly decreased when compared to that presented by SAL-SAL animals. GM1-SCO animals showed an increased LD when compared to SAL-SCO animals and were not significantly different from SAL-SAL rats. GM1-SCO and SAL-SAL (but not SAL-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the non-aversive enclosed arm. The results are consistent with the interpretation that GM1 attenuates scopolamine-induced amnesia. Although not eliminating the participation of other transmitter systems, the present study indicates a possible role of central cholinergic transmission in the action of this compound on learning and memory. PMID:9952034

  14. Functional interaction analysis of GM1-related carbohydrates and Vibrio cholerae toxins using carbohydrate microarray.

    PubMed

    Kim, Chang Sup; Seo, Jeong Hyun; Cha, Hyung Joon

    2012-08-01

    The development of analytical tools is important for understanding the infection mechanisms of pathogenic bacteria or viruses. In the present work, a functional carbohydrate microarray combined with a fluorescence immunoassay was developed to analyze the interactions of Vibrio cholerae toxin (ctx) proteins and GM1-related carbohydrates. Ctx proteins were loaded onto the surface-immobilized GM1 pentasaccharide and six related carbohydrates, and their binding affinities were detected immunologically. The analysis of the ctx-carbohydrate interactions revealed that the intrinsic selectivity of ctx was GM1 pentasaccharide ? GM2 tetrasaccharide > asialo GM1 tetrasaccharide ? GM3trisaccharide, indicating that a two-finger grip formation and the terminal monosaccharides play important roles in the ctx-GM1 interaction. In addition, whole cholera toxin (ctxAB(5)) had a stricter substrate specificity and a stronger binding affinity than only the cholera toxin B subunit (ctxB). On the basis of the quantitative analysis, the carbohydrate microarray showed the sensitivity of detection of the ctxAB(5)-GM1 interaction with a limit-of-detection (LOD) of 2 ng mL(-1) (23 pM), which is comparable to other reported high sensitivity assay tools. In addition, the carbohydrate microarray successfully detected the actual toxin directly secreted from V. cholerae, without showing cross-reactivity to other bacteria. Collectively, these results demonstrate that the functional carbohydrate microarray is suitable for analyzing toxin protein-carbohydrate interactions and can be applied as a biosensor for toxin detection. PMID:22770420

  15. Phase transition at the surface of mixed micelles of the ganglioside GM1 and dodecylphosphocholine

    NASA Astrophysics Data System (ADS)

    Cantů, Laura; Corti, Mario; DelFavero, Elena; Raudino, Antonio

    2000-02-01

    A temperature-dependent irreversible variation of the average aggregation number of GM1 micelles, with no change in the chemical structure of the molecule, has been observed by light and x-ray scattering. GM1 is an amphiphilic molecule of biological origin, similar to phospholipids but with an extended headgroup, made up of many sugar units. A simple model has been developed to describe the experimental results. It assumes that the polar headgroups of GM1 monomers may exist in two different stable conformations, each of them with a very similar energy, dependent on its own internal structure and displaying preferential interactions with the surrounding heads once inserted in the micelle. The interconversion between the conformational minima is then described as a cooperative transition occurring at the micelle surface, overcoming a naturally emerging barrier due to collective effects. To assess the extent of interactions among the GM1 conformer headgroups different amounts of an amphiphilic spacer have been inserted in GM1 micelles. The thermal hysteresis phenomenon was still observed on mixed micelles until a molar ratio GM1/spacer ~1/3 was reached, corresponding to the critical concentration calculated from the mean-field theory of dilute magnetic alloys in a 2D lattice. The observed behaviour, then, appears as a critical phenomenon of topological nature happening in a confined two-dimensional system, that is the micelle surface.

  16. Bis(monoacylglycero)phosphate and ganglioside GM1 spontaneously form small homogeneous vesicles at specific concentrations

    SciTech Connect

    Chebukati, Janetricks N.; Goff, Philip C.; Frederick, Thomas E. [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States)] [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States); Fanucci, Gail E., E-mail: fanucci@chem.ufl.edu [Department of Chemistry, P.O. Box 117200, University of Florida, Gainesville, FL 32611-7200 (United States)

    2010-04-09

    The morphology and size of hydrated lipid dispersions of bis(monoacylglycero)phosphate (BMP) mixed with varying mole percentages of the ganglioside GM1 were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Electron paramagnetic resonance (EPR) spectroscopy of these same mixtures, doped at 0.5 mol% with doxyl labeled lipids, was used to investigate acyl-chain packing. Results show that for 20-30% GM1, hydrated BMP:GM1 mixtures spontaneously form small spherical vesicles with diameters {approx}100 nm and a narrow size distribution profile. For other concentrations of GM1, hydrated dispersions with BMP have non-spherical shapes and heterogeneous size profiles, with average vesicle diameters >400 nm. All samples were prepared at pH 5.5 to mimic the lumen acidity of the late endosome where BMP is an essential component of intraendosomal vesicle budding, lipid sorting and trafficking. These findings indicate that GM1 and BMP under a limited concentration range spontaneously form small vesicles of homogeneous size in an energy independent manner without the need of protein templating. Because BMP is essential for intraendosomal vesicle formation, these results imply that lipid-lipid interactions may play a critical role in the endosomal process of lipid sorting and trafficking.

  17. Guillain-Barre Syndrome and Miller Fisher SyndromeAssociated Campylobacter jejuni Lipopolysaccharides Induce Anti-GM1 and Anti-GQ1b Antibodies in Rabbits

    Microsoft Academic Search

    C. W. Ang; M. A. De Klerk; H. P. Endtz; B. C. Jacobs; J. D. Laman; P. A. van Doorn

    2001-01-01

    Campylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain- Barresyndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopoly- saccharides (LPS) and gangliosides. We used purified LPS fractions from five Campylobacter strains to induce antiganglioside responses in rabbits. The animals that received injections with LPS from GBS-associated strains developed anti-GM1 and anti-GA1

  18. Soluble A? oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes.

    PubMed

    Hong, Soyon; Ostaszewski, Beth L; Yang, Ting; O'Malley, Tiernan T; Jin, Ming; Yanagisawa, Katsuhiko; Li, Shaomin; Bartels, Tim; Selkoe, Dennis J

    2014-04-16

    Soluble A? oligomers contribute importantly to synaptotoxicity in Alzheimer's disease, but their dynamics in vivo remain unclear. Here, we found that soluble A? oligomers were sequestered from brain interstitial fluid onto brain membranes much more rapidly than nontoxic monomers and were recovered in part as bound to GM1 ganglioside on membranes. A? oligomers bound strongly to GM1 ganglioside, and blocking the sialic acid residue on GM1 decreased oligomer-mediated LTP impairment in mouse hippocampal slices. In a hAPP transgenic mouse model, substantial levels of GM1-bound A??? were recovered from brain membrane fractions. We also detected GM1-bound A? in human CSF, and its levels correlated with A???, suggesting its potential as a biomarker of A?-related membrane dysfunction. Together, these findings highlight a mechanism whereby hydrophobic A? oligomers become sequestered onto GM1 ganglioside and presumably other lipids on neuronal membranes, where they may induce progressive functional and structural changes. PMID:24685176

  19. Object Tracking Algorithm Based on Grey Innovation Model GM (1, 1) of Fixed Length

    Microsoft Academic Search

    Qiang Fu; Yunshi Xiao; Huilin Yin

    2009-01-01

    An algorithm based on grey innovation model GM (1, 1) of fixed length is introduced for the localization and tracking of moving targets. Kalman filter is an efficient computational method for tracking, but motion and noise assumption limits its process model to constant velocity model or constant acceleration model. The grey system theory uses the data characteristic of extrinsic randomicity

  20. Condensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films

    E-print Network

    Lee, Ka Yee C.

    , are present in most animal cell plasma membranes and are thought to regulate various physiological events in nerve cells (5), and because they reside primarily on the outer leaflet of the cell membrane of the ganglioside molecules in a mixed membrane. The effects induced by GM1 on the mean molecular area of the binary

  1. Endogenous GM1 Ganglioside of the Plasma Membrane Promotes Neuritogenesis by Two Mechanisms

    Microsoft Academic Search

    Yu Fang; Gusheng Wu; Xin Xie; Zi-Hua Lu; Robert W. Ledeen

    2000-01-01

    The influence of GM1 on the neuritogenic phase of neuronal differentiation has been highlighted in recent reports showing upregulation of this ganglioside in the plasma and nuclear membranes concomitant with axonogenesis. These changes are accompanied by alterations in Ca2+ flux which constitute an essential component of the signaling mechanism for axon outgrowth. This study examines 2 distinct mechanisms of induced

  2. GM1 Ganglioside Treatment Facilitates Behavioral Recovery from Bilateral Brain Damage

    NASA Astrophysics Data System (ADS)

    Sabel, Bernhard A.; Slavin, Mary D.; Stein, Donald G.

    1984-07-01

    Adult rats with bilateral lesions of the caudate nucleus were treated with GM1 ganglioside. Although animals injected with a control solution were severely impaired in their ability to learn a complex spatial task, those treated with ganglioside were able to learn spatial reversals.

  3. GM1 Clustering Inhibits Cholera Toxin Binding in Supported Phospholipid Membranes

    E-print Network

    GM1 Clustering Inhibits Cholera Toxin Binding in Supported Phospholipid Membranes Jinjun Shi ligand-receptor interactions between pentameric cholera toxin B subunits (CTB) and the corresponding-pathogen interactions3-5 are associated with multiva- lent ligand-receptor binding. The recognition of cholera toxin (CT

  4. Using a set of GM(1,1) models to predict values of diagnostic symptoms

    NASA Astrophysics Data System (ADS)

    Tabaszewski, Maciej; Cempel, Czeslaw

    2015-02-01

    The main purpose of this study is to develop a methodology of predicting values of vibration symptoms of fan mills in a combined heat and power (CHP) plant. The study was based on grey system theory and GM(1,1) prognostic models with different window sizes for estimating model parameters. Such models have a number of features that are desirable from the point of view of data characteristics collected by the diagnostic system. When using moving window, GM(1,1) models tend to be adaptive. However, selecting an inappropriate window size can result in excessive forecast errors. The present study proposes three possible methods that can be used in automated diagnostic systems to counteract the excessive increase in the forecast error. A comparative analysis of their performance was conducted using data from fan mills in order to select the method which minimises the forecast error.

  5. Development of an Immunoassay for Rapid Detection of Ganglioside GM1 Mimicry in Campylobacter jejuni Strains

    Microsoft Academic Search

    MARTINA M. PRENDERGAST; TIMO U. KOSUNEN; ANTHONY P. MORAN

    2001-01-01

    Mimicry of peripheral nerve gangliosides by Campylobacter jejuni lipopolysaccharides (LPSs) has been pro- posed to induce cross-reacting antiganglioside antibodies in Guillain-Barresyndrome (GBS). Because current methods for LPS characterization are labor-intensive and inhibit the screening of large numbers of strains, a rapid GM1 epitope screening assay was developed. Biomass from two agar plates of confluent growth yielded sufficient LPS using a

  6. Facile method for the preparation of lyso-GM1 and lyso-GM2

    Microsoft Academic Search

    Takayuki Ando; Su-Chen Li; Makoto Ito; Yu-Teh Li

    2005-01-01

    This paper reports a facile method for the preparation of lyso-GM1 [Gal?1?3GalNAc?1?4(Neu5Ac?2?3)Gal?1?4Glc?1?1?-sphingosine] and lyso-GM2 [GalNAc?1?4(Neu5Ac?2?3)Gal?1?4Glc?1?1?-sphingosine], respectively, from GM1 [Gal?1?3GalNAc?1?4(Neu5Ac?2?3)Gal?1?4Glc?1?1?-Cer] and GM2 [GalNAc?1?4(Neu5Ac?2?3)Gal?1?4Glc?1?1?-Cer], using sphingolipid ceramide deacylase and high performance anion-exchange chromatography (HPAEC). The enzymatically released lyso-GM1 and\\/or lyso-GM2 was effectively separated from its parent ganglioside by HPAEC using a Mono Q HR 5\\/5 column with an Amersham Biosciences fast protein

  7. Mutations in the GM1 binding site of simian virus 40 VP1 alter receptor usage and cell tropism.

    PubMed

    Magaldi, Thomas G; Buch, Michael H C; Murata, Haruhiko; Erickson, Kimberly D; Neu, Ursula; Garcea, Robert L; Peden, Keith; Stehle, Thilo; DiMaio, Daniel

    2012-07-01

    Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution. PMID:22514351

  8. Synthesis of ganglioside GM1 containing a thioglycosidic bond to its labeled ceramide(s). A facile synthesis starting from natural gangliosides

    Microsoft Academic Search

    Günter Schwarzmann; Petra Hofmann; Ute Pütz

    1997-01-01

    Capitalizing on the readily available ganglioside, GM1, we have devised a simple synthesis of labeled GM1 analogues with sulfur in place of oxygen in their linkage to the ceramide residue (SGM1). The sugar moiety of ganglioside GM1 was released by ozonolysis and subsequent alkaline fragmentation in good yield. During acetylation of the ganglioside sugar, the carboxyl group of the sialic

  9. GM1 ganglioside attenuates the development of vacuous chewing movements induced by long-term haloperidol treatment of rats

    Microsoft Academic Search

    Ole A. Andreassen; Hugo A. Jřrgensen

    1994-01-01

    Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if TD may be a result of neuroleptic-induced excessive stimulation of striatal glutamate receptors, the effect of the anti-excitotoxic GM1 ganglioside was studied in a rat model of TD. In an acute experiment each of four groups of rats was treated with GM1 20 mg\\/kg SC

  10. Association to HeLa cells and surface behavior of exogenous gangliosides studied with a fluorescent derivative of GM1

    SciTech Connect

    Masserini, M.; Giuliani, A.; Palestini, P.; Acquotti, D.; Pitto, M.; Chigorno, V.; Tettamanti, G. (Univ. of Milan (Italy))

    1990-01-23

    Cultured HeLa cells were incubated with pyrene-GM1/{sup 3}H-radiolabeled GM1 ganglioside (1:4 M/M) mixtures for various times. The process of association of pyrene-GM1 with cells was qualitatively and quantitatively the same as that of {sup 3}H-GM1. The pyrene-GM1 and {sup 3}H-GM1 proportions in the various forms of association with cells were similar to that of the starting ganglioside mixture. After 2-h incubation, the association of ganglioside with cells was well established whereas almost no metabolic processing had occurred. During a 24-h incubation, pyrene- and {sup 3}H-GM1 underwent similar metabolic processing and gave rise to catabolic (GM2 and GM3) and anabolic (GDla) derivatives. Fluorescence spectroscopy experiments carried out with the excimer formation technique on subcellular fractions containing plasma membranes showed that exogenous ganglioside was, in part, associated with the cells in a micellar form removable by trypsin treatment, and in part inserted in a seemingly molecular dispersion. Addition of Ca{sup 2+} salts caused aggregation of the ganglioside, as indicated by the increase of the excimer:monomer fluorescence ratio. The phenomenon was Ca{sup 2+} concentration dependent (maximum at 10 mM), and subsequent addition of EDTA has no effect. The saccharide portion of exogenously incorporated pyrene-GM1 was available to interact with external ligands, as shown by its ability to bind cholera toxin whose addition reduced the collision rate among the ganglioside lipid moieties.

  11. Experimental autoimmune neuropathy with anti-GM1 antibodies and immunoglobulin deposits at the nodes of Ranvier

    Microsoft Academic Search

    F. P. Thomas; W. Trojaborg; C. Nagy; M. Santoro; S. A. Sadiq; N. Latov; A. P. Hays

    1991-01-01

    Antibodies to GM1 or Gal(ß1–3)GalNAc are associated with motor or sensorimotor neuropathy and with motor neuron disease. To investigate the role of these antibodies in the neurological disorder, rabbits were immunized with GM1 or with Gal(ß1–3)GalNAc-BSA, and studied serologically, electrophysiologically and pathologically. Development of antibodies to the immunizing antigens was associated with a fall in the ratio of the amplitudes

  12. The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons

    Microsoft Academic Search

    Nobuyuki Hirota; Ryuji Kaji; Hugh Bostock; Katsuro Shindo; Teruaki Kawasaki; Kotaro Mizutani; Nobuyuki Oka; Nobuo Kohara; Takahiko Saida; Jun Kimura

    1997-01-01

    Summary Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barresyndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera

  13. Soluble A? oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes

    PubMed Central

    Hong, Soyon; Ostaszewski, Beth L.; Yang, Ting; O'Malley, Tiernan T.; Jin, Ming; Yanagisawa, Katsuhiko; Li, Shaomin; Bartels, Tim; Selkoe, Dennis J.

    2014-01-01

    SUMMARY Soluble A? oligomers contribute importantly to synaptotoxicity in Alzheimer's disease, but their dynamics in vivo remain unclear. Here, we found that soluble A? oligomers were sequestered from brain interstitial fluid onto brain membranes much more rapidly than non-toxic monomers and were recovered in part as bound to GM1 ganglioside on membranes. A? oligomers bound strongly to GM1 ganglioside, and blocking the sialic acid residue on GM1 decreased oligomer-mediated LTP impairment in mouse hippocampal slices. In a hAPP transgenic mouse model, substantial levels of GM1-bound A?42 were recovered from brain membrane fractions. We also detected GM1-bound A? in human CSF, and its levels correlated with A?42, suggesting its potential as a biomarker of A?-related membrane dysfunction. Together, these findings highlight a novel mechanism whereby hydrophobic A? oligomers become sequestered onto GM1 ganglioside and presumably other lipids on neuronal membranes, where they may induce progressive functional and structural changes. PMID:24685176

  14. Neurophysiological and immunohistochemical studies of IgG anti-GM1 monoclonal antibody on neuromuscular transmission: effects in rat neuromuscular junctions.

    PubMed

    Hotta, Sayako; Nagaoka, Takumi; Taguchi, Kyoji; Nakatani, Yoshihiko; Utsnomiya, Iku; Masuda, Yutaka; Abe, Kenji; Yuki, Nobuhiro

    2014-02-01

    Guillain-Barré syndrome, which is a variant of acute inflammatory neuropathy, is associated with anti-GM1 antibodies and causes ataxia. We investigated the effects of IgG anti-GM1 monoclonal antibody (IgG anti-GM1 mAb) on spontaneous muscle action potentials in a rat spinal cord-muscle co-culture system and the localization of IgG anti-GM1 mAb binding in the rat hemi-diaphragm. The frequency of spontaneous muscle action potentials in innervated muscle cells was acutely inhibited by IgG anti-GM1 mAb. When cultures were pretreated with GM2 synthase antisense oligodeoxynucleotide, IgG anti-GM1 mAb failed to inhibit spontaneous muscle action potentials, demonstrating the importance of the GM1 epitope in the action of IgG anti-GM1 mAb. Immunohistochemistry of rat hemi-diaphragm showed that IgG anti-GM1 mAb binding overlapped with neurofilament 200 (NF200) antibodies staining, but not ?-bungarotoxin (?-BuTx) staining, demonstrating that IgG anti-GM1 mAb was localized at the presynaptic nerve terminal. IgG anti-GM1 mAb binding overlapped with syntaxin antibody and S-100 antibody in the nerve terminal. After collagenase treatment, IgG anti-GM1 mAb and NF200 antibodies did not show staining, but ?-BuTx selectively stained the hemi-diaphragm. IgG anti-GM1 mAb binds to the presynaptic nerve terminal of neuromuscular junctions. Therefore, we suggest that the inhibitory effect of IgG anti-GM1 mAb on spontaneous muscle action potentials is related to the GM1 epitope in presynaptic motor nerve terminals at the NMJs. PMID:23820959

  15. Spectra of PV Cep and GM1-29 (RNO 125) in 1976-1997

    NASA Astrophysics Data System (ADS)

    Magakian, T. Yu.; Movsesian, T. A.

    2001-10-01

    The main spectral characteristics of PV Cep, a T Tau star, and of the variable nebula GM1-29 associated with it are considered. Their variations during 1976-1997, based on observations on the 6-m telescope and literature data, are described. In the period of maximum brightness (1977-1979), the star had a well-developed emission spectrum, typical of classical T Tau stars, with clearly defined P Cyg components in the H and H lines, strong Na D absorption features shifted in the blue direction, and well-defined fluorescence in Fe I emission features. After the end of the latter eruption, the star's spectrum has remained more or less in a stable state; emission lines are considerably weaker. The ejected matter continues to be observed in the form of shifted components in emission lines. There are also indications of the possible existence of a collimated jet 1.5-2 long in the star's immediate vicinity. Also clearly seen is HH215 P1 — the first HH knot in the giant jet emerging from PV Cep. At the epoch of the object's maximum brightness, there were clear signs of spectral asymmetry of the stellar envelope in the nebula's spectrum, due to the directional outflow, manifested in variation of the profiles and intensities of Balmer lines. PV Cep and GM1-29 thereby prove to be another object in which the phenomenon first noted in R Mon and NGC 2261 is observed.

  16. The morphology of GM1 x/SM 0.6-x/Chol 0.4 planar bilayers supported on SiO 2 surfaces

    NASA Astrophysics Data System (ADS)

    Mao, Yanli; Tero, Ryugo; Imai, Yosuke; Hoshino, Tyuji; Urisu, Tsuneo

    2008-07-01

    Ganglioside GM1 (GM1), sphingomyelin (SM) and cholesterol (Chol) are dominant lipid components of rafts in plasma membranes. The morphology of GM1 x/SM 0.6-x/Chol 0.4 SPBs on SiO 2 surfaces has been studied by atomic force microscopy and fluorescence microscopy at various ratios of GM1/SM ( x = 0-0.25). The unique changes in morphology depending on the GM1 concentrations are qualitatively explained by hydrogen bonding and the hydrophobic interactions between SM and Chol, and by hydrogen bonding and the steric effects between bulky GM1 headgroups under Ca 2+ existing conditions and the electrostatic repulsion between the negative charges of GM1 headgroups under Ca 2+ nonexisting conditions.

  17. Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders

    Microsoft Academic Search

    J. Patrick van der Voorn; Petra J. W. Pouwels; Wout Kamphorst; James M. Powers; Martin Lammens; Frederik Barkhof; Marjo S. van der Knaap

    2005-01-01

    BACKGROUND AND PURPOSE: Radially oriented hypointense stripes in hyperintense cerebral white matter are recognized on T2-weighted images of certain lysosomal storage disorders. We compared in vivo and postmortem MR imaging with histopathologic findings in three patients with metachromatic leukodystrophy (MLD), globoid cell leukodystrophy (GLD), and infantile GM1 gangliosidosis (GM1) to understand this characteristic MR imaging pattern. METHODS: The in vivo

  18. GM1-27: A cometary nebula associated with anisotropic outflow

    NASA Astrophysics Data System (ADS)

    Magakian, T. Yu.; Movsessian, T. A.

    1995-03-01

    Spectral studies of the small emission knot (HH-object), located inside the cometary nebula GM1-27 (GN20.18.3), were performed with high spatial resolution. The radial velocities of the emission lines and maps of isointensities are given. Also the emission lines ratios and their spatial distribution are investigated. The velocity of the low excitation lines changes along the knot; for higher excitation lines this effect is absent. In addition, the lines of different excitation are shifted in position with regard to each other. The peak of the electron density in the head of the knot is prominent. It seems as if two zones of different excitation spatially separated for 1017 cm, could exist inside the knot. A conclusion is drawn about the possibility of observational resolution of two excitation regions - bow-shock and Mach disk - in the knot. The star which drives the outflow appears to be of Herbig Ae type.

  19. Measuring Positive Cooperativity Using the Direct ESI-MS Assay. Cholera Toxin B Subunit Homopentamer Binding to GM1 Pentasaccharide

    NASA Astrophysics Data System (ADS)

    Lin, Hong; Kitova, Elena N.; Klassen, John S.

    2014-01-01

    Direct electrospray ionization mass spectrometry (ESI-MS) assay was used to investigate the stepwise binding of the GM1 pentasaccharide ?- D-Gal p-(1?3)-?-D-Gal pNAc-(1?4)[?-D-Neu5Ac-(2?3)]-?- D-Gal p-(1?4)-?-D-Glc p (GM1os) to the cholera toxin B subunit homopentamer (CTB5) and to establish conclusively whether GM1os binding is cooperative. Apparent association constants were measured for the stepwise addition of one to five GM1os to CTB5 at pH 6.9 and 22 °C. The intrinsic association constant, which was established from the apparent association constant for the addition of a single GM1os to CTB5, was found to be (3.2 ± 0.2) × 106 M-1. This is in reasonable agreement with the reported value of (6.4 ± 0.3) × 106 M-1, which was measured at pH 7.4 and 25 °C using isothermal titration calorimetry (ITC). Analysis of the apparent association constants provides direct and unambiguous evidence that GM1os binding exhibits small positive cooperativity. Binding was found to be sensitive to the number of ligand-bound nearest neighbor subunits, with the affinities enhanced by a factor of 1.7 and 2.9 when binding occurs next to one or two ligand-bound subunits, respectively. These findings, which provide quantitative support for the binding model proposed by Homans and coworkers [14], highlight the unique strengths of the direct ESI-MS assay for measuring cooperative ligand binding.

  20. GPR37 Protein Trafficking to the Plasma Membrane Regulated by Prosaposin and GM1 Gangliosides Promotes Cell Viability*

    PubMed Central

    Lundius, Ebba Gregorsson; Vukojevi?, Vladana; Hertz, Ellen; Stroth, Nikolas; Cederlund, Andreas; Hiraiwa, Masao; Terenius, Lars; Svenningsson, Per

    2014-01-01

    The subcellular distribution of the G protein-coupled receptor GPR37 affects cell viability and is implicated in the pathogenesis of parkinsonism. Intracellular accumulation and aggregation of GPR37 cause cell death, whereas GPR37 located in the plasma membrane provides cell protection. We define here a pathway through which the recently identified natural ligand, prosaposin, promotes plasma membrane association of GPR37. Immunoabsorption of extracellular prosaposin reduced GPR37tGFP surface density and decreased cell viability in catecholaminergic N2a cells. We found that GPR37tGFP partitioned in GM1 ganglioside-containing lipid rafts in the plasma membrane of live cells. This partitioning required extracellular prosaposin and was disrupted by lipid raft perturbation using methyl-?-cyclodextrin or cholesterol oxidase. Moreover, complex formation between GPR37tGFP and the GM1 marker cholera toxin was observed in the plasma membrane. These data show functional association between GPR37, prosaposin, and GM1 in the plasma membrane. These results thus tie together the three previously defined components of the cellular response to insult. Our findings identify a mechanism through which the receptor's natural ligand and GM1 may protect against toxic intracellular GPR37 aggregates observed in parkinsonism. PMID:24371137

  1. GPR37 protein trafficking to the plasma membrane regulated by prosaposin and GM1 gangliosides promotes cell viability.

    PubMed

    Lundius, Ebba Gregorsson; Vukojevic, Vladana; Hertz, Ellen; Stroth, Nikolas; Cederlund, Andreas; Hiraiwa, Masao; Terenius, Lars; Svenningsson, Per

    2014-02-21

    The subcellular distribution of the G protein-coupled receptor GPR37 affects cell viability and is implicated in the pathogenesis of parkinsonism. Intracellular accumulation and aggregation of GPR37 cause cell death, whereas GPR37 located in the plasma membrane provides cell protection. We define here a pathway through which the recently identified natural ligand, prosaposin, promotes plasma membrane association of GPR37. Immunoabsorption of extracellular prosaposin reduced GPR37(tGFP) surface density and decreased cell viability in catecholaminergic N2a cells. We found that GPR37(tGFP) partitioned in GM1 ganglioside-containing lipid rafts in the plasma membrane of live cells. This partitioning required extracellular prosaposin and was disrupted by lipid raft perturbation using methyl-?-cyclodextrin or cholesterol oxidase. Moreover, complex formation between GPR37(tGFP) and the GM1 marker cholera toxin was observed in the plasma membrane. These data show functional association between GPR37, prosaposin, and GM1 in the plasma membrane. These results thus tie together the three previously defined components of the cellular response to insult. Our findings identify a mechanism through which the receptor's natural ligand and GM1 may protect against toxic intracellular GPR37 aggregates observed in parkinsonism. PMID:24371137

  2. The analysis of development trend for Beijing Cultural and Creative Industry based on GM(1,1) Model

    Microsoft Academic Search

    Yao Cuiyou

    2010-01-01

    Cultural and Creative Industry is a domain that Beijing adjusts industrial structure and transforms pattern of growth. This paper builds GM(1,1) model by analyzing actual data of Beijing Cultural and Creative Industry added value from year 2004 to year 2009. The author predicts Beijing Cultural and Creative Industry added value for several years in future by the model created in

  3. Absence of ganglioside GM1 in astroglial cells from 21-day old rat brain: Immunohistochemical, histochemical, and biochemical studies

    Microsoft Academic Search

    Hiroaki Asou; Eric G. Brunngraber

    1983-01-01

    A procedure was developed for the cultivation of cells derived from the cerebral hemispheres of the 21-day old rat. Approximately 98 percent of the cells in a 10 day culture are astrocytes that contain glial fibrillary acidic protein. Analysis of the extracted gangliosides by thin layer chromatography revealed that ganglioside GM1 was absent and that the predominant ganglioside was GM3.

  4. Echinophilic proteins stomatin, sorcin, and synexin locate outside gangliosideM1 (GM1) patches in the erythrocyte membrane

    E-print Network

    Iglic, Ales

    in the erythrocyte membrane Lucyna Mrówczyn´ ska a, , Ulrich Salzer b , Sárka Perutková c , Ales Iglic c , Henry Erythrocyte DRM Fluorescence microscopy a b s t r a c t The detergent (Triton X-100, 4 °C)-resistant membrane gangliosideM1 (GM1) raft patches in flat (discocytic) and curved (echinocytic) human erythrocyte membrane

  5. Molecular and structural studies of the GM2 gangliosidosis 0 variant

    Microsoft Academic Search

    Hitoshi Sakuraba; Fumiko Matsuzawa; Sei-ichi Aikawa; Hirofumi Doi; Masaharu Kotani; Hou Lin; Kousaku Ohno; Akemi Tanaka; Hideo Yamada; Ei-ichiro Uyama

    2002-01-01

    To determine the molecular basis of the GM2 gangliosidosis 0 variant, we constructed a three-dimensional structure of the\\u000a human ?-hexosaminidase ?-subunit by homology modeling. It is composed of two domains, domains I and II, and has three disulfide\\u000a bonds. C534 is located on an extra helix in domain II and forms a disulfide bond with C551. The extra helix is

  6. Genetic complementation in somatic cell hybrids of four variants of infantile G M2 gangliosidosis

    Microsoft Academic Search

    S. Sonderfeld; S. Brendler; K. Sandhoff; H. Galjaard; A. T. Hoogeveen

    1985-01-01

    Summary  Cell hybridizations between fibroblasts of four variants (B, O, AB, and B1) of infantile GM2 gangliosidosis were performed. Cocultivated as well as hybrid cells were analyzed for their capability to degrade exogenously\\u000a added [3H]-GM2. Hybridization of variant AB fibroblasts with fibroblasts of variant O, variant B, or variant B1 resulted in an enhanced\\u000a rate of GM2 hydrolysis, showing intergenic complementation.

  7. Role of Lipid Rafts and GM1 in the Segregation and Processing of Prion Protein

    PubMed Central

    Botto, Laura; Cunati, Diana; Coco, Silvia; Sesana, Silvia; Bulbarelli, Alessandra; Biasini, Emiliano; Colombo, Laura; Negro, Alessandro; Chiesa, Roberto; Masserini, Massimo; Palestini, Paola

    2014-01-01

    The prion protein (PrPC) is highly expressed within the nervous system. Similar to other GPI-anchored proteins, PrPC is found in lipid rafts, membrane domains enriched in cholesterol and sphingolipids. PrPC raft association, together with raft lipid composition, appears essential for the conversion of PrPC into the scrapie isoform PrPSc, and the development of prion disease. Controversial findings were reported on the nature of PrPC-containing rafts, as well as on the distribution of PrPC between rafts and non-raft membranes. We investigated PrPC/ganglioside relationships and their influence on PrPC localization in a neuronal cellular model, cerebellar granule cells. Our findings argue that in these cells at least two PrPC conformations coexist: in lipid rafts PrPC is present in the native folding (?-helical), stabilized by chemico-physical condition, while it is mainly present in other membrane compartments in a PrPSc-like conformation. We verified, by means of antibody reactivity and circular dichroism spectroscopy, that changes in lipid raft-ganglioside content alters PrPC conformation and interaction with lipid bilayers, without modifying PrPC distribution or cleavage. Our data provide new insights into the cellular mechanism of prion conversion and suggest that GM1-prion protein interaction at the cell surface could play a significant role in the mechanism predisposing to pathology. PMID:24859148

  8. Clostridium perfringens Alpha-Toxin Induces Gm1a Clustering and Trka Phosphorylation in the Host Cell Membrane

    PubMed Central

    Takagishi, Teruhisa; Oda, Masataka; Kabura, Michiko; Kurosawa, Mie; Tominaga, Kaori; Urano, Shiori; Ueda, Yoshibumi; Kobayashi, Keiko; Kobayashi, Toshihide; Sakurai, Jun; Terao, Yutaka; Nagahama, Masahiro

    2015-01-01

    Clostridium perfringens alpha-toxin elicits various immune responses such as the release of cytokines, chemokines, and superoxide via the GM1a/TrkA complex. Alpha-toxin possesses phospholipase C (PLC) hydrolytic activity that contributes to signal transduction in the pathogenesis of gas gangrene. Little is known about the relationship between lipid metabolism and TrkA activation by alpha-toxin. Using live-cell fluorescence microscopy, we monitored transbilayer movement of diacylglycerol (DAG) with the yellow fluorescent protein-tagged C1AB domain of protein kinase C-? (EYFP-C1AB). DAG accumulated at the marginal region of the plasma membrane in alpha toxin-treated A549 cells, which also exhibited GM1a clustering and TrkA phosphorylation. Annexin V binding assays showed that alpha-toxin induced the exposure of phosphatidylserine on the outer leaflet of the plasma membrane. However, H148G, a variant toxin which binds cell membrane and has no enzymatic activity, did not induce DAG translocation, GM1a clustering, or TrkA phosphorylation. Alpha-toxin also specifically activated endogenous phospholipase C?-1 (PLC?-1), a TrkA adaptor protein, via phosphorylation. U73122, an endogenous PLC inhibitor, and siRNA for PLC?-1 inhibited the formation of DAG and release of IL-8. GM1a accumulation and TrkA phosphorylation in A549 cells treated with alpha-toxin were also inhibited by U73122. These results suggest that the flip-flop motion of hydrophobic lipids such as DAG leads to the accumulation of GM1a and TrkA. We conclude that the formation of DAG by alpha-toxin itself (first step) and activation of endogenous PLC?-1 (second step) leads to alterations in membrane dynamics, followed by strong phosphorylation of TrkA. PMID:25910247

  9. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis.

    PubMed

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratě, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillŕ, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis. PMID:25313007

  10. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis

    PubMed Central

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratě, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillŕ, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis. PMID:25313007

  11. Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions of Mammary Carcinoma

    E-print Network

    Gleeson, Joseph G.

    Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions Curie, CNRS UMR144, 26 rue d'Ulm, 75248 Paris Cedex 05, France, and the Department of Medical Genetics-cadherin and GM1 ganglioside. Conclusion: Galectin-3 is a novel regulator of N-cadherin dynamics and cell

  12. Induction of antibody to asialo GM1 by spermatozoa and its occurrence in the sera of homosexual men with the acquired immune deficiency syndrome (AIDS).

    PubMed Central

    Witkin, S S; Sonnabend, J; Richards, J M; Purtilo, D T

    1983-01-01

    Compared to healthy homosexual and heterosexual men, homosexual men with acquired immune deficiency syndrome (AIDS) possessed significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1 (ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36% possessed levels of this antibody that were at least two standard deviations above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed from serum by adsorption with spermatozoa. Weekly rectal insemination of male rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15 weeks. These results suggest that asialo GM1 is a component of ejaculated spermatozoa and demonstrate that rectal insemination by itself can lead to the production of antibodies to this glycolipid in the rabbit. In addition, asialo GM1 antibodies may be of value as a serological marker for the early detection of individuals with AIDS. PMID:6652964

  13. A Maximum Entropy Analysis of the M\\/G\\/ 1 and G\\/M\\/ 1 Queueing Systems at Equilibrium

    Microsoft Academic Search

    M. A. El-affendi; Demetres D. Kouvatsos

    1983-01-01

    The M\\/G\\/1 and G\\/M\\/1 queueing models are of great interest in the performance analysis of computer systems. For both models, the equilibrium solution for the number of jobs in the system varies with the probability distribution function representing the general (G-type) distribution. Even in the presence of empirical data, the characterisation of this function involves a degree of arbitrariness that

  14. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    PubMed Central

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  15. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading.

    PubMed

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C-55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C-25°C and even after freeze-thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  16. Gangliosides GM1 and GM3 in the Living Cell Membrane Form Clusters Susceptible to Cholesterol Depletion and Chilling

    Microsoft Academic Search

    Akikazu Fujita; Jinglei Cheng; Minako Hirakawa; Koichi Furukawa; Susumu Kusunoki; Toyoshi Fujimoto

    2007-01-01

    Presence of microdomains has been postulated in the cell membrane, but two-dimensional distribution of lipid molecules has been difficult to determine in the submicrometer scale. In the present paper, we examined the distribution of gangliosides GM1 and GM3, putative raft molecules in the cell membrane, by immunoelectron microscopy using quick-frozen and freeze-fractured specimens. This method physically immobilized molecules in situ

  17. Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity.

    PubMed

    Reich, Christian; Horton, Margaret R; Krause, Bärbel; Gast, Alice P; Rädler, Joachim O; Nickel, Bert

    2008-07-01

    The cell membrane comprises numerous protein and lipid molecules capable of asymmetric organization between leaflets and liquid-liquid phase separation. We use single supported lipid bilayers (SLBs) to model cell membranes, and study how cholesterol and asymmetrically oriented ganglioside receptor G(M1) affect membrane structure using synchrotron x-ray reflectivity. Using mixtures of cholesterol, sphingomyelin, and 1,2-dioleoyl-sn-glycero-3-phosphocholine, we characterize the structure of liquid-ordered and liquid-disordered SLBs in terms of acyl-chain density, headgroup size, and leaflet thickness. SLBs modeling the liquid-ordered phase are 10 A thicker and have a higher acyl-chain electron density (rho(chain) = 0.33 e(-)/A(3)) compared to SLBs modeling the liquid-disordered phase, or pure phosphatidylcholine SLBs (rho(chain) = 0.28 e(-)/A(3)). Incorporating G(M1) into the distal bilayer leaflet results in membrane asymmetry and thickening of the leaflet of 4-9 A. The structural effect of G(M1) is more complex in SLBs of cholesterol/sphingomyelin/1,2-dioleoyl-sn-glycero-3-phosphocholine, where the distal chains show a high electron density (rho(chain) = 0.33 e(-)/A(3)) and the lipid diffusion constant is reduced by approximately 50%, as measured by fluorescence microscopy. These results give quantitative information about the leaflet asymmetry and electron density changes induced by receptor molecules that penetrate a single lipid bilayer. PMID:18375517

  18. The sterile alpha-motif (SAM) domain of p63 binds in vitro monoasialoganglioside (GM1) micelles.

    PubMed

    Rufini, Stefano; Lena, Anna Maria; Cadot, Bruno; Mele, Sonia; Amelio, Ivano; Terrinoni, Alessandro; Desideri, Alessandro; Melino, Gerry; Candi, Eleonora

    2011-11-15

    The transcription factor p63 plays pivotal roles in epidermal barrier formation and in embryonic development. The protein structures of TAp63 and ?Np63? isoforms include a C-terminal steril alpha-motif (SAM) involved in protein-protein interaction. Identification of p63 SAM domain interactors could lead to the explanation of novel mechanisms of regulation of p63 activity, possibly relevant in the physiological role of p63 and in genetic disorders associated with mutations of the p63 gene. In this work, we have performed a biochemical analysis of p63 SAM domain preferences in lipid binding. We have identified the ganglioside GM1 as a high affinity interactor, capable of modulating p63 transcriptional ability exclusively on epidermal target genes. In agreement with these data we report a consistent expression profile and localization analysis of p63 and GM1 in primary keratinocytes and in human epidermal biopsies. Therefore, we propose a potential biological role of p63-GM1 interaction in regulation of p63 during epidermal differentiation. PMID:21820419

  19. Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat

    Microsoft Academic Search

    Daisuke Hasegawa; Osamu Yamato; Masanori Kobayashi; Michio Fujita; Shinichiro Nakamura; Kimimasa Takahashi; Hiroyuki Satoh; Toru Shoda; Daisuke Hayashi; Masahiro Yamasaki; Yoshimitsu Maede; Toshiro Arai; Hiromitsu Orima

    2007-01-01

    This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and

  20. Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain.

    PubMed

    Saslowsky, David E; te Welscher, Yvonne M; Chinnapen, Daniel J-F; Wagner, Jessica S; Wan, Joy; Kern, Eli; Lencer, Wayne I

    2013-09-01

    Cholera toxin causes diarrheal disease by binding ganglioside GM1 on the apical membrane of polarized intestinal epithelial cells and trafficking retrograde through sorting endosomes, the trans-Golgi network (TGN), and into the endoplasmic reticulum. A fraction of toxin also moves from endosomes across the cell to the basolateral plasma membrane by transcytosis, thus breeching the intestinal barrier. Here we find that sorting of cholera toxin into this transcytotic pathway bypasses retrograde transport to the TGN. We also find that GM1 sphingolipids can traffic from apical to basolateral membranes by transcytosis in the absence of toxin binding but only if the GM1 species contain cis-unsaturated or short acyl chains in the ceramide domain. We found previously that the same GM1 species are needed to efficiently traffic retrograde into the TGN and endoplasmic reticulum and into the recycling endosome, implicating a shared mechanism of action for sorting by lipid shape among these pathways. PMID:23884419

  1. N-Alpha-Acetylation of ?-Synuclein Increases Its Helical Folding Propensity, GM1 Binding Specificity and Resistance to Aggregation

    PubMed Central

    Bartels, Tim; Kim, Nora C.; Luth, Eric S.; Selkoe, Dennis J.

    2014-01-01

    A switch in the conformational properties of ?-synuclein (?S) is hypothesized to be a key step in the pathogenic mechanism of Parkinson’s disease (PD). Whereas the beta-sheet-rich state of ?S has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to ?-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian ?S. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human ?S to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced ?-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of ?S with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated ?S enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of ?S-membrane interaction, and for a protective function of N-terminal-acetylation against ?S aggregation mediated by GM1. PMID:25075858

  2. Inhibition of neurite outgrowth of neuroblastoma neuro-2a cells by cholera toxin B-subunit and anti-GM1 antibody

    Microsoft Academic Search

    Gusheng Wu; Kazuo Nakamura; Robert W. Ledeen

    1994-01-01

    The role of cell surface GM1 ganglioside in neurite outgrowth of Neuro-2a neuroblastoma cells was investigated by application\\u000a of anti-GM1 antibody and the B subunit of cholera toxin (cholera B) to cultured cells stimulated to grow neurites in various\\u000a ways. When the cells were simultaneously treated with stimulatory agent and cholera B, inhibition, as measured by percent\\u000a of neurite-bearing cells,

  3. Dose-dependent effect of GM1 ganglioside during development on inhibitory avoidance behaviour in mice: influence of the period of administration

    Microsoft Academic Search

    Sandro Fagioli; Clelia Rossi-Arnaud; Claudio Castellano

    1992-01-01

    Groups of C57BL\\/6 mice were injected intraperitoneally with GM1 monosialoganglioside at different ages during development and subsequently tested for the retention of an inhibitory avoidance task 24 h after training. Results show improvements in inhibitory avoidance retention according to the age of the animals, the doses of GM1 used and the length of treatment. The effective doses ranged from 20

  4. Formulation of HIV-envelope protein with lipid vesicles expressing ganglioside GM1 associated to cholera toxin B enhances mucosal immune responses

    Microsoft Academic Search

    Tianshun Lian; Tot Bui; Rodney J. Y Ho

    1999-01-01

    Taking advantage of the ability of pentameric cholera toxin B subunit (CTB) to bind selectively to GM1, we developed recently a CTB-mediated GM1 lipid vesicle delivery system to target drugs and proteins to mucosal tissues [1]. In this report, we present the use of such a strategy to deliver an HIV envelope protein (HIV-env) to mucosal tissues via intranasal route.

  5. Lysosomal multienzymatic complex-related diseases: a genetic study among Portuguese patients.

    PubMed

    Coutinho, M F; Lacerda, L; Macedo-Ribeiro, S; Baptista, E; Ribeiro, H; Prata, M J; Alves, S

    2012-04-01

    The functional activity of lysosomal enzymes sialidase, ?-galactosidase and N-acetylaminogalacto-6-sulfate-sulfatase in the cell depends on their association in a multienzyme complex with cathepsin A. Mutations in any of the components of this complex result in functional deficiency thereby causing severe lysosomal storage disorders. Here, we report the molecular defects underlying sialidosis (mutations in sialidase; gene NEU1), galactosialidosis (mutations in cathepsin A; gene PPGB) and GM1 gangliosidosis (mutations in ?-galactosidase; gene GLB1) in Portuguese patients. We performed molecular studies of the PPGB, NEU1 and GLB1 genes in biochemically diagnosed Portuguese patients. Gene expression was determined and the effect of each mutation predicted at protein levels. In the NEU1 gene, we found three novel missense mutations (p.P200L, p.D234N and p.Q282H) and one nonsense mutation (p.R341X). In the PPGB gene, we identified two missense mutations, one novel (p.G86V) and one already described (p.V104M), as well as two new deletions (c.230delC and c.991-992delT) that give rise to non-functional proteins. We also present the first molecular evidence of a causal missense mutation localized to the cathepsin A active site. Finally, in the GLB1 gene, we found six different mutations, all of them previously described (p.R59H, p.R201H, p.H281Y, p.W527X, c.1572-1577InsG and c.845-846delC). Seven novel mutations are reported here, contributing to our knowledge of the mutational spectrum of these diseases and to a better understanding of the genetics of the lysosomal multienzymatic complex. The results of this study will allow carrier detection in affected families and prenatal molecular diagnosis, leading to the improvement of genetic counseling. PMID:21214877

  6. A Trp474Cys mutation in the alpha-subunit of beta-hexosaminidase causes a subacute encephalopathic form of G{sub M2} gangliosidosis, type 1

    SciTech Connect

    Petroulakis, E.; Cao, Z.; Salo, T. [Univ. of Manitoba, Winnipeg (Canada)] [and others

    1994-09-01

    Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affected brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.

  7. Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

    PubMed

    Jamrozik, Z; Lugowska, A; Go??biowski, M; Królicki, L; M?czewska, J; Ku?ma-Kozakiewicz, M

    2013-09-25

    A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. PMID:23820084

  8. Carbohydrate-based anti-adhesive inhibition of Vibrio cholerae toxin binding to GM1-OS immobilized into artificial planar lipid membranes.

    PubMed

    Sinclair, Haydn R; Kemp, Fred; Slegte, Jaap de; Gibson, Glenn R; Rastall, Robert A

    2009-10-12

    We have studied 'food grade' sialyloligosaccharides (SOS) as anti-adhesive drugs or receptor analogues, since the terminal sialic acid residue has already been shown to contribute significantly to the adhesion and pathogenesis of the Vibrio cholerae toxin (Ctx). GM1-oligosaccharide (GM1-OS) was immobilized into a supporting POPC lipid bilayer onto a surface plasmon resonance (SPR) chip, and the interaction between uninhibited Ctx and GM1-OS-POPC was measured. SOS inhibited 94.7% of the Ctx binding to GM1-OS-POPC at 10mg/mL. The SOS EC(50) value of 5.521mg/mL is high compared with 0.2811microg/mL (182.5rhoM or 1.825x10(-10)M) for GM1-OS. The commercially available sialyloligosaccharide (SOS) mixture Sunsial E((R)) is impure, containing one monosialylated and two disialylated oligosaccharides in the ratio 9.6%, 6.5% and 17.5%, respectively, and 66.4% protein. However, these inexpensive food-grade molecules are derived from egg yolk and could be used to fortify conventional food additives, by way of emulsifiers, sweeteners and/or preservatives. The work further supports our hypothesis that SOS could be a promising natural anti-adhesive glycomimetic against Ctx and prevent subsequent onset of disease. PMID:19665695

  9. Biochemical and Molecular Aspects of Late-Onset GM2Gangliosidosis: B1 Variant as a Prototype

    Microsoft Academic Search

    Kunihiko Suzuki; Marie T. Vanier

    1991-01-01

    Clinical phenotypes of GM2-gangliosidosis are complex. In the past 5 years it has become possible to dissect out the phenotypic complexity on the basis of abnormalities on the DNA level. Available data on the 18 disease-causing mutations so far identified in the P-hexosaminidase ?-gene allow an oversimplified generalization; mutations that produce no or highly unstable mRNA cause the most severe

  10. GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease.

    PubMed

    Sanders, Douglas N; Zeng, Rong; Wenger, David A; Johnson, Gary S; Johnson, Gayle C; Decker, Jared E; Katz, Martin L; Platt, Simon R; O'Brien, Dennis P

    2013-01-01

    GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of ?-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an ? and a ? subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two ? subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of G(M2) gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins. PMID:23266199

  11. Penner's serotype 4 of Campylobacter jejuni has a lipopolysaccharide that bears a GM1 ganglioside epitope as well as one that bears a GD1 a epitope.

    PubMed Central

    Yuki, N; Taki, T; Takahashi, M; Saito, K; Tai, T; Miyatake, T; Handa, S

    1994-01-01

    The carbohydrate structures of lipopolysaccharides (LPSs) of Campylobacter jejuni strains belonging to Penner's serotypes (PEN) 1, 2, 4, 19, 23, and 36 were studied by thin-layer chromatography and immunostaining with several monoclonal antiganglioside antibodies. Anti-GM1 and anti-GD1a antibodies reacted with the LPSs of PEN 1, 4, and 19. Aspinall et al. (G. O. Aspinall, A. G. McDonald, T. S. Raju, H. Pang, A. P. Moran, and J. L. Penner. Eur. J. Biochem. 213:1017-1027, 1993) recently reported that the LPS of PEN 4 has a GD1a ganglioside-like structure rather than a GM1-like structure. We found that the LPS fraction of C. jejuni (PEN 4) has an LPS that bears a GM1 epitope as well as an LPS that bears a GD1a epitope. Images PMID:7513313

  12. [Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

    PubMed

    Tsuji, Daisuke

    2013-01-01

    Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal ?-hexosaminidase ?-subunits and ?-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (?? heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (?? homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice. PMID:23370522

  13. Naloxone rapidly evokes endogenous kappa opioid receptor-mediated hyperalgesia in naďve mice pretreated briefly with GM1 ganglioside or in chronic morphine-dependent mice

    Microsoft Academic Search

    Stanley M. Crain; Ke-Fei Shen

    2007-01-01

    Low-dose naloxone-precipitated withdrawal hyperalgesia is a reliable indicator of physical dependence after chronic morphine treatment. A remarkably similar long-lasting (>3–4 h) hyperalgesia is evoked by injection of a low dose of naloxone (10 ?g\\/kg, s.c.) in naďve mice after acute pretreatment with the glycolipid, GM1 ganglioside (1 mg\\/kg) (measured by warm-water-immersion tail-flick assays). GM1 treatment markedly increases the efficacy of excitatory Gs-coupled opioid

  14. Gangliosides GM1 and GM2 Induce Vascular Smooth Muscle Cell Proliferation via Extracellular Signal-Regulated Kinase 1\\/2 Pathway

    Microsoft Academic Search

    Ioanna Gouni-Berthold; Claudia Seul; Yon Ko; Jürgen Hescheler; Agapios Sachinidis

    2010-01-01

    Gangliosides, sialic acid- containing glycophospholipids, accumulate in atherosclerotic vessels and appear to regulate the proliferation of various cell types. Furthermore, vascular smooth muscle cell (VSMC) proliferation is associated with the development and progression of cardiovascular diseases. To demonstrate whether gangliosides are able to modulate the VSMC growth, the effect of gangliosides GM1, GM2, and GM3 on cell DNA synthesis and

  15. Fibroblast screening for chaperone therapy in beta-galactosidosis.

    PubMed

    Iwasaki, Hiroyuki; Watanabe, Hiroshi; Iida, Masami; Ogawa, Seiichiro; Tabe, Miho; Higaki, Katsumi; Nanba, Eiji; Suzuki, Yoshiyuki

    2006-09-01

    We performed screening of beta-galactosidase-deficient fibroblasts for possible chemical chaperone therapy using N-octyl-4-epi-beta-valienamine (NOEV) in patients with GM1-gangliosidosis and Morquio B disease (beta-galactosidosis). Fibroblasts were cultured with NOEV for 4 days and beta-galactosidase activity was measured. Mutation analysis was performed simultaneously. Two separate criteria were set for evaluation of the chaperone effect: a relative increase of enzyme activity (more than 3-fold), and an increase up to more than 10% normal enzyme activity. Among the 50 fibroblast strains tested, more than 3-fold increase was achieved in 17 cell strains (34%), and more than 10% normal activity in 10 (20%). Both criteria were satisfied in 6 (12%), and either of them in 21 (42%). Juvenile GM1-gangliosidosis was most responsive, and then infantile GM1-gangliosidosis. This enhancement was mutation-specific. We estimate that the NOEV chaperone therapy will be effective in 20-40% of the patients, mainly in juvenile and infantile GM1-gangliosidosis patients. A molecular design may produce mutation-specific chaperone compounds for the other disease phenotypes. This cellular screening will be useful for identification of human patients with beta-galactosidase deficiency for chaperone therapy to be started in the near future. PMID:16617000

  16. Polycystic kidneys and GM2 gangliosidosis-like disease in neonatal springboks (Antidorcas marsupialis).

    PubMed

    Herder, V; Kummrow, M; Leeb, T; Sewell, A C; Hansmann, F; Lehmbecker, A; Wohlsein, P; Baumgärtner, W

    2015-05-01

    Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008-2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 ?m in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 ?m in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies. PMID:25232033

  17. Sites and temporal changes of gangliosides GM1\\/GM2 storage in the Niemann–Pick disease type C mouse brain

    Microsoft Academic Search

    Miyako Taniguchi; Yoko Shinoda; Haruaki Ninomiya; Marie T. Vanier; Kousaku Ohno

    2001-01-01

    Niemann–Pick disease type C (NPC) is a progressive neurodegenerative disorder with characteristic storage of glycolipids in the brain. This study investigated cellular origin and temporal changes of monosialoganglioside storage in the Balb\\/c npcnih mouse brain by immunohistochemistry. Anti-GM1 gave positive staining of the hippocampus, thalamus, cerebellar molecular and Purkinje cell layers in the 3-week old NPC mouse brain and in

  18. Searches for HH-objects and Emission Stars in Star Formation Regions. II. The Region of GM1-61 and V453 Ori

    NASA Astrophysics Data System (ADS)

    Magakian, T. Yu.; Movsessian, T. A.; Nikogossian, E. H.

    2004-04-01

    Observations of objects lying in the dark cloud L1582A, which contains the cometary nebulae GM1-61 and V453 Ori, are reported. Five previously unknown HH-objects are discovered in this region; they appear to form several flows. The morphology of the nebulae is examined and possible sources of the HH-flows are discussed. Another reflecting nebula is found that is visible mainly in the infrared.

  19. Antibody response after immunization with the gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse

    Microsoft Academic Search

    Philip O. Livingston; Gerd Ritter; Michele Jones Calves

    1989-01-01

    The gangliosides GM2, GD2 and GD3 are differentiation antigens expressed on the cell surface of human melanomas and other cancers of neuroectodermal origin. We have compared the antibody response after vaccination with gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse. Purified gangliosides were injected subcutaneously alone or attached to Salmonella minnesota mutant R595 after pretreatment of the mice

  20. Induction of GM1a\\/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function

    Microsoft Academic Search

    Lixian Dong; Yihui Liu; Anamaris M. Colberg-Poley; Karen Kaucic; Stephan Ladisch

    2011-01-01

    Neuroblastoma is the most common extracranial solid tumor in children and tumor ganglioside composition has been linked to\\u000a its biological and clinical behavior. We recently found that high expression of complex gangliosides that are products of\\u000a the enzyme GM1a\\/GD1b synthase predicts a more favorable outcome in human neuroblastoma, and others have shown that complex\\u000a gangliosides such as GD1a inhibit metastasis

  1. GM1 controlled lateral segregation of tyrosine kinase Lck predispose T-cells to cell-derived galectin-1-induced apoptosis.

    PubMed

    Novák, Julianna; Kriston-Pál, Éva; Czibula, Ágnes; Deák, Magdolna; Kovács, László; Monostori, Éva; Fajka-Boja, Roberta

    2014-02-01

    One prominent immunoregulatory function of galectin-1 (Gal-1), a ?-galactoside binding mammalian lectin, is induction of apoptosis in activated T-cells by a process depending on the activity of Src family tyrosine kinase, Lck. Although the requirement for Lck in Gal-1 induced T-cell death and the ability of Gal-1 to affect the membrane localization of extracellular Gal-1-binding proteins have been well documented, the consequence of the complex and related reorganization of extra- and intracellular signaling components upon Gal-1 treatment of T-cells has not yet been revealed. Therefore, we have analyzed the plasma membrane movement of Lck upon Gal-1 triggered signaling, and the significance of this event in Gal-1 induced T-cell death. Non-receptor tyrosine kinase, Lck primarily localized in the synapse of tumor cell-T-cell during 15 min of the established direct cell contact. Later, after 30 min, a lateral segregation of Lck from the cell synapse was observed. The migration of Lck to the opposite of the cell contact apparently depended on the expression and cell surface presentation of Gal-1 on the effector (tumor) cells and was accompanied by phosphorylation on the negative regulatory tyrosine residue, Tyr505. Receptor tyrosine phosphatase, CD45 played crucial role in this event since CD45 deficiency or inhibition of its phosphatase activity resulted in the failure of Lck membrane movement. Level of the Gal-1-binding glycolipid GM1 ganglioside also essentially regulated Lck localization. Segregation of Lck and Gal-1 induced apoptosis was diminished in T-cells with low GM1 expression compared to T-cells with high GM1. Our results show that spatial regulation of Lck by CD45 and GM1 ganglioside determines the outcome of apoptotic response to Gal-1 and this local regulation may occur only upon intimate effector (Gal-1 expressing) cell-T-cell attachment. PMID:24231767

  2. GM1 and GD1a gangliosides modulate toxic and inflammatory effects of E. coli lipopolysaccharide by preventing TLR4 translocation into lipid rafts.

    PubMed

    Nikolaeva, Svetlana; Bayunova, Lubov; Sokolova, Tatyana; Vlasova, Yulia; Bachteeva, Vera; Avrova, Natalia; Parnova, Rimma

    2015-03-01

    Exogenous gangliosides are known to inhibit the effects of Escherichia coli lipopolysaccharide (LPS) in different cells exhibiting a nti-inflammatory and immunosuppressive activities. The mechanisms underlying ganglioside action are not fully understood. Because LPS recognition and receptor complex formation occur in lipid rafts, and gangliosides play a key role in their maintenance, we hypothesize that protective effects of exogenous gangliosides would depend on inhibition of LPS signaling via prevention of TLR4 translocation into lipid rafts. The effect of GM1 and GD1a gangliosides on LPS-induced toxic and inflammatory reactions in PC12 cells, and in epithelial cells isolated from the frog urinary bladder, was studied. In PC12 cells, GD1a and GM1 significantly reduced the effect of LPS on the decrease of cell survival and on stimulation of reactive oxygen species production. In epithelial cells, gangliosides decreased LPS-stimulated iNOS expression, NO, and PGE2 production. Subcellular fractionation, in combination with immunoblotting, showed that pretreatment of cells with GM1, GD1a, or methyl-?-cyclodextrin, completely eliminated the effect of LPS on translocation of TLR4 into lipid rafts. The results are consistent with the hypothesis that ganglioside-induced prevention of TLR4 translocation into lipid rafts could be a mechanism of protection against LPS in various cells. PMID:25499607

  3. Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased ?1-integrin signaling and delayed wound repair.

    PubMed

    Itokazu, Yutaka; Pagano, Richard E; Schroeder, Andreas S; O'Grady, Scott M; Limper, Andrew H; Marks, David L

    2014-05-01

    Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function reduces chloride secretion and increases sodium uptake, but it is not clear why CFTR mutation also results in progressive lung inflammation and infection. We previously demonstrated that CFTR-silenced airway cells migrate more slowly during wound repair than CFTR-expressing controls. In addition, CFTR-deficient cells and mouse models have been reported to have altered sphingolipid levels. Here, we investigated the hypothesis that reduced migration in CFTR-deficient airway epithelial cells results from altered sphingolipid composition. We used cell lines derived from a human airway epithelial cell line (Calu-3) stably transfected with CFTR short hairpin RNA (CFTR-silenced) or nontargeting short hairpin RNA (controls). Cell migration was measured by electric cell substrate impedance sensing (ECIS). Lipid analyses, addition of exogenous glycosphingolipids, and immunoblotting were performed. We found that levels of the glycosphingolipid, GM1 ganglioside, were ~60% lower in CFTR-silenced cells than in controls. CFTR-silenced cells exhibited reduced levels of activated ?1-integrin, phosphorylated tyrosine 576 of focal adhesion kinase (pFAK), and phosphorylation of Crk-associated substrate (pCAS). Addition of GM1 (but not GM3) ganglioside to CFTR-silenced cells restored activated ?1-integrin, pFAK, and pCAS to near control levels and partially restored (~40%) cell migration. Our results suggest that decreased GM1 in CFTR-silenced cells depresses ?1-integrin signaling, which contributes to the delayed wound repair observed in these cells. These findings have implications for the pathology of cystic fibrosis, where altered sphingolipid levels in airway epithelial cells could result in a diminished capacity for wound repair after injury. PMID:24500283

  4. Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased ?1-integrin signaling and delayed wound repair

    PubMed Central

    Itokazu, Yutaka; Pagano, Richard E.; Schroeder, Andreas S.; O'Grady, Scott M.; Limper, Andrew H.

    2014-01-01

    Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function reduces chloride secretion and increases sodium uptake, but it is not clear why CFTR mutation also results in progressive lung inflammation and infection. We previously demonstrated that CFTR-silenced airway cells migrate more slowly during wound repair than CFTR-expressing controls. In addition, CFTR-deficient cells and mouse models have been reported to have altered sphingolipid levels. Here, we investigated the hypothesis that reduced migration in CFTR-deficient airway epithelial cells results from altered sphingolipid composition. We used cell lines derived from a human airway epithelial cell line (Calu-3) stably transfected with CFTR short hairpin RNA (CFTR-silenced) or nontargeting short hairpin RNA (controls). Cell migration was measured by electric cell substrate impedance sensing (ECIS). Lipid analyses, addition of exogenous glycosphingolipids, and immunoblotting were performed. We found that levels of the glycosphingolipid, GM1 ganglioside, were ?60% lower in CFTR-silenced cells than in controls. CFTR-silenced cells exhibited reduced levels of activated ?1-integrin, phosphorylated tyrosine 576 of focal adhesion kinase (pFAK), and phosphorylation of Crk-associated substrate (pCAS). Addition of GM1 (but not GM3) ganglioside to CFTR-silenced cells restored activated ?1-integrin, pFAK, and pCAS to near control levels and partially restored (?40%) cell migration. Our results suggest that decreased GM1 in CFTR-silenced cells depresses ?1-integrin signaling, which contributes to the delayed wound repair observed in these cells. These findings have implications for the pathology of cystic fibrosis, where altered sphingolipid levels in airway epithelial cells could result in a diminished capacity for wound repair after injury. PMID:24500283

  5. Häufigkeit der Sichttypen in den Erbsystemen Haptoglobin, Gc, saure Erythrocytenphosphatase, Phosphoglucomutase und Adenylatkinase sowie den Erbeigenschaften Gm(1), Gm(2) und Inv(1) bei Deutschen (aus dem Raum Freiburg i. Br. und Köln) und bei Türken

    Microsoft Academic Search

    K. Hummel; G. Pulverer; K. P. Schaal; V. Weidtman

    1970-01-01

    There was found a higher frequency of Hp1 and a lower of Inv1 in the population of Cologne than in the population of Freiburg. The frequencies of Hp2, Gm1, Pb and PGM2 in the Turkish population were found to be higher than those in the German population; the frequencies of Hp1, Gm1,2, Pa, Pc and PGM1 were found to be

  6. Stem Cell Transplant for Inborn Errors of Metabolism

    ClinicalTrials.gov

    2012-11-06

    Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

  7. Lipopolysaccharides from Campylobacter jejuni O:41 Strains Associated with Guillain-BarreSyndrome Exhibit Mimicry of GM1 Ganglioside

    Microsoft Academic Search

    MARTINA M. PRENDERGAST; ALBERT J. LASTOVICA; ANTHONY P. MORAN

    1998-01-01

    Three Campylobacter jejuni, biotype 2, serotype O:41 strains that were isolated from patients who developed Guillain-Barresyndrome (GBS) and one C. jejuni isolate from a patient who developed enteritis only were examined. The aim of the study was to determine the structure of the core oligosaccharide (OS) of the lipo- polysaccharide (LPS) of C. jejuni serotype O:41, a serotype rarely associated

  8. A Trp474Cys mutation in the alpha-subunit of beta-hexosaminidase causes a subacute encephalopathic form of G{sub M2} gangliosidosis, type 1

    Microsoft Academic Search

    E. Petroulakis; Z. Cao; T. Salo

    1994-01-01

    Mutations in the HEXA gene that encodes the α-subunit of the heterodimeric lysosomal enzyme β-hexosaminidase A, or Hex A (αβ), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who

  9. Antiganglioside antibody in patients with Guillain-Barré syndrome who show bulbar palsy as an initial symptom

    PubMed Central

    Koga, M.; Yuki, N.; Hirata, K.

    1999-01-01

    OBJECTIVES—To identify valuable antiganglioside antibodies that support the diagnosis of Guillain-Barré syndrome (GBS) and its variants in patients showing bulbar palsy as an initial symptom.?METHODS—Medical records of 602 patients with GBS or its variants were reviewed. Fifteen patients had bulbar palsy as an initial symptom. Serum antibodies against GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, and GQ1b were examined in 13 of them.?RESULTS—Serum antiganglioside antibodies were positive in 11 (85%) patients. IgG anti-GT1a (n=8; 62%) and anti-GM1b (n=7; 54%) antibodies were often present, whereas all the patients had low or no anti-GM1 antibody activity. High anti-GD1a and anti-GQ1b IgG antibody titres were also present in some patients, but most had higher IgG antibody titres to GM1b or GT1a. All five patients with high IgG antibody titre to GM1b or GT1a only had had antecedent diarrhoea. Some patients with pharyngeal-cervical-brachial weakness (PCB) had IgG antibody to GT1a which did not cross react with GQ1b. Other patients with PCB had antibody to GT1a which cross reacted with GQ1b or antibody to GM1b, but anti-GM1b and anti-GT1a antibodies were not associated with the presence of bulbar palsy. All the patients who had no IgG antiganglioside antibodies recovered completely.?CONCLUSIONS—Measurement of serum IgG anti-GT1a and anti-GM1b antibodies gives helpful support for the diagnosis of GBS and its variants when there is early involvement of the oropharyngeal function independently of other neurological findings which appear as the illness progresses.?? PMID:10201426

  10. A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease).

    PubMed

    Rahman, Mohammad M; Chang, Hye-Sook; Mizukami, Keijiro; Hossain, Mohammad A; Yabuki, Akira; Tamura, Shinji; Kitagawa, Masato; Mitani, Sawane; Higo, Takashi; Uddin, Mohammad M; Uchida, Kazuyuki; Yamato, Osamu

    2012-12-01

    GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations in the HEXB gene. Toy poodles recently were reported as the second breed of dog with SD. The present paper describes the molecular defect of this canine SD as the first identification of a pathogenic mutation in the canine HEXB gene. Genomic and complementary DNA sequences covering exonic regions of the canine HEXB gene, except exon 1, were analysed using DNA and RNA in an affected dog. A homozygous single base pair deletion of guanine in exon 3 was identified at nucleotide position 283 of the putative open reading frame (c.283delG). This mutation has the potential to cause a frameshift resulting in the alteration of valine at amino acid position 59 to a stop codon (p.V59fsX). Genotyping using the mutagenically separated PCR method demonstrated a correlation between phenotype and genotype in dogs with a pedigree related to the disease and that the mutation was rare in a randomly-selected population of toy poodles. These results strongly suggest that the deletion is pathogenic. PMID:22766310

  11. Fibroblast screening for chaperone therapy in ?-galactosidosis

    Microsoft Academic Search

    Hiroyuki Iwasaki; Hiroshi Watanabe; Masami Iida; Seiichiro Ogawa; Miho Tabe; Katsumi Higaki; Eiji Nanba; Yoshiyuki Suzuki

    2006-01-01

    We performed screening of ?-galactosidase-deficient fibroblasts for possible chemical chaperone therapy using N-octyl-4-epi-?-valienamine (NOEV) in patients with GM1-gangliosidosis and Morquio B disease (?-galactosidosis). Fibroblasts were cultured with NOEV for 4 days and ?-galactosidase activity was measured. Mutation analysis was performed simultaneously. Two separate criteria were set for evaluation of the chaperone effect: a relative increase of enzyme activity (more than

  12. Chaperone therapy for neuronopathic lysosomal diseases: competitive inhibitors as chemical chaperones for enhancement of mutant enzyme activities.

    PubMed

    Suzuki, Yoshiyuki; Ogawa, Seiichiro; Sakakibara, Yasubumi

    2009-01-01

    Chaperone therapy is a newly developed molecular approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. We found two valienamine derivatives, N-octyl-4-epi-beta-valienamine (NOEV) and N-octyl-beta-valienamine (NOV), as promising therapeutic agents for human beta-galactosidase deficiency disorders (mainly G(M1)-gangliosidosis) and beta-glucosidase deficiency disorders (Gaucher disease), respectively. We briefly reviewed the historical background of research in carbasugar glycosidase inhibitors. Originally NOEV and NOV had been discovered as competitive inhibitors, and then their paradoxical bioactivities as chaperones were confirmed in cultured fibroblasts from patients with these disorders. Subsequently G(M1)-gangliosidosis model mice were developed and useful for experimental studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced beta-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Furthermore, we executed computational analysis for prediction of molecular interactions between beta-galactosidase and NOEV. Some preliminary results of computational analysis of molecular interaction mechanism are presented in this article. NOV also showed the chaperone effect toward several beta-glucosidase gene mutations in Gaucher disease. We hope chaperone therapy will become available for some patients with G(M1)-gangliosidosis, Gaucher disease, and potentially other lysosomal storage diseases with central nervous system involvement. PMID:19812739

  13. Study on systematizing the synthesis of the a-series ganglioside glycans GT1a, GD1a, and GM1 using the newly developed N-Troc-protected GM3 and GalN intermediates

    Microsoft Academic Search

    Tatsuya Komori; Akihiro Imamura; Hiromune Ando; Hideharu Ishida; Makoto Kiso

    2009-01-01

    A first systematic synthesis of the glycan parts of the a-series gangliosides (GT1a, GD1a, and GM1) utilizing the newly developed N-Troc-protected GM3 and galactosaminyl building blocks is described. The key processes, including the assembly of the GM2 sequence and its conversion into the 3-hydroxy acceptor, were facilitated mainly by the high degree of participation and chemoselective cleavability of the Troc

  14. Real-Time PCR Genotyping Assay for GM2 Gangliosidosis Variant 0 in Toy Poodles and the Mutant Allele Frequency in Japan

    PubMed Central

    RAHMAN, Mohammad Mahbubur; YABUKI, Akira; KOHYAMA, Moeko; MITANI, Sawane; MIZUKAMI, Keijiro; UDDIN, Mohammad Mejbah; CHANG, Hye-Sook; KUSHIDA, Kazuya; KISHIMOTO, Miori; YAMABE, Remi; YAMATO, Osamu

    2013-01-01

    ABSTRACT GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the HEXB gene. In canine SD, a pathogenic mutation (c.283delG) of the canine HEXB gene has been identified in toy poodles. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid and large-scale genotyping and screening for this mutation. Furthermore, a genotyping survey was carried out in a population of toy poodles in Japan to determine the current mutant allele frequency. The real-time PCR assay clearly showed all genotypes of canine SD. The assay was suitable for large-scale survey as well as diagnosis, because of its high throughput and rapidity. The genotyping survey demonstrated a carrier frequency of 0.2%, suggesting that the current mutant allele frequency is low in Japan. However, there may be population stratification in different places, because of the founder effect by some carriers. Therefore, this new assay will be useful for the prevention and control of SD in toy poodles. PMID:24161966

  15. Real-time PCR genotyping assay for GM2 gangliosidosis variant 0 in toy poodles and the mutant allele frequency in Japan.

    PubMed

    Rahman, Mohammad Mahbubur; Yabuki, Akira; Kohyama, Moeko; Mitani, Sawane; Mizukami, Keijiro; Uddin, Mohammad Mejbah; Chang, Hye-Sook; Kushida, Kazuya; Kishimoto, Miori; Yamabe, Remi; Yamato, Osamu

    2014-03-01

    GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the HEXB gene. In canine SD, a pathogenic mutation (c.283delG) of the canine HEXB gene has been identified in toy poodles. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid and large-scale genotyping and screening for this mutation. Furthermore, a genotyping survey was carried out in a population of toy poodles in Japan to determine the current mutant allele frequency. The real-time PCR assay clearly showed all genotypes of canine SD. The assay was suitable for large-scale survey as well as diagnosis, because of its high throughput and rapidity. The genotyping survey demonstrated a carrier frequency of 0.2%, suggesting that the current mutant allele frequency is low in Japan. However, there may be population stratification in different places, because of the founder effect by some carriers. Therefore, this new assay will be useful for the prevention and control of SD in toy poodles. PMID:24161966

  16. Host Factors Determine Anti-GM1 Response Following Oral Challenge of Chickens with Guillain-Barré Syndrome Derived Campylobacter jejuni Strain GB11

    Microsoft Academic Search

    C. Wim Ang; Jeroen R. Dijkstra; Marcel A. de Klerk; Hubert Ph. Endtz; Pieter A. van Doorn; Bart C. Jacobs; Suzan H. M. Jeurissen; Jaap A. Wagenaar

    2010-01-01

    BackgroundAnti-ganglioside antibodies with a pathogenic potential are present in C. jejuni-associated Guillain-Barré syndrome (GBS) patients and are probably induced by molecular mimicry. Immunization studies in rabbits and mice have demonstrated that these anti-ganglioside antibodies can be induced using purified lipo-oligosaccharides (LOS) from C. jejuni in a strong adjuvant.Methodology\\/Principal FindingsTo investigate whether natural colonization of chickens with a ganglioside-mimicking C. jejuni

  17. Host Factors Determine Anti-GM1 Response Following Oral Challenge of Chickens with Guillain-Barre Syndrome Derived Campylobacter jejuni Strain GB11

    Microsoft Academic Search

    C. Wim Ang; Jeroen R. Dijkstra; Klerk de M. A; Hubert Ph. Endtz; Doorn van P. A; Bart C. Jacobs; Suzan H. M. Jeurissen; Jaap A. Wagenaar

    2010-01-01

    Background: Anti-ganglioside antibodies with a pathogenic potential are present in C. jejuni-associated Guillain-Barre syndrome (GBS) patients and are probably induced by molecular mimicry. Immunization studies in rabbits and mice have demonstrated that these anti-ganglioside antibodies can be induced using purified lipo-oligosaccharides (LOS) from C. jejuni in a strong adjuvant. Methodology\\/Principal Findings: To investigate whether natural colonization of chickens with a

  18. Genetics Home Reference: Dystonia

    MedlinePLUS

    ... Handbook Glossary Resources Conditions > Dystonia Related topics on Genetics Home Reference: dopa-responsive dystonia dystonia 6 early-onset primary dystonia GM1 gangliosidosis hypermanganesemia with dystonia, polycythemia, and cirrhosis Leigh syndrome ...

  19. Lipid Storage Diseases

    MedlinePLUS

    ... peripheral nervous systems. GM1 gangliosidosis has three clinical presentations: early infantile, late infantile, and adult. Signs of ... and causes severe deterioration of mental and motor skills. Other symptoms include muscle weakness, hypertonia (reduced ability ...

  20. Recurrent and novel GLB1 mutations in India.

    PubMed

    Bidchol, Abdul Mueed; Dalal, Ashwin; Trivedi, Rakesh; Shukla, Anju; Nampoothiri, Sheela; Sankar, V H; Danda, Sumita; Gupta, Neerja; Kabra, Madhulika; Hebbar, Shrikiran A; Bhat, Ramesh Y; Matta, Divya; Ekbote, Alka V; Puri, Ratna Dua; Phadke, Shubha R; Gowrishankar, Kalpana; Aggarwal, Shagun; Ranganath, Prajnya; Sharda, Sheetal; Kamate, Mahesh; Datar, Chaitanya A; Bhat, Kamalakshi; Kamath, Nutan; Shah, Hitesh; Krishna, Shuba; Gopinath, Puthiya Mundyat; Verma, Ishwar C; Nagarajaram, H A; Satyamoorthy, Kapaettu; Girisha, Katta Mohan

    2015-08-10

    GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme ?-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, ?-domain 1 and ?-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India. PMID:25936995

  1. Liquid chromatography/electrospray ionisation-tandem mass spectrometry quantification of GM2 gangliosides in human peripheral cells and plasma.

    PubMed

    Fuller, Maria; Duplock, Stephen; Hein, Leanne K; Rigat, Brigitte A; Mahuran, Don J

    2014-08-01

    GM2 gangliosidosis is a group of inherited neurodegenerative disorders resulting primarily from the excessive accumulation of GM2 gangliosides (GM2) in neuronal cells. As biomarkers for categorising patients and monitoring the effectiveness of developing therapies are lacking for this group of disorders, we sought to develop methodology to quantify GM2 levels in more readily attainable patient samples such as plasma, leukocytes, and cultured skin fibroblasts. Following organic extraction, gangliosides were partitioned into the aqueous phase and isolated using C18 solid-phase extraction columns. Relative quantification of three species of GM2 was achieved using LC/ESI-MS/MS with d35GM1 18:1/18:0 as an internal standard. The assay was linear over the biological range, and all GM2 gangliosidosis patients were demarcated from controls by elevated GM2 in cultured skin fibroblast extracts. However, in leukocytes only some molecular species could be used for differentiation and in plasma only one was informative. A reduction in GM2 was easily detected in patient skin fibroblasts after a short treatment with media from normal cells enriched in secreted ?-hexosaminidase. This method may show promise for measuring the effectiveness of experimental therapies for GM2 gangliosidosis by allowing quantification of a reduction in the primary storage burden. PMID:24769373

  2. Immunological properties of N-acetyl-?-d-glucosaminidase of normal human liver and of GM2-gangliosidosis liver

    PubMed Central

    Carroll, M.; Robinson, D.

    1973-01-01

    Antisera were raised to a partially purified preparation of human liver hexosaminidase and to highly purified preparations of hexosaminidase isoenzymes A and B. All the antisera precipitated the enzyme in an enzymically active form, which could be located on immunodiffusion and immunoelectrophoretic gels by using a histochemical substrate. The antisera to the purified isoenzymes were shown to react with hexosaminidase from human liver, kidney, brain and spleen, but did not cross-react with human liver ?-glucosidase, ?-galactosidase, ?-mannosidase, ?-xylosidase, arylsulphatase or acid phosphatase. Hexosaminidases A and B were immunologically identical. The immunological properties of the hexosaminidases from livers of patients with three types of GM2-gangliosidoses were closely similar. No evidence could be found for cross-reacting material in enzyme-deficient states. ImagesPLATE 1 PMID:4198585

  3. Population analysis of the GLB1 gene in South Brazil

    PubMed Central

    Baiotto, Cléia; Sperb, Fernanda; Matte, Ursula; da Silva, Cláudia Dornelles; Sano, Renata; Coelho, Janice Carneiro; Giugliani, Roberto

    2011-01-01

    Infantile GM1 gangliosidosis is caused by the absence or reduction of lysosomal beta-galactosidase activity. Studies conducted in Brazil have indicated that it is one of the most frequent lysosomal storage disorders in the southern part of the country. To assess the incidence of this disorder, 390 blood donors were tested for the presence of two common mutations (1622–1627insG and R59H) in the GLB1 gene. Another group, consisting of 26 GM1 patients, and the blood donors were tested for the presence of two polymorphisms (R521C and S532G), in an attempt to elucidate whether there is a founder effect. The frequencies of the R59H and 1622–1627insG mutations among the GM1 patients studied were 19.2% and 38.5%, respectively. The frequency of polymorphism S532G was 16.7%, whereas R521C was not found in the patients. The overall frequency of either R59H or 1622–1627insG was 57.7% of the disease-causing alleles. This epidemiological study suggested a carrier frequency of 1:58. Seven different haplotypes were found. The 1622–1627insG mutation was not found to be linked to any polymorphism, whereas linkage disequilibrium was found for haplotype 2 (R59H, S532G) (p < 0.001). These data confirm the high incidence of GM1 gangliosidosis and the high frequency of two common mutations in southern Brazil. PMID:21637542

  4. Inheritance of Lysosomal Acid ? Galactosidase Activity and Gangliosides in Crosses of DBA\\/2J and Knockout Mice

    Microsoft Academic Search

    Eric C. Hauser; Julie L. Kasperzyk; Alessandra d'Azzo; Thomas N. Seyfried

    2004-01-01

    GM1 gangliosidosis is a progressive neurodegenerative disease caused by deficiencies in lysosomal acid ß-galactosidase (ß-gal) and involves accumulation and storage of ganglioside GM1 and its asialo form (GA1) in brain and visceral tissues. Similar to the infantile\\/juvenile human disease forms, B6\\/129Sv ß-gal knockout (ko) mice express residual tissue ß-gal activity and significant elevations of brain GM1, GA1, and total gangliosides.

  5. Diagnostic Approach to Childhood-onset Cerebellar Atrophy: A 10-Year Retrospective Study of 300 Patients

    PubMed Central

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2013-01-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by the neuronal ceroid lipofuscinoses, ataxia telangectasia, and late GM2-gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

  6. Diagnostic approach to childhood-onset cerebellar atrophy: a 10-year retrospective study of 300 patients.

    PubMed

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2012-09-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by neuronal ceroid lipofuscinosis, ataxia telangiectasia, and late-onset GM2 gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

  7. Structural basis of pharmacological chaperoning for human ?-galactosidase.

    PubMed

    Suzuki, Hironori; Ohto, Umeharu; Higaki, Katsumi; Mena-Barragán, Teresa; Aguilar-Moncayo, Matilde; Ortiz Mellet, Carmen; Nanba, Eiji; Garcia Fernandez, Jose M; Suzuki, Yoshiyuki; Shimizu, Toshiyuki

    2014-05-23

    GM1 gangliosidosis and Morquio B disease are autosomal recessive diseases caused by the defect in the lysosomal ?-galactosidase (?-Gal), frequently related to misfolding and subsequent endoplasmic reticulum-associated degradation. Pharmacological chaperone (PC) therapy is a newly developed molecular therapeutic approach by using small molecule ligands of the mutant enzyme that are able to promote the correct folding and prevent endoplasmic reticulum-associated degradation and promote trafficking to the lysosome. In this report, we describe the enzymological properties of purified recombinant human ?-Gal(WT) and two representative mutations in GM1 gangliosidosis Japanese patients, ?-Gal(R201C) and ?-Gal(I51T). We have also evaluated the PC effect of two competitive inhibitors of ?-Gal. Moreover, we provide a detailed atomic view of the recognition mechanism of these compounds in comparison with two structurally related analogues. All compounds bind to the active site of ?-Gal with the sugar-mimicking moiety making hydrogen bonds to active site residues. Moreover, the binding affinity, the enzyme selectivity, and the PC potential are strongly affected by the mono- or bicyclic structure of the core as well as the orientation, nature, and length of the exocyclic substituent. These results provide understanding on the mechanism of action of ?-Gal selective chaperoning by newly developed PC compounds. PMID:24737316

  8. Structural Basis of Pharmacological Chaperoning for Human ?-Galactosidase*

    PubMed Central

    Suzuki, Hironori; Ohto, Umeharu; Higaki, Katsumi; Mena-Barragán, Teresa; Aguilar-Moncayo, Matilde; Ortiz Mellet, Carmen; Nanba, Eiji; Garcia Fernandez, Jose M.; Suzuki, Yoshiyuki; Shimizu, Toshiyuki

    2014-01-01

    GM1 gangliosidosis and Morquio B disease are autosomal recessive diseases caused by the defect in the lysosomal ?-galactosidase (?-Gal), frequently related to misfolding and subsequent endoplasmic reticulum-associated degradation. Pharmacological chaperone (PC) therapy is a newly developed molecular therapeutic approach by using small molecule ligands of the mutant enzyme that are able to promote the correct folding and prevent endoplasmic reticulum-associated degradation and promote trafficking to the lysosome. In this report, we describe the enzymological properties of purified recombinant human ?-GalWT and two representative mutations in GM1 gangliosidosis Japanese patients, ?-GalR201C and ?-GalI51T. We have also evaluated the PC effect of two competitive inhibitors of ?-Gal. Moreover, we provide a detailed atomic view of the recognition mechanism of these compounds in comparison with two structurally related analogues. All compounds bind to the active site of ?-Gal with the sugar-mimicking moiety making hydrogen bonds to active site residues. Moreover, the binding affinity, the enzyme selectivity, and the PC potential are strongly affected by the mono- or bicyclic structure of the core as well as the orientation, nature, and length of the exocyclic substituent. These results provide understanding on the mechanism of action of ?-Gal selective chaperoning by newly developed PC compounds. PMID:24737316

  9. Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature.

    PubMed

    Stork, Abraham C J; van der Pol, W-Ludo; Franssen, Hessel; Jacobs, Bart C; Notermans, Nicolette C

    2014-07-01

    The objective of this study was to investigate if the clinical and electrophysiological phenotype of patients with polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is related to the presence of antibodies against gangliosides or myelin-associated glycoprotein (MAG). We compared clinical and nerve conduction study (NCS) characteristics of 11 IgM-PNP patients with antibodies against asialo-GM1 or gangliosides (GM1, GD1a, GD1b, GM2 or GQ1b) to 11 consecutive IgM-PNP patients with anti-MAG neuropathy and to 9 IgM-PNP patients without antibodies against either MAG or gangliosides. Patients with anti-ganglioside antibodies could not be differentiated from those with anti-MAG antibodies based on clinical characteristics. However, within the group of anti-ganglioside antibody positive patients, antibodies against GD1b and GQ1b were associated with a purely sensory neuropathy (p = 0.002), while asymmetric weakness with symmetric sensory loss was associated with anti-asialo-GM1 antibodies. In conclusion, polyneuropathy associated with IgM monoclonal gammopathy and anti-ganglioside antibodies clinically resembles anti-MAG neuropathy. Pure sensory neuropathy and marked asymmetry may suggest the presence of anti-ganglioside rather than anti-MAG antibodies. PMID:24781837

  10. Macular cherry-red spot helps diagnose rare storage disorder in an infant with repeated respiratory tract infections: case report.

    PubMed

    Padhi, Tapas Ranjan; Pattnaik, Sibabrata; Kesarwani, Siddharth; Das, Taraprasad

    2015-05-01

    A seven-month-old male child was brought in for an eye test for poor vision and nystagmus noticed from four months of age. The child had delayed milestones of development and multiple (six times) episodes of unexplained lower respiratory tract infection (from two months of age) treated by pediatricians at different centers without complete cure. Fundus examination showed bilateral cherry-red spots at the macula. There were diffusely distributed hyper-pigmented patches (Mongolian spots) on the back and extensor aspect of the extremities. The case was sent back to the pediatricians for a re-evaluation to rule out storage disorder. Lysosomal enzyme assay in the leucocytes showed a significantly reduced ?-galactosidase level (15.6?nmol/hr/mg protein in contrast to a normal range of 79.6 to 480.0). This confirmed the patient to be a case of lysosomal storage disease, the GM1 gangliosidosis (type I). PMID:24124800

  11. Paradoxical influence of acid ?-galactosidase gene dosage on phenotype of the twitcher mouse (genetic galactosylceramidase deficiency)

    Microsoft Academic Search

    Jun Tohyama; Marie T. Vanier; Kinuko Suzuki; Takanori Ezoe; Junko Matsuda; Kunihiko Suzuki

    We have cross-bred twitcher mice (galactosylceram- idase deficiency) and acid ?-galactosidase knockout mice (GM1 gangliosidosis) and found that the acid ?-galactosidase gene dosage exerts an unexpected and paradoxical influence on the twitcher phenotype. Twitcher mice with an additional complete deficiency of acid ?-galactosidase have the mildest phenotype with the longest lifespan and nearly rescued CNS pathology. In contrast, twitcher mice

  12. Three Novel Mutations in Iranian Patients with Tay-Sachs Disease

    PubMed Central

    Jamali, Solmaz; Eskandari, Nasim; Aryani, Omid; Salehpour, Shadab; Zaman, Talieh; Kamalidehghan, Behnam; Houshmand, Massoud

    2014-01-01

    Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Results: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. Conclusion: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations. PMID:24518553

  13. Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in ?-galactosidase deficiency.

    PubMed

    Higaki, Katsumi; Li, Linjing; Bahrudin, Udin; Okuzawa, Soichiro; Takamuram, Ayumi; Yamamoto, Koichi; Adachi, Kaori; Paraguison, Rubigilda C; Takai, Tomoko; Ikehata, Hiroki; Tominaga, Lika; Hisatome, Ichiro; Iida, Masami; Ogawa, Seiichiro; Matsuda, Junichiro; Ninomiya, Haruaki; Sakakibara, Yasubumi; Ohno, Kousaku; Suzuki, Yoshiyuki; Nanba, Eiji

    2011-07-01

    ?-Galactosidase deficiency is a group of lysosomal lipid storage disorders with an autosomal recessive trait. It causes two clinically different diseases, G(M1) -gangliosidosis and Morquio B disease. It is caused by heterogeneous mutations in the GLB1 gene coding for the lysosomal acid ?-galactosidase. We have previously reported the chaperone effect of N-octyl-4-epi-?-valienamine (NOEV) on mutant ?-galactosidase proteins. In this study, we performed genotype analyses of patients with ?-galactosidase deficiency and identified 46 mutation alleles including 9 novel mutations. We then examined the NOEV effect on mutant ?-galactosidase proteins by using six strains of patient-derived skin fibroblast. We also performed mutagenesis to identify ?-galactosidase mutants that were responsive to NOEV and found that 22 out of 94 mutants were responsive. Computational structural analysis revealed the mode of interaction between human ?-galactosidase and NOEV. Moreover, we confirmed that NOEV reduced G(M1) accumulation and ameliorated the impairments of lipid trafficking and protein degradation in ?-galactosidase deficient cells. These results provided further evidence to NOEV as a promising chaperone compound for ?-galactosidase deficiency. PMID:21520340

  14. Sustained normalization of neurological disease after intracranial gene therapy in a feline model.

    PubMed

    McCurdy, Victoria J; Johnson, Aime K; Gray-Edwards, Heather L; Randle, Ashley N; Brunson, Brandon L; Morrison, Nancy E; Salibi, Nouha; Johnson, Jacob A; Hwang, Misako; Beyers, Ronald J; Leroy, Stanley G; Maitland, Stacy; Denney, Thomas S; Cox, Nancy R; Baker, Henry J; Sena-Esteves, Miguel; Martin, Douglas R

    2014-04-01

    Progressive debilitating neurological defects characterize feline G(M1) gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal ?-galactosidase. No effective therapy exists for affected children, who often die before age 5 years. An adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two brain targets (thalamus and deep cerebellar nuclei) of a feline model of G(M1) gangliosidosis. Gene therapy normalized ?-galactosidase activity and storage throughout the brain and spinal cord. The mean survival of 12 treated G(M1) animals was >38 months, compared to 8 months for untreated animals. Seven of the eight treated animals remaining alive demonstrated normalization of disease, with abrogation of many symptoms including gait deficits and postural imbalance. Sustained correction of the G(M1) gangliosidosis disease phenotype after limited intracranial targeting by gene therapy in a large animal model suggests that this approach may be useful for treating the human version of this lysosomal storage disorder. PMID:24718858

  15. Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.

    PubMed

    Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

    2013-01-01

    Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses. PMID:24386203

  16. Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

    PubMed Central

    Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

    2013-01-01

    Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses. PMID:24386203

  17. Comparison of the canine and human acid {beta}-galactosidase gene

    SciTech Connect

    Ahern-Rindell, A.J. [Weber State Univ., Ogden, UT (United States)] [Weber State Univ., Ogden, UT (United States); Kretz, K.A. [Recombinant BioCatalysis, Inc., La Jolla, CA (United States)] [Recombinant BioCatalysis, Inc., La Jolla, CA (United States); O`Brien, J.S. [Univ. of California at San Diego, La Jolla, CA (United States)] [Univ. of California at San Diego, La Jolla, CA (United States)

    1996-05-17

    Several canine cDNA libraries were screened with human {beta}-galactosidase cDNA as probe. Seven positive clones were isolated and sequenced yielding a partial (2060 bp) canine {beta}-galactosidase cDNA with 86% identity to the human {beta}-galactosidase cDNA. Preliminary analysis of a canine genomic library indicated conservation of exon number and size. Analysis by Northern blotting disclosed a single mRNA of 2.4 kb in fibroblasts and liver from normal dogs and dogs affected with GM1 gangliosidosis. Although incomplete, these results indicate canine GM1 gangliosidosis is a suitable animal model of the human disease and should further efforts to devise a gene therapy strategy for its treatment. 20 refs., 2 figs., 1 tab.

  18. Development and medical application of unsaturated carbaglycosylamine glycosidase inhibitors.

    PubMed

    Ogawa, Seiichiro; Kanto, Miki; Suzuki, Yoshiyuki

    2007-07-01

    This article reviews synthesis and structures of carbaglycosylamines, a group of carbocyclic sugar analogues. Some unsaturated derivatives are known to be potent glycosidase inhibitors. Among them, N-octyl-4-epi-beta-valienamine as a lysosomal beta-galactosidase inhibitor is currently undergoing a new molecular therapeutic trial (chemical chaperone therapy) for control of the human beta-galactosidase deficiency disorder, G(M1)-gangliosidosis. PMID:17627580

  19. Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors

    PubMed Central

    Schitter, Georg; Scheucher, Elisabeth; Steiner, Andreas J; Stütz, Arnold E; Thonhofer, Martin; Tarling, Chris A; Withers, Stephen G; Wicki, Jacqueline; Fantur, Katrin; Paschke, Eduard; Mahuran, Don J; Rigat, Brigitte A; Tropak, Michael

    2010-01-01

    Summary N-Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C6 alkyl chain followed by modification with different aromatic substituents provided lipophilic 1-deoxygalactonojirimycin derivatives which exhibit inhibitory properties against ?-glycosidases from E. coli and Agrobacterium sp. as well as green coffee bean ?-galactosidase. In preliminary studies, these compounds also showed potential as chemical chaperones for GM1-gangliosidosis related ?-galactosidase mutants. PMID:20502610

  20. Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase

    SciTech Connect

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. (Univ. of California, Los Angeles (USA))

    1989-04-01

    Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.

  1. Beta-galactosidase deficiency: an approach to chaperone therapy.

    PubMed

    Suzuki, Yoshiyuki

    2006-01-01

    We propose a new molecular therapeutic approach to lysosomal diseases with severe neurological manifestations. Some low-molecular-weight compounds, acting as competitive inhibitors of a lysosomal enzyme in vitro, were found to stabilize and restore catalytic activities of the enzyme molecule as a molecular chaperone. We started this trial first in Fabry disease (generalized vasculopathy) using galactose and 1-deoxygalactonojirimycin, and then in beta-galactosidase deficiency disorders (beta-galactosidosis) with generalized neurosomatic and/or systemic skeletal manifestations (GM(1)-gangliosidosis and Morquio B disease), using a newly developed chemical compound N-octyl-4-epi-beta-valienamine (NOEV). Administration of this chaperone compound resulted in elevation of intracellular enzyme activity in cultured fibroblasts from patients and genetically engineered model mice. In addition, substrate storage was improved after NOEV had been transported into the brain tissue via the blood-brain barrier. We hope this new approach (chemical chaperone therapy) will be useful for certain patients with beta-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement. PMID:16763919

  2. Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients

    PubMed Central

    McDonald, Georgia; Deepak, Shantal; Miguel, Laura; Hall, Cleo J.; Isenberg, David A.; Magee, Anthony I.; Butters, Terry; Jury, Elizabeth C.

    2014-01-01

    Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft–associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor ? (LXR?), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE. PMID:24463447

  3. Gangliosidoses.

    PubMed

    Patterson, Marc C

    2013-01-01

    The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of ?-galactosidase and ?-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. PMID:23622392

  4. Model on Dynamic Control of Project Costs Based on GM(1,1)for Construction Enterprises

    Microsoft Academic Search

    Jian-bing Liu; Hong Ren; Zhi-ming Li

    The gray fuzzy predictive model of project costs is built based on the gray fuzzy predictive theory, which can be used to\\u000a estimate the budget costs work scheduled of the unfinished project in construction phase, and then the budget costs work scheduled\\u000a can be optimized and adjusted. Besides the buffer management mechanism of the project in construction stage is designed,

  5. Audience rating prediction of new TV programs based on GM (1.1) envelopment model

    Microsoft Academic Search

    Zheng Yilei

    2009-01-01

    Audience rating is the core index of TV programs as well as the embodiment of core competitiveness of TV stations. Daily management of TV programs is mainly audience rating-centered. However, posterior survey and evaluation concerning audience rating has been incapable of meeting the demands of daily management of TV stations. It is then an important task for modern TV stations

  6. Forecasting the Global Photovoltaic Market by Using the GM(1,1) Grey Forecasting Method

    Microsoft Academic Search

    Chi-Yo Huang; Wei-Chang Tzeng; Yu-Wei Liu; Po-Yen Wang

    2011-01-01

    The solar photovoltaic (PV) technology is the fastest emerging energy technology during the past decade. Precise predictions of the PV market are essential for the governments' energy policy definitions, firms' expansion of their production of PV related equipment as well as investors' decisions regarding to investments in PV related firms. However, an accurate prediction of the PV market is not

  7. Comparison between the aggregation of human and rodent amyloid ?-proteins in GM1 ganglioside clusters.

    PubMed

    Ueno, Hiroshi; Yamaguchi, Takahiro; Fukunaga, Saori; Okada, Yuki; Yano, Yoshiaki; Hoshino, Masaru; Matsuzaki, Katsumi

    2014-12-01

    The abnormal deposition of amyloids by amyloid-? protein (A?) is a pathological hallmark of Alzheimer's disease (AD). Aged rodents rarely develop the characteristic lesions of the disease, which is different from the case in humans. Rodent A? (rA?) differs from human A? (hA?) only in the three substitutions of Arg to Gly, Tyr to Phe, and His to Arg at positions 5, 10, and 13, respectively. Understanding the reason why rodent A? does not form amyloids is important to revealing factors that cause the abnormal aggregation of A? under pathologic conditions. We have proposed that the binding of A? to membranes with ganglioside clusters plays an important role in the abnormal aggregation of A?. In this study, we compared hA? and rA? in terms of aggregation on neuronal cells, on raftlike model membranes, and in buffer. We found that rA? formed amyloid fibrils similar to those of hA? in buffer solution. In contrast, on cell membranes and raftlike membranes, hA? formed toxic, mature amyloid fibrils, whereas rA? produced less toxic protofibrils that were not stained by the amyloid-specific dye Congo red. Thus, our ganglioside cluster-mediated amyloidogenesis hypothesis explains the immunity of rodents from cerebral A? amyloid deposition, strengthening the importance of ganglioside clusters as a platform of abnormal A? deposition in the pathology of AD. PMID:25399921

  8. Scientific literature on monosialoganglioside in the Science Citation Index-Expanded

    PubMed Central

    Xu, Yanli; Li, Miaojing; Liu, Zhijun; Liu, Ruichun; Zhang, Jianzhong

    2012-01-01

    BACKGROUND: The monosialoganglioside (GM1) is a popular topic of research but the bibliometric analysis of GM1 over the decades in Science Citation Index-Expanded (SCI-E) remains poorly understood. OBJECTIVE: To identify the global research and to improve the understanding of research trends in the GM1 field from 1942 to 2011. DESIGN: A bibliometric study. DATA RETRIEVAL: We performed a bibliometric analysis based on the SCI-E published by the Institute of Scientific Information. INCLUSIVE CRITERIA: Articles closely related to GM1 were included. Exclusive criteria: (1) Articles related to gangliosidosis, disialo-ganglioside, trisialo-ganglioside or ganglioside GQIb. (2) Document types such as meeting abstracts, reviews, proceedings papers, notes, and letters. MAIN OUTCOME MEASURES: (1) Type of publication output; (2) number of author outputs; (3) distribution of output in subject categories; (4) publication distribution of countries; (5) distribution of output in journals, and (6) distribution of citations in each decade. RESULTS: During 1942 to 2011, there were 10 126 papers on GM1 that were added to the SCI. Articles (8 004) were the most frequently used document type comprising 79.0%, followed by meeting abstracts, reviews and proceedings papers. Research on GM1 could be found in the SCI from 1942, it was developed in the 1970s, greatly increased in the 1980s, and reached a peak in the 1990s, and it was slightly decreased in 2000. The distribution of subject categories showed that GM1 research covered both clinical and basic science research. The USA, Japan, and Germany were the three most productive countries, and the publication numbers in the USA were highest in all decades. The Journal of Biological Chemistry, Journal of Neurochemistry and Biochemistry were core subject journals in GM1 studies in each decade. CONCLUSION: This study highlights the topics in GM1 research that are being published around the world. PMID:25806062

  9. Patient Advocacy MIT Patient Advocate

    E-print Network

    Polz, Martin

    Patient Advocacy MIT Patient Advocate MIT Medical, Building E23 77 Massachusetts Avenue Cambridge, MA 02139 617-253-4976 Monday­Friday, 9 a.m.­4 p.m. http://web.mit.edu/medical/ The Patient Advocate patient advocates are available to help. MIT Medical's patient advocate program is designed to help

  10. Inflammatory infiltrates in the spinal cord of patients with Guillain-Barré syndrome.

    PubMed

    Müller, H D; Beckmann, A; Schröder, J M

    2003-12-01

    Guillain-Barré syndrome (GBS) is defined as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) of the peripheral nervous system. Reports on central nervous system involvement in patients with GBS are rare and the histopathological analysis was usually restricted to conventional staining techniques. We were able to investigate four cases with GBS at autopsy in respect to the inflammatory infiltrates and histopathological changes in the spinal cord by immunohistochemistry using a panel of antibodies recognizing lymphocytes and different macrophage-activation antigens. There were increased inflammatory cell infiltrates comprising lymphocytes and macrophages in the spinal cord of two cases. In one of these two cases, GBS predominantly affecting the motor system similar to acute motor axonal neuropathy (AMAN) developed following hepatitis B vaccination; in the second one, GBS developed rapidly 4 days after onset of intravenous purified GM1-ganglioside application affecting the motor as well as the sensory system, resembling acute motor sensory axonal neuropathy (AMSAN). Impairment of the spinal anterior horn cells with their axons was suggested to be responsible for prolonged motor symptoms and the predominantly axonal type of neuropathy at least as a late-stage feature in these two cases with fatal outcome. Insignificant cellular infiltrates in the spinal cord were noted in the other two GBS cases. Focal cellular infiltration of spinal nerve roots and meninges was similar in all cases. PMID:13680278

  11. Guillain-Barré syndrome and hemophagocytic lymphohistiocytosis in a patient with severe chronic active Epstein-Barr virus infection syndrome.

    PubMed

    Takahashi, Koji; Kunishige, Makoto; Shinohara, Masayuki; Kubo, Katsuyuki; Inoue, Hideo; Yoshino, Hiide; Asano, Atsuko; Honda, Souichi; Matsumoto, Toshio; Mitsui, Takao

    2005-12-01

    Epstein-Barr virus (EBV) infection causes a wide range of neurologic and hematologic manifestations. We report a 72-year-old Japanese male patient with severe chronic active EBV infection syndrome (SCAEBV) who presented with Guillain-Barré syndrome (GBS) and developed hemophagocytic lymphohistiocytosis (HLH) several months after the onset of GBS. He showed acute onset of distal muscle weakness, ophthalmoplegia and bulbar palsy. Results of nerve conduction study revealed acute motor-sensory axonal neuropathy (AMSAN). His serum was positive for anti-LM1 IgG and anti-GM1b IgM. Titers of antibodies to EBV-related antigens indicated chronic reactivated EBV infection. Treatment with IVIg resolved the acute ophthalmoplegia, but there was no notable improvement in the AMSAN and bulbar palsy despite repeated. Finally, he developed refractory HLH resulting in a fatal outcome. In the present patient, it seems that SCAEBV was associated with the development of GBS and fatal HLH via parainfectious autoimmunity and direct infectious immune mechanisms, respectively. PMID:16311154

  12. Patient management.

    PubMed

    Guptill, Lynn

    2015-03-01

    Hospital-associated infections, including those caused by zoonotic agents, represent an increasing concern in veterinary practice. Veterinarians and hospital staff are obligated and expected to provide education about and protection from transmission of pathogens among animal patients and between animal patients and human beings (eg, veterinary staff, volunteers, owners) who come into contact with infected animals. Patient management involves assessing risks of pathogen transmission, identification of animals either suspected of or proved to be infected with a transmissible infectious disease agent, and the implementation of measures that minimize the likelihood of transmission of the infectious agent. PMID:25721618

  13. Patient suicide.

    PubMed

    Greenberg, David; Shefler, Gabi

    2014-01-01

    A series of studies reveals that patient suicide is experienced by most psychiatrists, particularly adult psychiatrists in the public sector. Psychiatrists respond to patient suicide with symptoms of grief, with an intensity in 25-50% of cases similar to those who have lost a parent and sought help, although the duration is more brief. Patient suicide usually results in psychiatrists becoming more defensive in their practice: extra careful to ask about suicidal ideation, more likely to suggest hospitalization and compulsory care, and seek colleagues' consultation. The frequency of patient suicide and its emotional and professional impact have lead to recommendations that the psychiatrist is supported during the early phase of shock and grief, and receives ongoing support for a period after the suicide. Most families of suicide patients would wish to have contact with the psychiatrist after the event. While distress and fear of litigation may influence the psychiatrist's actions, meeting with the family should be seen as part of care, and the psychiatrist should receive guidance and support in this process. PMID:25618283

  14. A study of the strategic alliance for EMS industry: the application of a hybrid DEA and GM (1, 1) approach.

    PubMed

    Wang, Chia Nan; Nguyen, Nhu Ty; Tran, Thanh Tuyen; Huong, Bui Bich

    2015-01-01

    Choosing a partner is a critical factor for success in international strategic alliances, although criteria for partner selection vary between developed and transitional markets. This study aims to develop effective methods to assist enterprise to measure the firms' operation efficiency, find out the candidate priority under several different inputs and outputs, and forecast the values of those variables in the future. The methodologies are constructed by the concepts of Data Envelopment Analysis (DEA) and grey model (GM). Realistic data in four consecutive years (2009-2012) a total of 20 companies of the Electronic Manufacturing Service (EMS) industry that went public are completely collected. This paper tries to help target company-DMU1-to find the right alliance partners. By our proposed approach, the results show the priority in the recent years. The research study is hopefully of interest to managers who are in manufacturing industry in general and EMS enterprises in particular. PMID:25821859

  15. Naturally occurring G M2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B G M2 gangliosidosis)

    Microsoft Academic Search

    J. Fox; Y.-T. Li; G. Dawson; A. Alleman; J. Johnsrude; J. Schumacher; B. Homer

    1999-01-01

    Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated\\u000a macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies\\u000a throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had\\u000a pale granular to finely

  16. Carrier Rates of Four Single-Gene Disorders in Croatian Bayash Roma

    PubMed Central

    Bareši?, Ana

    2014-01-01

    To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Me?imurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1.5%. Carriers for other three mutations causing GM1, CCFDN, and LGMD2C were not found in our sample. The carrier rate for the HMSNL mutation in Baranja is lower than in other Vlax Roma groups. In addition, distinct differences in carrier rates between the Croatian Vlax groups point to different genetic history, despite their belonging to the same Roma migration category and subgroup. The difference in carrier rates is either the result of admixture or the reflection of a greater extent of genetic drift since recent founding, maintained by a high degree of endogamy. PMID:24180318

  17. Carrier rates of four single-gene disorders in Croatian Bayash Roma.

    PubMed

    Bareši?, Ana; Peri?i? Salihovi?, Marijana

    2014-02-01

    To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Me?imurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1.5%. Carriers for other three mutations causing GM1, CCFDN, and LGMD2C were not found in our sample. The carrier rate for the HMSNL mutation in Baranja is lower than in other Vlax Roma groups. In addition, distinct differences in carrier rates between the Croatian Vlax groups point to different genetic history, despite their belonging to the same Roma migration category and subgroup. The difference in carrier rates is either the result of admixture or the reflection of a greater extent of genetic drift since recent founding, maintained by a high degree of endogamy. PMID:24180318

  18. Counseling the Coronary Patient

    ERIC Educational Resources Information Center

    Semmler, Caryl; Semmler, Maynard

    1974-01-01

    The article discusses counseling sessions designed to a) help the coronary patient adjust to cardiovascular disease, b) diminish patient anxieties and fears, and c) educate the patient and family members on controlling risk factors to deter another coronary attack. (JS)

  19. [Patient education in France].

    PubMed

    Bertrand, Dominique

    2011-10-01

    Patient education is an increasingly important component of therapeutic strategies, especially for chronic illnesses, which currently affect about 12% of the French population and will undoubtedly increase in coming years. Patient education aims to enhance patients' personal responsibility and participation in their therapeutic management and quality of life. Article 84 of French health legislation passed in 2009 inscribes patient education in the Public Health Code for the first time. It distinguishes personalized therapeutic education, patient accompaniment, and learning programs. Direct links between patients and drug companies are prohibited. However, the notion of patient accompaniment remains to be defined, along with the evaluation of patient education, funding sources and practical modalities. PMID:22812156

  20. Therapeutic Potential of Intracerebroventricular Replacement of Modified Human ?-Hexosaminidase B for GM2 Gangliosidosis

    Microsoft Academic Search

    Kazuhiko Matsuoka; Tomomi Tamura; Daisuke Tsuji; Yukie Dohzono; Keisuke Kitakaze; Kazuki Ohno; Seiji Saito; Hitoshi Sakuraba; Kohji Itoh

    2011-01-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of ?-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human ?-subunit containing partial amino acid sequence of the ?-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary

  1. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    PubMed

    Cachón-González, M Begońa; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of ?-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human ?-hexosaminidase ? (HEXA) and ? (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of ?-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  2. Concise syntheses of potent chaperone drug candidates, N-octyl-4-epi-?-valinenamine (NOEV) and its 6-deoxy derivative, from (+)-proto-quercitol.

    PubMed

    Kuno, Shinichi; Takahashi, Atsushi; Ogawa, Seiichiro

    2013-03-01

    Described are the efficient syntheses of ?-galactose-type unsaturated carbasugar amine, N-octyl-4-epi-?-valienamine (1a, NOEV) and 6-deoxy NOEV (12), starting from (+)-proto-quercitol (2), which is readily provided by the bioconversion of myo-inositol. NOEV is a potent chemical chaperone drug candidate for G(M1)-gangliosidosis. An intermediate alkadiene benzoate was prepared from 2 in five steps, with the key step being a Wittig reaction with an enol ester. The 6-deoxy derivative 12 was conveniently synthesized from the versatile intermediate dibromo compound 6, which was also an intermediate in the synthesis of NOEV. Enzyme inhibition assays demonstrated that 12 possessed stronger inhibitory activity than the parent 1a, suggesting that the C-6 position of the 4-epi-?-valienamine-type inhibitor could have hydrophobic interactions at the ?-galactosidase active site residues. PMID:23314299

  3. Burns in diabetic patients

    PubMed Central

    Maghsoudi, Hemmat; Aghamohammadzadeh, Naser; Khalili, Nasim

    2008-01-01

    CONTEXT AND AIMS: Diabetic burn patients comprise a significant population in burn centers. The purpose of this study was to determine the demographic characteristics of diabetic burn patients. MATERIALS AND METHODS: Prospective data were collected on 94 diabetic burn patients between March 20, 2000 and March 20, 2006. Of 3062 burns patients, 94 (3.1%) had diabetes; these patients were compared with 2968 nondiabetic patients with burns. Statistical analysis was performed using the statistical analysis software SPSS 10.05. Differences between the two groups were evaluated using Student's t-test and the chi square test. P < 0.05 was considered as significant. RESULTS: The major mechanism of injury for the diabetic patients was scalding and flame burns, as was also the case in the nondiabetic burn patients. The diabetic burn patients were significantly older, with a lower percentage of total burn surface area (TBSA) than the nondiabetic burn population. There was significant difference between the diabetic and nondiabetic patients in terms of frequency of infection. No difference in mortality rate between diabetic and nondiabetic burn patients was observed. The most common organism in diabetic and nondiabetic burn patients was methicillin-resistant staphylococcus. Increasing %TBSA burn and the presence of inhalation injury are significantly associated with increased mortality following burn injury. CONCLUSIONS: Diabetics have a higher propensity for infection. Education for diabetic patients must include caution about potential burn mishaps and the complications that may ensue from burns. PMID:19902035

  4. Patient Education on Pain

    MedlinePLUS Videos and Cool Tools

    ... People with Pain Press Room Position Statements Patient Education on Pain AAPM Past President, Perry G. Fine, ... Member Center Patient Center Research Advocacy Practice Management Education Annual Meeting Contact Us Privacy Policy Sitemap Close ...

  5. Repositioning the Patient:

    PubMed Central

    Mold, Alex

    2013-01-01

    Summary This article explores how and why the patient came to be repositioned as a political actor within British health care during the 1960s and 1970s. Focusing on the role played by patient organizations, it is suggested that the repositioning of the patient needs to be seen in the light of growing demands for greater patient autonomy and the application of consumerist principles to health. Examining the activities of two patient groups—the National Association for the Welfare of Children in Hospital (NAWCH) and the Patients Association (PA)—indicates that while such groups undoubtedly placed more emphasis on individual autonomy, collective concerns did not entirely fall away. The voices of patients, as well as the patient, continued to matter within British health care. PMID:23811711

  6. Patient's Bill of Rights

    MedlinePLUS

    ... for which they were written. Patient’s rights and health insurance: the Affordable Care Act In 2010, a new ... AHA. (See the “To learn more” section below.) Health insurance problems If you have concerns about your insurance, ...

  7. Patient Information in Radiooncology

    Microsoft Academic Search

    Christof Schäfer; Barbara Dietl; Kurt Putnik; Daniel Altmann; Jörg Marienhagen; Manfred Herbst

    2002-01-01

    Background: As a result of increased interest and public demand, providing patients with adequate information about radiooncology has become more and more difficult for the doctor. Insufficient patient information can not only cause anxiety for the patient, but can also lead to legal action against the physician. In order to gain a deepter insight into our clinical practice of providing

  8. Malnutrition in hemodialysis patients

    Microsoft Academic Search

    M. BOSSOLA; L. TAZZA; N. PANOCCHIA; A. CICCIARELLI; M. LIBERATORI; G. LUCIANI

    2001-01-01

    In patients on maintenance hemodialysis (HD) malnutrition is frequent, affects quality of life and is associated with an increased risk of death. Causes of malnutrition in HD patients are numerous and various. Prevention and treatment of malnutrition becomes very im- portant. Patients must be prescribed adequate protein and energy intakes. More aggressive measures include addition of dietary protein and energy

  9. JISC Patients Participate charities' perspectives Patients Participate!

    E-print Network

    Rzepa, Henry S.

    their research in lay terms when applying for funding and in end of project reports (AMRC) together in partnership for a 7-month feasibility study which aims for patients and those interested in biomedical and health research. A report

  10. The quantified patient: a patient participatory culture.

    PubMed

    Appelboom, Geoff; LoPresti, Melissa; Reginster, Jean-Yves; Sander Connolly, E; Dumont, Emmanuel P L

    2014-12-01

    The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals. PMID:25118077

  11. Rehabilitation in diabetic patients.

    PubMed

    Zdrenghea, D; Pop, Dana; Penciu, Oana; Zdrenghea, V; Zdrenghea, M

    2009-01-01

    Physical activity is very important for diabetic patients. In normal subjects physical activity postpones diabetes mellitus and in diabetic patients postpones the cardiovascular complications. In diabetic patients with cardiovascular disease, physical training increases exercise capacity, decreases complications and prolongs survival. Physical activity can be applied in diabetic patients as physical activity counseling or physical training, the second being recommended to be ambulatory and supervised but, sometimes, also home rehabilitation can be useful. Aerobic exercises, but also resistance exercises will be applied for a 30-60 min duration at least 3x/ week, recommended 5x/ week, and optimal every day. Some specific aspects of diabetic patients as hyper or hypoglycemia, autonomic or peripheral neuropathy, retinopathy, have to be considered during physical rehabilitation and sometimes physical training has to be modulated according to them. In conclusion, physical activity and training represent a real chance for every diabetic patient and has to be recommended and applied in all of them. PMID:21179912

  12. The critically ill immunosuppressed patient

    SciTech Connect

    Parrillo, J.E.; Masur, H. (National Inst. of Health, Bethesda, MD (US))

    1987-01-01

    This book discusses the papers on the diagnosis and management of immunosuppressed patient. Some of the topics are: life-threatening organ failure in immunosuppressed patients; diagnosis and therapy of respiratory disease in the immunosuppressed patient; CNS complication of immunosuppression; infections; antineoplastic therapy of immunosuppressed patient; radiation therapy-issues in critically ill patient; AIDS; and management of bone marrow transplant patients.

  13. [Single-patient rooms].

    PubMed

    Jensen, Elisabeth Brřgger

    2009-05-18

    The Danish government has allocated funding to achieve the goal of replacing 50% of all existing hospital buildings by new facilities. Facing such a building boom, the debate for and against single-patient rooms is in progress. A review of the literature shows that single-patient rooms have a direct impact on patient safety. Patient Safety Leadership Walkrounds and failure modes and effects analysis can be used for identifying risks before designing single rooms in future hospitals. The acuity adaptability model needs to be revised. PMID:19454198

  14. The dying thoracic patient.

    PubMed

    Krishna, G; Raffin, T A

    1998-08-01

    Health care providers should understand that the practice of good medicine includes not only diagnosing and curing diseases, but also effectively communicating with patients and families and helping terminally ill patients die a peaceful and dignified death. Patients in America come from varied backgrounds, and it is important for physicians to consider cultural and religious issues. Physicians should combine their clinical judgment with objective outcome data to provide optimal care for patients. Informed consent should be obtained from patients after offering a detailed plan of care that would include appropriate interventions and the consequences of no intervention. The physician should then assist the patient in making a decision that would provide the best possible future for that individual. The four fundamental principles of biomedical ethics, namely beneficence, nonmaleficence, autonomy, and justice, should be considered when analyzing an ethical problem. Voluntary active euthanasia, which means performing a deliberate act (e.g., administering a lethal injection) to end a patient's life, should not be performed by a physician. Withholding and withdrawing basic and advanced life support constitutes passive euthanasia. Good communication with patients early in the clinical course whenever possible results in an ethically correct decision. A nonconfrontational, sympathetic, and compassionate approach to family members and legal surrogates facing the immediate death of their loved ones leads to the best possible outcome. It is the duty of the physician to assure the patient and the family that he or she will not abandon the patient. Effective communication is the key to solving almost all ethical dilemmas when caring for the dying thoracic patient. PMID:9742345

  15. Acute motor axonal neuropathy and acute motor-sensory axonal neuropathy share a common immunological profile.

    PubMed

    Yuki, N; Kuwabara, S; Koga, M; Hirata, K

    1999-10-15

    Griffin and colleagues (Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath DR, Macko C, McKhann GM, Asbury AK. Pathology of motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 1996;39:17-28 [4]) proposed that acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are part of the spectrum of a single type of immune attack on the axon. In contrast, IgG anti-GM1 antibody is associated closely with AMAN, but whether other IgG anti-ganglioside antibodies are associated with this neuropathy is not clear. We investigated whether IgG anti-ganglioside antibodies can be used as immunological markers to differentiate AMAN from acute inflammatory demyelinating polyneuropathy (AIDP) and whether these autoantibodies are present in AMSAN. The frequencies of anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies in 21 AMAN patients were significantly higher than in 19 AIDP patients. Anti-GM1b and anti-GD1a IgG, as well as anti-GM1 IgG antibodies, therefore are immunological markers for AMAN. The patients with AMSAN had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies, indicative that AMAN and AMSAN share a common immunological profile. PMID:10526194

  16. An analytical model based on G\\/M\\/1 with self-similar input to provide end-to-end QoS in 3G networks

    Microsoft Academic Search

    Mohsin Iftikhar; Björn Landfeldt; Mine Çaglar

    2006-01-01

    The dramatic increase in demand for wireless Internet access has lead to the introduction of new wireless architectures and systems including 3G, Wi-Fi and WiMAX. 3G systems such as UMTS and CDMA2000 are leaning towards an all-IP architecture for transporting IP multimedia services, mainly due to its scalability and promising capability of inter-working heterogeneous wireless access networks. During the last

  17. Savannah River Site's macro encapsulation processing of Less Than 3700 BQ\\/GM1 tru isotopic mixed waste for disposal at the Nevada Test Site

    Microsoft Academic Search

    G. W. Siry; L. T. Reid

    2007-01-01

    During the Fiscal Year of 2006 (FY2006) the Savannah River Site (SRS) made a commitment with the South Carolina Department of Health and Environmental Control (SC-DHEC) to remove 1000 cubic meters of Transuranic (TRU) waste from its TRU inventory. As SRS has been generating TRU waste for many years, there was a multi-thousand drum inventory of waste designated as TRU

  18. Communicating with patients.

    PubMed

    Kaplowitz, G J

    1999-01-01

    Dental care providers need to be able to communicate effectively with their patients in order to build rapport and trust. Highly developed communication skills also enable the dental care provider to extract more accurate diagnostic information and to more effectively present treatment options to the patient. Neurolinguistic programming techniques can be employed to accomplish these as well as other objectives. PMID:10687469

  19. Electronic Privacy: Patient Concerns

    Microsoft Academic Search

    Anza A. Akram

    2006-01-01

    This study postulates issues related to electronic privacy and addresses the factors that directly effect personal electronic information. There is no positivist study done to measure patient privacy concerns using Smith et a l(1996) privacy model and the effect of previous experience and media on these concerns. This study measures the four dimensions of patient concerns against the electronic privacy,

  20. A Patient Assessment Guide

    ERIC Educational Resources Information Center

    Fuller, Dorothy; Rosenaur, Janet Allan

    1974-01-01

    Use of a nursing assessment/patient history tool developed by project faculty at the school of nursing, University of California, San Francisco and used in a primary care clinic assisted nursing students in collecting patient information, making home visits, functioning as team members, recording data, and in defining their nursing role. (EA)

  1. NORD's Patient Assistance Programs

    MedlinePLUS

    ... Ulcerative colitis or ILEAL pouch Company: Sigma-tau Pharmaceuticals, Inc. Contact: 1-877-279-2459 Email: vsl3ds@rarediseases.org Fax: 1-203-349-8172 Alone we are rare. Together we are strong. ® For Patients and Families For Industry For Clinicians and Researchers For Patient Organizations Advocate ...

  2. When Our Patients Retire

    PubMed Central

    Rosser, W. W.

    1977-01-01

    With increases in the efforts of preventive medicine and lowering of mandatory retirement ages, many of our patients are experiencing the stresses involved in handling the loss of their lifetime's employment. Patients may be helped to relieve these stresses by appropriate advice about physical and mental activity, diet, use of medications, and use of health care facilities before and after retirement. PMID:21304780

  3. Infections in transplant patients.

    PubMed

    Pagalilauan, Genevieve L; Limaye, Ajit P

    2013-07-01

    Recipients of solid organ transplants (SOT) need primary care providers (PCPs) who are familiar with their unique needs and understand the lifelong infectious risks faced by SOT patients because of their need for lifelong immunosuppressive medications. SOT recipients can present with atypical and muted manifestations of infections, for which the knowledgable PCP will initiate a comprehensive evaluation. The goal of this article is to familiarize PCPs with the infectious challenges facing SOT patients. General concepts are reviewed, and a series of patient cases described that illustrate the specific learning points based on common presenting clinical symptoms. PMID:23809715

  4. Respecting patient confidentiality.

    PubMed

    Price, Bob

    2015-01-28

    Nurses face a particular challenge in respecting the confidentiality of patients in a world where information is quickly shared and where information about illness can be sensitive. We have a duty of care towards patients. That duty includes maintaining privacy (protecting them from undue intrusion), and confidentiality (by the discreet management of information about themselves that they share with us). Legislation on confidentiality comes from different sources and should be interpreted in the clinical setting. This article summarises the principal requirements set out in the legislation and directs readers to questions and tools designed to help them explore the extent to which patient confidentiality is respected where they work. PMID:25627535

  5. JAMA Patient Page: Gout

    MedlinePLUS

    ... of the American Medical Association JAMA PATIENT PAGE Gout G out is an excruciatingly painful inflammatory disease ... produce inflammation in the joints and surrounding tissues. Gout has been linked to major medical conditions such ...

  6. JAMA Patient Page: Malaria

    MedlinePLUS

    ... of the American Medical Association JAMA PATIENT PAGE Malaria M alaria is a potentially deadly disease caused ... the parasite. According to the World Health Organization, malaria is present in more than 100 countries—mostly ...

  7. Strongyloidiasis in Transplant Patients

    PubMed Central

    Roxby, Alison C.; Gottlieb, Geoffrey S.; Limaye1, Ajit P.

    2010-01-01

    Strongyloides stercoralis is an intestinal nematode that can persist in the human host for decades after the initial infection and can progress to fulminant hyperinfection syndrome in immunocompromised hosts. We describe a patient who died of Strongyloides hyperinfection syndrome 2 months after orthotopic heart transplantation and discuss approaches to prevention, diagnosis, and treatment. Current practice guidelines recommend screening for and treatment of Strongyloides infection before transplantation, but physicians in the United States often miss opportunities to identify patients with chronic strongyloidiasis. Screening tests have limitations, and clinical suspicion remains an important component of the evaluation before transplantation. After immunocompromised patients develop hyperinfection syndrome, diagnosis is often delayed and mortality is high, so emphasis must be placed on screening and treatment before transplantation. We review current strategies for prevention, diagnosis, and treatment of chronic intestinal strongyloidiasis in patients who will undergo transplantation and discuss the clinical features and management of Strongyloides hyperinfection syndrome in transplant recipients. PMID:19807271

  8. Why make people patients?

    PubMed Central

    Marinker, Marshall

    1975-01-01

    People confront their doctors with three modes of unhealth - disease, illness and sickness. Each is discussed, and the question is asked and answered as to why in this situation people wish to become patients. PMID:1177270

  9. National Patient Safety Foundation

    MedlinePLUS

    ... Membership ASPPS Welcome ASPPS Members ASPPS e-News Archive ASPPS Member News BMJ for ASPPS Members Current Awareness Alert Joint Commission Journal Focus Archive Stand Up for Patient Safety Welcome Stand Up ...

  10. [Structural basis for ?-galactosidase associated with lysosomal disease].

    PubMed

    Shimizu, Toshiyuki

    2013-01-01

    G(M1)-gangliosidosis and Morquio B are rare lysosomal storage diseases associated with a neurodegenerative disorder or dwarfism and skeletal abnormalities, respectively. These diseases are caused by deficiencies in the lysosomal enzyme human ?-D-galactosidase (h-?-GAL), which lead to accumulations of the h-?-GAL substrates, G(M1) ganglioside and keratan sulfate due to mutations in the h-?-GAL gene. H-?-GAL is an exoglycosidase that catalyzes the hydrolysis of terminal ?-linked galactose residues. Here, we present the crystal structures of h-?-GAL in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. H-?-GAL showed a novel homodimer structure; each monomer was comprised of a catalytic TIM barrel domain followed by ?-domain 1 and ?-domain 2. The long loop region connecting the TIM barrel domain with ?-domain 1 was responsible for the dimerization. To gain structural insight into the molecular defects of h-?-GAL in the above diseases, the disease-causing mutations were mapped onto the three-dimensional structure. Finally, the possible causes of the diseases are discussed. PMID:23649392

  11. The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany.

    PubMed

    Broeckx, Bart J G; Coopman, Frank; Verhoeven, Geert E C; Van Haeringen, Wim; van de Goor, Leanne; Bosmans, Tim; Gielen, Ingrid; Saunders, Jimmy H; Soetaert, Sandra S A; Van Bree, Henri; Van Neste, Christophe; Van Nieuwerburgh, Filip; Van Ryssen, Bernadette; Verelst, Elien; Van Steendam, Katleen; Deforce, Dieter

    2013-01-01

    The objective of this study was to screen a dog population from Belgium, the Netherlands and Germany for the presence of mutant alleles associated with hip dysplasia (HD), degenerative myelopathy (DM), exercise-induced collapse (EIC), neuronal ceroid lipofuscinosis 4A (NCL), centronuclear myopathy (HMLR), mucopolysaccharidosis VII (MPS VII), myotonia congenita (MG), gangliosidosis (GM1) and muscular dystrophy (Duchenne type) (GRMD). Blood samples (K3EDTA) were collected for genotyping with Kompetitive Allele Specific PCR (n = 476). Allele and genotype frequencies were calculated in those breeds with at least 12 samples (n = 8). Hardy-Weinberg equilibrium was tested. Genetic variation was identified for 4 out of 9 disorders: mutant alleles were found in 49, 15, 3 and 2 breeds for HD, DM, EIC and NCL respectively. Additionally, mutant alleles were identified in crossbreeds for both HD and EIC. For HD, DM, EIC and NCL mutant alleles were newly discovered in 43, 13, 2 and 1 breed(s), respectively. In 9, 2 and 1 breed(s) for DM, EIC and NCL respectively, the mutant allele was detected, but the respective disorder has not been reported in those breeds. For 5 disorders (HMLR, MPS VII, MG, GM1, GRMD), the mutant allele could not be identified in our population. For the other 4 disorders (HD, DM, EIC, NCL), prevalence of associated mutant alleles seems strongly breed dependent. Surprisingly, mutant alleles were found in many breeds where the disorder has not been reported to date. PMID:24069350

  12. The Prevalence of Nine Genetic Disorders in a Dog Population from Belgium, the Netherlands and Germany

    PubMed Central

    Broeckx, Bart J. G.; Coopman, Frank; Verhoeven, Geert E. C.; Van Haeringen, Wim; van de Goor, Leanne; Bosmans, Tim; Gielen, Ingrid; Saunders, Jimmy H.; Soetaert, Sandra S. A.; Van Bree, Henri; Van Neste, Christophe; Van Nieuwerburgh, Filip; Van Ryssen, Bernadette; Verelst, Elien; Van Steendam, Katleen; Deforce, Dieter

    2013-01-01

    The objective of this study was to screen a dog population from Belgium, the Netherlands and Germany for the presence of mutant alleles associated with hip dysplasia (HD), degenerative myelopathy (DM), exercise-induced collapse (EIC), neuronal ceroid lipofuscinosis 4A (NCL), centronuclear myopathy (HMLR), mucopolysaccharidosis VII (MPS VII), myotonia congenita (MG), gangliosidosis (GM1) and muscular dystrophy (Duchenne type) (GRMD). Blood samples (K3EDTA) were collected for genotyping with Kompetitive Allele Specific PCR (n?=?476). Allele and genotype frequencies were calculated in those breeds with at least 12 samples (n?=?8). Hardy-Weinberg equilibrium was tested. Genetic variation was identified for 4 out of 9 disorders: mutant alleles were found in 49, 15, 3 and 2 breeds for HD, DM, EIC and NCL respectively. Additionally, mutant alleles were identified in crossbreeds for both HD and EIC. For HD, DM, EIC and NCL mutant alleles were newly discovered in 43, 13, 2 and 1 breed(s), respectively. In 9, 2 and 1 breed(s) for DM, EIC and NCL respectively, the mutant allele was detected, but the respective disorder has not been reported in those breeds. For 5 disorders (HMLR, MPS VII, MG, GM1, GRMD), the mutant allele could not be identified in our population. For the other 4 disorders (HD, DM, EIC, NCL), prevalence of associated mutant alleles seems strongly breed dependent. Surprisingly, mutant alleles were found in many breeds where the disorder has not been reported to date. PMID:24069350

  13. Sex Education for Patients

    PubMed Central

    Zitner, David

    1985-01-01

    Sex education evokes a wide variety of responses in the community and from teachers. Consequently, physicians have a responsibility to present sex education material in a factual, objective way. Many people are misinformed about sexual behavior. Physicians can help patients and the community by being aware of appropriate sex education for each age group. A curriculum for sex education, and opportunities to provide sex information for patients of different ages and stages in the lifecycle, are described. PMID:21274069

  14. Patient care in radiography

    SciTech Connect

    Ehrlich, R.A.; McCloskey, E.D.

    1989-01-01

    This book focuses on patient care procedures for radiographers. The authors focus on the role of the radiographer as a member of the health care team. The authors report on such topics as communication in patient care: safety, medico-legal considerations, transfer and positioning; physical needs; infection control; medication; CPR standards, acute situations; examination of the GI tract; contrast media; special imaging techniques and bedside radiography.

  15. The somatizing patient

    Microsoft Academic Search

    Vicenzio Holder-Perkins; Thomas Wise; Darvin E. Williams

    2000-01-01

    The authors discuss the significance of identifying primary care patients with dramatic and persistent unexplained physical\\u000a (medical) symptoms, especially given the concerns about containing health care costs. Such patients are a cause of frustration\\u000a to the clinician, because the clinician may experience a sense of failure after using the state of the art and still being\\u000a eluded by a diagnosis.

  16. Cumulative Patient Profile

    PubMed Central

    Lewis, John

    1989-01-01

    Traditional record-keeping in family practice, based on the model of hospital charts, gives rise to some serious problems, illustrated in this article by a patient with an allergy to penicillin. The “cumulative patient profile,” which separates pertinent information in the history from the continually updated information on short-term problems, can prevent repetitive history-taking and can make information easily accessible to busy physicians.

  17. The intersexed patient.

    PubMed

    STOLLER, R J; ROSEN, A C

    1959-11-01

    There are at present two opposing points of view on problems of dealing with the intersexed patient (not the typical homosexual or transvestite) who has clearcut anatomical or biochemical qualities of the opposite sex. The first is that in the growing child or adult coming for treatment, the sex the patient should adopt is the summation of somatic sex. The other is that the sex role should be assigned according to the predominant psychological identification already present.A case history of a middle-aged pseudohermaphrodite, castrated in youth but raised from birth as a female and living thus in "homosexual" relations with women until examined and interviewed at UCLA Medical Center is presented to illustrate the psychological problems in sexual identity with which the patient had to cope. Psychiatric investigation revealed how confused the patient's sex identity was until treatment by a team consisting of psychiatrist, psychologist and endocrinologist permitted the patient, even at so late a date, finally to establish what his gender is. The patient was able, despite early rearing as a female and a castrating operation, to swing to a more masculine identification. This was possible because of some uncertainty of sexual role from an early age. PMID:13834894

  18. THE INTERSEXED PATIENT

    PubMed Central

    Stoller, Robert J.; Rosen, Alexander C.

    1959-01-01

    There are at present two opposing points of view on problems of dealing with the intersexed patient (not the typical homosexual or transvestite) who has clearcut anatomical or biochemical qualities of the opposite sex. The first is that in the growing child or adult coming for treatment, the sex the patient should adopt is the summation of somatic sex. The other is that the sex role should be assigned according to the predominant psychological identification already present. A case history of a middle-aged pseudohermaphrodite, castrated in youth but raised from birth as a female and living thus in “homosexual” relations with women until examined and interviewed at UCLA Medical Center is presented to illustrate the psychological problems in sexual identity with which the patient had to cope. Psychiatric investigation revealed how confused the patient's sex identity was until treatment by a team consisting of psychiatrist, psychologist and endocrinologist permitted the patient, even at so late a date, finally to establish what his gender is. The patient was able, despite early rearing as a female and a castrating operation, to swing to a more masculine identification. This was possible because of some uncertainty of sexual role from an early age. PMID:13834894

  19. Patient loyalty model.

    PubMed

    Sumaedi, Sik; Bakti, I Gede Mahatma Yuda; Rakhmawati, Tri; Astrini, Nidya Judhi; Yarmen, Medi; Widianti, Tri

    2015-07-01

    Purpose - This study aims to investigate the simultaneous effect of subjective norm, perceived behavioral control and trust on patient loyalty. Design/methodology/approach - The empirical data were collected through survey. The respondents of the survey are 157 patients of a health-care service institution in Bogor, Indonesia. Multiple regressions analysis was performed to test the conceptual model and the proposed hypotheses. Findings - The findings showed that subjective norm and trust influence patient loyalty positively. However, this research also found that perceived behavioral control does not influence patient loyalty significantly. Research limitations/implications - The survey was only conducted at one health-care service institution in Bogor, Indonesia. In addition, convenience sampling method was used. These conditions may cause that the research results can not be generalized to the other contexts. Therefore, replication research is needed to test the stability of the findings in the other contexts. Practical implications - Health-care service institutions need to pay attention to trust and subjective norm to establish patient loyalty. Originality/value - This study is believed to be the first to develop and test patient loyalty model that includes subjective norm, perceived behavioral control and trust. PMID:26083638

  20. Patient involvement in patient safety: Protocol for developing an intervention using patient reports of organisational safety and patient incident reporting

    Microsoft Academic Search

    Jane K Ward; Rosemary RC McEachan; Rebecca Lawton; Gerry Armitage; Ian Watt; John Wright

    2011-01-01

    Background  Patients have the potential to provide a rich source of information on both organisational aspects of safety and patient safety\\u000a incidents. This project aims to develop two patient safety interventions to promote organisational learning about safety -\\u000a a patient measure of organisational safety (PMOS), and a patient incident reporting tool (PIRT) - to help the NHS prevent\\u000a patient safety incidents

  1. The patient behind the image

    Microsoft Academic Search

    Barry L. Zaret

    2001-01-01

    Nuclear cardiologists, by the very nature of their practice, are often several steps removed from the patient, the patient’s family, and often the patient’s physician. As laboratory specialists, we obtain a set of high-quality images; from these images, we infer relevant diagnostic and prognostic information; from this information, on the basis of prior correlative studies involving large patient populations, inferences

  2. Patience and Patients: Understanding the

    E-print Network

    Chou, James

    Patience and Patients: Understanding the spectrum of Alzheimer's disease #12; Patience and Patients: Understanding the spectrum Alzheimer's disease, including a new National Institute on Aging Program Project grant

  3. The patient's view.

    PubMed

    Rachagan, S S; Sharon, K

    2003-03-01

    The medical practitioner has always had to juggle several roles. First and foremost, the doctor is a healer, a provider of curative services. Second, he is an examiner, an assessor of the patient's health status. Third, he is a researcher, always trying to push the boundaries of medical knowledge. Fourth, he is a rationer of services, he decides how best to apportion the limited resources at his disposal. Traditionally, the patient-doctor relationship has been largely exclusive in nature and the doctor would quite comfortably slip in and out of these roles, his focus centred on his patient's interests. In this era of large corporate health care providers, multi-billion-biotechnology industry, mammoth pharmaceutical companies, medical insurance schemes and international trade instruments, it has become increasingly difficult for the doctor to juggle these four roles. He is constantly subjected to conflicting demands. Patients' interests do not always come first anymore and patients are beginning to realise this. They no longer trust the medical profession unreservedly. There has been steady erosion of the patient-doctor relationship most clearly evidenced by the rising tide of litigation against doctors. There needs to be a reappraisal of these roles that the doctor plays. The conflicts must be recognised and addressed. Patients need to be informed and their interests must be protected if the doctor-patient relationship is to be restored. Medical malpractice suits are on the increase. The tort system as it exists is failing both doctors and patients. The question we must ask is what are patients looking for when they sue doctors? Most of the time they need compensation for the injuries suffered. Sometimes they are looking for accountability, they want the doctor to be punished in some way. Sometimes they merely want to air their grievances and know that they are heard. The current system more often than not takes too long to compensate, the process is a gamble and doctors who are clearly negligent quietly settle and are rarely censured. We need to revamp the existing system to allow for speedy and equitable compensation; true accountability; and articulation and auditing of standards of practice. PMID:14556356

  4. PATIENT NAME: PATIENT DATE OF BIRTH: PATIENT MEDICAL RECORD # (IF ADDRESSOGRAPH STAMP IS NOT USED)

    E-print Network

    Mootha, Vamsi K.

    PATIENT NAME: PATIENT DATE OF BIRTH: PATIENT MEDICAL RECORD # (IF ADDRESSOGRAPH STAMP IS NOT USED(s): Please List Confidential Details of: Psychotherapy (from a Psychiatrist, Psychologist, or Mental Health

  5. Transplantation in obese patient.

    PubMed

    Killackey, Mary T

    2012-01-01

    Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes. PMID:22678862

  6. Patient Safety Network

    NSDL National Science Digital Library

    The Agency for Healthcare Research and Quality (AHRQ) Patient Safety Network (PSNet) website contains recent news and resources to provide those studying to be in the medical profession and for those currently in the medical field. Resources include an extensive glossary as well as a vast supply of articles from various periodicals. The site also contains numerous �Did You Know?� articles that include visual aids and citations. Articles can be sorted or browsed by target audience, resource type, clinical area, error type, safety target, approach to improving safety, and setting of care. Users have the ability to sign up for the weekly AHRQ Patient Safety Network and monthly AHRQ Web Morbidity and Mortality (WEBM&M) newsletters. Users may also sign up for a free account on the AHRQ Patient Safety Network website to receive e-mail alerts that match the users' interests.

  7. JAMA Patient Page

    NSDL National Science Digital Library

    The Journal of the American Medical Association (JAMA) has been committed to providing the general public with a number of high-quality print and online resources in recent years, and their collection of Patient Pages is quite thorough and most welcome. With over 390 entries, each Patient Page contains a basic overview of such topics as Lyme disease, dementia, lymphoma, and dozens of other conditions, medical procedures, and practices. Along with succinct and accessible summaries for each entry, visitors will also find illustrations, graphs, and diagrams that help explain each topic. All in all, this site is a tremendous resource, and it is worth noting that many of these Patient Pages are also available in Spanish.

  8. Perinatal Patient Safety Project

    PubMed Central

    Nunes, Julie; McFerran, Sharon

    2005-01-01

    The Perinatal Patient Safety Project (PPSP) was created as a systemic strategy for creating high-reliability perinatal units by preventing identified causes of perinatal events in the clinical setting. With developmental funding from a Garfield grant, implementation of the PPSP has been completed at four pilot sites in the Kaiser Permanente Northern California (KPNC) Region. Its success has resulted in implementation at all perinatal units in the KPNC Region as well as being promoted by National Risk Management for nationwide implementation. PPSP emphasizes structured communication, multidisciplinary rounds, a definition of fetal well-being, and practicing for emergencies. Steps taken to create high reliability perinatal care include improved communication, patient safety focus, and satisfaction among perinatal patients, providers, and staff. PMID:21660157

  9. Galen and his patients.

    PubMed

    Horstmanshoff, H F

    1995-01-01

    A prosopography of Galen's patients can contribute to our knowledge of the social and cultural history of Rome in the second century AD. In his voluminous works Galen now and then mentions the patients he actually treated, observed, or whom he saw treated by others. Sometimes he mentions their names, so that we can recognize them from other sources, in the corpus Galenicum or elsewhere. Even if they remain anonymous, or if their data are only partially known, often other relevant information is given e.g. concerning their age, sex, social status etc. This inventory permits some answers to questions concerning Galen's daily routine, his patients, his therapy and his bedside manners. PMID:7705055

  10. Patient Participation: Current Knowledge and Applicability to Patient Safety

    PubMed Central

    Longtin, Yves; Sax, Hugo; Leape, Lucian L.; Sheridan, Susan E.; Donaldson, Liam; Pittet, Didier

    2010-01-01

    Patient participation is increasingly recognized as a key component in the redesign of health care processes and is advocated as a means to improve patient safety. The concept has been successfully applied to various areas of patient care, such as decision making and the management of chronic diseases. We review the origins of patient participation, discuss the published evidence on its efficacy, and summarize the factors influencing its implementation. Patient-related factors, such as acceptance of the new patient role, lack of medical knowledge, lack of confidence, comorbidity, and various sociodemographic parameters, all affect willingness to participate in the health care process. Among health care workers, the acceptance and promotion of patient participation are influenced by other issues, including the desire to maintain control, lack of time, personal beliefs, type of illness, and training in patient-caregiver relationships. Social status, specialty, ethnic origin, and the stakes involved also influence patient and health care worker acceptance. The London Declaration, endorsed by the World Health Organization World Alliance for Patient Safety, calls for a greater role for patients to improve the safety of health care worldwide. Patient participation in hand hygiene promotion among staff to prevent health care—associated infection is discussed as an illustrative example. A conceptual model including key factors that influence participation and invite patients to contribute to error prevention is proposed. Further research is essential to establish key determinants for the success of patient participation in reducing medical errors and in improving patient safety. PMID:20042562

  11. Hospital Patients Are Adult Learners.

    ERIC Educational Resources Information Center

    Caffarella, Rosemary S.

    Patient education is recognized by health care providers and patients themselves as an important component of adequate health care for hospital patients. Through this informational process, patients receive information about specific health problems, learn the necessary competencies to deal with them, and develop accepting attitudes toward the…

  12. A patient carrying HIV.

    PubMed

    Adeela, Bashir

    2009-01-01

    A 52-year-old Caucasian man presented to hospital with confusion and was treated for a urinary tract infection. He developed new and unexpected signs and symptoms during his stay in hospital. On further questioning, the story of his social background unfolded and, following further investigation, he was diagnosed with human immunodeficiency virus (HIV). This case reminds all clinicians to think about HIV in the older patient and it also gives direction for investigation and management of similar cases in the future. Identifying HIV early is imperative because it allows effective treatment to be initiated and this will impact upon the patient's quality and longevity of life. PMID:21686917

  13. Patient Education Strategies in Dermatology

    PubMed Central

    Holder, Jessica L.

    2009-01-01

    Patient education is an important aspect of patient care in dermatology. Successful education increases patient satisfaction and results in improved outcomes and adherence. This article discusses the role of patient education in dermatology. Specifically, Part I of the review examines evidence demonstrating the benefits of patient education and recognizes the challenges that limit effective patient education. These challenges can be summarized as barriers to understanding, poor patient recall, conflicting information, and barriers to physician delivery. Further descriptions and an assessment of these limitations along with methods to combat them are included in the review. PMID:20725581

  14. Choroidal melanomas in Hispanic patients.

    PubMed

    Hudson, H L; Valluri, S; Rao, N A

    1994-07-15

    The initial clinical manifestation and subsequent pathologic characteristics of choroidal melanomas were reviewed in 20 enucleated eyes of Hispanic patients identified between 1974 and 1992. We compared them to 125 choroidal melanomas of randomly selected white patients identified over the same time period. At the time of diagnosis and at subsequent enucleation, the Hispanic patients were younger (P = .002) than the white patients. Eye pain (P = .016), red eye (P = .0002), and tearing (P = .012) were reported more commonly by the Hispanic patients, and on clinical examination the intraocular pressure was higher (P = .001) and more rubeosis iridis was noted (P < .0001) in the Hispanic patients than in the white patients. The tumors of the Hispanic patients were larger in their greatest base dimension (P = .003), and were heavily pigmented compared with those of the white patients (P = .0001). A trend toward less inflammation within the tumor and toward more epithelioid cell type was noted in the Hispanic patients. PMID:8023876

  15. Chronic Illness and Patient Satisfaction

    PubMed Central

    Carlin, Caroline S; Christianson, Jon B; Keenan, Patricia; Finch, Michael

    2012-01-01

    Objective To examine how the relationship between patient characteristics, patient experience with the health care system, and overall satisfaction with care varies with illness complexity. Data Sources/Study Setting Telephone survey in 14 U.S. geographical areas. Study Design Structural equation modeling was used to examine how relationships among patient characteristics, three constructs representing patient experience with the health care system, and overall satisfaction with care vary across patients by number of chronic illnesses. Data Collection/Extraction Methods Random digital dial telephone survey of adults with one or more chronic illnesses. Principal Findings Patients with more chronic illnesses report higher overall satisfaction. The total effects of better patient–provider interaction and support for patient self-management are associated with higher satisfaction for all levels of chronic illness. The latter effect increases with illness burden. Older, female, or insured patients are more satisfied; highly educated patients are less satisfied. Conclusions Providers seeking to improve their patient satisfaction scores could do so by considering patient characteristics when accepting new patients or deciding who to refer to other providers for treatment. However, our findings suggest constructive actions that providers can take to improve their patient satisfaction scores without selection on patient characteristics. PMID:22515159

  16. The Adolescent Patient.

    ERIC Educational Resources Information Center

    Daniel, William A., Jr.

    Written to orient the physician and paramedical personnel to the adolescent patient, the book provides information concerning the changes of adolescence, and age-related problems and illnesses. Part 1 discusses the essence of adolescence by describing physical, mental, and emotional growth and development. Part 2, the major section, consists of 21…

  17. Patient & Family Support Programs

    E-print Network

    Myers, Lawrence C.

    's cancer diagnosis, treatment, and beyond. To make browsing this brochure easier, we have included an index with Pancreatic Cancer Action Network Support Services Room, Level 3, NCCC PSA at NCCC: Prostate Support Alliance, or the encouragement of peers in a facilitated group, Support Services helps cancer patients and their loved ones

  18. Nutrition in cancer patients

    Microsoft Academic Search

    Sebastiano Mercadante

    1996-01-01

    Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments capable of determining malabsorption. Cachexia is a complex disease characterized not only by a poor intake of nutrients or starvation, but also by metabolic derangement. Nausea and vomiting may limit the nutrient intake and are most often the consequences of

  19. A Patient's Best Friend.

    ERIC Educational Resources Information Center

    Haggard, Ann

    1985-01-01

    The author describes the development of a pet therapy program at a rehabilitation unit of a hospital. She discusses documentation of the success of pet therapy programs, picking out the right pets, responsibilities of caring for the pet, training the pet, patient response, and program policies. (CT)

  20. Gestational A PATIENT'S

    E-print Network

    Rau, Don C.

    and Human Services National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development #12;Dear Patient, The feelings that surround pregnancy--excitement, anxiety, and hope--often give way to many questions. Will my child's eyes be blue or brown? When will I have my baby? How big

  1. Prognosis of SMON patients.

    PubMed

    Sobue, I; Aoki, K; Ohtani, M

    1975-01-01

    The following points have become clear on prognosis of SMON through the analysis of 981 cases collected. 1) The prognosis of the old whose ages were 60 year old or over is not favorable, when compared with that of the young. However, there is no prognostic difference between male and female. 2) The cummulative death rate of SMON which was calculated by the life table method is approx twice as much as the generally expected value. 3) Approximately 80% of the patients showed some sort of improvement 7 to 12 months after the onset of the disease. The rate for 13 months or over if nearly the same. 4) The abdominal symptoms found at the time of the onset of the disease decreased markedly in the course of the disease. 5) Among neurological symptoms, the prognosis of motor disorders is more favorable. The complete recovery of sensory disturbances was extremely rare, but approx 60% showed more or less favorable in the course of the illness. Approximately 40% of the cases with visual disturbances completely recovered or showed favorable improvement, whereas 9% of them became worse. As for the prognosis of visual impairment, it is more serious than other symptoms. 6) The patients who had been administered clioquinol over long period displayed a higher rate of severe or moderate motor, sensory and visual disturbances, compared with the group with short-term administration of clioquinol. The death rate was also higher in the former group. 7) The rate of relapse as a whole was 16.7% and 68% of them was seen within 18 months after the onset. There is no difference in relapse according to sex. There was seen a high rate of relapse in the group of longterm administration of clioquinol. 8) A 10.5% of total cases were either unable to walk or in need of assistance in walking, whereas the rate of patients who cannot get dressed or who cannot defecate unassisted was lower. 9) Approximately 65% returned to the job in 12 months or more after the onset. The employment rate was not different according to sex, whereas it was lower along with the age advances. 10) Approximately 20% were not received medical treatment. The rate of non-treated patients is higher in the younger patients. The rate of hospitalized patients was higher in the older patients. PMID:136538

  2. Hope in Iranian cancer patients

    PubMed Central

    Abdullah-zadeh, Farahnaz; Agahosseini, Shima; Asvadi-Kermani, Iraj; Rahmani, Azad

    2011-01-01

    BACKGROUND: Hope is an important factor in the recovery of cancer patients. Few Iranian studies investigated the level of hope in cancer patients. Therefore, the present study aimed to investigate the level of hope in Iranian cancer patients and the related factors. METHODS: In a descriptive correlational study, 150 cancer patients were selected by a consecutive sampling method. Hope in patients was measured by the Herth Hope Index. Data analysis was performed using descriptive and inferential statistics. RESULTS: Results indicated that 61.1% of the patients had high levels of hope, 35.4% had moderate levels of hope, and 3.5% had low levels of hope. Hope has a statistically significant relationship with family support, but it is not statistically associated with other patient characteristics. CONCLUSIONS: Many cancer patients had a high level of hope. However, further studies are recommended to investigate the relation between hope and patient characteristics. PMID:23450037

  3. Gastric Cancer in Young Patients

    PubMed Central

    Dhobi, Manzoor A.; Wani, Khursheed Alam; Parray, Fazl Qadir; Wani, Rouf A.; Peer, G. Q.; Abdullah, Safiya; Wani, Imtiyaz A.; Wani, Muneer A.; Shah, Mubashir A.; Thakur, Natasha

    2013-01-01

    Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1?:?1.08 in young patients and 2.5?:?1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance. PMID:24381753

  4. Atypical Miller Fisher syndrome with GQ1b antibodies

    Microsoft Academic Search

    Mark A Paine; Geoff Keir; Gordon T Plant

    1996-01-01

    An atypical case of Miller Fisher syndrome is described in a patient with ophthalmoplegia and mild ataxia but no areflexia. High titres of acute phase antibodies to gangliosides asialo-GM1 and GQ1b were detected. Asialo-GM1 antibodies have not been previously reported in association with Miller Fisher syndrome. Considerable clinical recovery occurred in association with reduction in the ganglioside antibody titres. Ganglioside

  5. Metabolism of G M1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders

    Microsoft Academic Search

    B. Schmid; B. C. Paton; K. Sandhoff; K. Harzer

    1992-01-01

    Cultured skin fibroblasts from controls and patients with lysosomal storage diseases were loaded with GM1 ganglioside that had been labelled with tritium in its ceramide moiety. After a 65-h or 240-h incubation, a large percentage of this ganglioside remained undegraded in GM1 gangliosidoses, whereas in the other storage diseases studied, one of its metabolites accumulated by 2–4 fold relative to

  6. Patient Request for Email Communications Patient Name: _____________________________ Date of Birth: _____________________________

    E-print Network

    Qian, Ning

    Patient Request for Email Communications Patient Name: _____________________________ Date of Birth: _____________________________ Phone Number: ___________________________ Email Address:_____________________________ Communications over the Internet and / or using the email system may not be encrypted and may not be secure

  7. Apoptotic Cell Death in Mouse Models of GM2 Gangliosidosis and Observations on Human Tay-Sachs and Sandhoff Diseases

    Microsoft Academic Search

    Jing-Qi Huang; Jacquetta M. Trasler; Suleiman Igdoura; Jean Michaud; Nobuo Hanai; Roy A. Gravel

    1997-01-01

    Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by ?-hexos- aminidase A (Hex A) due to mutations of the ? subunit (Tay-Sachs disease) or ? subunit (Sandhoff disease) of Hex A. Hex B (?? homodimer) is also defective in Sand- hoff disease. We previously developed mouse models of both diseases and

  8. Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect

    Microsoft Academic Search

    Massimo Santoro; Anna Modoni; Mario Sabatelli; Francesca Madia; Fiorella Piemonte; Giulia Tozzi; Enzo Ricci; Pietro A. Tonali; Gabriella Silvestri

    2007-01-01

    We identified a novel c.1556A>G transition in exon 12 of the HEXB gene associated with chronic Sandhoff’s disease, changing a conserved aspartic acid to glycine at position 494 of the Hex ?-subunit; moreover, RT-PCR showed aberrant exon 12 skipping, causing a frame-shift and premature stop codon, consequent to the disruption of an exonic splicing enhancer motif by the mutation. These

  9. White Matter Changes Associated with Feline GM2 Gangliosidosis (Sandhoff Disease): Correlation of MR Findings with Pathologic and Ultrastructural Abnormalities

    Microsoft Academic Search

    Robert A. Kroll; Michael A. Pagel; Simon Roman-Goldstein; A. James Barkovich; Anthony N. D'Agostino; Edward A. Neuwelt

    1995-01-01

    PURPOSE: To establish changes on MR of the brain in a feline model of Sandhoff disease in order to develop standards by which this model may be used in future noninvasive studies. METHODS: Five affected felines and six age-matched, littermate controls were evaluated. T1- and T2-weighted images were obtained once or twice for each of four affected and five control

  10. Structured preoperative patient education for patient-controlled analgesia

    Microsoft Academic Search

    Kwok Key Lam; Matthew T. V Chan; Phoon Ping Chen; Warwick D. Ngan Kee

    2001-01-01

    Study Objective: To investigate the effectiveness of a structured preoperative education program in patients receiving patient-controlled analgesia (PCA).Design: Randomized controlled trial.Setting: University-affiliated hospital.Patients: 60 ASA physical status I and II women undergoing major gynecologic surgery.Interventions: Patients were randomly allocated to receive either standard information given during routine preanesthetic assessment (n = 30) or additional structured preoperative education on the use

  11. Is patient-controlled analgesia controlled by the patient?

    Microsoft Academic Search

    Neil Taylor; George M. Hall; Peter Salmon

    1996-01-01

    Using patient-controlled analgesia (PCA) after surgery, a patient can obtain pain-relieving injections of morphine without the direct involvement of a nurse or doctor. The present study was a response to the conventional view that patients value PCA because of the control which it affords them over their own treatment. Twenty-six patients underwent semi-structured interviews postoperatively, shortly after discontinuation of PCA.

  12. [A dissociative patient].

    PubMed

    de Jongh, A; Abkhezr, S; Broers, D L M

    2009-08-01

    A 45-year-old woman attended a centre for special dental care. Initially, it seemed that the patient suffered from an extreme form of dental anxiety. However, the fact that she displayed 'dissociations' suggested that she had a severe psychiatric disorder, in this case Dissociative Identity Disorder. The key feature of this condition is a dysfunction of the normal integrative functions of identity, memory and consciousness. In such instances it is recommended to contact a psychologist or psychiatrist and the referring care provider to consider the consequences of the psychiatric condition regarding informed consent, treatment plan and actual treatment. Because it was not likely that the patient would respond to an intervention specifically aimed to reduce anxiety in the dental setting, dental treatment under general anesthesia was the best suited option. PMID:19739405

  13. Patient with inoperable pheochromocytoma

    PubMed Central

    Brancíková, D.; Mechl, Z.; Adam, Z.; Jandáková, E.; Pavlovský, Z.; Válek, V.; Andrašina, Z.

    2015-01-01

    Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging. Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months. The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient. PMID:26089731

  14. Anemia in hemodialysis patients.

    PubMed

    Higgins, M R; Grace, M; Ulan, R A; Silverberg, D S; Bettcher, K B; Dossetor, J B

    1977-02-01

    The association between anemia and chronic renal failure has been recognized since the early 19th century. With the introduction of regular dialysis treatment, an understanding of all aspects of this uremic complication has become of great importance, including an appreciation of the hazards of multiple blood transfusions. This analysis of hemoglobin levels and transfusion requirements in 84 dialysis patients focuses specific attention on hemolytic mechanisms, blood loss, and the effect of bilateral nephrectomy on erythropoiesis. Because no replacement for renal erythropoietin is available, particular attention must be paid to less important, but partially correctable factors that contribute to anemia. Blood transfusion requirements can then be reduced to a minimum, together with the risks of hypersplenism, hepatitis, and sensitization of the patient to alloantigens. PMID:836115

  15. Patient Safety in Surgery

    PubMed Central

    Makary, Martin A.; Sexton, J Bryan; Freischlag, Julie A.; Millman, E Anne; Pryor, David; Holzmueller, Christine; Pronovost, Peter J.

    2006-01-01

    Background: Improving patient safety is an increasing priority for surgeons and hospitals since sentinel events can be catastrophic for patients, caregivers, and institutions. Patient safety initiatives aimed at creating a safe operating room (OR) culture are increasingly being adopted, but a reliable means of measuring their impact on front-line providers does not exist. Methods: We developed a surgery-specific safety questionnaire (SAQ) and administered it to 2769 eligible caregivers at 60 hospitals. Survey questions included the appropriateness of handling medical errors, knowledge of reporting systems, and perceptions of safety in the operating room. MANOVA and ANOVA were performed to compare safety results by hospital and by an individual's position in the OR using a composite score. Multilevel confirmatory factor analysis was performed to validate the structure of the scale at the operating room level of analysis. Results: The overall response rate was 77.1% (2135 of 2769), with a range of 57% to 100%. Factor analysis of the survey items demonstrated high face validity and internal consistency (? = 0.76). The safety climate scale was robust and internally consistent overall and across positions. Scores varied widely by hospital [MANOVA omnibus F (59, 1910) = 3.85, P < 0.001], but not position [ANOVA F (4, 1910) = 1.64, P = 0.16], surgeon (mean = 73.91), technician (mean = 70.26), anesthesiologist (mean = 71.57), CRNA (mean = 71.03), and nurse (mean = 70.40). The percent of respondents reporting good safety climate in each hospital ranged from 16.3% to 100%. Conclusions: Safety climate in surgical departments can be validly measured and varies widely among hospitals, providing the opportunity to benchmark performance. Scores on the SAQ can serve to evaluate interventions to improve patient safety. PMID:16632997

  16. Ions purify patient's air

    Microsoft Academic Search

    Ned J. Miller

    1984-01-01

    A New York psychiatric center sought means to both rid a geriatrics' lounge of unpleasant orders and clear an out-patient\\u000a program's hall of tobacco smoke. Many devices were tried, including scented mop water and ceiling vents. Small “air cleaners”\\u000a were found to be ineffective; electrostatic air cleaners would be both expensive and troublesome. Ceiling mounted ion generators\\u000a have done the

  17. Physician-Patient Communication and Patient Compliance: A Theoretical Orientation.

    ERIC Educational Resources Information Center

    Clampitt, Phillip G.; Williams, M. Lee

    This paper synthesizes much of the literature concerning physician/patient communication as it relates to patient compliance. Using the theoretical perspective that deals with belief, attitude, intention, and behavior (a perspective generated by Martin Fishbein and Icek Ajzen), a new theoretical orientation for predicting patient compliance is…

  18. Patients who stay.

    PubMed

    Glucksman, Myron L

    2011-01-01

    For Freud, the ideal goal of a successful analysis is to resolve unconscious conflicts, gain insight, strengthen the ego, modify pathological defenses, contain irrational superego demands, and work through transferential distortions. Termination is based on a satisfactory approximation of these goals. However, there are certain patients who are unable to achieve these therapeutic goals. They include those with severe personality, psychotic, mood, eating, chronic posttraumatic stress, and gender identity disorders. For many of them, perseverance of symptoms, impaired functioning, and maintenance medication preclude termination, necessitating ongoing or intermittent treatment. On the other hand, there are those patients who make significant therapeutic progress, but remain in treatment indefinitely. Many of them approximate the criteria for termination, but maintain a therapeutic relationship for a variety of reasons. These include: unresolved transference-countertransference issues, avoidance of separation, chronically stressful situations (work, interpersonal, illness), lack of an external support system, and gratification from ongoing intrapsychic processing. Although nontermination may be associated with pathological dynamics for both patient and therapist, it may also be connected to non-neurotic, realistic factors. In some cases, indefinite treatment may be preferable. A clinical illustration is provided. PMID:21434753

  19. Leptospirosis in elderly patients.

    PubMed

    Gancheva, Galya Ivanova

    2013-01-01

    Leptospirosis is a re-emerging zoonosis with broad clinical spectrum and high mortality in severe forms. The aim of this study was to analyze clinical manifestations, laboratory findings, epidemiological data, and management in elderly patients with leptospirosis. Toward that end, we performed a descriptive analysis of 15 leptospirosis elderly cases (age 60-78 years) treated at the Clinic of Infectious Diseases of University Hospital - Pleven (1976-2012). Patients were serologically confirmed by microscopic agglutination test. Twelve cases (80%) presented with the severe form of leptospirosis. Co-morbidity (hypertonic diseases, chronic pulmonary diseases, chronic alcohol abuse, and diabetes) was registered in 13 cases. All cases had fever, oliguria, conjunctival suffusions, hepatosplenomegaly. Jaundice (14/93%), hemorrhagic diathesis (13/87%), vomiting (11/73%), abdominal pain (10/67%), myalgia (7/47%) and hypotension (7/47%) also were observed. Renal dysfunction was expressed by increased blood urea nitrogen (mean 38.1±24.1mmol/L) and serum creatinine (mean 347.6±179.8?mol/L). Hepatic dysfunction was expressed by increased total serum bilirubin level (mean 274.6±210.7?mol/L) and slightly elevated aminotransferases (ASAT mean 125.8±61.6IU/L; ALAT mean 131.3±126.5IU/L). Five cases (33%) had a lethal outcome. In conclusion, leptospirosis in elderly patients is associated with severe course and higher risk for death, and requires prompt intensive treatment. PMID:23830052

  20. [Toxoplasmosis in immunocompromised patients].

    PubMed

    Machala, L; Kodym, P; Malý, M; Geleneky, M; Beran, O; Jilich, D

    2015-01-01

    In humans, toxoplasmosis mostly occurs as a latent infection, but in immunocompromised individuals, the agent may reactivate and cause severe to life-threatening disease. HIV positive individuals and transplant recipients, in particular hematopoietic stem cell transplant and heart transplant recipients, are at highest risk. The disease most often affects the central nervous system but can involve any organ. Because of the alteration of the immune response in these patients, the serodiagnosis is not reliable and direct detection of the causative agent is needed - namely by microscopy and DNA PCR. If inadequately treated or left untreated, toxoplasmosis generally has a fatal prognosis in immunocompromised patients and therefore, the treatment must be started as early and energetically as possible. The gold standard both in the treatment of reactivation and secondary prophylaxis is the pyrimethamine-sulfadiazine combination while co-trimoxazole can be used in the primary prophylaxis for high-risk patients.Key words: immune disorders - infection - Toxoplasma gondii - HIV - transplantation - diagnosis - treatment. PMID:26099608

  1. When is patient education unethical?

    PubMed

    Redman, Barbara K

    2008-11-01

    Although patient education is central to the ethical practice of nursing, it can be practiced in an ethically contested or unethical way. It is sometimes used to: forward a societal goal the individual might not have chosen; assume that patients should learn to accommodate unjust treatment; exclude the views of all except the dominant health care provider group; limit the knowledge a patient can receive; make invalid or unreliable judgments about what a patient can learn; or require a patient to change his or her identity to meet a medical ideal. Both health promotion education and manipulating patient beliefs in situations of uncertainty are ethically contested. Nussbaum's capabilities approach is used here as a moral framework through which to view the goals and practice of patient education. This provides better guidance than the current conception of patient education as an instrument to carry out the directives of medical practice. PMID:18849370

  2. JAMA Patient Page: Oral Contraceptives

    MedlinePLUS

    ... painful periods or premenstrual syndromes, polycystic ovarian syndrome, acne, uterine fibroids, and endometriosis. Other Considerations It is ... contraception.htm To find this and previous JAMA Patient Pages, go to the Patient Page link on ...

  3. Craniomandibular asymmetry in headache patients.

    PubMed

    Schokker, R P; Hansson, T L; Ansink, B J; Habets, L L

    1990-01-01

    The stomatognathic system was examined in 100 chronic recurrent headache patients, and the asymmetry in clinical and radiographic findings was studied. A clinically recorded facial asymmetry was found more frequently in patients with a definite CMD pain (P less than 0.001), in patients with mainly a unilateral headache (P less than 0.01), and in patients with a head injury in the history (P less than 0.05). The radiographically determined asymmetry in condylar height in these headache patients was high. More condylar asymmetry was found in migraine patients than in patients with tension headache (P less than 0.05). Asymmetric findings in the hard-tissue condition of the temporomandibular joint were more prevalent in patients with a definite CMD pain and in those with mainly bilateral headaches. PMID:2098397

  4. JAMA Patient Page: Lumbar Puncture

    MedlinePLUS

    ... Journal of the American Medical Association JAMA PATIENT PAGE Lumbar Puncture L umbar punctur e, also called ... about lumbar puncture to diagnose meningitis. This Patient Page is based on one previously published in the ...

  5. JAMA Patient Page: Retinal Detachment

    MedlinePLUS

    JAMA PATIENT PAGE Retinal Detachment CROSS SECTION V I T R E O U S Optic nerve Retinal vessel Pupil Iris Lens ... detachment from a type of antibiotic. This Patient Page is based on one previously published in the ...

  6. Health literacy and patient portals.

    PubMed

    Gu, Yulong; Orr, Martin; Warren, Jim

    2015-01-01

    Health literacy has been described as the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. Improving health literacy may serve to promote concordance with therapy, engage patients in their own health care, and improve health outcomes. Patient portal technology aims at enabling patients and families to have easy access to key information in their own medical records and to communicate with their health care providers electronically. However, there is a gap in our understanding of how portals will improve patient outcome. The authors believe patient portal technology presents an opportunity to improve patient concordance with prescribed therapy, if adequate support is provided to equip patients (and family/carers) with the knowledge needed to utilise the health information available via the portals. Research is needed to understand what a health consumer will use patient portals for and how to support a user to realise the technology's potential. PMID:26125067

  7. Profile of Your Geriatric Patient

    PubMed Central

    Longhurst, Mark F.; Slade, Debra

    1990-01-01

    The family doctor cares for many geriatric patients. Many of these patients enter the family practice for the first time, having either recently moved to the area or to a nearby long-term care facility. Obtaining a meaningful patient profile is essential to the physicians' care, allowing future medical decisions to be made in the best interest of that person. Patients' beliefs motivate their functioning in a system. Any system has its own history, structure, and function. PMID:21234029

  8. The physician-patient relationship revisited: the patient's view.

    PubMed

    Schneider, Udo; Ulrich, Volker

    2008-12-01

    The importance of the physician-patient relationship for the health care market is beyond controversy. Recent work emphasizes a two-sided asymmetric information relationship between physician and patient. In contrast to most work looking only at the physician's perspective, our paper concentrates on the patient's view. Estimation results support the hypotheses that physician consultation and health relevant behavior are not stochastically independent. In the recursive bivariate probit model, patient's health relevant behavior has a significant influence on the probability of a physician visit. This means that health care demand and not only the contact decision is determined by both, patient and physician. PMID:18597172

  9. Insomnia in Diabetic Hemodialysis Patients

    Microsoft Academic Search

    Sang-Youb Han; Jong-Woo Yoon; Sang-Kyung Jo; Jin-Ho Shin; Chol Shin; Jung-Bok Lee; Dae-Ryong Cha; Won-Yong Cho; Heui-Jung Pyo; Hyoung-Kyu Kim; Kyu-Bec Lee; Hyang Kim; Kyung-Wook Kim; Yong-Seop Kim; Jeong-Ho Lee; Sang-Eun Park; Chang-Soo Kim; Kyeong-So Wea; Kyung-Shik Oh; Tae-See Chung; Sang-Yeol Suh

    2002-01-01

    Background: Insomnia is one of the most common problems in dialysis patients, and likely to contribute impairment in quality of life, which has a positive correlation with patients’ survival. In diabetic patients, morbidity and mortality are substantially higher than in the nondiabetic counterparts, and also the incidence of sleep disturbances. However, there is no means to predict sleep disturbance in

  10. [Mental disorders in migraine patients].

    PubMed

    Sviridova, E I; Vladimirova, S M

    1986-01-01

    The mental state was studied in patients with different forms of migraine. Using experimental psychological, electroencephalographic, rheoencephalographic, echoencephalographic and dermatoglyphic methods patients with simple and associated migraine were examined. Characteristic mental disturbances were identified. The authors emphasize the significance of psychodiagnosis for selection of the correct management of patients and the selection of adequate therapy. PMID:3751429

  11. Counseling Patients With Genital Warts

    Microsoft Academic Search

    1997-01-01

    Counseling patients about any sexually transmitted disease (STD) is difficult, for both the physician and the patient, but a diagnosis of genital warts presents particular challenges. For many patients, being told that they have any STD comes as a shock. Although fear is a common reaction, the relationship between human papillomavirus (HPV) and cancer has made the presence of genital

  12. OHSU Healthcare Patient rights, responsibilities

    E-print Network

    Chapman, Michael S.

    OHSU Healthcare Patient rights, responsibilities and safety OHSU Patient Relations Mail code: UHS-3 3181 S.W. Sam Jackson Park Rd. Portland, Oregon 97239 503 494-7959 advocate@ohsu.edu www.OHSUhealth.com Your health care is our priority. You are why we are here. At OHSU, we provide patient- and family

  13. Treatment of osteoporotic patients.

    PubMed Central

    Johnston, C C

    1989-01-01

    The best approach to treatment of osteoporosis is prevention of bone loss as discussed elsewhere in this volume. However, some currently approved therapeutic agents are helpful in the management of the patient who presents with an osteoporotic fracture. These agents include an adequate calcium intake, estrogen replacement therapy, and administration of calcitonin. A number of experimental therapies are being evaluated, providing hope for improved treatment in the future. These include sodium fluoride, low-dose parathyroid hormone, anabolic steroids, various forms of cyclical therapy, growth hormone, and various bone growth factors. PMID:2517706

  14. When a vulnerable patient absconds.

    PubMed

    Aspinall, P

    1994-03-01

    This case-study examines the nurse's role when a patient at risk absconds. It highlights possible weaknesses in the system for dealing with absconding patients who are so cognitively and emotionally impaired, that they may present a danger to themselves. The issues of patient identification and stigmatization are raised along with the possible conflict this may cause in psychiatric nurses. Recommendations for care at ward level are made, including asking the vulnerable patient to wear an identity bracelet and the instigation of a prepared action plan which involves engaging the help of outside agencies should a patient abscond. PMID:8156133

  15. Financial Distress in Cancer Patients

    PubMed Central

    de Souza, Jonas A.; Wong, Yu-Ning

    2013-01-01

    Novel diagnostic and therapeutic options offer hope to cancer patients with both localized and advanced disease. However, many of these treatments are often costly and even well-insured patients can face high out-of-pocket costs. Families may also be at risk of financial distress due to lost wages and other treatment-related expenses. Research is needed to measure and characterize financial distress in cancer patients and understand how it affects their quality of life. In addition, health care providers need to be trained to counsel patients and their families so they can make patient-centered treatment decisions that reflect their preferences and values. PMID:24349677

  16. Increasing access to patient records.

    PubMed

    Gladwin, Jacqui

    By 2015, all patients are expected to be able to order prescriptions and book appointments online, as well as being able to access their own GP-held records. This will undoubtedly hold benefits for patients and health professionals, but is likely to present significant challenges for nurses in terms of managing patient expectation and ensuring fair access. This article discusses the background to records access and outlines the possible benefits for patients and nurses. It gives a personal perspective of the challenges for nurses and patients in accessing online GP services. PMID:24266242

  17. Understanding respect: learning from patients

    PubMed Central

    Dickert, N W; Kass, N E

    2011-01-01

    Background The importance of respecting patients and participants in clinical research is widely recognised. However, what it means to respect persons beyond recognising them as autonomous is unclear, and little is known about what patients find to be respectful. Objective To understand patients’ conceptions of respect and what it means to be respected by medical providers. Design Qualitative study from an academic cardiology clinic, using semistructured interviews with 18 survivors of sudden cardiac death. Results Patients believed that respecting persons incorporates the following major elements: empathy, care, autonomy, provision of information, recognition of individuality, dignity and attention to needs. Conclusions Making patients feel respected, or valued as a person, is a multi-faceted task that involves more than recognising autonomy. While patients’ views of respect do not determine what respect means, these patients expressed important intuitions that may be of substantial conceptual relevance. PMID:19567690

  18. Neuroendocrine alterations in uveitis patients.

    PubMed

    Wollmann, H A; Pleyer, U; Friedel, S; Zierhut, M; Thiel, H J; Gupta, D

    1994-05-01

    Experimental models of autoimmune uveitis are consistently associated with pinealitis. To investigate the interaction between the neuroendocrine and immune systems in humans with uveitis, we measured serum levels of the predominant pineal hormone melatonin (MEL), prolactin (PRL) and interleukin-2 (IL-2). A total of 100 patients with different forms of uveitis and 30 age-matched, healthy blood donors were evaluated retrospectively. The day-time MEL was reduced significantly (P < or = 0.01) in patients with iritis and iridocyclitis, and highly significantly (P < or = 0.001) in patients with intermediate uveitis, chorioretinitis and panuveitis. In 38% of patients day-time MEL levels in plasma were below the limit of detection. PRL was significantly reduced (P < 0.01) in patients with intermediate uveitis. IL-2 was reduced to about 50% of control values in all groups of patients. The results suggest a possible neuroendocrine-immune interaction in uveitis patients. PMID:8045439

  19. The 'Patient experience' revolution.

    PubMed

    Hooten, Doug; Zavadsky, Matt

    2014-02-01

    We're arguably at the most pivotal time in our young profession. The ACA has provided EMS an unprecedented opportunity to become a part of the healthcare system, a move that many of us have dreamed about for decades. We need to pay attention to the changing dynamics of the environment in which we operate. The factors that currently impact hospitals, doctors and other healthcare providers will also impact us sooner than we think. Take the time to help shape our future and how we participate in this new healthcare system. It's time to focus on the patient and the patient's experience with our service. Wayne Gretzky said two important things during an interview when he was asked what makes him such a great hockey player. One was, "You miss 100% of the shots you don't take." The other was, "A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be. I skate to where the puck is going to be, not where it has been." Our advice to you is to go ahead, take the shot, get ahead of the other team and focus on improved customer satisfaction sooner rather than later. PMID:24660359

  20. Hyponatremia in cancer patients.

    PubMed

    Platania, Marco; Verzoni, Elena; Vitali, Milena

    2015-04-28

    Hyponatremia is the most frequent electrolyte disorder in hospitalized patients but also a well known poor prognostic factor in cancer patients. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is often misdiagnosed by oncologist because of difficulties in the interpretation of laboratory tests.Etiology is heterogeneous but the predominant cause is represented by the unbalance between excessive presence of water and serum sodium deficiency.Ectopic production of arginine vasopressin (AVP) develops more frequently in small cell lung cancer but it is not so rare in other malignancies.Neurological impairment may range from subclinical to life-threating symptoms depending by the rate of serum sodium deficiency. Appropriate diagnosis is essential to set a proper therapy. When hyponatremia is caused by SIADH, hypertonic saline infusion is indicated for acute presentation whereas fluid restriction is preferred in case of chronic asymptomatic evolution.Other options include vaptans, vasopressin receptor antagonists, targeted specifically for the correction of euvolemic hyponatremia.The aim of this brief report is to provide concise and specific informations for the management of SIADH in oncology clinical practice. PMID:25908038

  1. When patients and families disagree.

    PubMed

    Erlen, Judith A

    2005-01-01

    Advance care planning is meant to safeguard the patient's autonomy when that individual is unable to make his or her own healthcare decisions. Yet, families do not always agree with the specific wishes of their family member when there is a need to make critical decisions, such as continuing treatment because of some new research protocol or providing comfort through palliative care. When there are patient-family disagreements, the decision-making process is even more complicated if the patient is fully able to participate because competent patients have the right to make their own healthcare decisions. In addition, family members may not agree with each other. Thus, even though healthcare providers want to respect their patients' wishes, they are uncertain about the most appropriate course of action. This article discusses why families and patients may disagree, describes relevant ethical perspectives for understanding the issues, and identifies possible strategies to help nurses address these ethical dilemmas. Valuing the patient as a person, the vulnerability of the patient, whose interests should prevail, and quality of life are pertinent and overlapping ethical issues in this case. Possible strategies that nurses can implement to address the "thorny" issues raised by patient-family disagreements include helping the patient to remain in control, facilitating responsible decision making, requesting an ethics consultation, and requesting a palliative care consultation. PMID:16056173

  2. Patient reported outcomes and patient empowerment in clinical genetics services.

    PubMed

    McAllister, M; Dearing, A

    2015-08-01

    Evaluation of clinical genetics services (CGS), including genetic counseling and genetic testing, has been problematic. Patient mortality and morbidity are unlikely to be directly improved by interventions offered in CGS. Patient-reported outcomes (PROs) are not routinely measured in CGS evaluation, but this may change as patient-reported outcome measures (PROMs) become a key part of how healthcare services are managed and funded across the world. However, there is no clear consensus about which PROMs are most useful for CGS evaluation. This review summarizes the published research on how PROs from CGS have been measured and how patients may benefit from using those services, with a focus on patient empowerment. Many patient benefits (PROs) identified repeatedly in the research literature can be re-interpreted within a patient empowerment framework. Other important PROs identified include family functioning, social functioning, altruism, sense of purpose, enabling development of future research and treatment/participating in research. Well-validated measures are available to capture (dimensions of) patient empowerment. Although generic measures of family functioning are available, suitable measures capturing social functioning, development of future treatments, and altruism were not identified in this review. Patient empowerment provides one useful approach to measuring PROs from CGS. PMID:25307491

  3. Simulation: improving patient outcomes.

    PubMed

    Smith, Abi; Siassakos, Dimitrios; Crofts, Joanna; Draycott, Tim

    2013-06-01

    Effective training has been shown to improve perinatal care and outcome, decrease litigation claims and reduce midwifery sick leave. To be effective, training should be incentivised, in a realistic context, and delivered to inter-professional teams similar to those delivering actual care. Teamwork training is a useful addition, but it should be based on the characteristics of effective teamwork as derived from the study of frontline teams. Implementation of simulation and teamwork training is challenging, with constraints on staff time, facilities and finances. Local adoption and adaptation of effective programmes can help keep costs down, and make them locally relevant whilst maintaining effectiveness. Training programmes need to evolve continually in line with new evidence. To do this, it is vital to monitor outcomes and robustly evaluate programmes for their impact on patient care and outcome, not just on participants. PMID:23721770

  4. Noise control considerations for patient rooms

    Microsoft Academic Search

    Benjamin Davenny

    2005-01-01

    The patient room envelope is a path between outside noise sources and the patient receiver. Within the patient room there are several sources including televisions, clinical monitor alarms, medical pumps, etc. Noise control in patient rooms relies on a combination of the sound transmission loss of the patient room envelope and the level of background sound at the patient's head.

  5. Craniomandibular disorders in headache patients.

    PubMed

    Schokker, R P; Hansson, T L; Ansink, B J

    1989-01-01

    Fifty patients with recurrent headache who had been referred to a neurologist were randomly invited for an examination of their stomatognathic system. The prevalence and distribution of the findings in many ways resemble the clinical findings in CMD patients. In 66% of the patients, a myogenous or arthrogenous origin of CMD pain could be detected. Headache occurred more bilaterally, but unilateral findings were more common at the functional examination. The results did not show any statistical differences between the sexes. PMID:2606999

  6. Patients’ participation in medical care

    Microsoft Academic Search

    Sheldon Greenfield; Sherrie H. Kaplan; John E. Ware; Elizabeth Martin Yano; Harrison J. L. Frank

    1988-01-01

    To maximize disease control, patients must participate effectively in their medical care. The authors developed an intervention\\u000a designed to increase the involvement of patients in medical decision making. In a 20-minute session just before the regular\\u000a visit to a physician, a clinic assistant reviewed the medical record of each experimental patient with him\\/her, guided by\\u000a a diabetes algorithm. Using systematic

  7. JAMA Patient Page: Abdominal Hernia

    MedlinePLUS

    JAMA PATIENT PAGE Abdominal Hernia Common abdominal hernias Inguinal hernia Indirect inguinal hernia Direct inguinal hernia Intestinal loop Umbilical annulus Peritoneum Peritoneum Abdominal wall Intestinal ...

  8. Hepatitis prevalence in trauma patients.

    PubMed

    Levine, E A; Alverdy, J C; Agrawal, A

    1991-06-01

    The risks of viral transmission from trauma patients is a continuing concern to those involved in their care. However, the prevalence of hepatitis (HPT) in trauma patients is poorly described. The purpose of this study is to evaluate the prevalence of HPT in trauma patients admitted to an urban trauma center. Two hundred sixty-four consecutive admissions to an urban Level I trauma center underwent serologic screening for HPT. Risk factors were assessed by direct patient questioning. Serologic evidence of HPT B was found in 19.7 per cent of patients. Intravenous (IV) drug abusers represented eight per cent of the study population; this group had a 67 per cent rate of seropositivity. Hepatitis A was not found in any patient. Antigenemia was found in 1.9 per cent of patients. It is concluded that HPT B seropositivity is common in trauma patients. IV drug abusers have particularly high prevalence of HPT. This high prevalence rate of HPT B serology poses a significant risk to those involved with the care of trauma patients. The authors suggest that specific protocols to avoid the transmission of viral disease should be mandatory in urban trauma centers. PMID:2048852

  9. Health centres assessed by patients

    PubMed Central

    Woods, J. O.; Patten, M. P.; Pyper, H. M.

    1974-01-01

    This study consists of a postal questionnaire sent to patients attached to four practices in a health centre during the third year of operation after various exploratory studies and a series of group discussions. The study showed that about three out of four patients preferred health centre-practice to non health-centre practice. The appointment system as a cause of dissatisfaction with the health-centre concept is discussed. The doctor-patient relationship, privacy and confidentiality, and representation of patients on health-centre management committees were studied and are discussed. PMID:4465442

  10. Fungal laryngitis in immunocompetent patients.

    PubMed

    Ravikumar, A; Prasanna Kumar, S; Somu, L; Sudhir, B

    2014-01-01

    The diagnosis of fungal laryngitis is often overlooked in immunocompetent patients because it is commonly considered a disease of the immunocompromised. Further confusion is caused by clinical and histological similarity to more common conditions like Leukoplakia. Demonstration of hyperkeratosis particularly if associated with intraepithelial neutrophils on biopsy should trigger a search for fungus using specialized stains. These patients usually present with hoarseness of voice. Pain is present inconsistently along with dysphagia and odynophagia. We present three cases of fungal laryngitis in immunocompetent patients out of which one underwent microlaryngeal surgery with excision biopsy. All these patients responded well with oral antifungal therapy. PMID:24533421

  11. Effective writing that attracts patients.

    PubMed

    Baum, Neil

    2015-01-01

    Doctors today not only must communicate verbally, they must also realize that the written word is important to their ability to connect with the patients that they already have and also to attract new patients. Doctors will be expected to write blogs, to create content for their Web sites, to write articles for local publications, and even to learn to express themselves in 140 characters or less (i.e., Twitter). This article presents 10 rules for selecting the right words to enhance your communication with existing patients and potentially to attract new patients to your practice. PMID:26062324

  12. Improving patients privacy with Pseudonymization.

    PubMed

    Neubauer, Thomas; Riedl, Bernhard

    2008-01-01

    e-Health requires the sharing of patient related data when and where necessary. Electronic health records promise to improve communication between health care providers, thus leading to better quality of patients' treatment and reduced costs. As highly sensitive patient information provides a promising goal (e.g., for attackers), there is an increasing social and political pressure to guarantee patients privacy. This paper presents the new system PIPE (Pseudonymization of Information for Privacy in e-Health), that differs from existing approaches in its ability to securely integrate primary and secondary usage of health data. PMID:18487812

  13. Patient Request for Email Communications Patient Name: Date of Birth

    E-print Network

    Columbia University

    Patient Request for Email Communications Patient Name: Date of Birth: Phone Number: Email Address: Communications over the Internet and / or using the email system may not be encrypted and may not be secure. There is no assurance of confidentiality when communicating via email. To request that this provider/program communicate

  14. Expanding patient involvement in care. Effects on patient outcomes

    Microsoft Academic Search

    Sheldon Greenfield; Sherrie H. Kaplan; Ware John E. Jr

    1985-01-01

    An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session

  15. Respiratory failure in elderly patients.

    PubMed

    Sevransky, Jonathan E; Haponik, Edward F

    2003-02-01

    Elderly individuals comprise an increasing proportion of the population and represent a progressively expanding number of patients admitted to the ICU. Because of underlying pulmonary disease, loss of muscle mass, and other comorbid conditions, older persons are at increased risk of developing respiratory failure. Recognition of this vulnerability and the adoption of proactive measures to prevent decompensation requiring intrusive support are major priorities together with clear delineation of patients' wishes regarding the extent of support desired should clinical deterioration occur. Further, the development of coordinated approaches to identify patients at risk for respiratory failure and strategies to prevent the need for intubation, such as the use of NIV in appropriate patients, are crucial. As soon as endotracheal intubation and mechanical ventilation are implemented strategies that facilitate the liberation of elderly patients from the ventilator are especially important. The emphasis on a team approach, which characterizes geriatric medicine, is essential in coordinating the skills of multiple health care professionals in this setting. Respiratory failure can neither be effectively diagnosed nor managed in isolation. Integration with all other aspects of care is essential. Patient vulnerability to nosocomial complications and the "cascade effect" of these problems such as the effects of medications and invasive supportive procedures all impact on respiratory care of elderly patients. For example, prolonged mechanical ventilation may be required long after resolution of the underlying cause of respiratory failure because of unrecognized and untreated delirium or residual effects of small doses of sedative and/or analgesic agents or other medications in elderly patients with altered drug metabolism. The deleterious impact of the foreign and sometimes threatening ICU environment and/or sleep deprivation on the patient's course are too often overlooked because the physician focuses management on physiologic measurements, mechanical ventilator settings, and other technologic nuances of care [40]. Review of the literature suggests that the development of respiratory failure in patients with certain disease processes such as COPD, IPF, and ARDS in elderly patients may lead to worsened outcome but it appears that the disease process itself, rather than the age of the patient, is the major determinant of outcome. Additional studies suggest that other comorbid factors may be more important than age. Only when comorbid processes are taken into account should decisions be made about the efficacy of instituting mechanical ventilation. In addition, because outcome prediction appears to be more accurate for groups of patients rather than for individual patients a well-structured therapeutic trial of instituting mechanical ventilation, even if comorbidities are present, may be indicated in certain patients if appropriately informed patients wish to pursue this course. This approach requires careful and realistic definition of potential outcomes, focus on optimizing treatment of the reversible components of the illness, and continuous communication with the patient and family. Although many clinicians share a nihilistic view regarding the potential usefulness of mechanical ventilation in elderly patients few data warrant this negative prognostication and more outcome studies are needed to delineate the optimum application of this element of supportive care. As with other interventions individualization of the decision must take into account the patient's premorbid status, concomitant conditions, the nature of the precipitating illness and its prospects for improvement, and most important, patient preferences. In this determination pursuing the course most consistent with the patient's wishes is essential and it must be appreciated that caregivers' impressions regarding the vigor of support desired by the patient are often erroneous. The SUPPORT investigators observed that clinicians often underestimated the degree of i

  16. What Do Patients Want? Patient Preference in Wound Care

    PubMed Central

    Corbett, Lisa Q.; Ennis, William J.

    2014-01-01

    Patient preferences are statements made or actions taken by consumers that reflect their desirability of a range of health options. The concept occupies an increasingly prominent place at the center of healthcare reform, and is connected to all aspects of healthcare, including discovery, research, delivery, outcome, and payment. Patient preference research has focused on shared decisions, decisional aids, and clinical practice guideline development, with limited study in acute and chronic wound care populations. The wound care community has focused primarily on patient focused symptoms and quality of life measurement. With increasing recognition of wound care as a medical specialty and as a public health concern that consumes extensive resources, attention to the preferences of end-users with wounds is necessary. This article will provide an overview of related patient-centered concepts and begin to establish a framework for consideration of patient preference in wound care. PMID:25126474

  17. Gustometry of diabetes mellitus patients and obese patients.

    PubMed

    Stolbová, K; Hahn, A; Benes, B; Andel, M; Treslová, L

    1999-01-01

    The sensation of adequate taste detection can be associated with satisfaction of food intake. The impairment of taste detection may be associated with the development of obesity. Taste detection is determined hereditarily, but it can be influenced also by the occurrence of neuropathy. To find an explanation for these phenomena, we investigated 73 patients with diabetes mellitus (DM) 2 (i.e., non-insulin-dependent DM); 11 patients with DM 1 (i.e., insulin-dependent DM); 12 obese patients (body-mass index >30) without DM; and 29 control patients. All subjects underwent electrogustometric examination with Hortmman's electrogustometer. During this examination, we obtained electrical thresholds of taste by stimulating appropriate parts of the tongue. We stimulated the apex, middle, and near tongue radix areas on both sides. The resulting value is the average on the left and right sides of the mentioned areas. We considered a value of less than 40 microA to be normal. Values in excess of 100 microA are considered as hypogeusia. Values between 40 and 100 microA are taken as borderline, and ageusia is in excess of 500 microA. According to these criteria, in the DM 2 group, we found 40% of patients with hypogeusia, whereas in the DM 1 group, we found 33% of patients; 25% of patients were in the obese group. Among normal subjects (people without obesity or DM), no hypogeusia was found. We found ageusia in 5% of patients with DM 2, in 3% of patients with DM 1, and in 14% of obese patients. Among normal subjects, we found no ageusia. These results support the hypothesis that diminished taste detection can evoke hyperphagia and later obesity. PMID:10753433

  18. Patient safety: lessons learned.

    PubMed

    Bagian, James P

    2006-04-01

    The traditional approach to patient safety in health care has ranged from reticence to outward denial of serious flaws. This undermines the otherwise remarkable advances in technology and information that have characterized the specialty of medical practice. In addition, lessons learned in industries outside health care, such as in aviation, provide opportunities for improvements that successfully reduce mishaps and errors while maintaining a standard of excellence. This is precisely the call in medicine prompted by the 1999 Institute of Medicine report "To Err Is Human: Building a Safer Health System." However, to effect these changes, key components of a successful safety system must include: (1) communication, (2) a shift from a posture of reliance on human infallibility (hence "shame and blame") to checklists that recognize the contribution of the system and account for human limitations, and (3) a cultivation of non-punitive open and/or de-identified/anonymous reporting of safety concerns, including close calls, in addition to adverse events. PMID:16479407

  19. Patient Relations and Workplace Communication.

    ERIC Educational Resources Information Center

    Career Resources Development Center, Inc., San Francisco, CA.

    The workbook contains lessons and exercises in patient relations and workplace communication in a medical services office, particularly for interactions involving one or more non-native speaker of English. Seven units address these topics: (1) greetings and basic assistance, greeting established patients, and measuring height and weight and taking…

  20. The Coronary Patient in Industry

    NASA Technical Reports Server (NTRS)

    Schuster, B.

    1971-01-01

    The coronary patient, as he pertains to industry particularly NASA, is discussed. Concepts of precoronary care, acute attacks which may develop while on the job, and the return of the cardiac patient to work are covered. Major emphasis was on the prevention of sudden death due to coronary disease.

  1. Fluid management in hospitalized patients

    Microsoft Academic Search

    Laura Meinke; Geoffrey K. Lighthall

    2005-01-01

    Intravenous fluid administration is critical to the care of hospitalized patients. Despite the lack of a clear consensus on\\u000a fluid administration, one may use the principles in this article to develop an organized framework for patient care.

  2. Nurse Burnout and Patient Satisfaction

    Microsoft Academic Search

    Doris C. Vahey; Linda H. Aiken; Douglas M. Sloane; Sean P. Clarke; Delfino Vargas

    2004-01-01

    Background: Amid a national nurse shortage, there is growing concern that high levels of nurse burnout could adversely affect patient outcomes. Objectives: This study examines the effect of the nurse work environment on nurse burnout, and the effects of the nurse work environment and nurse burnout on patients' satisfaction with their nursing care. Research Design\\/Subjects: We conducted cross-sectional surveys of

  3. Idiom Comprehension in Aphasic Patients

    ERIC Educational Resources Information Center

    Papagno, Costanza; Tabossi, Patrizia; Colombo, Maria Rosa; Zampetti, Patrizia

    2004-01-01

    Idiom comprehension was assessed in 10 aphasic patients with semantic deficits by means of a string-to-picture matching task. Patients were also submitted to an oral explanation of the same idioms, and to a word comprehension task. The stimuli of this last task were the words following the verb in the idioms. Idiom comprehension was severely…

  4. Work design and patient safety

    Microsoft Academic Search

    P. Carayon; C. J. Alvarado; A. Schoofs Hundt

    2007-01-01

    This paper describes the linkages between work design and patient safety. The focus is on nursing work; however, many of the concepts and methods are equally applicable to other healthcare professions. Work design relies on a large body of knowledge, including ergonomics, job stress and job\\/organizational design. First, a general framework of work design and patient safety is proposed. The

  5. Pharmacotherapeutics for the AIDS Patient.

    ERIC Educational Resources Information Center

    Fife, Kenneth H.

    1991-01-01

    Anticipated shifts in the demographics of the Acquired Immune Deficiency Syndrome (AIDS) epidemic are examined, current state-of-the-art AIDS patient management is summarized, and some unique facets of drug therapy in the AIDS patient are discussed, including adverse reactions, complex drug interactions, use of investigational drugs, and…

  6. Treating infertility in autoimmune patients

    Microsoft Academic Search

    D. Coli

    2008-01-01

    In Western countries, the rate of infertility is about 10-20% and is age dependent. Since the infertile partner among couples can be either the man or the woman, specification of which sex con- tributes to infertility is necessary in studies of patients with autoimmune diseases. This review focuses on patients with SLE—the only group for which extensive data are available.

  7. Patient-centered Communication Research

    Cancer.gov

    Several recent reports, including NCI's Strategic Plan for Leading the Nation and the NCI-designated cancer center directors' report Accelerating Successes Against Cancer, have recognized the salience of patient-clinician communication in optimizing cancer patients' and survivors' health outcomes.

  8. Hemoperitoneum in Patients Receiving Hemodialysis

    Microsoft Academic Search

    Arnaud Stolz; Jacques Fourcade; Arnaud Klisnick; Bertrand Souweine; Armand Abergel; Jean-Claude Baguet; Patrice Deteix

    2000-01-01

    Acute abdominal pain in chronic hemodialysis patients has well-known causes, including acute pancreatitis, mesenteric arterial insufficiency, or complicated duodenal ulcer. Others, such as hemoperitoneum, are far less common. Although hemoperitoneum occurs in patients receiving peritoneal dialysis, dialysis is seldom if ever the direct cause of the bleeding. Hemoperitoneum is often related to menses or ovulation, particularly to ovarian cyst rupture;

  9. Staffing levels and patient outcomes

    Microsoft Academic Search

    P. Griffiths

    2009-01-01

    There is considerable evidence of an association between nurse staffing levels and patient outcomes. The evidence has been used to support calls for mandatory nurse-patient ratios although the precise significance of the relationship remains unclear. In this article, the evidence is examined to establish what is known and, crucially, what is not known about this relationship.

  10. Virtual Patients in Geriatric Education

    ERIC Educational Resources Information Center

    Tan, Zaldy S.; Mulhausen, Paul L.; Smith, Stephen R.; Ruiz, Jorge G.

    2010-01-01

    The virtual patient is a case-based computer program that combines textual information with multimedia elements such as audio, graphics, and animation. It is increasingly being utilized as a teaching modality by medical educators in various fields of instruction. The inherent complexity of older patients and the shortage of geriatrics educators…

  11. [Takayasu arteritis in pediatric patients].

    PubMed

    Katsicas, María Martha; Pompozi, Luis; Russo, Ricardo

    2012-01-01

    Takayasu's arteritis is a chronic inflammatory disease that primarily affects the large vessels, such as the aorta and its branches. It represents the third most frequent vasculitis during pediatric age. Our objective was to describe clinical and complementary exams features as well as treatment modalities of a case series of pediatric patients. We present 11 patients (10 girls) with median age at onset of 8 years (range: 2-15). The median diagnosis delay was 16 months (range: 2-96). Clinical presentations were lower limb claudication, arterial hypertension, CNS involvement, presence of murmurs, systemic symptoms, lymphadenopathy, chest pain, abdominal pain and arthritis. Laboratory tests showed: elevated ESR, anemia and trombocytosis. Vascular imaging studies exhibited stenosis, dilatation, occlussion and aneurysms. The outcome of the disease was persistent active condition (1 patient), relapse (4 patients), remission (3 patients), motor sequelae (1 patient) and death (2 patients). All patients were treated with steroids and immunosuppressants. Takayasu 's arteritis is a condition that can potentially be life-threatening. The diagnosis should be suspected in a variety of clinical manifestations during childhood. PMID:22760753

  12. Microperimetric biofeedback in AMD patients.

    PubMed

    Vingolo, Enzo M; Cavarretta, Sonia; Domanico, Daniela; Parisi, Francesca; Malagola, Romualdo

    2007-12-01

    To analyse biofeedback training by microperimeter MP-1 (Nidek Technologies) on patients with Age Related Maculopathy (AMD). We enrolled 15 patients (10 female and 5 male) and examined total of 27 eyes with AMD. All the patient underwent 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. All patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity an reading speed. The mean character size value improved from 36.4 to 11.7; this result was statistically significant (p = 0.031). A biofeedback examination using the MP-1 microperimeter can help the brain to memorize the final fixation location by increasing attention modulation, thereby providing an efficient preferred retinal locus for visual tasks in patients with macular disease and central scotoma. PMID:17574525

  13. Are rhinoplasty patients potentially mad?

    PubMed

    Slator, R; Harris, D L

    1992-01-01

    Rhinoplasty patients have long been considered to be psychologically unstable and therefore a "risky" group upon which to operate. Patients who had rhinoplastic operations more than 5 years ago were contacted by post and their psychological health assessed by the use of psychometric tests. The results show no evidence to support earlier suggestions that requests for rhinoplasty may be early symptoms of severe psychiatric disease. However, several points do emerge. Male patients show more symptoms of anxiety and depression than normal, and female patients who give no history of injury preceding their operation behave in a more extrovert and sociable manner than normal. Furthermore, patients of both sexes who give no history of injury before their operation, even though pleased with the operative results, are more self-conscious of their appearance than those who were injured prior to their rhinoplasty. PMID:1623348

  14. Preferences of patients for patient centred approach to consultation in primary care: observational study

    Microsoft Academic Search

    Paul Little; Hazel Everitt; Ian Williamson; Greg Warner; Michael Moore; Clare Gould; Kate Ferrier; Sheila Payne

    2001-01-01

    Objective To identify patient's preferences for patient centred consultation in general practice. Design Questionnaire study. Setting Consecutive patients in the waiting room of three doctors' surgeries. Main outcome measures Key domains of patient centredness from the patient perspective. Predictors of preferences for patient centredness, a prescription, and examination. Results 865 patients participated: 824 (95%) returned the pre›consultation questionnaire and were

  15. Venous Thromboembolism in Patients with

    PubMed Central

    Scoville, Elizabeth A; Konijeti, Gauree G; Nguyen, Deanna D; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N

    2014-01-01

    Introduction Inflammatory bowel disease is a well known risk factor for venous thromboembolism (VTE). Existing guidelines for thromboprophylaxis in hospitalized patients do not extend to other clinical scenarios that may also be associated with VTE risk. Our aim was to estimate the fraction of VTE events in IBD patients that could be prevented. Methods A retrospective analysis assessed all IBD patients diagnosed with VTE at a single academic medical center from 2002–2012. Confirmed cases were analyzed for VTE risk factors, inpatient status, the use of DVT prophylaxis, and when applicable the reason for omission of prophylaxis. IBD VTE cases were compared with age- and sex-matched non-IBD VTE controls with regards to risk factors and potential opportunities for VTE prevention. Results There were 204 IBD patients (108 UC, 96 CD) diagnosed with VTE (110 DVT, 66 PE, 27 intra-abdominal thromboses, 1 other). One third of the VTE events occurred in hospitalized patients. Two-third of the medical inpatients and 44% of surgical in-patients who developed VTE did not receive prophylaxis. Importantly, 129 VTE events occurred in outpatients. The proportion of outpatients hospitalized within 4 weeks of developing venous thrombosis was higher in IBD patients than non-IBD controls (33 vs. 15%, p=0.0003). One-third of patients (36%) were experiencing ambulatory disease flares at the time of VTE diagnosis. Conclusions A substantial portion of VTE events in IBD patients occurred in clinical scenarios not routinely recommended for thromboprophylaxis. Further investigation of primary prophylaxis for IBD patients in high risk outpatients may be warranted. PMID:24552828

  16. The cancer patient at work.

    PubMed

    Mellette, S J

    1985-01-01

    The person who has been treated for cancer may have unique problems resuming employment or starting a new job. Cancer represents a spectrum of diseases, and posttreatment impairments may vary from none, in the majority of cases, to major functional disability. Employers understandably have difficulty recognizing the variability that exists, both in terms of functional capacity and prognosis, and they are often unaware of the improved prognosis for many cancers. Today, many patients receive adjuvant chemotherapy or prolonged intermittent treatment and need to adjust their work schedule to allow for this. Some people need job training or vocational counseling; in many states, vocational rehabilitation agencies now have an increased interest in providing services to cancer patients. Discrimination against the cancer patient has been demonstrated; the major problems are in the area of hiring practices. Efforts need to be continued to educate employers and the public and to ensure that the rights of the cancer patient are recognized. We may, however, do our patients a disservice if we overemphasize potential problems to a degree that increases patient fear and insecurity in regard to employment. Instead, we as physicians may be able to help prevent problems by more effective communication with employers on behalf of our patients, as well as by direct patient counseling. The insurance problems of cancer patients, particularly those relating to health insurance, do require major attention. The potential productivity, as well as the quality of life, of the cancer patient are jeopardized when he or she feels unable to change jobs because of fear of loss of insurance coverage. The relatively high number of reported cancellations and changes in insurance benefits that have been reported by cancer patients also represents an area of concern, since some of these appear medically unjustified. The physician's opinion and input may be of importance in preventing or solving individual insurance problems. The physician can also help the cancer patient who has employment problems by providing information about available resources. The above-mentioned employment booklet (#4585-PS), available from the ACS, may be useful and contains information about legal resources. Referral to a vocational rehabilitation agency may be indicated. The best medicine of all may be a positive and optimistic attitude toward the patient's participation in the work force. PMID:3931869

  17. PATIENT-REPORTED OUTCOMES (PROs): PUTTING THE PATIENT PERSPECTIVE IN PATIENT-CENTERED OUTCOMES RESEARCH

    PubMed Central

    Snyder, Claire F.; Jensen, Roxanne E.; Segal, Jodi B.; Wu, Albert W.

    2013-01-01

    Patient-centered outcomes research (PCOR) aims to improve care quality and patient outcomes by providing information that patients, clinicians, and family members need regarding treatment alternatives, and emphasizing patient input to inform the research process. PCOR capitalizes on available data sources and generates new evidence to provide timely and relevant information and can be conducted using prospective data collection, disease registries, electronic medical records, aggregated results from prior research, and administrative claims. Given PCOR’s emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are critical. PROs are defined by the U.S. Food & Drug Administration as “Any report coming directly from patients… about a health condition and its treatment.” However, PROs have not routinely been collected in a way that facilitates their use in PCOR. Electronic medical records, disease registries, and administrative data have only rarely collected, or been linked to, PROs. Recent technological developments facilitate the electronic collection of PROs and linkage of PRO data, offering new opportunities for putting the patient perspective in PCOR. This paper describes the importance of and methods for using PROs for PCOR. We (1) define PROs; (2) identify how PROs can be used in PCOR, and the critical role of electronic data methods for facilitating the use of PRO data in PCOR; (3) outline the challenges and key unanswered questions that need to be addressed for the routine use of PROs in PCOR; and (4) discuss policy and research interventions to accelerate the integration of PROs with clinical data. PMID:23774513

  18. Transport of the trauma patient.

    PubMed

    Davies, G; Chesters, A

    2015-07-01

    The transport of the seriously injured patient is associated with risk and requires particular expertise and attention. The aim of this review is to provide a historical overview of transport services available to trauma patients in the UK, describe the various transport platforms that are used, identify risks from a system and disease perspective and how they may be mitigated, and make international comparisons. The transfer of patients requiring medical attention has developed over the years and now includes complex undertakings that undoubtedly confer a degree of risk on the patient. A number of different transport platforms are in regular use in the UK, and a number of different health-care professions of varying training, experience, and seniority undertake these transfers. The general principles are to provide no worse care en route than has been provided at the departure destination and to transport patients to a destination capable of delivering whichever intervention the patient is deemed to require. When deciding to transport an injured patient, there are risks, and appropriate mitigation must be in place, particularly if primary transfer to a major trauma centre involves bypassing a nearer facility. It is clear that those clinicians who undertake medical transfers must be appropriately trained and must have access to local or national guidelines. Medical transfers must be the subject of ongoing research, both to ensure that best practice is in place and to continue to understand the safest way of achieving essential transfers effectively. PMID:26089445

  19. Treating statin-intolerant patients

    PubMed Central

    Arca, Marcello; Pigna, Giovanni

    2011-01-01

    Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase) and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients’ adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient. PMID:21779147

  20. RESEARCH Open Access Patient-reported outcomes among patients using

    E-print Network

    Paris-Sud XI, Université de

    (compared with patients who did not meet this endpoint) and Diabetes Health Profile-18 scores (versus of blood glucose, contributes to re- ducing the clinical, psychological, and economic burden of T2DM

  1. Autobiographical Memory in Patients with Tinnitus

    Microsoft Academic Search

    Gerhard Andersson; Christian Ingerholt; Markus Jansson

    2003-01-01

    Studies on psychiatric patients have found that their memories of the past are often unspecific and overgeneral, but the extent to which this is the case for patients with somatic problems has so far only been examined in patients with chronic pain and in patients with diabetes. The present study investigated autobiographical memories in 19 tinnitus patients and 19 controls

  2. Patient Opinions Regarding ‘Pay for Performance for Patients

    PubMed Central

    Helweg-Larsen, Marie; Volpp, Kevin G.

    2008-01-01

    Background Pay for performance (P4P) programs have shown only modest improvements in outcomes and do not target patient behaviors. Many large employers and payers are turning to pay for performance for patients (P4P4P) to reduce health costs and improve the health of their covered populations. How these programs may be perceived by patients is unknown. Objective To assess patients’ opinion of the acceptability of P4P4P. Design Cross-sectional self-administered survey. Participants Patients in waiting rooms in two university-based primary care clinics. Measurements Participants were asked their opinions about paying people to quit smoking, lose weight, control their blood pressure, or control their diabetes. Results Respondents were split on whether P4P4P is desirable. Thrity-six to 42% thought it was a good/excellent idea to pay smokers to quit smoking, obese people to lose weight, people with hypertension to control their blood pressure, or people with diabetes to control their blood sugar, while 41–44% of the sample thought it was a bad/very bad idea. Smokers and patients who were obese endorsed P4P4P more favorably as a means to achieving tobacco cessation and weight loss than their non-smoking and non-obese counterparts. Conclusions Acceptance of paying patients for performance by the general population is equivocal. Establishing the efficacy of paying patients for performance may help it gain wider acceptance. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0739-1) contains supplementary material, which is available to authorized users. PMID:18663540

  3. [Adenovirus infection in immunocompromised patients].

    PubMed

    Rynans, Sylwia; Dzieci?tkowski, Tomasz; M?ynarczyk, Gra?yna

    2013-01-01

    Human adenoviruses belong to the Adenoviridae family and they are divided into seven species, including 56 types. Adenoviruses are common opportunistic pathogens that are rarely associated with clinical symptoms in immunocompetent patients. However, they are emerging pathogens causing morbidity and mortality in recipients of hematopoietic stem cell and solid organ transplants, HIV infected patients and patients with primary immune deficiencies. Clinical presentation ranges from asymptomatic viraemia to respiratory and gastrointestinal disease, haemorrhagic cystitis and severe disseminated illness. There is currently no formally approved therapy for the treatment of adenovirus infections. This article presents current knowledge about adenoviruses, their pathogenicity and information about available methods to diagnose and treat adenoviral infections. PMID:24088540

  4. JAMA Patient Page: Subclinical Hypothyroidism

    MedlinePLUS

    ... the American Medical Association JAMA PATIENT PAGE Subclinical Hypothyroidism T he thyroid gland , a 2-inch-long, ... thyroid to work harder. Subclinical (without obvious symptoms) hypothyroidism (low thyroid function) describes a situation in which ...

  5. JAMA Patient Page: Vaginal Symptoms

    MedlinePLUS

    ... of the American Medical Association JAMA PATIENT PAGE Vaginal Symptoms V aginal symptoms are one of the ... includes an article about diagnosing vaginal symptoms. DIAGNOSING VAGINAL SYMPTOMS FOR MORE INFORMATION • American College of Obstetricians ...

  6. JAMA Patient Page: Acute Sinusitis

    MedlinePLUS

    ... the American Medical Association JAMA PATIENT PAGE Acute Sinusitis R espiratory tract infections, including the common cold ... person to person, and are usually short-lived. Sinusitis (infection of the paranasal sinuses) usually occurs as ...

  7. Medical Technology for Superior Patient

    E-print Network

    Hayden, Nancy J.

    Trusted Medical Technology for Superior Patient Care Technical Services Partnership ­ Comprehensive healthcare technology management and services Technical Services Partnership (TSP) helps healthcare throughout the life cycle Keeping up with the rapid advances in health care technology is a complex

  8. JAMA Patient Page: Palliative Sedation

    MedlinePLUS

    ... or for which treatments have failed have a terminal illness . These patients can receive comfort care, which ... To purchase bulk reprints, call 718/946-7424. Terminal illnesses can cause distressing symptoms, such as severe ...

  9. JAMA Patient Page: Chest Pain

    MedlinePLUS

    ... of the American Medical Association JAMA PATIENT PAGE Chest Pain C hest pain can have many causes. ... about cardiac causes of chest pain. CAUSES OF CHEST PAIN FOR MORE INFORMATION • National Heart, Lung, and ...

  10. Learning problems in neurofibromatosis patients.

    PubMed

    Stine, S B; Adams, W V

    1989-08-01

    Learning problems in patients with neurofibromatosis (NF) are probably the most frequent characteristics after those that define the disorder. They are not secondary to the physical problems. A recent survey that compared children who have NF with their siblings revealed a 37% greater incidence of learning disabilities in the children with NF. Intelligence quotient (IQ) data from several studies indicate that almost all patients with NF have a normal IQ, but there is a progression from low normal to normal as these patients reach adulthood. The most common psychoeducational problems include visual-perceptual-motor delay, spelling and arithmetic disabilities, and a cluster of weaknesses related to cortical organization, similar to those seen in children with attention-deficit disorders. A type of learning disability unique to patients with NF has not been identified, and the diagnosis and treatment of the learning problems are generally the same as for children without NF. PMID:2502350

  11. JAMA Patient Page: Helicobacter pylori

    MedlinePLUS

    ... of the American Medical Association JAMA PATIENT PAGE Helicobacter pylori H elicobacter pylori ( H pylori ) is a common ... of people older than 60 years are affected. Helicobacter pylori is found in the mucous lining of the ...

  12. JAMA Patient Page: Chronic Sinusitis

    MedlinePLUS

    ... Nasal irrigation with salt water may be recommended. • Sinus endoscopy (using a lighted instrument to look at the sinuses through the nose) and endoscopic sinus surgery may be offered to patients who have ...

  13. JAMA Patient Page: Kidney Transplantation

    MedlinePLUS

    ... with renal failure is a candidate for a kidney transplant, so treatment options should be discussed with your ... 2011, issue of JAMA includes an article about kidney transplantation. This Patient Page is based on one published ...

  14. LAPAROSCOPIC HEMINEPHROURETERECTOMY IN PEDIATRIC PATIENTS

    Microsoft Academic Search

    Gunter Janetschek; Jorg Seibold; Christian Radmayr; Georg Bartsch

    1997-01-01

    PurposeAn increasing number of operative procedures in pediatric urology can be performed by laparoscopy. We report our experience with laparoscopic heminephroureterectomy, which is a typical operation in pediatric patients.

  15. Transfusion medicine in trauma patients

    PubMed Central

    Murthi, Sarah B; Dutton, Richard P; Edelman, Bennett B; Scalea, Thomas M; Hess, John R

    2011-01-01

    Injured patients stress the transfusion service with frequent demands for uncrossmatched red cells and plasma, occasional requirements for large amounts of blood products and the need for new and better blood products. Transfusion services stress trauma centers with demands for strict accountability for individual blood component units and adherence to indications in a clinical field where research has been difficult, and guidance opinion-based. New data suggest that the most severely injured patients arrive at the trauma center already coagulopathic and that these patients benefit from prompt, specific, corrective treatment. This research is clarifying trauma system requirements for new blood products and blood-product usage patterns, but the inability to obtain informed consent from severely injured patients remains an obstacle to further research. PMID:21083009

  16. Immunoregulation in pancreatic cancer patients

    Microsoft Academic Search

    Janet M. D. Plate; Susan Shott; Jules E. Harris

    1999-01-01

    Metastatic pancreatic cancer is one of the most aggressive cancer known in man yet specific anti-tumor immunity has been\\u000a demonstrated in lymph nodes draining the sites of pancreatic tumors. Despite this immunity, pancreatic cancer patients suffer\\u000a a quick demise. To further define tumor immunity in patients with metastatic pancreatic cancer, we sought to characterize\\u000a helper T cell subsets, serum cytokines,

  17. Candida infection in surgical patients

    Microsoft Academic Search

    Joseph S. Solomkin; Richard L. Simmons

    1980-01-01

    Candida infections have become a common and serious problem in non-neutropenic general surgical patients. This paper reviews the\\u000a etiologic factors, pathogenesis of systemic candidiasis, and the more common syndromes of infection in surgical patients.\\u000a Prophylactic and systemic therapy is detailed. The most significant factor inCandida infections is depression of host immune function. Significant abnormalities of T-cells, monocytes, and neutrophils have

  18. Antinuclear antibodies in rosacea patients

    PubMed Central

    Salamon, Ma?gorzata; McCauliffe, Daniel; Sysa-J?drzejowska, Anna

    2013-01-01

    Introduction Rosacea is a common inflammatory disorder, characterized by a spectrum of facial manifestations. The clinical similarity to other dermatoses, like lupus erythematosus, might lead to misdiagnosis, particularly in patients with elevated antinuclear antibody titers. Aim To assess the frequency, titer and specificity of antinuclear antibodies in rosacea patients and correlate these findings with clinical features. Material and methods The study included 101 rosacea patients and 26 sex- and age-matched controls. Immunofluorescence antinuclear antibody testing was performed on HEp-2 substrates. Patients’ sera with ANA titers of 1 : 160 or higher were evaluated by Euroline analysis. Results Over a half (53.5%) of rosacea patients had an ANA titer greater than or equal to 1 : 160. Within this group 13.86% had a titer of 1 : 320, 8.91% had a titer of 1 : 640, and 6.93% had a titer of 1 : 1,280 or higher. The specificity of these antibodies could not be identified. Elevated ANA titers were present more often in women (55.8%) than in men (44.15%). Only two of 26 healthy volunteers had elevated ANA titers. One had a titer of 1 : 160 and the other of 1 : 320. During a two-year observation period, after the initial ANA testing, none of the patients with ANA titers above 1 : 640 developed an apparent autoimmune disorder. Conclusions Elevated ANA titers are commonly found in rosacea patients, what with simultaneously existing facial erythema and photosensitivity might lead to misdiagnosis of lupus erythematosus. Clinicians should beware of these findings to avoid misdiagnosing lupus erythematosus in rosacea patients with elevated ANA titers. PMID:24278039

  19. Information technologies and patient safety.

    PubMed

    Ellner, Scott J; Joyner, Paul W

    2012-02-01

    Advances in health information technology provide significant opportunities for improvements in surgical patient safety. The adoption and use of electronic health records can enhance communication along the surgical spectrum of care. Bar coding and radiofrequency identification technology are strategies to prevent retained surgical sponges and for tracking the operating room supply chain. Computerized intraoperative monitoring systems can improve the performance of the operating room team. Automated data registries collect patient information to be analyzed and used for surgical quality improvement. PMID:22269262

  20. [Anal cancer in HIV patients].

    PubMed

    Quéro, Laurent; Duval, Xavier; Abramowitz, Laurent

    2014-11-01

    Despite effective highly active antiretroviral treatment, anal cancer incidence has recently strongly increased in HIV-infected population. Treatment strategy in HIV-infected patients does not differ from general population. HIV-infected patients treated by chemo-radiotherapy are exposed to high-grade toxicities and should be closely monitored to deliver the optimal treatment. Close collaboration between oncologist and infectiologist is highly recommended to adjust antiretroviral therapy if necessary. PMID:25418596

  1. Patient-empowerment interactive technologies.

    PubMed

    Bruggers, Carol S; Altizer, Roger A; Kessler, Robert R; Caldwell, Craig B; Coppersmith, Kurt; Warner, Laura; Davies, Brandon; Paterson, Wade; Wilcken, Jordan; D'Ambrosio, Troy A; German, Massiell L; Hanson, Glen R; Gershan, Lynn A; Korenberg, Julie R; Bulaj, Grzegorz

    2012-09-19

    Video games capture the rapt attention of an individual player's mind and body, providing new opportunities for personalized health care. An example of therapeutic interactive technologies is an incentive-based video game that translates physical exercise into mental empowerment via motivational metaphoric visualization in order to help patients psychologically overcome cancer. Such nonpharmacological interventions may enhance patients' resilience toward various chronic disorders via neuronal mechanisms that activate positive emotions and the reward system. PMID:22993292

  2. Patient Simulators Train Emergency Caregivers

    NASA Technical Reports Server (NTRS)

    2014-01-01

    Johnson Space Center teamed up with Sarasota, Florida-based METI (now CAE Healthcare) through the STTR program to ruggedize the company’s patient simulators for training astronauts in microgravity environments. The design modifications were implemented in future patient simulators that are now used to train first responders in the US military as well as fire departments and other agencies that work in disaster zones.

  3. Patient Safety: Guide to Safe Plastic Surgery

    MedlinePLUS

    ... Gallery Do Your Homework Dangers of Plastic Surgery Tourism Patient and Consumer Information Patients of Courage Patient ... on Breast Implants The Dangers of Plastic Surgery Tourism Plastic Surgery Glossary Menu Cosmetic Reconstructive Articles & Videos ...

  4. Hepatitis C in hemodialysis patients

    PubMed Central

    Marinaki, Smaragdi; Boletis, John N; Sakellariou, Stratigoula; Delladetsima, Ioanna K

    2015-01-01

    Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the “silent” clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the “beneficial” impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of “hepatoprotective” cytokines such as interferon (IFN)-? and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking. PMID:25848478

  5. Postoperative analgesia in elderly patients.

    PubMed

    Falzone, Elisabeth; Hoffmann, Clément; Keita, Hawa

    2013-02-01

    Elderly people represent the fastest-growing segment of our society and undergo surgery more frequently than other age groups. Effective postoperative analgesia is essential in these patients because inadequate pain control after surgery is associated with adverse outcomes in elderly patients. However, management of postoperative pain in older patients may be complicated by a number of factors, including a higher risk of age- and disease-related changes in physiology and disease-drug and drug-drug interactions. Physiological changes related to aging need to be carefully considered because aging is individualized and progressive. Assessment of pain management needs to include chronological age, biological age with regard to renal, liver and cardiac functions, and the individual profile of pathology and prescribed medications. In addition, ways in which pain should be assessed, particularly in patients with cognitive impairment, must be considered. Cognitively intact older patients can use most commonly used unidimensional pain scales such as the visual analogue scale (VAS), verbal rating scale (VRS), numeric rating scale (NRS) and facial pain scale (FPS). VRS and NRS are the most appropriate pain scales for the elderly. In older patients with mild to moderate cognitive impairment, the VRS is a better tool. For severe cognitively impaired older patients, behavioural scales validated in the postoperative context, such as Doloplus-2 or Algoplus, are appropriate. For postoperative pain treatment, most drugs (e.g. paracetamol, nonsteroidal anti-inflammatory drugs, nefopam, tramadol, codeine, morphine, local anaesthetics), techniques (e.g. intravenous morphine titration, subcutaneous morphine, intravenous or epidural patient-controlled analgesia, intrathecal morphine, peripheral nerve block) and strategies (e.g. anticipated intraoperative analgesia or multimodal analgesia) used for acute pain management can be used in older patients. However, in view of pharmacokinetic and pharmacodynamic changes in older persons, the higher incidence of co-morbidities and concurrent use of other drugs, each must be carefully adjusted to suit each patient. Evaluation of treatment efficacy and incidence and severity of adverse events should be monitored closely, and the concept of 'start low and go slow' should be adopted for most analgesic strategies. PMID:23288604

  6. Research without informed patient consent in incompetent patients.

    PubMed

    Dobb, G J

    2015-05-01

    Most patients needing intensive care cannot give informed consent to participation in research. This includes the most acutely and severely ill, with the highest mortality and morbidity where research has the greatest potential to improve patient outcomes. In these circumstances consent is usually sought from a substitute decision maker, but while survivors of intensive care believe substitute decision makers will look after their interests, evidence suggests substitute decision makers are poorly equipped for this task. Various models have been suggested for research without patient informed consent when intervention is urgent and cannot wait until first person consent is possible, including a waiver of consent if conditions are met. A nationally consistent model is proposed for Australia with a robust process for initial waiver of consent followed by first person consent to further research-related procedures or ongoing follow-up when this can be competently provided. PMID:25943603

  7. Assessment of Patient Reported Outcomes (PROs) in Melanoma Patients

    PubMed Central

    Cormier, Janice N.; Askew, Robert L.

    2010-01-01

    SYNOPSIS Assessment of patient reported outcomes (PROs) has been shown to provide important information to assist with clinical decision-making. There has been significant progress in the field of PROs over the last two decades with the introduction of a variety of validated disease- and symptom-specific instruments. The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) is a melanoma-specific module to accompany the FACT-General which has been validated to assess health-related quality of life (HRQOL) for patients with all stages of melanoma. Melanoma-specific health state utilities, which are essential for calculating quality adjusted life years and performing cost-effectiveness studies, have also been reported from a number of studies. Assessment of PROs should be incorporated into routine clinical practice to inform clinicians and researchers of the patient perspective for clinical decision-making and to evaluate the effects of psychosocial and medical interventions. PMID:21111967

  8. Immunoglobulin KM allotypes are associated with the prevalence of autoantibodies to GD1a ganglioside, but not with susceptibility to the disease, in Japanese patients with Guillain–Barré syndrome

    Microsoft Academic Search

    Janardan P. Pandey; Michiaki Koga; Nobuhiro Yuki

    2005-01-01

    Guillain–Barré syndrome (GBS), an autoimmune disease of the peripheral nervous system, is associated with antecedent Campylobacter jejuni infection. GM and KM allotypes—genetic markers of immunoglobulin ? and ? chains, respectively—are implicated in the etiopathogenesis\\u000a of several autoimmune diseases. To determine if GM\\/KM phenotypes are associated with GBS and influence antibody responses\\u000a to C. jejuni and to GM1 and GD1a gangliosides,

  9. [Exercise testing in cardiac patients].

    PubMed

    Koike, A; Hiroe, M; Marumo, F

    1995-08-01

    Symptom-limited incremental exercise tests have been used, to estimate the severity of cardiovascular disease and the patients' daily activity. However, there is a considerable amount of interest in obtaining submaximal measurements of aerobic function rather than parameters requiring maximal exercise effort. We compared the parameters obtained during the incremental exercise with those during the 6 minutes of moderate constant work rate exercise. Peak oxygen uptake (VO2) and the anaerobic threshold were significantly decreased in patients with cardiovascular disease as compared to normal subjects. The slope of the increase in carbon dioxide output (VCO2) to the increase in VO2 (delta VCO2/delta VO2) above the anaerobic threshold was significantly increased and the slope of the increase in VO2 to the increase in work rate (delta VO2/delta WR) was significantly decreased in patients with cardiovascular disease. The anaerobic threshold was found to occur at the work rate above which left ventricular function decreased during exercise in these patients. The time constant of VO2 during and following recovery from 6 minutes of 50 watts of constant work rate exercise was significantly longer (the kinetics of VO2 were slower) in patients with cardiovascular disease than in normal subjects. The time constant of VO2 was significantly negatively correlated with peak VO2 and maximum work rate obtained during the incremental exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7474442

  10. [COMMUNICATION WITH TERMINALLY ILL PATIENT].

    PubMed

    2014-12-01

    The communication is a essential therapeutic instrument in every process of relationship in the team patient-family, and mainly in the transmission of bad news. The communication is not just a simple transmission of information. It is a process whose goal is to enable the adaptation of the patient and family to their actual situation and where the "what", "how" and "how much do you want to know", are belonged to the own patient. Along this article, we will expose some thoughts that the team has to take into account when informing the patient. We are going to explain the SPIKES protocol, or its Spanish version EPICEE. 6-step protocol, based on those recommended by the experts to deliver bad news procedures. And finally we'll talk about the conspiracy of silence, one of the most common and difficult situations to handle in day to day due to paternalism by professionals and families, in which they prefer to hide the situation to the patient, thinking it's the best for him. PMID:26121886

  11. Creating Simulated Microgravity Patient Models

    NASA Technical Reports Server (NTRS)

    Hurst, Victor; Doerr, Harold K.; Bacal, Kira

    2004-01-01

    The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

  12. Audiological Manifestations in Vitiligo Patients

    PubMed Central

    Mahdi, Parvane; Rouzbahani, Masomeh; Amali, Amin; Rezaii Khiabanlu, Samad; Kamali, Mohammad

    2012-01-01

    Introduction: The hallmark of vitiligo is the disappearance of melanocytes from the skin due to an as yet unidentified mechanism. The presence of melanocytes in the auditory apparatus suggests that this system could possibly be affected by vitiligo, which targets the melanocytes of the whole body and not just the skin. The purpose of this study was to assess the incidence of auditory alterations in patients with vitiligo Materials and Methods: A total of 21 patients diagnosed with vitiligo were enrolled in this study. A group of 20 healthy subjects served as a control group. Pure tone audiometry (PTA) and measurements of auditory brain stem responses (ABR) were carried out in all participants. Results: High frequency sensory neural hearing loss was detected in 8 patients (38.09%). Analysis of ABR revealed that 10 patients (47.61%) had an abnormal increase in the latency of Wave III and 6 (28.57%) had an abnormal prolongation of the inter peak latency between Wave I and III. There was no correlation between age, duration of disease, and any of the recorded parameters. Conclusion: This study highlights the involvement of the auditory system in patients with vitiligo, suggesting that vitiligo is a systemic disease rather than a purely cutaneous problem. PMID:24303383

  13. Behçet's disease in Iraqi patients.

    PubMed Central

    Al-Rawi, Z S; Sharquie, K E; Khalifa, S J; Al-Hadithi, F M; Munir, J J

    1986-01-01

    The clinical features of 60 patients (45 male, 15 female) with Behçet's disease (BD) are reported in this prospective study. Ninety seven per cent had mouth ulceration, 83% genital ulceration, 75% skin lesions, 48% ocular involvement, 48% synovitis, 17% thrombophlebitis, and 22% of the male patients had epidiymitis, while constitutional symptoms were reported by 63%. The arthritis was intermittent, self limiting, and non-destructive, involving large joints, mainly the knees and ankles. The pathergy test was positive in 37 of 52 patients with BD, and negative in all 120 healthy controls and in 20 healthy volunteers who possessed the HLA-B51 antigen. HLA-B51 was present in 32 of 52 (62%) patients with BD compared with 51 of 175 (29%) unrelated normal controls. Both the pathergy and HLA-B51 tests were negative in four of 52 patients with BD. Behçet's disease is not uncommon in Iraq. Practising physicians, dermatologists, and ophthalmologists must be more aware of its existence. PMID:3813669

  14. Bedside Evaluation of Dizzy Patients

    PubMed Central

    Huh, Young-Eun

    2013-01-01

    In recent decades there has been marked progress in the imaging and laboratory evaluation of dizzy patients. However, detailed history taking and comprehensive bedside neurotological evaluation remain crucial for a diagnosis of dizziness. Bedside neurotological evaluation should include examinations for ocular alignment, spontaneous and gaze-evoked nystagmus, the vestibulo-ocular reflex, saccades, smooth pursuit, and balance. In patients with acute spontaneous vertigo, negative head impulse test, direction-changing nystagmus, and skew deviation mostly indicate central vestibular disorders. In contrast, patients with unilateral peripheral deafferentation invariably have a positive head impulse test and mixed horizontal-torsional nystagmus beating away from the lesion side. Since suppression by visual fixation is the rule in peripheral nystagmus and is frequent even in central nystagmus, removal of visual fixation using Frenzel glasses is required for the proper evaluation of central as well as peripheral nystagmus. Head-shaking, cranial vibration, hyperventilation, pressure to the external auditory canal, and loud sounds may disclose underlying vestibular dysfunction by inducing nystagmus or modulating the spontaneous nystagmus. In patients with positional vertigo, the diagnosis can be made by determining patterns of the nystagmus induced during various positional maneuvers that include straight head hanging, the Dix-Hallpike maneuver, supine head roll, and head turning and bending while sitting. Abnormal smooth pursuit and saccades, and severe imbalance also indicate central pathologies. Physicians should be familiar with bedside neurotological examinations and be aware of the clinical implications of the findings when evaluating dizzy patients. PMID:24285961

  15. Age-Related Differences in Doctor-Patient Interaction and Patient Satisfaction

    PubMed Central

    Peck, B. Mitchell

    2011-01-01

    Background. Relatively little is known about patient characteristics associated with doctor-patient interaction style and satisfaction with the medical visit. Objective. The primary study objectives are to assess: whether doctors interact in a more or less patient-centered style with elderly patients and whether patient age moderates the relationship between interaction style and satisfaction, that is, whether elderly patients are more or less satisfied with patient-centered medical encounters. Methods. We collected pre- and post-visit questionnaire data from 177 patients at a large family medicine clinic. We audiotaped the encounters between doctors and patients. Patient-centered interaction style was measured from coding from the audiotapes of the doctor-patient interactions. Patient satisfaction was measured using the Patient Satisfaction Questionnaire. Results. We found physicians were more likely to have patient-centered encounters with patients over age 65. We also found patient age moderated the association between interaction style and patient satisfaction: older patients were more satisfied with patient-centered encounters. Conclusion. Patient age is associated with style of interaction, which is, in turn, associated with patient satisfaction. Understanding the factors and processes by which doctors and patients interact has the potential to improve many facets of health care delivery. PMID:22007206

  16. Transforming consumer health informatics through a patient work framework: connecting patients to context.

    PubMed

    Valdez, Rupa S; Holden, Richard J; Novak, Laurie L; Veinot, Tiffany C

    2015-01-01

    Designing patient-centered consumer health informatics (CHI) applications requires understanding and creating alignment with patients' and their family members' health-related activities, referred to here as 'patient work'. A patient work approach to CHI draws on medical social science and human factors engineering models and simultaneously attends to patients, their family members, activities, and context. A patient work approach extends existing approaches to CHI design that are responsive to patients' biomedical realities and personal skills and behaviors. It focuses on the embeddedness of patients' health management in larger processes and contexts and prioritizes patients' perspectives on illness management. Future research is required to advance (1) theories of patient work, (2) methods for assessing patient work, and (3) techniques for translating knowledge of patient work into CHI application design. Advancing a patient work approach within CHI is integral to developing and deploying consumer-facing technologies that are integrated with patients' everyday lives. PMID:25125685

  17. Polyneuropathy in critically ill patients.

    PubMed Central

    Bolton, C F; Gilbert, J J; Hahn, A F; Sibbald, W J

    1984-01-01

    Five patients developed a severe motor and sensory polyneuropathy at the peak of critical illness (sepsis and multiorgan dysfunction complicating a variety of primary illnesses). Difficulties in weaning from the ventilator as the critical illness subsided and the development of flaccid and areflexic limbs were early clinical signs. However, electrophysiological studies, especially needle electrode examination of skeletal muscle, provided the definite evidence of polyneuropathy. The cause is uncertain, but the electrophysiological and morphological features indicate a primary axonal polyneuropathy with sparing of the central nervous system. Nutritional factors may have played a role, since the polyneuropathy improved in all five patients after total parenteral nutrition had been started, including the three patients who later died of unrelated causes. The features allow diagnosis during life, and encourage continued intensive management since recovery from the polyneuropathy may occur. Images PMID:6094735

  18. The diabetic patient in Ramadan.

    PubMed

    Chamsi-Pasha, Hassan; Aljabri, Khalid S

    2014-04-01

    During the month of Ramadan, all healthy, adult Muslims are required to fast from dawn to sunset. Fasting during Ramadan involves abstaining from food, water, beverages, smoking, oral drugs, and sexual intercourse. Although the Quran exempts chronically ill from fasting, many Muslims with diabetes still fast during Ramadan. Patients with diabetes who fast during the month of Ramadan can have acute complications. The risk of complications in fasting individuals with diabetes increases with longer periods of fasting. All patients with diabetes who wish to fast during Ramadan should be prepared by undergoing a medical assessment and engaging in a structured education program to undertake the fast as safely as possible. Although some guidelines do exist, there is an overwhelming need for better designed clinical trials which could provide us with evidence-based information and guidance in the management of patients with diabetes fasting Ramadan. PMID:24761380

  19. Influenza vaccination in oncology patients.

    PubMed

    Baluch, Aliyah; Pasikhova, Yanina

    2013-12-01

    It is well established that the immunological response to the seasonal trivalent influenza vaccine is attenuated in cancer patients. Furthermore, rates of seroprotection and seroconversion vary by malignancy type and are higher in patients with solid tumors, as compared either with those with hematologic malignancies or with allogeneic hematopoietic stem cell recipients. In 2009, a novel influenza strain prompted development of new vaccines and evaluation of alternative dosing strategies in an attempt to increase the rates of seroconversion in immunocompromised patients, further complicating this issue. Recent literature has demonstrated that the use of myeloablative chemotherapy regimens and biologics is correlated with decreased immunogenicity and response to influenza vaccines. Much debate still exists as to the optimal timing of influenza vaccination. Delaying vaccination from 1 week following standard chemotherapy up to 6 months following rituximab is increasingly supported by studies in this heterogeneous population. PMID:24258350

  20. Dermatoglyphics in patients with schizophrenia*

    PubMed Central

    Shakibaei, Fereshteh; Asadollahi, Ghorban Ali; Tabibi, Amirpooyan

    2011-01-01

    BACKGROUND: There are controversial evidences on the association between fingerprint traits and schizophrenia. We compared fingerprint traits of patients with schizophrenia and normal individuals in Iranian population. METHODS: Finger tip dermal ridge of 290 patients with schizophrenia and 290 normal subjects were studied for four dermal traits. Data was analyzed with Pearson correlation and student's tests. RESULTS: Finger print patterns and secondary creases were not significantly different between the two groups (p > 0.05). Although mean ridge counts of left and right index fingers of the case group were greater than the control group (p < 0.05), these differences were not significant in females. CONCLUSIONS: Probably the left index ridge counts and fluctuating asymmetry in schizophrenic patients are different from those of the normal population. This difference may serve as a diagnostic biological marker for screening people susceptible to schizophrenia. Further studies are needed to determine predictive value of fingerprint trait as a biomarker for the schizophrenia. PMID:22279482

  1. The diabetic patient in Ramadan

    PubMed Central

    Chamsi-Pasha, Hassan; Aljabri, Khalid S.

    2014-01-01

    During the month of Ramadan, all healthy, adult Muslims are required to fast from dawn to sunset. Fasting during Ramadan involves abstaining from food, water, beverages, smoking, oral drugs, and sexual intercourse. Although the Quran exempts chronically ill from fasting, many Muslims with diabetes still fast during Ramadan. Patients with diabetes who fast during the month of Ramadan can have acute complications. The risk of complications in fasting individuals with diabetes increases with longer periods of fasting. All patients with diabetes who wish to fast during Ramadan should be prepared by undergoing a medical assessment and engaging in a structured education program to undertake the fast as safely as possible. Although some guidelines do exist, there is an overwhelming need for better designed clinical trials which could provide us with evidence-based information and guidance in the management of patients with diabetes fasting Ramadan. PMID:24761380

  2. [Enteral feeding of critical patients].

    PubMed

    Gómez-Garrido, M; Martínez González, E; Botella Romero, F; Gómez-Garrido, J

    2009-01-01

    Artificial nutrition support forms part of the basic care of critical patients. Enteral feeding has been shown to be better than total parenteral nutrition at improving morbidity (infectious complications) and reducing the length of hospital stays, number of days with mechanical ventilation, and costs. As with any other treatment, enteral feeding has associated complications and side effects which should be understood and treated in order to obtain the greatest benefit from it and reduce possible adverse effects. In this review, we attempt to provide a practical summary of the use of enteral feeding in critical patients. We cover the management of the most frequent associated complications, based on new studies and current scientific evidence. The review is intended to serve as a practice guide for the routine care of severely ill patients. PMID:19284126

  3. Seizure Treatment in Transplant Patients

    PubMed Central

    Shepard, Paul W.

    2013-01-01

    Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and fosphenytoin are the traditional and best evidence-based options, although intravenous levetiracetam, valproate, and lacosamide are emerging options. Availability of several newer AEDs has greatly expanded the therapeutic armamentarium for safe and efficacious treatment of post-transplant seizures, but future prospective clinical trials and pharmacokinetic studies within this specific patient population are needed. PMID:22660960

  4. Deinstitutionalizing Elderly Patients: A Program of Resocialization

    ERIC Educational Resources Information Center

    Siegel, Barry; Lasker, Judith

    1978-01-01

    In a program of deinstitutionalization 61 elderly state hospital patients were successfully placed outside the institution. Changes in definition of the patients' situation, collective approach to resocialization, careful medical evaluation, and familiarity of patients with possible alternatives help reduce patients' commitment to the institution…

  5. Determinants of Compliance among Pediatric Amblyopia Patients.

    ERIC Educational Resources Information Center

    Wolff, Hans; Juhasz, Anne McCreary

    Given the recent focus on patient responsibility for health status and improvement, it is important to understand the dynamics involved in patient compliance to treatment regimens. The determinants of patching compliance among 30 pediatric amblyopia patients and their parents were investigated by means of parent, patient, and physician…

  6. Rehabilitation of the elderly patient on dialysis

    Microsoft Academic Search

    Nancy G. Kutner

    1996-01-01

    Rehabilitation for geriatric patients, as well as rehabilitation for patients with a chronic disease, strives to mobilize individuals' residual capacity for optimal function in their usual environment. It is clear from observational studies that chronic dialysis patients often experience marked limitations in physical functioning, and these limitations tend to increase with patients' age. However, both prospective studies and controlled trials

  7. Mortality in patients treated for pulmonary embolism

    Microsoft Academic Search

    Joseph S. Alpert; Roger E. Smith; C. Jeffrey Carlson; Ira S. Ockene; Lewis Dexter; James E. Dalen

    1976-01-01

    The hospital course of 144 consecutive patients with pulmonary embolism (PE) demonstrated by pulmonary angiography was reviewed to determine the mortality of patients with treated PE. Twelve patients (8%) died of PE, and eight died of causes other than PE; 124 (86%) survived. Pulmonary embolism was the primary cause of death in only four of the 12 patients who died

  8. ACE inhibitors and survival of hemodialysis patients

    Microsoft Academic Search

    Shai Efrati; Ronit Zaidenstein; Victor Dishy; Ilia Beberashvili; Moshe Sharist; Zhan Averbukh; Ahuva Golik; Joshua Weissgarten

    2002-01-01

    Background: Cardiovascular disease is a leading cause of death in patients with end-stage renal disease (ESRD). Hypertension is a major risk factor for cardiovascular complications in these patients. Angiotensin-converting enzyme (ACE) inhibitors are an effective treatment for hypertension in patients with ESRD and are known to improve prognosis in patients with chronic renal failure. We investigated their effect on mortality

  9. The dose of hemodialysis and patient mortality

    Microsoft Academic Search

    Philip J Held; Friedrich K Port; Robert A Wolfe; David C Stannard; Caitlin E Carroll; John T Daugirdas; Wendy E Bloembergen; Joel W Greer; Raymond M Hakim

    1996-01-01

    The dose of hemodialysis and patient mortality. The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study

  10. Online statistical monitoring of critical patient data increases patient safety

    Microsoft Academic Search

    Svante Lifvergren; Alexander Chakunashvili; Bo Bergman; Peter Docherty

    2008-01-01

    In this paper we present an improvement project conducted at a unit responsible for blood thinning treatment at Lidkoping hospital in Sweden. The unit coordinates and monitors the treatment of 1200 patients and consists of a heart specialist and five specially trained nurses. Warfarin is an oral anticoagulant (blood thinning) treatment effective for the prevention and treatment of thromboembolic events

  11. Stakeholders in Cutaneous Investigation: Patients and Patient Advocates Are Essential

    Microsoft Academic Search

    Paul R Bergstresser; John T Grupenhoff; Vicki Kalabokes

    2012-01-01

    A diverse array of stakeholders supports biomedical investigation, the major goal of which is to improve human health. For patients with dermatological disease, the Coalition of Skin Diseases (CSD) has for more than two decades provided a base from which public advocacy, education, fund-raising, and communication have flourished. Their efforts, combined with that of investigators and national funding agencies, have

  12. Patient Dose in Diagnostic Radiology

    NASA Astrophysics Data System (ADS)

    Noel, Alain

    One of the basic principles, stated explicitly in Article 4 of the EC Council Directive 97/43 Euratom, is optimization. This means that all radiological examinations should be performed with a dose that is As Low As Reasonably Achievable (ALARA principle applied to the protection of the patient) in order to obtain the required diagnostic information. Therefore, dose needs to be determined with the relationship between image quality and dose always kept in mind. In this paper, radiation quantities and units to report patient doses in diagnostic radiology will be identified.

  13. Space Technology for Patient Monitoring

    NASA Astrophysics Data System (ADS)

    1989-01-01

    A contract for the development of an astronaut monitoring system in the early days of the space program provided Mennen Medical, Inc. with a foundation in telemetry that led to the development of a computerized medical electronic system used by hospitals. Mennen was the first company to adopt solid state design in patient monitoring and to offer multipatient telemetry monitoring. Telemetry converts instrument data to electrical signals and relays them to a remote receiver where they are displayed. From a central station, a nurse can monitor several patients. Company products include VISTA systems and Horizon 2000 Monitor.

  14. Dyspnea Management of Hospice Patients.

    PubMed

    Beasley, Amy; Stanton, Marietta; Aldridge, Julie

    2015-01-01

    Up to 70% of hospice patients are reported to experience dyspnea at end of life. Despite the high prevalence of this burdensome symptom, there is little in the literature to guide effective treatment. Assessment of subjective symptoms and objective signs as well as physical, psychospiritual, sociocultural, or environmental barriers is critical to an effective plan of care. The purpose of the article is to review the current literature on assessment and management of dyspnea in hospice patients and provide implications for hospice clinicians. PMID:26121510

  15. Patient-friendly financial options.

    PubMed

    Levin, R P

    1999-03-01

    Having flexible payment options ensures that patients will have all of the motivation and information they need to accept care in your office. The HCCC simply offers the chance to make more expensive treatment available to those who need or want it. The small cost of using a HCCC program more than pays for itself--in fact, it costs less than one-third of what you would spend if you were to bill these patients instead. Having consistent financial policies and flexible payment options can dramatically increase your office's productivity and profitability, while expressing your commitment to customer service and high-quality dentistry. PMID:10344121

  16. Perioperative management of elderly patients.

    PubMed

    Schlitzkus, Lisa L; Melin, Alyson A; Johanning, Jason M; Schenarts, Paul J

    2015-04-01

    The older population only represents 13.7% of the US population but has grown by 21% since 2002. The centenarian population is growing at a faster rate than the total US population. This unprecedented growth has significantly increased surgical demand. The establishment of quality and performance improvement data has allowed researchers to focus attention on the older patient population, resulting in an exponential increase in studies. Although there is still much work to be done in this field, overlying themes regarding the perioperative management of elderly patients are presented in this article based on a thorough literature review. PMID:25814114

  17. Contact dermatitis in hospital patients.

    PubMed

    Ancona, A; Arévalo, A; Macotela, E

    1990-01-01

    Contact dermatitis in hospital patients resulting from diagnostic and therapeutic procedures presents various causes and clinical aspects. Antiseptics are the most frequent cause of contact dermatitis in patients undergoing surgery. Thimerosal may cause allergic sensitization mainly in patients previously exposed to contact with different sources of these mercurials, such as tinctures and preservatives in other products. Iodine-containing solutions and quaternary ammonium compounds rarely sensitize. They may cause irritation under certain circumstances, however. Adhesive tapes formulated on a rubber and colophony base are rarely found nowadays in medical adhesives; however, some tapes and skin closures have still been found to contain them. Acrylate-based adhesives sensitize less frequently. Cardiology patients may present contact dermatitis from several different sources. Electrode gels and pastes may cause allergic contact dermatitis mainly from preservatives. Modern electrocardiographic equipment does not require the use of these products, so many of these problems are now easy to avoid. Adhesive-coated pregelled foam disks for holding long-term chest contacts may cause irritant dermatitis. Transdermal drug delivery systems such as nitroglycerin disks may cause irritation attributable to the acrylic adhesives. Silicone-based adhesive disks are a good alternative in this case. Sensitization to nitroglycerin itself is rare. Dermatitis originated from implantation of pacemakers is attributable either to epoxy resin or to the metal used for the casing of the pacemaker. Changing to a different material solves the problem. In other instances, the etiology remains unclear. Dermatoses in patients with stomas constitute an important problem not only because of their frequency but also because of the multiplicity of pictures involved. Irritant dermatitis from intestinal efflux in ileostomy patients is the most frequent problem. Allergic dermatitis may originate from the ostomy device, cementing materials, or topical medicaments. Individuals receiving hemodialysis have been reported to develop widespread dermatitis, probably secondary to rubber or metal components leached out from the hemodialysis apparatus. Systemic exposure to these compounds, although not certainly proved, seems to be the explanation. Allergic dermatitis at the puncture site on arteriovenous shunts has been demonstrated to be produced by epoxy resin adhesives present in catheters. Identification of the allergen allows one to find a safe alternative for these patients who depend on this procedure to survive. Contact dermatitis in hospital patients requires a precise diagnosis. Extensive patch testing is sometimes needed for establishing the cause, which in turn provides a more accurate prognosis and a rational treatment. PMID:2406065

  18. [Other treatments for depressive patients].

    PubMed

    Tamaoki, Toshio; Motohashi, Nobutaka

    2007-09-01

    Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT. PMID:17876990

  19. Treatment utilization by patients with personality disorders

    Microsoft Academic Search

    Donna S. Bender; Regina T. Dolan; Andrew E. Skodol; Charles A. Sanislow; Ingrid R. Dyck; Thomas H. McGlashan; M. Tracie Shea; Mary C. Zanarini; John M. Oldham; John G. Gunderson

    2001-01-01

    Objective: Utilization of mental health treatment was compared in patients with personality disorders and patients with major depressive disorder without personality disorder.\\u000aMethod: Semistructured interviews were used to assess diagnosis and treatment history of 664 patients in four representative personality disorder groups—schizotypal, borderline, avoidant, and obsessive-compulsive—and in a comparison group of patients with major depressive disorder.\\u000aResults: Patients with personality

  20. Ergonomics: safe patient handling and mobility.

    PubMed

    Hallmark, Beth; Mechan, Patricia; Shores, Lynne

    2015-03-01

    This article reviews and investigates the issues surrounding ergonomics, with a specific focus on safe patient handling and mobility. The health care worker of today faces many challenges, one of which is related to the safety of patients. Safe patient handling and mobility is on the forefront of the movement to improve patient safety. This article reviews the risks associated with patient handling and mobility, and informs the reader of current evidence-based practice relevant to this area of care. PMID:25680494

  1. Peak bone mass in patients with phenylketonuria

    Microsoft Academic Search

    D. Modan-Moses; I. Vered; G. Schwartz; Y. Anikster; S. Abraham; R. Segev; Ori Efrati

    2007-01-01

    Summary  \\u000a Objective: Several studies have suggested a compromised bone mass in phenylketonuria patients but most reported on heterogeneous or\\u000a small patient groups. Our aim was to evaluate peak bone mass in adult PKU patients and to relate BMD to nutritional parameters.\\u000a Patients and methods: BMD was measured by dual-energy x-ray absorptiometry in 31 adult PKU patients (18 female), mean age

  2. Prescribing Exercise for Patients with Diabetes

    Microsoft Academic Search

    Dalynn T. Badenhop

    Exercise prescription for patients with diabetes follows guidelines regarding frequency, intensity, duration, and mode of\\u000a exercise established for patients participating in a medically supervised exercise program. Physicians and health care professionals\\u000a should devise an exercise care plan that maximizes the benefits and minimizes the risks for each patient. The distinction\\u000a between prescribing exercise for patients with T1DM and patients with

  3. An intelligent assistant for patient health care

    Microsoft Academic Search

    Silvia Miksch; Kenneth Cheng; Barbara Hayes-Roth

    1997-01-01

    The Patient Advocate is designed to be an intelligent assistant for patient-centered health care. Residing on a home computer or special-purpose device and operating within an extended health-care information network, the Patient Advocate will extend medical expertise into the outpatient setting. It will have remote access to the patient's medical record, an understanding of the patient's health status and history,

  4. [Enriching patient care with aromatherapy].

    PubMed

    Sogno-Lalloz, Isabelle

    2014-01-01

    There are increasing numbers of initiatives in healthcare institutions focusing on the benefits of essential oils. Received positively by patients who appreciate the resulting wellbeing, these innovative approaches around aromatherapy are based on the initiative of pioneering caregivers. Following on from an international congress held each year in Grasse, this article presents some example schemes. PMID:25065196

  5. Physicians' Reactions to Overweight Patients

    NSDL National Science Digital Library

    Lane, David M.

    This case study, by David M. Lane of Rice University, assesses the question, "Do physicians discriminate against overweight patients?" This study indicates that, at least in one respect, they do. Basic concepts are t-test, means, and boxplots. The experimental design, materials, descriptive statistics, inferential statistics, and raw data are given.

  6. Our Chancellor UCSF Patient Care

    E-print Network

    Klein, Ophir

    generates: In San Francisco: 32,110 jobs (including those at UCSF) and produces an esti- mated $4.7 billion by employees, students and visitors. In the nine-county San Francisco Bay Area: 39,134 jobs (including thoseOur Chancellor UCSF Patient Care San Francisco Powerhouse About UCSF UCSF Research Funding Sam

  7. Our Chancellor UCSF Patient Care

    E-print Network

    Mullins, Dyche

    impact report, UCSF generates: In San Francisco: 32,110 jobs (including those at UCSF) and producesOur Chancellor UCSF Patient Care San Francisco Powerhouse About UCSF UCSF Research Funding Sam Francisco's energy, innovation and diversity. UCSF capitalizes on our proximity to other San Francisco Bay

  8. Our Chancellor UCSF Patient Care

    E-print Network

    Yamamoto, Keith

    impact report, UCSF generates: In San Francisco: 32,110 jobs (including those at UCSF) and producesOur Chancellor UCSF Patient Care San Francisco Powerhouse About UCSF UCSF Research Funding Susan Francisco's energy, innovation and diversity. UCSF capitalizes on our proximity to other San Francisco Bay

  9. Our Chancellor UCSF Patient Care

    E-print Network

    Lim, Wendell

    impact report, UCSF generates: In San Francisco: 32,110 jobs (including those at UCSF) and producesOur Chancellor UCSF Patient Care San Francisco Powerhouse About UCSF UCSF Research Funding Sam Children's Hospital San Francisco rankamong the nation's best hospitals. Together, these hospitals have 722

  10. Our Chancellor UCSF Patient Care

    E-print Network

    Yamamoto, Keith

    report, UCSF generates: In San Francisco: 32,110 jobs (including those at UCSF) and produces an estiOur Chancellor UCSF Patient Care San Francisco Powerhouse About UCSF UCSF Research Funding Susan contributor to San Francisco's energy, innovation and diversity. UCSF capitalizes on our proximity to other

  11. Pseudogout in a young patient

    Microsoft Academic Search

    M. Hammoudeh; A. R. Siam

    1998-01-01

    Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is conventionally classified into cases that are hereditary, idiopathic (sporadic) or associated with other disorders. In the idiopathic form, the disease usually occurs in middle-aged or elderly patients. An earlier age of disease onset is observed in the hereditary form and the form associated with other disorders. Therefore, the occurrence of CPPD crystal

  12. Patients with primary brain tumors.

    PubMed

    Behrend, Susan Weiss

    2014-05-01

    The purpose of this prospective phase II/III trial was to study the effect of therapy intensification when combining procarbazine, lomustine, and vincristine (PCV) chemotherapy with a standard course of radiation therapy (RT) on cognitive functioning for patients with World Health Organization grade 2 low-grade gliomas (LGGs). Initial results of the trial demonstrated a progression-free survival benefit with adjuvant PCV, but no overall survival benefit in the intention-to-treat analysis. Because patients with LGGs have favorable prognostic indicators, the five-year overall survival rates range from 60%-70%. The effect of cancer treatment on neurocognitive function is a topic of increasing interest to healthcare providers and patients. The negative effect is commonly called "chemobrain" and refers to diminished concentration and compromised short-term memory following treatment. Chemobrain has been studied in other populations of patients with cancer (e.g., breast cancer) with associated statistically significant chemotherapy-associated compromised cognitive function when chemotherapy was added to RT. PMID:24769600

  13. Exercise for the Overweight Patient.

    ERIC Educational Resources Information Center

    Work, Janis A.

    1990-01-01

    Exercise can help patients maintain lean body mass during weight loss. Although exercise is not extremely useful in shedding excess pounds, it helps keep off weight lost through calorie restriction. This article discusses the specifics of exercise prescription, types of exercise, motivation to exercise, and special problems such as diabetes. (SM)

  14. Patient advocacy: barriers and facilitators

    Microsoft Academic Search

    Reza Negarandeh; Fatemeh Oskouie; Fazlollah Ahmadi; Mansoure Nikravesh; Ingalill Rahm Hallberg

    2006-01-01

    BACKGROUND: During the two recent decades, advocacy has been a topic of much debate in the nursing profession. Although advocacy has embraced a crucial role for nurses, its extent is often limited in practice. While a variety of studies have been generated all over the world, barriers and facilitators in the patient advocacy have not been completely identified. This article

  15. Transferrin changes in haemodialysed patients.

    PubMed

    Formanowicz, Dorota; Formanowicz, Piotr

    2012-06-01

    Transferrin (Tf) is a glycoprotein responsible for iron transport in the human body. Physiologically in reaction with Concanavalin A, Tf occurs in four distinct variants Tf1, Tf2, Tf3 (apo-Tf) and Tf4. It was reported recently that Tf is changing, particularly during acute phase response, taking place among others in end-stage renal disease. In this study, we wanted to find the answer to three main questions: firstly, how Tf is changing in patients treated with maintenance haemodialysis (mHD), secondly, whether there are any Tf changes in the course of mHD treatment, and thirdly, what factors can affect Tf microheterogeneity in these patients. Studies were performed on 80 haemodialysed patients and 21 healthy volunteers. The Tf concentration was determined by the rocket immunoelectrophoresis, and its microheterogeneity was assessed by the ConA crossed immunoaffinity electrophoresis. During the annual observation of the distribution of the Tf variants, we have found both changes of the percentage contents of all Tf variants in the whole Tf concentration and a significant decrease in Tf2, Tf3 and Tf4 serum concentrations. Moreover, we found that decrease in the renal function, duration of mHD, and inflammation may contribute to these above-mentioned changes, which are probably the factors that should be taken into account when explaining the mechanisms of persistence of anaemia in haemodialysed patients. PMID:21455763

  16. JAMA Patient Page: Head Lice

    MedlinePLUS

    JAMA PATIENT PAGE Head Lice Removal of nits Louse on scalp Nits are tightly attached to strands of hair Lice are free and crawl ... sharing combs or brushes with someone who has head lice. Having head lice does not mean you have ...

  17. Managing aggressive and violent patients

    Microsoft Academic Search

    Gordian Fulde; Paul Preisz

    2011-01-01

    All healthcare workers, especially general practitioners and staff in emergency departments, are likely to encounter aggression and violence. This behaviour may be caused by a medical illness, a psychiatric illness or drug intoxication or withdrawal. These problems can occur in combination. It is important that a diagnosis is made, but in some cases the patient may need sedation before they

  18. Evaluation of Online Patient Safety

    E-print Network

    Connor, Ed

    , 2009) The Armstrong Institute's (AI) online program uses distance learning to train clinicians in how/Docu ments/Ambient-Insight-2009-US-Academic- eLearning-Market.pdf . (2) Armstrong institute online patient, and time and resource constraints precluded major content changes. (2) AI online program development staff

  19. JAMA Patient Page: Myocardial Infarction

    MedlinePLUS

    ... Heart Blocked Coronary Artery Insertion of Stent After Balloon Angioplasty Stent in Place and Blood Flow Restored Aorta Femoral artery Catheter for stent insertion H E A R T D I S E A S E The Journal of the American Medical Association JAMA PATIENT PAGE Myocardial Infarction M yocardial ...

  20. Hospital treatment of HIV patients.

    PubMed

    Ola, Samuel Olawale

    2006-12-01

    Treatment of patients with HIV/AIDS in Nigeria has progressed from the stage of inactivity, unconcern, abandonment and neglect to the present stage of holistic care involving treatment of the infection with Highly Active Anti Retroviral Agents, complications of the disease and side effects of antiretroviral therapy as well as that of human behavioural responses towards the disease with hope and promising outcome. The goal of the treatment is to prolong the patient's life while maintaining the best possible quality of health and life. It is now a continuum of care between the hospital and the different sectors of the community. Hospital treatment of patients with HIV-AIDS is complex and yet a simple task if there is healthy interaction of the patients and health care providers in a milieu of well equipped hospital setting with available treatment facilities for proper management of diseases. Similarly, for the care to achieve its goal, it requires a joint participation of the community and the commitment of the government not only on curtailment of the reservoir of HIV infection by antiretroviral therapy but total eradication of diseases, poverty and ignorance in all its entirety. PMID:18050774

  1. JAMA Patient Page: Brain Death

    MedlinePLUS

    ... need to be used to declare brain death. BRAIN DEATH AND ORGAN TRANSPLANTATION Some organs (such as the heart) can only ... is not involved until the patient is declared brain dead, and staff involved in organ donation or transplantation do not declare brain death. Downloaded From: http:// ...

  2. Fusarium Infections in Immunocompromised Patients

    PubMed Central

    Nucci, Marcio; Anaissie, Elias

    2007-01-01

    Fusarium species cause a broad spectrum of infections in humans, including superficial, locally invasive, and disseminated infections. The clinical form of fusariosis depends largely on the immune status of the host and the portal of entry, with superficial and localized disease occurring mostly in immunocompetent patients and invasive and disseminated disease affecting immunocompromised patients. Risk factors for severe fusariosis include prolonged neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell transplant recipients with severe graft-versus-host disease. The most frequent presentation of disseminated fusariosis is a combination of characteristic cutaneous lesions and positive blood cultures, with or without lung or sinus involvement. The prognosis is poor and is determined largely by degree of immunosuppression and extent of infection, with virtually a 100% death rate among persistently neutropenic patients with disseminated disease. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy. Treatment options include the lipid formulations of amphotericin B, voriconazole, and posaconazole. Prevention of fusarial infection among high-risk patients should be considered. PMID:17934079

  3. Stratifying prostate patients for olaparib.

    PubMed

    2015-06-01

    Data from the phase II TOPARP-A clinical trial indicate that men with metastatic castration-resistant prostate cancer are more likely to respond to the PARP inhibitor olaparib if they have mutations in DNA damage repair genes. The study provides the first data supporting molecular stratification for patients with this disease. PMID:25904654

  4. Patient perspectives of telemedicine quality

    PubMed Central

    LeRouge, Cynthia M; Garfield, Monica J; Hevner, Alan R

    2015-01-01

    Background The purpose of this study was to explore the quality attributes required for effective telemedicine encounters from the perspective of the patient. Methods We used a multi-method (direct observation, focus groups, survey) field study to collect data from patients who had experienced telemedicine encounters. Multi-perspectives (researcher and provider) were used to interpret a rich set of data from both a research and practice perspective. Results The result of this field study is a taxonomy of quality attributes for telemedicine service encounters that prioritizes the attributes from the patient perspective. We identify opportunities to control the level of quality for each attribute (ie, who is responsible for control of each attribute and when control can be exerted in relation to the encounter process). This analysis reveals that many quality attributes are in the hands of various stakeholders, and all attributes can be addressed proactively to some degree before the encounter begins. Conclusion Identification of the quality attributes important to a telemedicine encounter from a patient perspective enables one to better design telemedicine encounters. This preliminary work not only identifies such attributes, but also ascertains who is best able to address quality issues prior to an encounter. For practitioners, explicit representation of the quality attributes of technology-based systems and processes and insight on controlling key attributes are essential to implementation, utilization, management, and common understanding. PMID:25565781

  5. Patients' satisfaction with stroke services

    Microsoft Academic Search

    Pandora Pound; Patrick Gompertz; Shah Ebrahim

    1994-01-01

    Patient satisfaction with stroke services is a key aspect of the evaluation of the quality of services but there are no adequate means of assessing satisfaction in this area. A questionnaire derived from in-depth interviews was piloted on two samples. The resulting questionnaire consisted of two sections, one on inpatient services (Hospsat) and the other on services in the community

  6. Social Work Patient & Family Services

    E-print Network

    Goldman, Steven A.

    Social Work and Patient & Family Services 601 Elmwood Avenue RM. 1-1450 P. O. Box 650 Rochester, NY Social Work office lo- cated? The Social Work office is located on the first floor of Strong Memorial Hospital, Rm. 1-1450 How do I get in touch with a social worker? The social work department is open Monday

  7. Identifying COPD Patients Near Death

    Microsoft Academic Search

    Matthew T. Stark

    2009-01-01

    Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive terminal illness that can hospitalize those with the affliction multiple times during its evolution. COPD often also requires care in the Intensive Care Unit (ICU) and mechanical ventilation with or without intubation. The care provided to COPD patients at the end of their life is invasive and shows a high mortality

  8. Counteracting malnutrition in COPD patients

    Microsoft Academic Search

    R. ANTONIONE; G. BIOLO

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a common and serious condition, frequently characterized by involuntary weight loss, low body mass index and low fat-free mass. Since these parameters are accurate predictors of poor prognosis and low survival rates, nutri- tional assessment is strongly warranted in these patients but unfortunately still underconsidered. Skeletal muscle impairment and dysfunction are key factors in

  9. Patient Safety in Clinical Trials

    Cancer.gov

    Information for patients, their families and friends, and the general public about how the rights and safety of people who take part in clinical trials are protected. Learn about informed consent, institutional review boards (IRB's), and how trials are closely monitored for safety.

  10. Visitor/Patient Parking Information

    E-print Network

    Portman, Douglas

    with locating your vehicle. If you are unable to locate your vehicle in the garage, please take the elevator/patients on each level of the garage, near the elevators. Upon request, Parking will provide jump starts, tire inflation and lock de-icer (free of charge). Lobby Automated Pay Stations (APS) Automatic Pay Stations

  11. Approach to the poisoned patient

    Microsoft Academic Search

    Jerrold B. Leikin

    1996-01-01

    Routine poison management involves the following: (1) stabilization, (2) toxidrome recognition, (3) decontamination, (4) antidote administration, (5) enhanced elimination of toxin, and (6) supportive care. Stabilization involves airway, ventilation, and circulation support. In the patient with altered mental status, oxygen, naloxone, glucose, and thiamine should be administered. Symptom complexes that relate to specific classifications of toxins are referred to as

  12. Hospitalized Patients and Fungal Infections

    MedlinePLUS

    ... up the amount of fungal spores in the air. Top of Page Preventing fungal infections in hospitalized patients Fungi are difficult to avoid because they are a natural part of the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on many ...

  13. Patient Rights: An Advocate's Perspective

    Microsoft Academic Search

    Marc D. Hiller; Maureen J. McHugh

    1978-01-01

    The current growing concern about patients' rights and the delivery of student health care precipitates an environment of fear, distrust, and uneasiness within university health services. This paper addresses several selected clinical, ethical, and legal issues which have come into conflict during recent years. Our examination surveys ethical and legal principles of confidentiality, defines areas in which breaches are most

  14. When a Patient Commits Suicide.

    ERIC Educational Resources Information Center

    Marshall, Karol A.

    1980-01-01

    Suicide is a tragic and upsetting event which sometimes occurs when a person is in some form of therapy. This paper advocates a process after a patient commits suicide which allows for a thorough and orderly working through of the event by involved treatment personnel. (Author)

  15. Presidential address: The patient advocate

    Microsoft Academic Search

    Ralph H. Jennings

    1997-01-01

    The business environment in which we practice is changing. Social and medical problems of women continue for large numbers of our population. The obstetrician-gynecologist as the primary care provider for women must be active as the patient's advocate in the areas of sex education, contraceptive counseling, teenage pregnancy, domestic violence, healthy lifestyles, and decisions regarding appropriate health care. (Am J

  16. Informal Caregiving in HCT Patients

    PubMed Central

    Cooke, Liz; Grant, Marcia; Eldredge, Deborah H.; Maziaiz, Robert T.; Nail, Lillian M.

    2011-01-01

    Purpose Hematopoietic cell transplant patients are among the most vulnerable and acutely ill cancer populations (Bevans, Mitchell, & Marden, 2008). The responsibility of caring for the daily physical and psychosocial needs of these patients after transplant is placed mostly on family caregivers(Williams, 2007). The purpose of this descriptive correlational research study was to describe caregiving experiences of 56 caregivers of HCT patients 3–12 months following transplant. Methods & Sample Patients and caregivers were recruited from two west coast regional transplant programs in the United States. Variables studied were: relationship quality, rewards of caregiving, predictability, role strain, patient function, caregiving activities, and caregiver quality of life (QOL). Key Results Results indicated that all areas of role strain are significantly negatively correlated with caregiver's QOL. Predictability was negatively associated with problem solving and emotional strain indicating that as the level of predictability of the situation decreases, caregiver strain and problem solving increase. Predictability was positively correlated to caregiver QOL indicating that as the situation is more predictable caregiver QOL increases. Emotional strain, problem-solving strain, and usual care strain were significantly positively related, indicating that emotional strain and problem solving strain increased together. As usual care strain increased, so did problem-solving strain and emotional strain. Conclusions Suggestions for interventions include assessing and responding to caregiver issues such as emotional strain, problem-solving strain, usual care strain, unpredictability, and QOL. Examples of caregiver-focused interventions include providing timely appropriate information about these caregiver concerns including elements that make the caregiving situation predictable, and incorporating best practices for preventing and minimizing PMID:21306952

  17. Patient specific respiratory motion modeling using a 3D patient’s external surface

    PubMed Central

    Fayad, Hadi; Pan, Tinsu; Pradier, Olivier; Visvikis, Dimitris

    2012-01-01

    Purpose: Respiratory motion modeling of both tumor and surrounding tissues is a key element in minimizing errors and uncertainties in radiation therapy. Different continuous motion models have been previously developed. However, most of these models are based on the use of parameters such as amplitude and phase extracted from 1D external respiratory signal. A potentially reduced correlation between the internal structures (tumor and healthy organs) and the corresponding external surrogates obtained from such 1D respiratory signal is a limitation of these models. The objective of this work is to describe a continuous patient specific respiratory motion model, accounting for the irregular nature of respiratory signals, using patient external surface information as surrogate measures rather than a 1D respiratory signal. Methods: Ten patients were used in this study having each one 4D CT series, a synchronized RPM signal and patient surfaces extracted from the 4D CT volumes using a threshold based segmentation algorithm. A patient specific model based on the use of principal component analysis was subsequently constructed. This model relates the internal motion described by deformation matrices and the external motion characterized by the amplitude and the phase of the respiratory signal in the case of the RPM or using specific regions of interest (ROI) in the case of the patients’ external surface utilization. The capability of the different models considered to handle the irregular nature of respiration was assessed using two repeated 4D CT acquisitions (in two patients) and static CT images acquired at extreme respiration conditions (end of inspiration and expiration) for one patient. Results: Both quantitative and qualitative parameters covering local and global measures, including an expert observer study, were used to assess and compare the performance of the different motion estimation models considered. Results indicate that using surface information [correlation coefficient (CC): 0.998?±?0.0006 and model error (ME): 1.35?±?0.21 mm] is superior to the use of both motion phase and amplitude extracted from a 1D respiratory signal (CC and ME of 0.971?±?0.02 and 1.64?±?0.28 mm). The difference in performance was more substantial compared to the use of only one parameter (phase or amplitude) used in the motion model construction. Similarly, the patient surface based model was better in estimating the motion in the repeated 4D CT acquisitions and those CT images acquired at the full inspiration (FI) and the full expiration (FE). Once more, within this context the use of both amplitude and phase in the model building was substantially more robust than the use of phase or amplitude only. Conclusions: The present study demonstrates the potential of using external patient surfaces for the construction of patient specific respiratory motion models. Such information can be obtained using different devices currently available. The use of external surface information led to the best performance in estimating internal structure motion. On the other hand, the use of both amplitude and phase parameters derived from an 1D respiration signal led to largely superior model performance relative to the use of only one of these two parameters in the model building process. PMID:22755719

  18. Patient Radiation Doses in Interventional Cardiology Procedures

    PubMed Central

    Pantos, Ioannis; Patatoukas, Georgios; Katritsis, Demosthenes G; Efstathopoulos, Efstathios

    2009-01-01

    Interventional cardiology procedures result in substantial patient radiation doses due to prolonged fluoroscopy time and radiographic exposure. The procedures that are most frequently performed are coronary angiography, percutaneous coronary interventions, diagnostic electrophysiology studies and radiofrequency catheter ablation. Patient radiation dose in these procedures can be assessed either by measurements on a series of patients in real clinical practice or measurements using patient-equivalent phantoms. In this article we review the derived doses at non-pediatric patients from 72 relevant studies published during the last 22 years in international scientific literature. Published results indicate that patient radiation doses vary widely among the different interventional cardiology procedures but also among equivalent studies. Discrepancies of the derived results are patient-, procedure-, physician-, and fluoroscopic equipmentrelated. Nevertheless, interventional cardiology procedures can subject patients to considerable radiation doses. Efforts to minimize patient exposure should always be undertaken. PMID:20066141

  19. Creating an anticoagulant patient education class.

    PubMed

    Eickhoff, Jennifer S; Wangen, Tina M; Notch, Katie B; Ferguson, Tanya J; Nickel, Travis W; Schafer, Amy R; Bush, Diana L

    2010-12-01

    A patient education workgroup was developed on a progressive care medical/vascular surgical unit. The workgroup identified patient education needs regarding discharge education for postsurgical patients and those discharging with oral anticoagulants (OAC). Staff surveys aided the workgroup in identifying a need for additional discharge education for patients and families. After various methods of patient education were explored, it was determined the workgroup could best meet the needs of the patient population through a class format providing group discussion and interaction. Logistical details and class formatting were configured to meet both the needs of the patients and the nursing staff. Current institutional patient education pamphlets were used to develop the content for the class. Physician review and input were obtained during the development of the content. A patient education specialist was also consulted to ensure proper literacy levels were used. To meet the Joint Commission National Patient Safety Goal regarding anticoagulant safety, the content focused on home management, which included the following: knowledge of INR goal range, dietary factors, when to call the provider and safety precautions. Other topics to promote self-efficacy in anticoagulation therapy were also included in the content. Postclass evaluations completed by patients and families provided useful feedback for continuous improvement and patient satisfaction. Preliminary survey results indicate high patient satisfaction with the class. Plans include a quality improvement project to evaluate the effectiveness of the patient education class on OAC. PMID:21074115

  20. 76 FR 9351 - Patient Safety Organizations: Voluntary Delisting From West Virginia Center for Patient Safety

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ...its status as a Patient Safety Organization (PSO). The Patient Safety and Quality Improvement...Act and Patient Safety Rule, including when a PSO chooses to voluntarily relinquish its status as a PSO for any reason. DATES: The directories...

  1. 78 FR 40146 - Patient Safety Organizations: Voluntary Relinquishment From Northern Metropolitan Patient Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ...on May 29, 2013. Northern Metropolitan Patient Safety Institute has patient safety work product (PSWP) in its possession. The PSO will...section 3.108(c)(2)(i) of the Patient Safety Rule regarding notification of providers that...

  2. 76 FR 71345 - Patient Safety Organizations: Voluntary Relinquishment From Emergency Medicine Patient Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ...Voluntary Relinquishment From Emergency Medicine Patient Safety Foundation AGENCY: Agency...voluntary relinquishment from Emergency Medicine Patient Safety Foundation of its status...accepted a notification from Emergency Medicine Patient Safety Foundation, PSO...

  3. 76 FR 71345 - Patient Safety Organizations: Voluntary Relinquishment From Child Health Patient Safety...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ...Voluntary Relinquishment From Child Health Patient Safety Organization, Inc...of voluntary relinquishment from Child Health Patient Safety Organization, Inc...has accepted a notification from Child Health Patient Safety Organization,...

  4. Mongolian spots: How important are they?

    PubMed Central

    Gupta, Divya; Thappa, Devinder Mohan

    2013-01-01

    Mongolian spots (MS) are congenital birthmarks seen most commonly over the lumbosacral area. They are bluish-green to black in color and oval to irregular in shape. They are most commonly found in individuals of African or Asian ethnic background. Although these lesions resolve by one to two years of age, widespread, extrasacral and dark colored MS sometimes persist into adulthood. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although traditionally believed to be benign in nature, they have now been shown to co-exist with inborn errors of metabolism, most commonly GM1 gangliosidosis and mucopolysaccharidosis type?I?(Hurler’s disease), followed by mucopolysaccharidosis type II (Hunter’s syndrome), mucolipidosis, Niemann-Pick disease and mannosidosis. They have also been seen to co-exist with various vascular or other pigmented birthmarks like café-au-lait macules. Co-existing Mongolian spots and vascular birthmarks like nevus flammeus, nevus anemicus or nevus spilus is termed as phakomatosis pigmentovascularis. This review focuses on the important associations of Mongolian spots and stresses upon the importance of screening babies with extensive MS. PMID:24340274

  5. Mongolian spots: How important are they?

    PubMed

    Gupta, Divya; Thappa, Devinder Mohan

    2013-11-16

    Mongolian spots (MS) are congenital birthmarks seen most commonly over the lumbosacral area. They are bluish-green to black in color and oval to irregular in shape. They are most commonly found in individuals of African or Asian ethnic background. Although these lesions resolve by one to two years of age, widespread, extrasacral and dark colored MS sometimes persist into adulthood. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although traditionally believed to be benign in nature, they have now been shown to co-exist with inborn errors of metabolism, most commonly GM1 gangliosidosis and mucopolysaccharidosis type?I?(Hurler's disease), followed by mucopolysaccharidosis type II (Hunter's syndrome), mucolipidosis, Niemann-Pick disease and mannosidosis. They have also been seen to co-exist with various vascular or other pigmented birthmarks like café-au-lait macules. Co-existing Mongolian spots and vascular birthmarks like nevus flammeus, nevus anemicus or nevus spilus is termed as phakomatosis pigmentovascularis. This review focuses on the important associations of Mongolian spots and stresses upon the importance of screening babies with extensive MS. PMID:24340274

  6. Lysosomal Multienzyme Complex: Pros and Cons of Working Together

    PubMed Central

    Bonten, Erik J.; Annunziata, Ida; d’Azzo, Alessandra

    2014-01-01

    The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, Protective Protein/Cathepsin A (PPCA), the sialidase, Neuraminidase-1 (NEU1), and the glycosidase ?-Galactosidase (?-GAL). Next to this ‘core’ complex, the existence of sub-complexes, that may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1 and ?-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders. PMID:24337808

  7. Lysosomal multienzyme complex: pros and cons of working together.

    PubMed

    Bonten, Erik J; Annunziata, Ida; d'Azzo, Alessandra

    2014-06-01

    The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, protective protein/cathepsin A (PPCA), the sialidase, neuraminidase-1 (NEU1), and the glycosidase ?-galactosidase (?-GAL). Next to this 'core' complex, the existence of sub-complexes, which may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1, and ?-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders. PMID:24337808

  8. Patient Moderator Interaction in Online Health Communities

    PubMed Central

    Huh, Jina; McDonald, David W.; Hartzler, Andrea; Pratt, Wanda

    2013-01-01

    An increasing number of people visit online health communities to share experiences and seek health information. Although studies have enumerated reasons for patients’ visits to online communities for health information from peers, we know little about how patients gain health information from the moderators in these communities. We qualitatively analyze 480 patient and moderator posts from six communities to understand how moderators fulfill patients’ information needs. Our findings show that patients use the community as an integral part of their health management practices. Based on our results, we suggest enhancements to moderated online health communities for their unique role to support patient care. PMID:24551364

  9. Patient advocacy: the role of the nurse.

    PubMed

    Choi, Pin Pin

    2015-06-10

    The role of nurses as patient advocates is well recognised by healthcare professionals, yet the processes and practices involved in patient advocacy are not clearly understood. A suboptimal level of advocacy is often apparent in the literature, encompassing paternalistic concepts of protecting patients from harm. This article examines the concept of patient advocacy and its relevance to nursing, associated goals and outcomes of advocacy and the processes and practices involved. It provides insights into how nurses practise patient advocacy in healthcare settings and how they may develop this role further, through formal education, workplace learning, role modelling by expert nurses and promoting an organisational culture conducive to patient advocacy. PMID:26058653

  10. Professional boundaries: communication after patient discharge.

    PubMed

    Petraits, Laura R

    2013-10-01

    The blurring of professional boundaries commonly takes place when a nurse cares for a patient for an extended period of time. This article focuses on the aspects of professional boundaries in neonatal nursing, particularly in regard to communication after patient discharge. Modes of caring are investigated to understand the nature of the therapeutic relationship between nurse and patient and how this can present an ethical dilemma at the end of a patient's hospital stay. A discussion of how a patient reunion is organized is discussed at the end of this article as a possible solution to reconnecting patient-nurse ties in a professional manner. PMID:24042137

  11. Improving patient safety in haemodialysis

    PubMed Central

    Bray, Benjamin D.; Metcalfe, Wendy

    2015-01-01

    Thomas Inman (1820–76) wrote ‘Practice two things in your dealings with disease: either help or do not harm the patient’, echoing writings from the Hippocratic school. The challenge of practicing safely with the avoidance of complications or harm is perhaps only heightened in the context of modern medical settings such as the haemodialysis unit where complex interventions and treatment are routine. The current issue of CKJ reports two studies aimed at improving the care of haemodialysis patients targeting early use of arteriovenous grafts as access for haemodialysis and the implementation of a dialysis checklist to ensure the prescribed dialysis treatment is delivered. The further challenge of ensuring that such evidence-based tools are used appropriately and consistently falls to all members of the clinical team.

  12. [Stress and patients undergoing surgery].

    PubMed

    D?dek, T; Fiala, O; Grmela, M

    1991-01-01

    Stressory reactions in surgical patients are studied as the main adaptative reaction occurring in loads both in physiological limits and graded measure, where the reaction itself appears to action as a pathological nuisance. The human stressors are reviewed as well as up-to-date data on the pathophysiology, diagnostics and prevention of stressory reaction including the therapeutical measures in order to prevent the development of organ damages with graded anxious reaction. Of special attention are interrelations of neurohumoral and immune reactions in syndromes of the so-called acute phase holoorganic reaction in the response of the organism on the graded aggression. In addition, the multifactorial stress is scrutinised in detail as the patient goes through the diagnosis and treatment with both its objectivation and minimalization. In conclusion, the modifications are mentioned of the course of stressory reaction in endocrynopathies as well as risks and measures on how to prevent such surprising and harmful interactions. PMID:1842312

  13. Protecting patient confidentiality in hospitals.

    PubMed

    Mulligan, E

    1998-01-01

    As new methods of electronic data storage and distribution appear in hospitals, new challenges in protecting confidentiality have emerged. At the same time, demands for 'seamless' care and the desire to share information between clinicians are motivating hospitals to relax barriers to the transfer of patient information. Increasing numbers of users at multiple sites compound the difficulty of ensuring information systems security. Hospital policy may demand that requests by patients to restrict the distribution of personal information be respected, while existing electronic systems are not able to deliver on this promise. Compliance with the Information Privacy Principles of the Commonwealth Privacy Act 1988 and the Australian Standard 4400-1995 'Personal privacy protection in health care information systems' will provide a useful framework for managing these challenges. However, their implementation will require some forethought. PMID:10185694

  14. Ventilatory strategies in trauma patients

    PubMed Central

    Arora, Shubhangi; Singh, Preet Mohinder; Trikha, Anjan

    2014-01-01

    Lung injury in trauma patients can occur because of direct injury to lung or due to secondary effects of injury elsewhere for example fat embolism from a long bone fracture, or due to response to a systemic insult such as; acute respiratory distress syndrome (ARDS) secondary to sepsis or transfusion related lung injury. There are certain special situations like head injury where the primary culprit is not the lung, but the brain and the ventilator strategy is aimed at preserving the brain tissue and the respiratory system takes a second place. The present article aims to delineate the strategies addressing practical problems and challenges faced by intensivists dealing with trauma patients with or without healthy lungs. The lung protective strategies along with newer trends in ventilation are discussed. Ventilatory management for specific organ system trauma are highlighted and their physiological base is presented. PMID:24550626

  15. Dialysis in the poisoned patient.

    PubMed

    Bayliss, George

    2010-04-01

    Patients who ingest toxic substances may require extracorporeal removal of the poisons or their toxic metabolites if native renal clearance is not sufficient because of acute kidney injury, acuity of symptoms, or burden of toxin. Here, a case is presented, and the literature on renal replacement therapy in the event of acute intoxication is reviewed. Extracorporeal therapy efficacy is examined in terms of the characteristics of the toxin (molecular size, charge, protein, or lipid binding); the patient (body habitus and volume of distribution); and the process (membrane effects on extraction ratios and sieving, role of blood, and dialysate flow rates). The choice of extracorporeal therapy and hemodialysis prescriptions for specific poisonings are discussed. PMID:20337746

  16. Cardiac Emergencies in Neurosurgical Patients

    PubMed Central

    Petropolis, Andrea; Cappellani, Ronald B.

    2015-01-01

    Perioperative safety concerns are a major area of interest in recent years. Severe cardiac perturbation such as cardiac arrest is one of the most dreaded complications in the intraoperative period; however, little is known about the management of these events in the patients undergoing elective neurosurgery. This special group needs further attention, as it is often neither feasible nor appropriate to apply conventional advanced cardiac life support algorithms in patients undergoing neurosurgery. Factors such as neurosurgical procedure and positioning can also have a significant effect on the occurrence of cardiac arrest. Therefore, the aim of this paper is to describe the various causes and management of cardiac emergencies with special reference to cardiac arrest during elective neurosurgical procedures, including discussion of position-related factors and resuscitative considerations in these situations. This will help to formulate possible guidelines for management of such events. PMID:25692145

  17. Improving patient safety in haemodialysis.

    PubMed

    Bray, Benjamin D; Metcalfe, Wendy

    2015-06-01

    Thomas Inman (1820-76) wrote 'Practice two things in your dealings with disease: either help or do not harm the patient', echoing writings from the Hippocratic school. The challenge of practicing safely with the avoidance of complications or harm is perhaps only heightened in the context of modern medical settings such as the haemodialysis unit where complex interventions and treatment are routine. The current issue of CKJ reports two studies aimed at improving the care of haemodialysis patients targeting early use of arteriovenous grafts as access for haemodialysis and the implementation of a dialysis checklist to ensure the prescribed dialysis treatment is delivered. The further challenge of ensuring that such evidence-based tools are used appropriately and consistently falls to all members of the clinical team. PMID:26034585

  18. Semantic remote patient monitoring system.

    PubMed

    Shojanoori, Reza; Juric, Radmila

    2013-02-01

    We propose an automated and personalized remote patient monitoring (RPM) system, which is applied to care homes and is dependent on the manipulation of semantics describing situations during patient monitoring in ontological models. Decision making in RPM is based on reasoning performed upon ontologies, which secures the delivery of appropriate e-health services in care homes. Our working experiment shows an example of preventive e-healthcare, but it can be extended to any situation that requires either urgent action from healthcare professionals or a simple recommendation during RPM. We use Semantic Web technology and OWL/SWRL-enabled ontologies to illustrate the proposal and feasibility of implementing this RPM system as a software solution in pervasive healthcare. It will be of interest to healthcare professionals, who can directly shape and populate the proposed ontological model, and software engineers, who would consider using OWL/SWRL when creating e-health services in general. PMID:23363406

  19. Prediction on Cold Chain Logistics Demand of Urban Residents in Jiangsu Province during the Twelfth Five-Year Plan Period: Based on Estimates of GM (1,1) Model

    Microsoft Academic Search

    Yan-min Zheng; Yan-cai Zhang; Hong-feng Xu

    2011-01-01

    This paper takes the total yield of products that need refrigerated transport as the impact factors of transport aggregate of cold chain logistics, such as meat, aquatic products, quick-frozen noodle, fruits, vegetables, dairy, and medicine. Through selecting the consumption data of urban residents on transported products via cold chain in Jiangsu Province from 2005 to 2000 as sample, this paper

  20. Nurse-patient communication in cancer care: does responding to patient's cues predict patient satisfaction with communication

    Microsoft Academic Search

    Ruud Uitterhoeve; Jozien Bensing; Eefje Dilven; A. R. T. Donders; P. H. M. de Mulder; Theo van Achterberg

    2009-01-01

    Objective: The aim is to investigate the relationship between nurses' cue-responding behaviour and patient satisfaction. Methods: One hundred patient-nurse conversations about present concerns were videotaped and patients' expression of emotional cues and nurses' cue responses were coded using the Medical Interview Aural Rating Scale. Nurses (N=34) and patients (N=100) were recruited from seven oncology inpatient clinics from a University Medical