Note: This page contains sample records for the topic gm1 gangliosidosis patients from
While these samples are representative of the content of,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of
to obtain the most current and comprehensive results.
Last update: November 12, 2013.

Genetics Home Reference: GM1 gangliosidosis  


... gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some ... GM1 ganglioside is important for normal functioning of nerve cells in the brain. Mutations in the GLB1 gene ...


Primary and Secondary Elastin-Binding Protein Defect Leads to Impaired Elastogenesis in Fibroblasts from GM1-Gangliosidosis Patients  

PubMed Central

GM1-gangliosidosis is a lysosomal storage disorder caused by acid ?-galactosidase deficiency. Aside from the lysosomal ?-galactosidase enzyme, the ?-galactosidase gene also encodes the elastin-binding protein (EBP), deficiency in which impairs elastogenesis. Using expression studies and Western blots of COS-1 cells, we identified and characterized four new and two known ?-galactosidase gene mutations detected in GM1-gangliosidosis patients with infantile, juvenile, or adult forms of disease. We then focused on impaired elastogenesis detected in fibroblasts from patients with infantile and juvenile disease. The juvenile patient showed connective-tissue abnormalities, unusual urinary keratan sulfate excretion, and an EBP reduction, despite mutations affecting only ?-galactosidase. Because galactosugar-bearing moieties may alter EBP function and impair elastogenesis, we assessed infantile and juvenile patients for the source of altered elastogenesis. We confirmed that the infantile patient’s impaired elastogenesis arose from a primary EBP defect, according to molecular analysis. We examined the juvenile’s fibroblasts by immunohistochemistry, addition of keratanase, soluble/insoluble elastin assay, and radiolabeling of tropoelastin. These experiments revealed that the juvenile’s impaired elastogenesis likely arose from secondary EBP deficiency caused by keratan sulfate accumulation. Thus, impaired elastogenesis in GM1-gangliosidosis can arise from primary or secondary EBP defects in fibroblasts from infantile and juvenile patients, respectively.

Caciotti, Anna; Donati, Maria Alice; Bardelli, Tiziana; d'Azzo, Alessandra; Massai, Graziella; Luciani, Luciana; Zammarchi, Enrico; Morrone, Amelia



beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement.  


GM1-gangliosidosis is a lysosomal storage disorder caused by deficiency of acid beta-galactosidase (GLB1). We report five new beta-galactosidase gene mutations in nine Italian patients and one fetus, segregating in seven unrelated families. Six of the eight patients with the infantile, severe form of the disease presented cardiac involvement, a feature rarely associated with GM1-gangliosidosis. Molecular analysis of the patients' RNA and DNA identified two new RNA splicing defects, three new and three previously described amino acid substitutions. Interestingly, all patients with cardiac involvement were homozygous for one of these mutations: R59H, Y591C, Y591N, or IVS14-2A>G. In contrast, all other patients were compound heterozygous for one of the following mutations: R201H, R482H, G579D, IVS8+2T>C. Although we could not directly correlate the presence of cardiac abnormalities with specific genetic lesions, the mutations identified in patients with cardiomyopathy fell in the GLB1 cDNA region common to the lysosomal enzyme and the Hbeta-Gal-related protein, also known as the elastin binding protein (EBP). Consequently, both molecules are affected by the mutations, and they may contribute differently to the occurrence of specific clinical manifestations. PMID:10737981

Morrone, A; Bardelli, T; Donati, M A; Giorgi, M; Di Rocco, M; Gatti, R; Parini, R; Ricci, R; Taddeucci, G; D'Azzo, A; Zammarchi, E



Motor and reflex testing in GM1-gangliosidosis model mice.  


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 G(M1)-gangliosidosis model mice. Two genetically engineered model mouse strains were used for this study: the beta-galactosidase-deficient knockout mouse representing infantile G(M1)-gangliosidosis (severe form), and transgenic mouse representing juvenile G(M1)-gangliosidosis (mild form). We modified human child neurology techniques, and selected eleven tests for motor assessment and reflex testing. The test results were scored in four grades: 0 (normal), 1 (slightly abnormal), 2 (moderately abnormal), and 3 (severely abnormal). Both disease model mouse strains showed high scores even at the apparently pre-symptomatic stage of the disease, particularly with abnormal tail and hind limb postures. Individual and total test scores were well correlated with the progression of the disease. This method is simple, quick, and reproducible. The testing is sensitive enough to detect early neurological abnormalities, and will be useful for monitoring the natural clinical course and effect of therapeutic experiments in various neurogenetic disease model mice, such as chemical chaperone therapy for G(M1)-gangliosidosis model mice. PMID:17027211

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



962. Treatment of Feline GM1 Gangliosidosis with Mesenchymal Stem Cells and Lentiviral Gene Therapy  

Microsoft Academic Search

Deficiency of lysosomal ?-galactosidase causes GM1 gangliosidosis, an inherited, progressive neurological disorder in which GM1 ganglioside accumulates in all tissues, including thymus, liver and brain. In addition to abnormal neuronal histology and function, gangliosidosis pathology involves a significant inflammatory component and therefore is similar to other neurodegenerative disorders such as Alzheimer and Parkinson disease. GM1 gangliosidosis occurs in humans, mice

Douglas R. Martin; Karin Haack; Glenn P. Niemeyer; Nancy R. Cox; Tal Kafri; Henry J. Baker



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


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 and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes showed that all the amino acid replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease. PMID:21497194

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



GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings  

PubMed Central

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 and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes, showed that all the amino acids replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease.

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



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

Microsoft Academic Search

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,

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



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

Microsoft Academic Search

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

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



Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis  

PubMed Central

GM1 gangliosidosis is an inherited, fatal neurodegenerative disease caused by deficiency of lysosomal ?-D-galactosidase (EC 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. The putative signal sequence consists of amino acids 1–24 of the ?-galactosidase precursor protein, which contains seven potential N-linked glycosylation sites, as in the human protein. Overall sequence homology between feline and human ?-galactosidase is 74% for the open reading frame and 82% for the amino acid sequence. After normal ?-galactosidase was sequenced, the mutation responsible for feline GM1 gangliosidosis was defined as a G to C substitution at position 1448 of the open reading frame, resulting in an amino acid substitution at arginine 483, known to cause GM1 gangliosidosis in humans. Feline ?-galactosidase messenger RNA levels were normal in cerebral cortex, as determined by quantitative RT-PCR assays. Although enzymatic activity is severely reduced by the mutation, a full-length feline ?-galactosidase cDNA restored activity in transfected GM1 fibroblasts to 18-times normal. ?-Galactosidase protein levels in GM1 tissues were normal on Western blots, but immunofluorescence analysis demonstrated that the majority of mutant ?-galactosidase protein did not reach the lysosome. Additionally, GM1 cat fibroblasts demonstrated increased expression of glucose-related protein 78/BiP and protein disulfide isomerase, suggesting that the unfolded protein response plays a role in pathogenesis of feline GM1 gangliosidosis.

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



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


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

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



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

Microsoft Academic Search

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

Yasmeen Khan



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

PubMed Central

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.

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.



AAV-Mediated Gene Delivery in Adult GM1Gangliosidosis Mice Corrects Lysosomal Storage in CNS and Improves Survival  

Microsoft Academic Search

BackgroundGM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid ?-galactosidase (?gal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation in humans. Currently, there are no effective therapies for the

Rena C. Baek; Marike L. D. Broekman; Stanley G. Leroy; Laryssa A. Tierney; Michael A. Sandberg; Alessandra D'Azzo; Thomas N. Seyfried; Miguel Sena-Esteves; Alfred Lewin



Serial MRI Features of Canine GM1 Gangliosidosis: A Possible Imaging Biomarker for Diagnosis and Progression of the Disease  

PubMed Central

GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of ?-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies.

Hasegawa, Daisuke; Yamato, Osamu; Nakamoto, Yuya; Ozawa, Tsuyoshi; Yabuki, Akira; Itamoto, Kazuhito; Kuwabara, Takayuki; Fujita, Michio; Takahashi, Kimimasa; Mizoguchi, Shunta; Orima, Hiromitsu



Serial MRI features of canine GM1 gangliosidosis: a possible imaging biomarker for diagnosis and progression of the disease.  


GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of ?-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies. PMID:22536126

Hasegawa, Daisuke; Yamato, Osamu; Nakamoto, Yuya; Ozawa, Tsuyoshi; Yabuki, Akira; Itamoto, Kazuhito; Kuwabara, Takayuki; Fujita, Michio; Takahashi, Kimimasa; Mizoguchi, Shunta; Orima, Hiromitsu



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

PubMed Central

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.

Kreutzer, Robert; Leeb, Tosso; Muller, Gundi; Moritz, Andreas; Baumgartner, Wolfgang



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.  


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

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



Neurovisceral and Skeletal GM1Gangliosidosis in Dogs with beta Galactosidase Deficiency  

Microsoft Academic Search

beta -galactosidase-deficient siblings in two litters of English springer spaniel puppies showed a progressive neurological impairment, dwarfism, orbital hypertelorism, and dysostosis multiplex. An excess of GM1-ganglioside was found in the brain. Three abnormal oligosaccharides were present in samples of urine, brain, liver, and cartilage. Light microscopy of selected tissue specimens revealed cytoplasmic vacuoles in neurons, circulating blood cells, macrophages, and

Joseph Alroy; Uri Orgad; Angelo A. Ucci; Scott H. Schelling; Kenneth L. Schunk; Christopher D. Warren; Srinivasa S. Raghavan; Edwin H. Kolodny



961. AAV1-Mediated Gene Delivery to the Adult GM1Gangliosidosis Mouse Hippocampus Leads to Marked Reduction in Storage in Physically and Synaptically-Connected Areas of the Brain  

Microsoft Academic Search

GM1-gangliosidosis is a lysosomal storage disease caused by an autosomal recessive deficiency of lysosomal acid beta-galactosidase (b-gal) leading to accumulation of GM1-ganglioside in the central nervous system, and often accompanied by severe mental retardation. Knock-out mouse models (GM1 KO) of this disease mimic the biochemical findings in humans, with absence of b-gal activity and extensive GM1-ganglioside storage throughout the brain.

Miguel Sena-Esteves; Marike Broekman; Fabricio F. Costa; Stanley G. LeRoy; Laryssa A. Comer



Rapid and reliable genotyping technique for GM1 gangliosidosis in Shiba dogs by real-time polymerase chain reaction with TaqMan minor groove binder probes.  


Real-time polymerase chain reaction (PCR) with TaqMan minor groove binder (MGB) probes was examined to establish a rapid and reliable genotyping technique for GM1 gangliosidosis in Shiba dogs. This technique was applied to DNA samples extracted from the blood, umbilical cord, or postmortem liver tissue specimens, and to DNA-containing solutions prepared from blood and saliva that had been applied to Flinders Technology Associates filter papers (FTA cards). The amplification of the targeted sequence in all the samples was sufficient to determine the genotypes of GM1 gangliosidosis. Forty-seven DNA samples that had previously been obtained from blood or tissue specimens of Shiba dogs were examined using this real-time PCR technique, and the findings were consistent with the data obtained by the earlier PCR-restriction fragment length polymorphism (RFLP) assay. In addition, the use of this new technique in combination with FTA cards for sampling could markedly shorten the time required for genotyping, as well as simplify the procedure. Furthermore, in the present study, the results of a previous epidemiological screening of 96 Shiba dogs in the Czech Republic were rechecked by this real-time PCR technique using stored crude buccal cell DNA-containing solutions directly as DNA templates. The results provided clear-cut genotyping in all the samples although the earlier PCR-RFLP assay could not determine the genotype in all cases. In conclusion, this new real-time PCR technique is a simple, rapid, and reliable choice for large-scale screening to detect an abnormal allele indicating GM1 gangliosidosis in Shiba dogs. PMID:20224082

Chang, Hye-Sook; Arai, Toshiro; Yabuki, Akira; Hossain, Mohammad A; Rahman, Mohammad M; Mizukami, Keijiro; Yamato, Osamu



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


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

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



A fluorescent probe for GM1 gangliosidosis related ?-galactosidase: N-(dansylamino)hexylaminocarbonylpentyl-1,5-dideoxy-1,5-imino-D-galactitol.  


N-(Dansylamino)hexylaminocarbonylpentyl-1,5-dideoxy-1,5-imino-D-galactitol, a strong competitive inhibitor of ?-galactosidase, enhances residual ?-galactosidase activities in fibroblasts and serves as lead en route to diagnostic compounds for tracking the fate of mutant ?-gal as well as aberrant GM1 gangliosides by live cell imaging. PMID:21974950

Fröhlich, Richard F G; Fantur, Katrin; Furneaux, Richard H; Paschke, Eduard; Stütz, Arnold E; Wicki, Jacqueline; Withers, Stephen G; Wrodnigg, Tanja M



Generalized Gangliosidosis: Beta-Galactosidase Deficiency  

Microsoft Academic Search

A profound deficiency (10- to 30-fold) of beta -galactosidase activity was found in tissues (liver, spleen, kidney, and brain) from two patients with generalized gangliosidosis; this deficiency is demonstrated as a failure to cleave both p-nitrophenyl-beta -D-galactopyranoside and ganglioside GM1 labeled with C14 in the terminal galactose. We believe that this enzymic defect is responsible for the accumulation of ganglioside

Shintaro Okada; John S. O'Brien



[Antibodies to ganglioside GM1 and Campylobacter jejuni in patients with Guillain-Barré syndrome].  


Guillain-Barré syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF). Recently, the heterogeneity of GBS has been noticed with definition of several GBS variants. The axonal GBS associated with anti-GM1 antibodies is the most important variant with the specific role of Campylobacterjejuni (CJ) in the induction of the disease. The role of our study was to determine the frequency of antecedent infection with CJ in the population of our patients with GBS, the association with anti-GM1 antibodies and the distribution of these antibodies within clinical forms of the disease. The diagnosis of GBS has been established in 17 patients according to clinical, electrophysiological and laboratory (CSF) criteria. The serum antibodies to 63 kDa flagellar protein isolated from CJ serotype 0:19 were determined by ELISA and Western blot and serum anti-GM1 antibodies by ELISA. In relation to the disability score two patients were ambulatory, five were ambulatory with support, seven were bedridden and two patients needed respirator. Five (29%) patients had pure motor, while 12 (71%) had sensorimotor GBS. The cranial nerves were involved in 11 (65%) and 9 (53%) patients had autonomic dysfunction. Electromyoneurography showed primary axonal, predominantly motor neuropathy in 6 (35%) and demyelinating sensorimotor neuropathy in 11 (65%) patients. The CSF protein content ranged from 0.47 to 3.88 g/L. The antecedent infection with CJ was shown by serum antibodies to CJ flagellar protein in 12 (71%) patients. Fifteen (88%) patients had IgG anti-GM1 antibodies. Twelve (71%) patients had both antibodies. In relation to the clinical form, anti-CJ antibodies were found in 8 (73%) out of 11 patients with demyelinating GBS and in 4 (66.6%) out of 6 patients with axonal GBS. The high titer of anti-GM1 antibodies was found in all patients (100%) with axonal and in 9 (82%) out of 11 patients with demyelinating GBS. The association of IgG anti-CJ and IgG anti-GM1 antibodies was found in 4 (66.6%) out of 6 patients with axonal and in 8 (73%) out of 11 patients with demyelinating GBS. The main features of our patients with GBS were high frequency of antecedent infection with CJ, unusually frequent association with anti-GM1 antibodies, and equally frequent association of anti-CJ and anti-GM1 antibodies in both, axonal and demyelinating GBS. PMID:16206698

Basta, Ivana; Suturkova, Ljubica; Vuji?, Ana; Aleksi?, Stojanka; Poceva, Ana; Paskoska, Aleksandra; Milenikova, Katerina; Triki?, Rajko; Apostolski, Slobodan


Subclass of IgG antibody to GM1 epitope-bearing lipopolysaccharide of Campylobacter jejuni in patients with Guillain-Barré syndrome  

Microsoft Academic Search

Sera of patients who develop Guillain-Barré syndrome (GBS) subsequent to Campylobacter jejuni enteritis frequently have IgG anti-GM1 antibody. Lipopolysaccharide (LPS) of C. jejuni isolated from a GBS patient has a GM1 ganglioside-like structure. IgG subclass distribution of the anti-GM1 antibody in GBS patients is mainly restricted to IgGl and IgG3. Since IgG antibodies to bacterial polysaccharide generally are restricted to

Nobuhiro Yuki; Yasuo Ichihashi; Takao Taki



Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors  

PubMed Central

Background Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. Methods In this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. Results The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann–Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). Conclusion The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors.



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

SciTech Connect

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.

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



Ashkenazi-Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect.  

PubMed Central

The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive neurological disorder caused by a partial deficiency of beta-hexosaminidase A. We had previously identified, in Ashkenazi-Jewish adult GM2 gangliosidosis patients, a Gly269----Ser mutation in the beta-hexosaminidase alpha-subunit. All of the Ashkenazi patients were found to be compound heterozygotes with an allele containing the Gly269----Ser mutation together with one of the Ashkenazi infantile Tay-Sachs alleles. We have now found the same Gly269----Ser mutation in six adult GM2 gangliosidosis patients from four different non-Jewish families. Genomic DNA from three of the patients, two of whom were brothers, exhibited a hybridization pattern consistent with homozygosity for the Gly269----Ser mutation. The remaining non-Jewish patients were compound heterozygotes of the Gly269----Ser mutation together with an unidentified alpha-subunit mutation. The results demonstrate that individuals homozygous for the Gly269----Ser change can be clinically affected. The same Gly269----Ser mutation in both the Ashkenazi and non-Jewish patients may be the result of a common ancestor, given that the ancestry of these non-Jewish patients, like the Ashkenazim, can be traced to eastern Europe. Images Figure 1 Figure 2 Figure 3

Navon, R; Kolodny, E H; Mitsumoto, H; Thomas, G H; Proia, R L



Motor and reflex testing in G M1-gangliosidosis model mice  

Microsoft Academic Search

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

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



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

SciTech Connect

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.

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



Improvement of GM (1, 1) model  

Microsoft Academic Search

Base on analysis of GM(1,1), two simplified computational methods are given. Their computational efforts are less than that of the traditional GM(1,1) model, so they can get quick modeling. Moreover their precisions are as high as the GM(1,1) model. The conclusion, which the initiative number has no effect on the prediction, is got, and an improved GM (1, 1) model

Gao Shang



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

Microsoft Academic Search

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 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

Jurgen Horst; Friedrich Kluge; Konrad Beyreuther; Wolfgang Gerok



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

Microsoft Academic Search

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.

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



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)  

PubMed Central

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ?-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 premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the ? or ? subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period. The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ?-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were noted. However, the study also found that significant side effects were experienced by most patients at or above 75 mg pyrimethamine per day. We concluded that pyrimethamine treatment enhances leukocyte Hex A activity in patients with late-onset GM2 gangliosidosis at doses lower than those associated with unacceptable side effects. Further plans are underway to extend these trials and to develop methods to assess clinical efficacy.

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



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).  


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 premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the ? or ? subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were noted. However, the study also found that significant side effects were experienced by most patients at or above 75 mg pyrimethamine per day. We concluded that pyrimethamine treatment enhances leukocyte Hex A activity in patients with late-onset GM2 gangliosidosis at doses lower than those associated with unacceptable side effects. Further plans are underway to extend these trials and to develop methods to assess clinical efficacy. PMID:20926324

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



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

SciTech Connect

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.

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



A comparative trial of anti-glycoconjugate antibody assays: IgM antibodies to GM1  

Microsoft Academic Search

IgM class antibodies against the ganglioside GM1 have been found in a subgroup of patients with lower motor neuron syndromes and multifocal motor neuropathies (MMN). The pathogenic relevance of these antibodies is still unclear, but some MMN patients with IgM antibodies against GM1 seem to profit from immunosuppressive therapy. A reliable test for IgM antibodies against GMl may be useful

J. Zielasek; G. Ritter; S. Magi; H. P. Hartung; K. V. Toyka



Spectrum of neurological diseases associated with antibodies to minor gangliosides GM1b and GalNAc-GD1a  

Microsoft Academic Search

The authors reported the neurological disease spectrum associated with autoantibodies against minor gangliosides GM1b and GalNAc-GD1a. IgG and IgM antibody reactivity against gangliosides GM1, GM2, GM1b, GD1a, GalNAc-GD1a and GQ1b was investigated in sera from 7000 consecutive patients who had various neurological conditions. The clinical diagnoses for 456 anti-GM1b-positive patients were Guillain-Barré syndrome (GBS, 71%), atypical GBS with preserved deep

M. Tatsumoto; M. Koga; M. Gilbert; M. Odaka; K. Hirata; S. Kuwabara; N. Yuki



[Guillain-Barre syndrome and antibodies to ganglioside GM1. Case report].  


A sudden onset of the syndrome Guillain-Barré in 48-year-old woman presenting as an acute motor neuropathy was associated with antibodies against ganglioside GM1 detected by ELISA. The neurological examination revealed flaccid quadriplegia without affection of the sensory system, and the additional investigation showed mild increase of the CSF protein content, demyelination of the peripheral motor nerves and significantly increased titer of the serum and CSF anti-GM1 antibodies. Several copruculture for Campylobacter jejuni gave negative results. There was a significant correlation between the severity of the clinical picture and the titer of the serum anti-GM1 antibodies. The patient completely and spontaneously recovered after five weeks. According to the clinical and laboratory parameters the patient could be classified as an axonal, and according to electromyographic findings and the course of the disease as the classical form of the syndrome Guillain-Barré. PMID:9102850

Triskovi?, I; Dimitrijevi?, Lj; Rakocevi?-Stojanovi?, V; Triki?, R; Apostolski, S


Optimization of GM(1,1) power model  

NASA Astrophysics Data System (ADS)

GM (1,1) power model is the expansion of traditional GM (1,1) model and Grey Verhulst model. Compared with the traditional models, GM (1,1) power model has the following advantage: The power exponent in the model which best matches the actual data values can be found by certain technology. So, GM (1,1) power model can reflect nonlinear features of the data, simulate and forecast with high accuracy. It's very important to determine the best power exponent during the modeling process. In this paper, according to the GM(1,1) power model of albino equation is Bernoulli equation, through variable substitution, turning it into the GM(1,1) model of the linear albino equation form, and then through the grey differential equation properly built, established GM(1,1) power model, and parameters with pattern search method solution. Finally, we illustrate the effectiveness of the new methods with the example of simulating and forecasting the promotion rates from senior secondary schools to higher education in China.

Luo, Dang; Sun, Yu-ling; Song, Bo



The development of GM(1,1) error toolbox  

Microsoft Academic Search

In the prediction research, the main purpose is to minimize the prediction error; however, the goals cannot be fulfilled completely. Even we choose GM(1,1) model, we also need to minimize the prediction error. Hence, in this paper, we first focus on the influence parameter alpha in GM(1,1) model, then, analyze the characteristics of alpha step by step. Second, we give

Kun-Li Wen; Yi-Fung Huang; Mei-Li You; Wei-Shiuan Tsai



Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.  

PubMed Central

The basis for the unique association of Pseudomonas aeruginosa and the cystic fibrosis (CF) lung has remained obscure despite major advances in the understanding of the molecular genetic cause of this disease. There is evidence to suggest that abnormalities in CF transmembrane conductance regulator function result in alterations in the glycosylation of epithelial components. The number of asialoGM1 residues, as representative of a class of glycolipids which contain a GalNAc beta 1-4Gal sequence for P. aeruginosa attachment, was quantified by flow cytometric studies of respiratory epithelial cells in primary culture from both CF patients and normal subjects. Superficial asialoGM1 was detected on 12% of the CF cells as compared with 2.9% of the cells from normal control subjects (P = 0.03, chi 2 = 4.73), and more asialoGM1 residues were exposed on CF cells after modification by P. aeruginosa exoproducts. AsialoGM1, but not the sialylated glycolipid GM1, was demonstrated to be a receptor for 125I-labeled P. aeruginosa pilin, a major adhesin for this organism, and exogenous asialoGM1 was found to competitively inhibit P. aeruginosa adherence to epithelial cells, thus, confirming the biological role of the asialoGM1 receptor. Quantitative and qualitative differences in the sialylation of superficial glycolipids in CF epithelial cells may directly contribute to the colonization of the CF lung by P. aeruginosa. Images

Saiman, L; Prince, A



Anti-GM1 antibodies can block neuronal voltage-gated sodium channels.  


Anti-GM1 antibodies, frequently found in the serum of patients with Guillain-Barré syndrome (GBS), have been suggested to interfere with axonal function. We report that IgG anti-GM1 antibodies, raised in rabbits, can reversibly block the voltage-gated Na(+) channels of nerve cells, thus causing a reduction of the excitatory Na(+) current. The block was, however, only substantial when the antibodies were applied together with rabbit complement factors. A solution containing anti-GM1 sera (dilution 1:100) and complement (1:50) reduced the Na(+) current to 0.5 +/- 0.2 times control (mean value +/- SD). Applications of the antibody by itself, complement by itself, or anti-GM2 or anti-GM4 antibodies (1:100) plus complement had little effect. The complexes of anti-GM1 antibodies and complement factors block the ion-conducting pore of the channel directly. In addition, they increase the fraction of channels that are inactivated at the resting potential and alter channel function by changing the membrane surface charge. The described effects may be responsible for conduction slowing and reversible conduction failure in some GBS patients. PMID:10951445

Weber, F; Rüdel, R; Aulkemeyer, P; Brinkmeier, H



World population projections using metabolic GM (1,1) model  

Microsoft Academic Search

Forecasts of population size allow city planners, economists, public agencies, environmentalists, and social scientists to prepare for what is to come, so the research on population projections has become a focus of demographers' research. In the study, population system is regarded as a grey system and a method based on GM (1,1) model from Grey system theory is introduced to

Caimei Lu; Yonghong Hao; Xuemeng Wang



Improvement and application of GM(1,1) model  

Microsoft Academic Search

The paper puts forward a new conversion method that convert original sequence using cosine function, which proves discrete data sequence can improve smoothness by this conversion in theory. And this conversion is used in GM(1,1) model, which is used in example prediction at the end of this paper, which proves the effectiveness of the method of this paper.

Liu Danhua; Dang Yaoguo; Li Xuemei



Immunization of mice with fucosyl-GM1 conjugated with keyhole limpet hemocyanin results in antibodies against human small-cell lung cancer cells  

Microsoft Academic Search

Fucosyl-GM1 (Fuc-GM1) [Fuc?1???2Gal?1 ??3GalNAc?1???4(NeuAc?2-3)Gal?1???4Glc?1???O-Cer] is a small-cell-lung-cancer (SCLC)-associated ganglioside initially defined by the murine monoclonal antibody F12. On\\u000a the basis of its known distribution, Fuc-GM1 is a potential target for active immunotherapy in SCLC patients. Fuc-GM1 has\\u000a been extracted and purified from bovine thyroid. The immunogenicity of Fuc-GM1 was tested in mice either alone, mixed with\\u000a carrier protein keyhole limpet

Sarah Cappello; Nancy X. Liu; Cristina Musselli; Fred-Thomas Brezicka; Philip O. Livingston; Govindaswami Ragupathi



Cholera Toxin Assault on Lipid Monolayers Containing Ganglioside GM1  

PubMed Central

Many bacterial toxins bind to and gain entrance to target cells through specific interactions with membrane components. Using neutron reflectivity, we have characterized the structure of mixed DPPE:GM1 lipid monolayers before and during the binding of cholera toxin (CTAB5) or its B-subunit (CTB5). Structural parameters such as the density and thickness of the lipid layer, extension of the GM1 oligosaccharide headgroup, and orientation and position of the protein upon binding are reported. The density of the lipid layer was found to decrease slightly upon protein binding. However, the A-subunit of the whole toxin is clearly located below the B-pentameric ring, away from the monolayer, and does not penetrate into the lipid layer before enzymatic cleavage. Using Monte Carlo simulations, the observed monolayer expansion was found to be consistent with geometrical constraints imposed on DPPE by multivalent binding of GM1 by the toxin. Our findings suggest that the mechanism of membrane translocation by the protein may be aided by alterations in lipid packing.

Miller, C. E.; Majewski, J.; Faller, R.; Satija, S.; Kuhl, T. L.



Dependence of rat liver CMP N-acetylneuraminate:GM 1 sialyltransferase (SAT IV) activity on the ceramide composition of GM 1 ganglioside  

Microsoft Academic Search

The dependence of CMP-N-acetylneuraminate:GM1 sialyltransferase (SAT IV) activity of rat liver Golgi apparatus on GM1 ganglioside ceramide composition was evaluated. SAT IV activity was assayed on GM1 molecular species carrying homogeneous ceramide moieties containing long chain bases of different length (18 or 20 C atoms) unsaturated or not, linked to 14:0, 16:0, 18:0 or 22:0 fatty acids. The results obtained

Marina Pitto; Paola Palestini; Massimo Masserini



Life prediction of mechanical products of GM(1,1) based on particle swarm optimization  

Microsoft Academic Search

When GM(1,1) is used in the life prediction of mechanical products, the experiment cost is saved and the experimental period is shortened. The research on the whitening differential equation of GM(1,1) indicates that both the background value and the initial value of GM(1,1) have important effect on the prediction accuracy. In this paper, a new PSO-GM(1,1, lambda, b ) optimization

Liu Hong; Zhang Qishan



Optimized GM (1, 1) based on Romber algorithm and quadratic interpolation method  

Microsoft Academic Search

This text analyzed the reason of generating error of GM (1, 1), from the integral calculus angle discrete GM (1, 1). A kind of method putting forward making use of Romberg integral calculus formula and quadratic interpolation method to construct the background value of the model, raised simulation and prediction precision of GM(1,1), and the actual example verify the feasibility

Bo Li; Sheng-Li Zhao; Ling Fang



Adaptability of the GM(1,1) model for simulation of Jinci Springs discharge  

Microsoft Academic Search

To tackle of the examination problem of the adaptability of GM (1, 1) model to simulate spring discharge, we set up GM (1, 1) models by using different lengths of observed spring discharge data series of Jinci Springs China. Then we evaluate their adaptability by error analysis. Results showed the average errors of GM (1, 1) models declined from three

Jiaojuan Zhao; Huamin Li; Yonghong Hao



The application of GM (1,1) — Connection improved genetic algorithm in power load forecasting  

Microsoft Academic Search

In this paper, a GM (1, 1)-connection improved genetic algorithm (GM (1, 1)-IGA) is put forward to solve the problem of short-term load forecasting (STLF) in power system. While Traditional GM (1, 1) forecasting model is not accurate and the value of parameter OC is constant, the proposed algorithm could overcome these disadvantages. In order to construct optimal grey model

Wei Li; Zhu-hua Han



Brain content of glycosphingolipids after oral administration of monosialogangliosides GM1 and LIGA20 to rats  

Microsoft Academic Search

Natural (GM1) and semisynthetic [113-Neu-5-AcGgOse4-2-D-erythro-1,3-dihydroxy-2-dichloroacetylamide-4-trans-octadecene (LIGA20)] glycosphingolipids, given parenterally, protect neurones against glutamate-induced death without producing\\u000a the side effects typical of glutamate receptor antagonists. Chronic glutamate-related neurotoxicity (e.g., in recurring strokes\\u000a in elderly hypertensive patients, and in Parkinson disease) could be prevented also by glycosphingolipids treatment, but this\\u000a therapeutic intervention will require a protracted administration of orally active glycosphingolipids. Here

A. Polo; G. Kirschner; A. Guidotti; E. Costa



Alzheimer disease - effect of continuous intracerebroventricular treatment with GM1 ganglioside and a systematic activation programme.  


Five patients with the early-onset form of Alzheimer disease (AD) received GM1 ganglioside by continuous injection into the frontal horns of the lateral ventricles for a period of 12 months. The optimal GM1 dose varied between 20 and 30 mg/24 h. The patients were trained twice a week for 4-5 h with an individually designed cognitive programme, which included the use of a word processor. Neurological, neuropsychological, psychiatric and neurochemical examinations were performed a week before surgery and on days 30, 90, 180, 270 and 365 after surgery. The cerebrospinal fluid levels of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased. The regional cerebral blood flow showed a tendency to increase. The progression of deterioration was stopped, and motor performance and neuropsychological assessments improved. The patients became more active and felt safer in relation to other people and performing various activities. They had improved reading comprehension and a better feeling for language. They were able to write reports and short letters on a word processor. When interviewed at the end of the study, all 5 patients stated that they felt better, and their relatives reported that they had regained integrity and their joie de vivre. PMID:12218255

Svennerholm, Lars; Bråne, Görel; Karlsson, Ingvar; Lekman, Annika; Ramström, Ingalill; Wikkelsö, Carsten



A photoreactive derivative of radiolabeled GM1 ganglioside: Preparation and use to establish the involvement of specific proteins in GM1 uptake by human fibroblasts in culture  

SciTech Connect

A new procedure was used to synthesize a derivative of ganglioside GM1 containing a photoreactive nitrophenyl azide group at the end of the fatty acyl moiety, using deAc-deAcyl-GM1 obtained by deacetylation of the sialic acid and deacylation of the ceramide portion of GM1. This deAc-deAcyl-GM1 was first acylated at the long chain base amino group with 12-aminododecanoic acid, which has the amino group protected by a fluorenyl residue, and tritium labeled at the sialic acid amino group with ({sup 3}H)acetic anhydride of very high specific radioactivity. Cultured human fibroblasts were exposed to mixtures of radioactive photolabeled GM1 for different times and then illuminated and the radioactive protein patterns studied by SDS-PAGE. After 2 h of exposure, the photolabeled GM1 was stably associated to the cells and underwent almost no metabolic processing, behaving exactly as the underivatized natural GM1. Under these conditions very few proteins became radioactive. Thus, it is evident that the ganglioside binding to fibroblasts and insertion into the outer layer of the plasma membrane involve few individual proteins. When the incubation was prolonged to 24 h, photolabeled GM1 underwent extensive metabolic processing and gave origins to the corresponding ganglioside derivatives of GM2, GM3, and GD1a. Under these conditions many proteins became radioactive, a consequence of GM1 transfer from the surface to the interior or the cell and of the ready availability of interaction of GM1 and its metabolites.

Sonnino, S.; Chigorno, V.; Acquotti, D.; Pitto, M.; Kirschner, G.; Tettamanti, G. (Univ. of Milan (Italy))



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

Microsoft Academic Search

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.

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



Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis.  


Late-onset GM2 gangliosidosis is composed of two related, autosomal recessive, neurodegenerative diseases, both resulting from deficiency of lysosomal, heterodimeric beta-hexosaminidase A (Hex A, alphabeta). Pharmacological chaperones (PC) are small molecules that can stabilize the conformation of a mutant protein, allowing it to pass the quality control system of the endoplasmic reticulum. To date all successful PCs have also been competitive inhibitors. Screening for Hex A inhibitors in a library of 1040 Food Drug Administration-approved compounds identified pyrimethamine (PYR (2,4-diamino 5-(4-chlorophenyl)-6-ethylpyrimidine)) as the most potent inhibitor. Cell lines from 10 late-onset Tay-Sachs (11 alpha-mutations, 2 novel) and 7 Sandhoff (9 beta-mutations, 4 novel) disease patients, were cultured with PYR at concentrations corresponding to therapeutic doses. Cells carrying the most common late-onset mutation, alphaG269S, showed significant increases in residual Hex A activity, as did all 7 of the beta-mutants tested. Cells responding to PC treatment included those carrying mutants resulting in reduced Hex heat stability and partial splice junction mutations of the inherently less stable alpha-subunit. PYR, which binds to the active site in domain II, was able to function as PC even to domain I beta-mutants. We concluded that PYR functions as a mutation-specific PC, variably enhancing residual lysosomal Hex A levels in late-onset GM2 gangliosidosis patient cells. PMID:17237499

Maegawa, Gustavo H B; Tropak, Michael; Buttner, Justin; Stockley, Tracy; Kok, Fernando; Clarke, Joe T R; Mahuran, Don J



Tissue Receptor for Cholera Exotoxin: Postulated Structure from Studies with GM1 Ganglioside and Related Glycolipids  

PubMed Central

By a double-diffusion precipitation-in-gel technique, isolated cholera toxin as well as its natural toxoid were shown to be fixed and precipitated by the ganglioside GM1 but not by any of the related glycolipids GM3, GM2, GM1-GlcNAc, GD1a, GD1b, GT1, globoside, GA1, and tetrahexoside-GlcNAc. Twenty-five nanograms of GM1 was enough to give a precipitation line with 1.2 ?g of toxin, whereas about 50 ng was required with this amount of toxoid. GM1 also inactivated the toxin in the ileal loop as well as in the intradermal models in rabbits. A 1: 1 molar ratio of ganglioside to toxin was found limiting, e.g., 100 pg of GM1 could inactivate 5 ng (about 50 blueing doses) of isolated toxin. GM1 inactivated crude toxin (culture fil rate) with the same efficiency as isolated toxin, and the inactivating capacity of GM1 was unaffected by mixing with other gangliosides, indicating the specificity in the reaction between GM1 and toxin. The other glycolipids tested did not inactivate toxin except GD1a and GA1 which did so with approximately 1,000 times less efficiency than GM1. This identified the portion Gal ? GalNAc [Formula: see text] as the critical region in GM1 for toxin fixation, and it is postulated that this may be the tissue receptor structure for the cholera toxin. Images

Holmgren, J.; Lonnroth, I.; Svennerholm, L.



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


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

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



Biochemical characterization of the GM2 gangliosidosis B1 variant.  


The deficiency of the A isoenzyme of beta-hexosaminidase (Hex) produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease) has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age) with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphabeta heterodimer Hex A means that its activation energy (41.8 kJ/mol) is significantly lower than that of the betabeta homodimer Hex B (75.1 kJ/mol); however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme. PMID:15264019

Tutor, J C



Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and GalNAc-GD1a  

Microsoft Academic Search

This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE) associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to Campylobacter jejuni enteritis, the patient rapidly developed consciousness disturbance and hyperreflexia in addition to external ophthalmoplegia and cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic ? activities, predominantly in the front-central area. He received high doses of

Muneaki Matsuo; Masaaki Odaka; Michiaki Koga; Katsunori Tsuchiya; Yuhei Hamasaki; Nobuhiro Yuki



GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA.  


The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction. PMID:7790879

Rabin, S J; Mocchetti, I



Condensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films  

PubMed Central

Mixed monolayers of the ganglioside GM1 and the lipid dipalmitoylphosphatidlycholine (DPPC) at air-water and solid-air interfaces were investigated using various biophysical techniques to ascertain the location and phase behavior of the ganglioside molecules in a mixed membrane. The effects induced by GM1 on the mean molecular area of the binary mixtures and the phase behavior of DPPC were followed for GM1 concentrations ranging from 5 to 70 mol %. Surface pressure isotherms and fluorescence microscopy imaging of domain formation indicate that at low concentrations of GM1 (<25 mol %), the monolayer becomes continually more condensed than DPPC upon further addition of ganglioside. At higher GM1 concentrations (>25 mol %), the mixed monolayer becomes more expanded or fluid-like. After deposition onto a solid substrate, atomic force microscopy imaging of these lipid monolayers showed that GM1 and DPPC pack cooperatively in the condensed phase domain to form geometrically packed complexes that are more ordered than either individual component as evidenced by a more extended total height of the complex arising from a well-packed hydrocarbon tail region. Grazing incidence x-ray diffraction on the DPPC/GM1 binary mixture provides evidence that ordering can emerge when two otherwise fluid components are mixed together. The addition of GM1 to DPPC gives rise to a unit cell that differs from that of a pure DPPC monolayer. To determine the region of the GM1 molecule that interacts with the DPPC molecule and causes condensation and subsequent expansion of the monolayer, surface pressure isotherms were obtained with molecules modeling the backbone or headgroup portions of the GM1 molecule. The observed concentration-dependent condensing and fluidizing effects are specific to the rigid, sugar headgroup portion of the GM1 molecule.

Frey, Shelli L.; Chi, Eva Y.; Arratia, Cristobal; Majewski, Jaroslaw; Kjaer, Kristian; Lee, Ka Yee C.



The comparison of transfer model and metabolism GM(1, 1) model in Fuzhou port's throughput prediction  

Microsoft Academic Search

Both transfer model and metabolism GM(1, 1) model are usually used to establish dynamic prediction model. This paper applies these two models to Fuzhou port's throughput prediction and compares the results. The results show that both models can obtain satisfying predicted values. Furthermore, metabolism GM(1, 1) needs fewer data and performs better in terms of prediction accuracy.

Chen Kejia; Chen Jiaying; Zhang Qishan



Airport gate assignment based on improved GM(1,1) model  

Microsoft Academic Search

In order to improve the robustness of gate assignment, a strategy is proposed. It forecasts the arrival time and departure time of each flight, and then assigns flights to gates according to the forecasting results. To enhance the low forecasting precision of traditional GM(1, 1) model for oscillating sequences, a moving operator is introduced to improve the traditional GM(1, 1)

Shangwen Yang; Minghua Hu



GM1 Clustering Inhibits Cholera Toxin Binding in Supported Phospholipid Membranes  

PubMed Central

The present studies explore multivalent ligand–receptor interactions between pentameric cholera toxin B subunits (CTB) and the corresponding membrane ligand, ganglioside GM1. CTB binding was monitored on supported phospholipid bilayers coated on the walls and floors of microfluidic channels. Measurements were made by total internal reflection fluorescence microscopy (TIRFM). Apparent dissociation constants were extracted by fitting the binding data to both the Hill–Waud and Langmuir adsorption isotherm equations. Studies of the effect of ligand density on multivalent CTB–GM1 interactions revealed that binding weakened with increasing GM1 density from 0.02 mol % to 10.0 mol %. Such a result could be explained by the clustering of GM1 on the supported phospholipid membranes, which in turn inhibited the binding of CTB. Atomic force microscopy (AFM) experiments directly verified GM1 clustering within the supported POPC bilayers.

Shi, Jinjun; Yang, Tinglu; Kataoka, Sho; Zhang, Yanjie; Diaz, Arnaldo J.; Cremer, Paul S.



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

Microsoft Academic Search

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,

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



Partitioning and confinement of GM1 ganglioside induced by amyloid aggregates.  


Growing evidence shows that GM1 ganglioside is involved in amyloid deposition and toxicity. By means of real-time single particle tracking, we show that amyloid oligomers and aggregates formed by A?1-42 and amylin, two peptides associated, respectively, with the development of Alzheimer's disease and type II diabetes, interact with GM1 and decrease dramatically its lateral diffusion on the plasma membrane of living neuroblastoma cells. The confinement of GM1, a constituent of membrane rafts involved in neuroprotection, at the level of both types of amyloid aggregates can interfere with cell signaling pathways and contribute to the loss of neuroprotection. PMID:23523632

Calamai, Martino; Pavone, Francesco S



Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.  


Autopsy studies of late-onset GM2 gangliosidosis are sparse and only one adult case is on record. The case of partial Hex A deficiency presented here started in childhood as spinal muscular atrophy which progressed slowly over 4 decades. Cognitive function remained intact throughout the entire course, but during the last few years of life allodynia supervened. The patient died at 44 years of age. In good correlation with clinical observations the autopsy findings showed the most severe accumulation of lipid and consequent regressive change in the anterior horns of the spinal cord. Extensive but less severe storage was found in other spinal cord neurons, brain stem and selected basal ganglia. Cerebral cortex was virtually spared by storage but was the site of excessive formation of lipofuscin which was also present in many other neurons in the CNS. Marked storage and ganglionic loss was also found in the dorsal root ganglia, and the fasciculus gracilis was severely depleted of myelinated fibers. Electron microscopy showed accumulated gangliosides almost exclusively in the form of single and coalescing zebra bodies. In conclusion, the pathology in this case of chronic GM2 gangliosidosis, though in part conforming with previous observations, differed in several aspects. First, the cerebral cortex was--with only a few exceptions--free of ganglioside storage. Also spared was the cerebellum. In addition, homogeneous accumulation of zebra bodies contrasted with heterogeneity of neuronal inclusions found in other chronic cases. Finally, the involvement of sensory neurons was prominent and potentially related to allodynia. Molecular study of HEXA gene in this patient showed an TATC1278/? genotype. PMID:18808061

Kornfeld, M


Simulation of karst hydrological processes using GM(1,1) metabolic model  

Microsoft Academic Search

In this paper, the GM(1,1) metabolic model was applied to simulation of the spring discharge of Niangziguan Springs. We identified the models by error analysis and found that the GM(1,1) metabolic models with data sequence of seven and eight dimensions can reflect the future variation of the springs flow. The results showed that the predicted spring flow of the models

Yajie Wang; Yonghong Hao; Xuemeng Wang



Ameliorating GM (1, 1) Model Based on the Structure of the Area under Trapezium  

Microsoft Academic Search

According to the research on the structure of background value in the GM(1,1) model, the structure method of background value, a exact formula about the background value of chi (1)(t) in the region [k,k + 1],which is used when establishing GM(1,1), is established by integrating chi (1)(t) from k to k + 1 .The modeling precision and prediction precision of

Cuifeng Li



Ganglioside GM1 binding the N-terminus of amyloid precursor protein  

Microsoft Academic Search

Secreted amyloid precursor protein (APPs) plays a role in several neuronal functions, including the promotion of synaptogenesis, neurite outgrowth and neuroprotection. Previous study has demonstrated that ganglioside GM1 inhibits the secretion of APPs; however the underlying mechanism remains unknown. Here we reported that GM1 can bind cellular full length APP and APPs secreted from APP695 stably-transfected SH-SY5Y cells. To characterize

Handi Zhang; Jixin Ding; Wenqiang Tian; Lijun Wang; Lixin Huang; Yan Ruan; Tianlan Lu; Yinlin Sha; Dai Zhang




PubMed Central

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.

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



Functional and structural effects of GM-1 ganglioside treatment on peripheral nerve grafting in the rat.  


Peripheral nerve regeneration after traumatic injury and standard repair with a nerve autograft is usually incomplete. This study tested the influence of graft vascularity and pharmacological intervention with GM-1 ganglioside on nerve regeneration in a rat sciatic nerve model. Controls included an unoperated contralateral side and sham-operated groups either with or without the GM-1. During the 5 months of recovery, locomotion was tested by the sciatic function index (SFI). At killing, anesthetized animals were prepared for nerve conduction velocity (NCV) studies, followed by the wet weight of the gastrocnemius muscle (expression of atrophy), toe-chewing (expression of lesion severity and sensory loss), and histological examination of the nerve segments. The SFI showed a slight but significant recovery for both the vascular and avascular groups (34% at 20 weeks), but when GM-1 ganglioside treatment was included, the SFI was poor throughout (20-33%). The average NCV of the graft groups without GM-1 was 46% to 57% of the normal nerve (52.7 m/s), whereas for the groups treated with GM-1, it was 63% to 64% of normal; treatment of the non-vascular graft group significantly improved recovery. A uniformly poor recovery from muscle atrophy was seen for all nerve graft groups (62-67%) compared with normal controls. The mean number of toes per foot chewed was 1.9 and 2.4 in graft groups without GM-1 treatment and 0.9 and 1.3 in graft groups treated with GM-1. This treatment significantly reduced both the extent and the number of animals exhibiting autotomy. The qualitative microscopic appearance of the distal nerve segment in all surgical groups was similar. We conclude that the systemic addition of GM-1 ganglioside enhances only some aspects of regeneration in grafted nerves, possibly with a preferential effect on sensory nerve regeneration and functional recovery. PMID:11372071

Sobeski, J K; Kerns, J M; Safanda, J F; Shott, S; Gonzalez, M H



Clostridium perfringens Alpha-toxin Recognizes the GM1a-TrkA Complex*  

PubMed Central

Clostridium perfringens alpha-toxin is the major virulence factor in the pathogenesis of gas gangrene. Alpha-toxin is a 43-kDa protein with two structural domains; the N-domain contains the catalytic site and coordinates the divalent metal ions, and the C-domain is a membrane-binding site. The role of the exposed loop region (72–93 residues) in the N-domain, however, has been unclear. Here we show that this loop contains a ganglioside binding motif (H … SXWY … G) that is the same motif seen in botulinum neurotoxin and directly binds to a specific conformation of the ganglioside Neu5Ac?2-3(Gal?1-3GalNAc?1-4)Gal?1-4Glc?1Cer (GM1a) through a carbohydrate moiety. Confocal microscopy analysis using fluorescently labeled BODIPY-GM1a revealed that the toxin colocalized with GM1a and induced clustering of GM1a on the cell membranes. Alpha-toxin was only slightly toxic in ?1,4-N-acetylgalactosaminyltransferase knock-out mice, which lack the a-series gangliosides that contain GM1a, but was highly toxic in ?2,8-sialyltransferase knock-out mice, which lack both b-series and c-series gangliosides, similar to the control mice. Moreover, experiments with site-directed mutants indicated that Trp-84 and Tyr-85 in the exposed alpha-toxin loop play an important role in the interaction with GM1a and subsequent activation of TrkA. These results suggest that binding of alpha-toxin to GM1a facilitates the activation of the TrkA receptor and induces a signal transduction cascade that promotes the release of chemokines. Therefore, we conclude that GM1a is the primary cellular receptor for alpha-toxin, which can be a potential target for drug developed against this pathogen.

Oda, Masataka; Kabura, Michiko; Takagishi, Teruhisa; Suzue, Ayaka; Tominaga, Kaori; Urano, Shiori; Nagahama, Masahiro; Kobayashi, Keiko; Furukawa, Keiko; Furukawa, Koichi; Sakurai, Jun



Clostridium perfringens alpha-toxin recognizes the GM1a-TrkA complex.  


Clostridium perfringens alpha-toxin is the major virulence factor in the pathogenesis of gas gangrene. Alpha-toxin is a 43-kDa protein with two structural domains; the N-domain contains the catalytic site and coordinates the divalent metal ions, and the C-domain is a membrane-binding site. The role of the exposed loop region (72-93 residues) in the N-domain, however, has been unclear. Here we show that this loop contains a ganglioside binding motif (H … SXWY … G) that is the same motif seen in botulinum neurotoxin and directly binds to a specific conformation of the ganglioside Neu5Ac?2-3(Gal?1-3GalNAc?1-4)Gal?1-4Glc?1Cer (GM1a) through a carbohydrate moiety. Confocal microscopy analysis using fluorescently labeled BODIPY-GM1a revealed that the toxin colocalized with GM1a and induced clustering of GM1a on the cell membranes. Alpha-toxin was only slightly toxic in ?1,4-N-acetylgalactosaminyltransferase knock-out mice, which lack the a-series gangliosides that contain GM1a, but was highly toxic in ?2,8-sialyltransferase knock-out mice, which lack both b-series and c-series gangliosides, similar to the control mice. Moreover, experiments with site-directed mutants indicated that Trp-84 and Tyr-85 in the exposed alpha-toxin loop play an important role in the interaction with GM1a and subsequent activation of TrkA. These results suggest that binding of alpha-toxin to GM1a facilitates the activation of the TrkA receptor and induces a signal transduction cascade that promotes the release of chemokines. Therefore, we conclude that GM1a is the primary cellular receptor for alpha-toxin, which can be a potential target for drug developed against this pathogen. PMID:22847002

Oda, Masataka; Kabura, Michiko; Takagishi, Teruhisa; Suzue, Ayaka; Tominaga, Kaori; Urano, Shiori; Nagahama, Masahiro; Kobayashi, Keiko; Furukawa, Keiko; Furukawa, Koichi; Sakurai, Jun



A case of GM2 gangliosidosis of late onset  

PubMed Central

A case of GM2-gangliosidosis commencing by the age of 5 years is described, in which hyperacusis, dementia, and fits were prominent clinical features. In addition to the typical ganglioside pattern on thin layer chromatography and the presence of membranous bodies in electron microscopic studies and characteristic histology and histochemistry, there was biochemical evidence of a gross reduction in heat-labile hexosaminidase activity in white blood cells and brain. A younger unaffected sibling showed the same enzyme defect in white blood cells. Images

Buxton, P.; Cumings, J. N.; Ellis, R. B.; Lake, B. D.; Mair, W. G. P.; Roberts, J. R.; Young, E. P.



Synthesis of novel NBD-GM1 and NBD-GM2 for the transfer activity of GM2-activator protein by a FRET-based assay system.  


The ganglioside-activator protein is an essential cofactor for the lysosomal degradation of ganglioside GM2 (GM2) by beta-hexosaminidase A. It mediates the interaction between the water-soluble exohydrolase and its membrane-embedded glycolipid substrate at the lipid-water interphase. Mutations in the gene encoding this glycoprotein result in a fatal neurological storage disorder, the AB variant of GM2-gangliosidosis. In order to efficiently and sensitively probe the glycolipid binding and membrane activity of this cofactor, we synthesized two new fluorescent glycosphingolipid (GSL) probes, 2-NBD-GM1 and 2-NBD-GM2. Both compounds were synthesized in a convergent and multistep synthesis starting from the respective gangliosides isolated from natural sources. The added functionality of 2-aminogangliosides allowed us to introduce the chromophore into the region between the polar head group and the hydrophobic anchor of the lipid. Both fluorescent glycolipids exhibited an extremely low off-rate in model membranes and displayed very efficient resonance energy transfer to rhodamine-dioleoyl phosphoglycerol ethanolamine (rhodamine-PE) as acceptor. The binding to GM2-activator protein (GM2AP) and the degrading enzyme was shown to be unaltered compared to their natural analogues. A novel fluorescence-resonance energy transfer (FRET) assay was developed to monitor in real time the protein-mediated intervesicular transfer of these lipids from donor to acceptor liposomes. The data obtained indicate that this rapid and robust system presented here should serve as a valuable tool to probe quantitatively and comprehensively the membrane activity of GM2AP and other sphingolipid activator proteins and facilitate further structure-function studies aimed at delineating independently the lipid- and the enzyme-binding mode of these essential cofactors. PMID:16079415

Schwarzmann, Günter; Wendeler, Michaela; Sandhoff, Konrad



Pathology of GM2 gangliosidosis in Jacob sheep.  


The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model. PMID:21123862

Porter, B F; Lewis, B C; Edwards, J F; Alroy, J; Zeng, B J; Torres, P A; Bretzlaff, K N; Kolodny, E H



Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide.  

PubMed Central

Cholera toxin (CT) is an AB5 hexameric protein responsible for the symptoms produced by Vibrio cholerae infection. In the first step of cell intoxication, the B-pentamer of the toxin binds specifically to the branched pentasaccharide moiety of ganglioside GM1 on the surface of target human intestinal epithelial cells. We present here the crystal structure of the cholera toxin B-pentamer complexed with the GM1 pentasaccharide. Each receptor binding site on the toxin is found to lie primarily within a single B-subunit, with a single solvent-mediated hydrogen bond from residue Gly 33 of an adjacent subunit. The large majority of interactions between the receptor and the toxin involve the 2 terminal sugars of GM1, galactose and sialic acid, with a smaller contribution from the N-acetyl galactosamine residue. The binding of GM1 to cholera toxin thus resembles a 2-fingered grip: the Gal(beta 1-3)GalNAc moiety representing the "forefinger" and the sialic acid representing the "thumb." The residues forming the binding site are conserved between cholera toxin and the homologous heat-labile enterotoxin from Escherichia coli, with the sole exception of His 13. Some reported differences in the binding affinity of the 2 toxins for gangliosides other than GM1 may be rationalized by sequence differences at this residue. The CTB5:GM1 pentasaccharide complex described here provides a detailed view of a protein:ganglioside specific binding interaction, and as such is of interest not only for understanding cholera pathogenesis and for the design of drugs and development of vaccines but also for modeling other protein:ganglioside interactions such as those involved in GM1-mediated signal transduction.

Merritt, E. A.; Sarfaty, S.; van den Akker, F.; L'Hoir, C.; Martial, J. A.; Hol, W. G.



Interaction of Treponema denticola TD-4, GM-1, and MS25 with human gingival fibroblasts.  

PubMed Central

The adherence of Treponema denticola GM-1, TD-4, and MS25 to human gingival fibroblasts (HGFs) was studied to serve as an introduction to investigations into the interactions of these oral bacteria with human host cells. Under both aerobic (5% CO2) and anaerobic (85% N2 plus 10% H2 plus 5% CO2) environments, the interactions with the HGFs were such that strains GM-1 and MS25 were consistently more adherent than strain TD-4. Polyclonal antibodies to GM-1 inhibited GM-1 adherence by 70%, while MS25 and TD-4 showed differing degrees of cross-reactive inhibition, indicative of common but not identical epitopes on the surface of the three T. denticola strains. Pretreatment of the three strains with trypsin did not inhibit adherence; proteinase K did, however, inhibit this interaction by 80%. Trypsin pretreatment of the HGFs resulted in increases in adherence of 50 and 86% for GM-1 and MS25, respectively, while a decrease of 41% was noted for TD-4. Exposure of the T. denticola strains to sugars and lectin pretreatment of the HGFs implicated adherence mediation by mannose and galactose residues on the HGF surface. Periodate treatment of HGFs resulted in a 50% drop in adherence for GM-1 and MS25, but did not decrease that of TD-4. Addition of fetal bovine serum inhibited adherence of the three strains to differing degrees, with TD-4 being the most susceptible. Addition of purified fibronectin (100 micrograms/ml) resulted in greater than 50% inhibition in GM-1 and MS25 adherence, while a 25% increase occurred with TD-4. While strain differences were noted in some of the parameters studied, the results indicate two possibilities for T. denticola-HGF adherence: a lectinlike adhesin(s) on the T. denticola surface with affinity for galactose and mannose on the HGF surface, and a serum host factor(s) bridging T. denticola and HGFs. Images

Weinberg, A; Holt, S C



Hexosaminidase isozyme in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease).  

PubMed Central

The residual enzyme of the fibroblasts of a child with homozygous type 0 GM2 gangliosidosis (Sandhoff-Jatzkewitz disease) has been found to correspond with a minor fraction of enzyme which can be isolated from normal fibroblasts by repeated chromatography. This enzyme is designated as hexosaminidase (hex) S. It reacts with antiserum prepared against homogeneous hex A but not with serum prepared against homogeneous hex B. These findings support our previously described model of the relationship between hex A and hex G: hex A has the structure (alpha beta)3, while hex B is (beta)6. Type B GM2 gangliosidosis (Tay-Sachs disease) is the alpha- mutation, while type 0 GM2 gangliosidosis (Sandhoff-Jatzkewitz disease) is the beta- mutation. In the absence of normal beta subunits there is increased polymerization of alpha subunits forming hex S, which probably has a structure of (alpha)6. A parallel between the thalassemias and GM2 gangliosidosis is evident: deficiency of one of the chains of which the protein is composed leads to an excess of polymers comprised of the other chains. In type B GM2 gangliosidosis, the excess of beta chanis leads to increased amounts of hex B beta)6; in type 0 GM2 gangliosidosis, the excess of alpha chains leads to formation of increased amounts of the alpha chain polymer, hex S.

Beutler, E; Kuhl, W; Comings, D



Modulation of dihydropyridine-sensitive gastric mucosal calcium channels by GM1-ganglioside.  


1. A dihydropyridine-sensitive calcium channel complex was solubilized from gastric mucosal cell membranes and purified by affinity chromatography on wheat germ agglutinin. 2. The calcium channel complex labeled with [3H]PN200-110, when reconstituted into phosphatidylcholine vesicles, exhibited active 45Ca2+ uptake into intravesicular space as evidenced by La3+ displacement and osmolarity studies. The channel complex responded in a dose-dependent manner to dihydropyridine calcium antagonist, PN200-110, which at 0.5 microM exerted maximal inhibitory effect of 66% in 45Ca2+ uptake. 3. The uptake of 45Ca2+ into vesicle-reconstituted gastric mucosal calcium channel complex was inhibited by GM1-ganglioside. Maximum inhibitory effect was achieved at 10-15 nM GM1, at which point a 74% decrease in 45Ca2+ uptake occurred. Furthermore, GM1 also inhibited dihydropyridine binding to gastric mucosal membranes, indicating the extracellular orientation of calcium channel domains for GM1. 4. The ability of GM1 to modulate the intracellular calcium levels may be an important feature in gastric mucosal protection by this ganglioside. PMID:1322845

Slomiany, B L; Liu, J; Fekete, Z; Yao, P; Slomiany, A



Ordering Transitions in Micrometer-Thick Films of Nematic Liquid Crystals Driven by Self-Assembly of Ganglioside GM1  

PubMed Central

We report an investigation of the self-assembly of the monosialoganglioside (GM1) at interfaces formed between aqueous solutions of 10 µM GM1 (at 25°C) and micrometer-thick films of the nematic liquid crystal (LC) 4’-pentyl-4-cyanobiphenyl (5CB). We observe the process of spontaneous transfer of GM1 onto the interfaces to be accompanied by continuous ordering transitions within the micrometer-thick films of the LC. At saturation coverage, the GM1 orders the LC in an orientation that is perpendicular to the interface, an orientation that is similar to that caused by phospholipids such as dilaurylphosphatidylcholine (DLPC). This result suggests an interaction between the LC and GM1 that is dominated by the hydrophobic tails of the GM1. Relative to DLPC, however, we observe the dynamics of the LC ordering transition driven by GM1 to be slow (2 hours for DLPC versus 100 hours for GM1). To provide insight into the origins of the slow dynamics of the GM1-induced ordering transition in the LC, we performed two additional measurements. First, we quantified the time-dependent adsorption of GM1 at the LC interface by using fluorescently-labeled GM1. Second, we used the Langmuir-Schaefer method to transfer preorganized monolayers of GM1 from an air-water interface to the aqueous-LC interface. Results obtained from these two experiments are consistent with a physical picture in which the final stages of spontaneous adsorption/ordering of GM1 at the aqueous-LC interface dictate the dynamics of the LC ordering transition. This rate limiting process underlying the ordering transition was substantially accelerated by heating the system above the phase transition temperature of GM1 (26 °C), suggesting that the phase state of the GM1 micellar aggregates in bulk solution strongly influences the kinetics of the final stages of ordering/adsorption of GM1 at the LC interface. Overall, these results and others presented in this manuscript reveal that it is possible to decorated interfaces of a nematic LC with GM1, and that the assembly of GM1 at these interfaces impacts the dynamic and equilibrium ordering of the LC.

Lin, I-Hsin; Meli, Maria-Victoria; Abbott, Nicholas L.



Ordering transitions in micrometer-thick films of nematic liquid crystals driven by self-assembly of ganglioside GM1.  


We report an investigation of the self-assembly of the monosialoganglioside (GM(1)) at interfaces formed between aqueous solutions of 10 microM GM(1) (at 25 degrees C) and micrometer-thick films of the nematic liquid crystal (LC) 4'-pentyl-4-cyanobiphenyl (5CB). We observe the process of spontaneous transfer of GM(1) onto the interfaces to be accompanied by continuous ordering transitions within the micrometer-thick films of the LC. At saturation coverage, the GM(1) orders the LC in an orientation that is perpendicular to the interface, an orientation that is similar to that caused by phospholipids such as dilauroylphosphatidylcholine (DLPC). This result suggests an interaction between the LC and GM(1) that is dominated by the hydrophobic tails of the GM(1). Relative to DLPC, however, we observe the dynamics of the LC ordering transition driven by GM(1) to be slow (2 h for DLPC versus 100 h for GM(1)). To provide insight into the origins of the slow dynamics of the GM(1)-induced ordering transition in the LC, we performed two additional measurements. First, we quantified the time-dependent adsorption of GM(1) at the LC interface by using fluorescently-labeled GM(1). Second, we used the Langmuir-Schaefer method to transfer preorganized monolayers of GM(1) from an air-water interface to the aqueous-LC interface. Results obtained from these two experiments are consistent with a physical picture in which the final stages of spontaneous adsorption/ordering of GM(1) at the aqueous-LC interface dictate the dynamics of the LC ordering transition. This rate limiting process underlying the ordering transition was substantially accelerated by heating the system above the phase transition temperature of GM(1)(26 degrees C), suggesting that the phase state of the GM(1) micellar aggregates in bulk solution strongly influences the kinetics of the final stages of ordering/adsorption of GM(1) at the LC interface. Overall, these results and others presented in this manuscript reveal that it is possible to decorate interfaces of a nematic LC with GM(1), and that the assembly of GM(1) at these interfaces impacts the dynamic and equilibrium ordering of the LC. PMID:19428021

Lin, I-Hsin; Meli, Maria-Victoria; Abbott, Nicholas L



Ganglioside GM1 Deficiency in Effector T Cells From NOD Mice Induces Resistance to Regulatory T-Cell Suppression  

PubMed Central

OBJECTIVE To detect GM1 deficiency and determine its role in effector T cells (Teffs) from NOD mice in establishing resistance to regulatory T-cell (Treg) suppression. RESEARCH DESIGN AND METHODS CD4+ and CD8+ Teffs were isolated from spleens of prediabetic NOD mice for comparison with similar cells from Balb/c, C57BL/6, and NOR mice. GM1 was quantified with thin-layer chromatography for total cellular GM1 and flow cytometry for cell-surface GM1. Suppression of Teff proliferation was determined by application of GM1 cross-linking agents or coculturing with Tregs. Calcium influx in Teffs was quantified using fura-2. RESULTS Resting and activated CD4+ and CD8+ Teffs of NOD mice contained significantly less GM1 than Teffs from the other three mouse strains tested. After activation, NOD Teffs resisted suppression by Tregs or GM1 cross-linking agents in contrast to robust suppression of Balb/c Teffs; this was reversed by preincubation of NOD Teffs with GM1. NOD Teffs also showed attenuated Ca2+ influx via transient receptor potential channel 5 (TRPC5) channels induced by GM1 cross-linking, and this, too, was reversed by elevation of Teff GM1. CONCLUSIONS GM1 deficiency occurs in NOD Teffs and contributes importantly to failed suppression, which is rectified by increasing Teff GM1. Such elevation also reverses subthreshold Ca2+ influx via TRPC5 channels, an essential aspect of suppression. Our results also support a critical role for galectin-1 as a GM1 cross-linking counter-receptor that fittingly is upregulated and released by Tregs during activation. These findings suggest a novel mechanism by which pathogenic Teffs evade regulatory suppression, thereby leading to autoimmune ?-cell destruction and type 1 diabetes.

Wu, Gusheng; Lu, Zi-Hua; Gabius, Hans-Joachim; Ledeen, Robert W.; Bleich, David



The forecast of gold price based on the GM (1, 1) and Markov chain  

Microsoft Academic Search

Due to gold plays an important role in maintain value, investment and national economic stability , therefore, forecasting the trend of gold price exactly is undoubtedly important. In this paper, author firstly uses GM (1, 1) model to simulate and predict the international gold price. On the basis of the method, using Markov chain to divide and predict the relative

Chengbiao Wang; Yanhui Chen; Lihong Li



Research on the Limitations of Deformation Prediction with GM (1, 1) Model  

Microsoft Academic Search

In this paper, grey system theory model of GM (1, 1) is applied on the deformation prediction of subgrade. Application condition, modeling method and method of precision treat with for the theory are explained combining a engineering sample. Limitations of deformation prediction for subgrade using the grey system theory are educed from the comparison the result of prediction and measured

Li Hui; Yan Echuan; Yan Min; Hu Zhongqi; Hu Chunhua; Zhuang Xinshan; Zhu Changqing



G\\/M\\/1 queue study of buffer behavior in the decoding system of computer communication  

Microsoft Academic Search

This paper deals with the buffer behavior at the decoding center of a computer communication system in which the messages are in the Huffman code of English text. It is assumed that the arrival of messages has an arbitrary distribution, with the message lengths having negative exponential distribution. The situation is well described by the G\\/M\\/1 model of queue theory.

H. M. Srivastava; H. B. Kekre; Y. N. Bapat



Skin Physiology Analysis via Grey GM(1, N) and GM(0, N) Model  

Microsoft Academic Search

This paper focuses on the skin physiological factor relationship analysis using grey GM(1, N) and GM(0, N) model. First, skin physiological factor sampling are done for Taiwan female subjects aged from 18 ~ 52, where the factors include skin elasticity, pH value, skin pigmentation, skin surface lipids and skin epidermal hydration. With the acquired data, we can then establish the

Ya-Ting Lee; Chian-Song Chiu



Micro-mechanical gyro drift modeling based on GM(1,1) of reconstruction of background value  

Microsoft Academic Search

After analyzing the essence of the traditional GM(1,1) model, background value was identified as key factor for precision and adaptability of GM(1,1) model, and a novel method was proposed to improve GM(1,1) model. Taking into calculation quantity and error, quadratic curve fitting was adopted to solve the unknown value, and Simpson integral formula was used to replace trapezoidal numerical integration

Jinxian Yang; Ying Zhang



Construction and application of unequal interval GM (1,1) prediction model based on multilevel residual amendment  

Microsoft Academic Search

Prediction for slope displacement can prevent the occurrence of slope disasters effectively. Original grey GM(1,1) model is usually used in simulation and prediction of equidistant monitoring data sequence, but the actual situation is the monitoring data which obtained appear unequal interval phenomenon. So, unequal interval grey GM(1,1) model is established after analyzing the establishing principal of original equal interval GM(1,1)

Li Kegang



Intracellular Distribution of a Biotin-labeled Ganglioside, GM1, by Immunoelectron Microscopy After Endocytosis in Fibroblasts  

Microsoft Academic Search

SUMMARY A radioactive and biotin-labeled analogue of GM1 (biotin-GM1) was synthe- sized which enabled us to analyze its intracellular distribution in the compartments of the endocytic route by electron microscopic immunocytochemistry using thin sections of hu- man skin fibroblasts labeled with gold-conjugated antibiotin antibodies. Metabolic studies with the biotin-GM1 showed its partial degradation to the corresponding GM2 and GM3 derivatives.

Wiebke Möbius; Volker Herzog; Konrad Sandhoff; Günter Schwarzmann



Fucoganglioside ?-fucosyl(?-galactosyl)-GM1: a novel member of lipid membrane microdomain components involved in PC12 cell neuritogenesis  

PubMed Central

In order to search for novel components of lipid membrane microdomains involved in neural signalling pathways, mAbs (monoclonal antibodies) were raised against the detergent-insoluble membrane fraction of PC12 (pheochromocytoma) cells. Among the 22 hybrid clones, mAb PR#1 specifically detected a fucoganglioside Fuc(Gal)-GM1 [?-fucosyl(?-galactosyl)-GM1], a ganglioside homologous with GM1a (II3NeuAc,GgOse4Cer), as a novel member of microdomain components with biological functions. In the presence of mAb PR#1 in the culture medium, the outgrowth of neurites was induced in PC12 cells in a dose-dependent manner, with no effects on cell proliferation, suggesting that Fuc(Gal)-GM1 is preferentially involved in PC12 cell neuritogenesis. Effects through Fuc(Gal)-GM1 were different from those through GM1a during differentiation, e.g. under PR#1 treatment on Fuc(Gal)-GM1, round cell bodies with thinner cell processes were induced, whereas treatment with CTB (cholera toxin B subunit), a specific probe for GM1a, produced flattened cell bodies with thicker pro-cesses. Molecular analysis demonstrated that the PR#1–Fuc(Gal)-GM1 pathway was associated with Fyn and Yes of the Src family of kinases, although Src itself was not involved. No association was found with TrkA (tropomyosin receptor kinase A) and ERKs (extracellular-signal-regulated kinases), which are responsible for GM1a-induced differentiation. From these findings, it is suggested that a fucoganglioside Fuc(Gal)-GM1 provides a functional platform distinct from that of GM1a for signal transduction in PC12 cell differentiation.

Yamazaki, Yasuhiro; Horibata, Yasuhiro; Nagatsuka, Yasuko; Hirabayashi, Yoshio; Hashikawa, Tsutomu



GM1 expression in caco-2 cells: characterisation of a fundamental passage-dependent transformation of a cell line.  


Caco-2 cells, which are known to spontaneously differentiate in cell culture, adopt typical epithelial characteristics and are widely used as a model to study cellular uptake, transport and metabolism processes. However, groups of flat and undifferentiated cells have been observed amid differentiating Caco-2 cell monolayers. In this study, we isolated and characterised these morphologically distinct, flat and island-forming Caco-2 cells. We visualised the undifferentiated cell islands with the aid of optical and electron microscopy and identified mono-sialo-ganglioside one (GM1) as their unique marker. Furthermore, two distinct subpopulations of morphology and GM1 expression were dilution cloned (Caco-2(GM1-) and Caco-2(GM1+) ), leading to the first documented Caco-2 clone that does not show differentiation characteristics. Caco-2(GM1+) cells were flat, non-polarising with extremely low transepithelial electrical resistance (TEER), whereas Caco-2(GM1-) cells showed typical epithelial features and high TEER. Importantly, the proportion of Caco-2(GM1+) cells in a culture increased with passage number and eventually dominated the cell culture. The novel GM1 passage-dependent cell transformation described here shows that careful monitoring is required when performing in vitro cell studies. Therefore, to guarantee consistent and valid experimental data, GM1 expression and the loss of differentiation characteristics should be carefully monitored and the use of fresh cultures should be standard practice. PMID:21739432

Jahn, Kristina A; Biazik, Joanna M; Braet, Filip



Distal acquired demyelinating symmetric neuropathy associated with anti-GM1 antibodies: is this a CIDP variant?  


Distal acquired demyelinating symmetric (DADS) neuropathy is clinically characterised by distal motor and sensory disturbances. Typically DADS does not respond or responds poorly to intravenous immunoglobulins (IVIg). We report the case of a 58-year-old patient who developed distal paraparesis. Serum electrophoresis demonstrated monoclonal IgM paraproteinemia having an anti-GM1 but no anti-MAG activity. Conduction velocities showed demyelinating pattern. Work-up excluded a lymphoproliferative disorder After IVIg treatment we observed a clinical and neurophysiological improvement. Regarding these peculiar findings, we suggest that DADS needs to be splitted in several forms determined among others by clinical, neurophysiological and antiganglioside profile and therapeutic response. We advocate to perform systematic antiganglioside antibodies assay additionnaly to anti-MAG when DADS is suspected in order to improve dysimmune neuropathies classification. PMID:20514936

Remiche, Gauthier; Kentos, Alain; Mavroudakis, Nicolas



Modification of GM(1,1) and its application in analysis of rock-slope deformation  

Microsoft Academic Search

Rock slope is an unknown and complicated system; the GS (grey system) theory may release some of its implicated rules. This paper was aimed to discover the evolution rules of the complicated high rock-slope, using the GS Theory. The GM(1,1), deprived from the GS theory, was widely used in analysis of the ordinary time series, but it did not work

Z. B. Liu; W. Y. Xu; Y. D. Meng; H. J. Chen



An Improved Method for Image Edge Detection Based on GM(1,1) Model  

Microsoft Academic Search

The GM(1,1) model usually uses the first component of the first order accumulated generating operation(AGO) sequence X(1) as the initial condition to model in the research and application of image edge detection. This model has the disadvantage of being unable to completely utilize the latest information. Also it can't detect out all edge points because it detects the image only

Jianxin Zhang; Lang Wu



Human Motion Tracking Based on Adaptive Template Matching and GM(1,1)  

Microsoft Academic Search

To solve the defect of poor robustness and real- timeliness of traditional correlation matching algorithm, this paper proposes a novel method that combines normalized autocorrelation matching algorithm, template updating strategy and grey forecasting model GM(1,1) with priority of new information. The real-time updating of the template image size improves the deformation resistance capability of the autocorrelation matching algorithm, and assignment

Xuhua Fang; Jianhong Fang



Structural evaluation of GM1-related carbohydrate-cholera toxin interactions through surface plasmon resonance kinetic analysis.  


Surface plasmon resonance (SPR) can provide kinetic information about an interaction, and it can also be used to rapidly monitor dynamic processes, such as adsorption and degradation, without the need for sample labeling. Here, we employed SPR to analyze carbohydrate-protein interactions, particularly GM1-related carbohydrate-Vibrio cholera toxin interactions. The interaction between cholera toxin subunits A (ctxA) and B (ctxB) was similar to general ligand-receptor interactions. After the direct immobilization of thiol-containing GM1 pentasaccharide on a gold surface, the GM1-ctxB interaction kinetics were evaluated, and they showed a similar degree of kinetics as reported in previous reports. We found that ctxA had a high affinity for the GM1-ctxAB complex, although its equilibrium dissociation constant was 10 times lower than that of GM1-ctxB binding. Comparative analyses of GM1-related carbohydrate-ctxAB interactions were also conducted to determine the kinetic values of several GM1 analogues with different structures, although their kinetic values were one order of magnitude lower than those of the GM1-ctxAB interaction. The kinetic analysis results for the interactions of GM1 analogues and ctxAB indicated that the sialic acid thumb is important for recognition, and the terminal galactose and N-acetylgalactosamine fingers are required to stabilize the GM1-ctxAB interaction. Taken together, our results indicate that the direct immobilization of carbohydrate in an SPR-based analytical system can be used to evaluate the structural contribution of carbohydrate moieties in carbohydrate-protein interactions, as well as provide valuable information that can be used to understand the interactions. PMID:24081216

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



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

PubMed Central

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 and thus minimized the possibility of artifactual perturbation. By point pattern analysis of immunogold labeling, GM1 was shown to make clusters of <100 nm in diameter in normal mouse fibroblasts. GM1-null fibroblasts were not labeled, but developed a similar clustered pattern when GM1 was administered. On cholesterol depletion or chilling, the clustering of both endogenous and exogenously-loaded GM1 decreased significantly, but the distribution showed marked regional heterogeneity in the cells. GM3 also showed cholesterol-dependent clustering, and although clusters of GM1 and GM3 were found to occasionally coincide, these aggregates were separated in most cases, suggesting the presence of heterogeneous microdomains. The present method enabled to capture the molecular distribution of lipids in the cell membrane, and demonstrated that GM1 and GM3 form clusters that are susceptible to cholesterol depletion and chilling.

Fujita, Akikazu; Cheng, Jinglei; Hirakawa, Minako; Furukawa, Koichi; Kusunoki, Susumu



Binding and aggregation mechanism of amyloid ?-peptides onto the GM1 ganglioside-containing lipid membrane.  


Accumulation and fibril formation of amyloid ? (A?) peptides onto a ganglioside-rich lipid membrane is a cause of neuro-disturbance diseases. To find out a measure for suppressing the nucleation of a seed for amyloid fibrils, the mechanism of the initial binding of A? to the membrane should be clarified. Molecular dynamics simulations were carried out to investigate the adhesion process of A? peptides onto a GM1-ganglioside-containing membrane. Multiple computational trials were executed to analyze the probability of occurrence of A? binding by using calculation models containing a mixed lipid membrane, water layer, and one, two, or three A?s. The simulations demonstrated that A? peptides approached the membrane after fluctuation in the water layer and occasionally made steady contact with the membrane. Once the steady contact had been established, A? was unlikely to be detached from the membrane and developed into a more stably bound form. In the stably bound form, neuraminic acids on the GM1 cluster strongly held the side chain of Lys28 of A?, which caused deformation of the C-terminal region of the A?. Since the C-terminal region of the A? peptide contains many hydrophobic residues, its deformation on the membrane enhances the hydrophobic interaction with other A? peptides. The contact region of two A?s evolved into a parallel ?-sheet form, and the third A? was observed to be bound to the complex of two A?s to make a bundle of A? peptides. Some key structures involved in the A? aggregation on the GM1-containing membrane were deduced from the multiple simulations. PMID:23688073

Hoshino, Tyuji; Mahmood, Md Iqbal; Mori, Kenichi; Matsuzaki, Katsumi



Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1.  


The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it retrograde from the plasma membrane (PM) through endosomes, the trans-Golgi (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a membrane lipid can specify trafficking in these pathways, we synthesized GM1 isoforms with alternate ceramide domains and imaged their trafficking in live cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable, but membrane cholesterol and the lipid raft-associated proteins actin and flotillin were required. The results implicate a protein-dependent mechanism of lipid sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells. PMID:22975326

Chinnapen, Daniel J-F; Hsieh, Wan-Ting; te Welscher, Yvonne M; Saslowsky, David E; Kaoutzani, Lydia; Brandsma, Eelke; D'Auria, Ludovic; Park, Hyejung; Wagner, Jessica S; Drake, Kimberly R; Kang, Minchul; Benjamin, Thomas; Ullman, M David; Costello, Catherine E; Kenworthy, Anne K; Baumgart, Tobias; Massol, Ramiro H; Lencer, Wayne I



An improved GLP model base on complete center approach GM(1,1) for emergency logistics distribution  

Microsoft Academic Search

The emergency logistics distribution in disaster response activities both in china and abroad was investigated in the paper. The traditional GM(1,1) model was used to forecast value when there was very little information, but the result precision was not very exact, and a new GM(1,1) was improved by complete center approach in order to improve this aspect, then grey linear

Liu Ming; Zhao Lin-du



A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity  

Microsoft Academic Search

GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is widely accepted to initiate toxin action by triggering uptake and delivery of the toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been found to modulate leukocyte function, resulting in the down-regulation of

A. T. Aman; S. Fraser; E. A. Merritt; C. Rodigherio; M. Kenny; M. Ahn; W. G. J. Hol; N. A. Williams; W. I. Lencer; T. R. Hirst



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

Microsoft Academic Search

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

Ole A. Andreassen; Hugo A. Jørgensen



Improved Recovery of Immunoglobulin Fraction from Egg Yolk of Chicken Immunized with AsialoGM1.  


Chicken egg yolk is an abundant, yet inexpensive source of polyclonal antibodies. However, removal of the contaminating lipids and lipoproteins from immunoglobulins of egg yolk (IgY) is considered to be a laborious task during the purification. Liposomal asialoGM1 was used as a model immunogen for raising polyclonal IgY and tested with various methodological approaches. To overcome certain difficulties posed during IgY purification, several detergents (cationic, anionic and non-ionic) were tested for their effect on yolk protein and lipoprotein separation during water dilution processing of IgY. Cetrimide showed a pronounced effect on improving the immunoglobulin separation with only less than 3% of the lipid contaminants as compared to other detergents. The least effective detergent was sodium dodecyl sulphate with 14-35% contaminating lipids. The usefulness of egg yolk acetone powder for long-term storage prior to IgY purification was also determined. The use of acetone precipitated proteins for IgY processing showed a 25-30% loss in antigen specific immunoreactivity despite of an optimum total immunoglobulin recovery of 80%. A combination of delipidation of yolk with 50% acetone and treatment of the resultant acetone precipitated protein with a low ionic buffer (pH 5.5) containing 200 &mgr;M of cetrimide yields electrophoretically homogeneous IgY with an optimum total immunoglobulin recovery of 85-90%. The antigen specific immunoreactivity of anti-asialoGM1 IgY was preserved well during the cetrimide treatment and was found to be higher than all other recovery processes, as tested by radial immunodiffusion and immunoblot assays. PMID:12687120

Sriram, Venkataraman; Yogeeswaran, Ganesa



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

Microsoft Academic Search

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.

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



Stimulation of neurite outgrowth in neuroblastoma cells by neuraminidase: putative role of GM1 ganglioside in differentiation.  


Treatment of three neuroblastoma cell types in culture with neuraminidase resulted in enhanced neurite outgrowth. These included the mouse Neuro-2A and rat B104 and B50 lines. The morphological changes depended on the presence of exogenous Ca2+ and were accompanied by modest but statistically significant increases in 45Ca2+ influx. Neuraminidase-stimulated neuritogenesis was blocked by the B subunit of cholera toxin (cholera B) and anti-GM1 antibody, a finding suggesting the effect was due to an increased amount of GM1 on the cell surface. Cholera B also blocked the increase in 45Ca2+ influx. The mouse N1A-103 line, previously characterized as "neurite minus," did not respond to neuraminidase with either neurite outgrowth or enhanced Ca2+ influx. These results point to an influence of GM1 on neuritogenesis in cells with differentiation potential and suggest a mechanism involving modulation of Ca2+ flux. PMID:1987326

Wu, G; Ledeen, R W



GM1 ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole.  


Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). In this study, we show that GA inhibits Na+,K+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances-TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 micromol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na+,K+-ATPase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na+,K+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance ex vivo. In addition, GM1 (50-200 microM) protected against Na+,K+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 micromol/striatum) seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na+,K+-ATPase and GABA(A) receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1. PMID:16516483

Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider; Fiorenza, Natália Gindri; Frussa-Filho, Roberto; Petry, João Carlos; Coelho, Rafael Correa; Mello, Carlos Fernando



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

NASA Astrophysics Data System (ADS)

Direct electrospray ionization mass spectrometry (ESI-MS) assay was used to investigate the stepwise binding of the GM1 pentasaccharide ?-uc(D)-Galp-(1?3)-?-D-GalpNAc-(1?4)[?-D-Neu5Ac-(2?3)]-?-uc(D)-Galp-(1?4)-?-D-Glcp (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.

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



Repeatability of ellipsometric data in cholera toxin GM1 ELISA structures  

NASA Astrophysics Data System (ADS)

The need for repeated measurements in a wide range of biological testing due to statistical variations is well known. In this paper, we discuss a specific example in which the measurement probe is a spectroscopic ellipsometer. Repeatable results are needed in a wide range of applications such as drug testing, immunoassays and other tests for disease, and fundamental biomaterial research. The present paper seeks to help reduce the non-meaningful causes of lack of repeatability by identifying a large number of externally controllable factors. Another goal of this work was to quantify the effects of many of these factors on ellipsometric measurements. By exploiting the sensitivity of spectroscopic ellipsometry to ultrathin layers, improved ways to detect and quantitatively differentiate biological events can be explored. This initial work was motivated from an interest to distinguish one disease from another or discern effects of one drug from another using the high surface sensitivity of spectroscopic ellipsometry. In this paper, we investigate the example biological system of cholera toxin (CT) in an ELISA structure with monosialoganglioside (GM1).

Castro, Leon G.; Thompson, Daniel W.; Tiwald, Thomas; Berberov, Emil M.; Woollam, John A.



1H-NMR assignments of GM1-oligosaccharide in deuterated water at 500 MHz by two-dimensional spin-echo J-correlated spectroscopy  

Microsoft Academic Search

The 1H-NMR spectra of the oligosaccharide derived from monosialoganglioside GM1 (GM1 = beta-D-galactosyl-(1-3)-beta-D-N-acetylgalactosaminyl-(1-4)- (alpha-N-acetylneuraminyl-(2-3)-)-beta-D-galactosyl-(1-4)-b eta-D-glucosylceramide) (GM1OS) and its reduced form (GM1OS-R) have been obtained at 500 MHz in D2O. Through the combined use of one-dimensional and homonuclear two-dimensional spin-echo J-correlated (2D SECSY) spectra of GM1OS-R, the assignments for the ring protons of GM1OS are made. Data on chemical shifts and

R. L. Ong; R. K. Yu



PSoC design in GM(1,1) error analysis and its application in temperature prediction  

Microsoft Academic Search

In the study of prediction filed, no matter what methods we used, the main purpose is to minimize the prediction error; however, the goals cannot be fulfilled completely. Even we choose GM(1,1) model, which in the newest soft computing method, we also need to minimize the prediction error. Hence, in this paper, we focus on the influence parameter alpha in

Kun-Li Wen; Hung-Chih Chang; Ching-Hsiang Liu; Huei-Chu Wen



Clustering T-cell GM1 lipid rafts increases cellular resistance to shear on fibronectin through changes in integrin affinity and cytoskeletal dynamics  

Microsoft Academic Search

Lipid rafts are small laterally mobile microdomains that are highly enriched in lymphocyte signaling molecules. GM1 gangliosides are a common lipid raft component and have been shown to be important in many T-cell functions. The aggregation of specific GM1 lipid rafts can control many T-cell activation events, including their novel association with T-cell integrins. We found that clustering GM1 lipid

Jason S Mitchell; Wells S Brown; Darren G Woodside; Peter Vanderslice; Bradley W McIntyre



Expression of GM1, a marker of lipid rafts, defines two subsets of human monocytes with differential endocytic capacity and lipopolysaccharide responsiveness  

PubMed Central

Monocytes constitute 5–10% of total human peripheral blood leucocytes and remain in circulation for several days before replenishing the tissue macrophage populations. Monocytes display heterogeneity in size, granularity and nuclear morphology, and in the expression of cell membrane molecules, such as CD14, CD16, CD32, CD64, major histocompatibility complex class II, CCR2, CCR5, among others. This has led to the suggestion that individual monocyte/macrophage populations have specialized functions within their microenvironments. This study provides evidence for the occurrence of two peripheral blood monocyte subpopulations on the basis of their differential expression of GM1, a sphingolipid found mostly in lipid rafts, a CD14+ GM1low population and a CD14+ GM1high population comprising about 97·5% and 2·5% of total CD14+ cells, respectively. GM1 expression correlates with functional differences in terms of endocytic activity, susceptibility to mycobacterial infection, and response to lipopolysaccharide (LPS) (modulation of Toll-like receptor-4 expression). CD14+ GM1low cells proved to be less endocytic and more responsive to LPS, whereas CD14+ GM1high cells are more endocytic and less responsive to LPS. In addition, during monocyte to macrophage differentiation in vitro, the percentage of CD14+ GM1high cells increases from about 2·5% at day 1 to more than 50% at day 7 of culture. These results suggest that GM1low and GM1high monocytes in peripheral blood, represent either different stages of maturation or different subsets with specialized activities. The expression of CD16 on GM1high favours the first possibility and, on the other hand that up-regulation of GM1 expression and probably lipid rafts function is involved in the monocyte to macrophage differentiation process.

Moreno-Altamirano, M Maximina Bertha; Aguilar-Carmona, Israel; Sanchez-Garcia, F Javier



Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor  

Microsoft Academic Search

Cholera toxin (CT) is an archetypal bacterial toxin that binds with a high affinity to the receptor ganglioside GM1 on the intestinal epithelial surface and that causes the severe watery diarrhea characteristic of the disease cholera. Blockage of the interaction of CT with the GM1 receptor is an attractive approach for therapeutic intervention. We report here that crude bile prevents

Arpita Chatterjee; Rukhsana Chowdhury



Evaluating impact level of different factors in environmental impact assessment for incinerator plants using GM (1, N) model.  


In this study, the impact levels in environmental impact assessment (EIA) reports of 10 incinerator plants were quantified and discussed. The relationship between the quantified impact levels and the plant scale factors of BeiTou, LiZe, BaLi, LuTsao, RenWu, PingTung, SiJhou and HsinChu were constructed, and the impact levels of the GangShan (GS) and YongKong (YK) plants were predicted using grey model GM (1, N). Finally, the effects of plant scale factors on impact levels were evaluated using grey model GM (1, N) too. According to the predicted results of GM, the relative errors of topography/geology/soil, air quality, hydrology/water quality, solid waste, noise, terrestrial fauna/flora, aquatic fauna/flora and traffic in the GS plant were 17%, 14%, 15%, 17%, 75%, 16%, 13%, and 37%, respectively. The relative errors of the same environmental items in the YK plant were 1%, 18%, 10%, 40%, 37%, 3%, 25% and 33%, respectively. According to GM (1, N), design capacity (DC) and heat value (HV) were the plant scale factors that affected the impact levels significantly in each environmental item, and thus were the most significant plant scale factors. GM (1, N) was effective in predicting the environmental impact and analyzing the reasonableness of the impact. If there is an EIA for a new incinerator plant to be reviewed in the future, the official committee of the Taiwan EPA could review the reasonableness of impact levels in EIA reports quickly. PMID:17919897

Pai, T Y; Chiou, R J; Wen, H H



GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo\\/reperfusion rat  

Microsoft Academic Search

Objective: To determine the protective effect of monosialoganglionside (GM1) and evaluate the influence of GMI on expression\\u000a of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in Sprague-Dawley (SD) rats with focal cerebral ischemia-reperfusion (I\\/R).\\u000a Methods: Left middle cerebral artery (MCA) was occluded by an intraluminal suture for 1 h and the brain was reperfused for\\u000a 72 h in SD rats when infarct

Liu Jian-ren; Ding Mei-ping; Wei Er-qing; Luo Jian-hong; Song Ying; Huang Jian-zheng; Ge Qiu-fu; Hu Hua; Zhu Li-jun



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



Cholesterol accelerates the binding of Alzheimer's ?-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation  

PubMed Central

Age-related alterations of membrane lipids in brain cell membranes together with high blood cholesterol are considered as major risk factors for Alzheimer's disease. Yet the molecular mechanisms by which these factors increase Alzheimer's risk are mostly unknown. In lipid raft domains of the plasma membrane, neurotoxic Alzheimer's beta-amyloid (Abeta) peptides interact with both cholesterol and ganglioside GM1. Recent data also suggested that cholesterol could stimulate the binding of Abeta to GM1 through conformational modulation of the ganglioside headgroup. Here we used a combination of physicochemical and molecular modeling approaches to decipher the mechanisms of cholesterol-assisted binding of Abeta to GM1. With the aim of decoupling the effect of cholesterol on GM1 from direct Abeta-cholesterol interactions, we designed a minimal peptide (Abeta5-16) containing the GM1-binding domain but lacking the amino acid residues involved in cholesterol recognition. Using the Langmuir technique, we showed that cholesterol (but not phosphatidylcholine or sphingomyelin) significantly accelerates the interaction of Abeta5-16 with GM1. Molecular dynamics simulations suggested that Abeta5-16 interacts with a cholesterol-stabilized dimer of GM1. The main structural effect of cholesterol is to establish a hydrogen-bond between its own OH group and the glycosidic-bond linking ceramide to the glycone part of GM1, thereby inducing a tilt in the glycolipid headgroup. This fine conformational tuning stabilizes the active conformation of the GM1 dimer whose headgroups, oriented in two opposite directions, form a chalice-shaped receptacle for Abeta. These data give new mechanistic insights into the stimulatory effect of cholesterol on Abeta/GM1 interactions. They also support the emerging concept that cholesterol is a universal modulator of protein-glycolipid interactions in the broader context of membrane recognition processes.

Fantini, Jacques; Yahi, Nouara; Garmy, Nicolas



Alterations on Na(+),K (+)-ATPase and Acetylcholinesterase Activities Induced by Amyloid-? Peptide in Rat Brain and GM1 Ganglioside Neuroprotective Action.  


Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis involves production and aggregation of amyloid-? peptide (A?). A?-induced toxicity is believed to involve alterations on as Na(+),K(+)-ATPase and acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to prevent or to reverse these biochemical changes promote neuroprotection. GM1 is a ganglioside proposed to have neuroprotective roles in AD models, through mechanisms not yet fully understood. Therefore, this study aimed to investigate the effect of A?1-42 infusion and GM1 treatment on recognition memory and on Na(+),K(+)-ATPase and AChE activities, as well as, on antioxidant defense in the brain cortex and the hippocampus. For these purposes, Wistar rats received i.c.v. infusion of fibrilar A?1-42 (2 nmol) and/or GM1 (0.30 mg/kg). Behavioral and biochemical analyses were conducted 1 month after the infusion procedures. Our results showed that GM1 treatment prevented A?-induced cognitive deficit, corroborating its neuroprotective function. A? impaired Na(+),K(+)-ATPase and increase AChE activities in hippocampus and cortex, respectively. GM1, in turn, has partially prevented A?-induced alteration on Na(+),K(+)-ATPase, though with no impact on AChE activity. A? caused a decrease in antioxidant defense, specifically in hippocampus, an effect that was prevented by GM1 treatment. GM1, both in cortex and hippocampus, was able to increase antioxidant scavenge capacity. Our results suggest that A?-triggered cognitive deficit involves region-specific alterations on Na(+),K(+)-ATPase and AChE activities, and that GM1 neuroprotection involves modulation of Na(+),K(+)-ATPase, maybe by its antioxidant properties. Although extrapolation from animal findings is difficult, it is conceivable that GM1 could play an important role in AD treatment. PMID:24013887

Kreutz, Fernando; Scherer, Emilene B; Ferreira, Andréa G K; Petry, Fernanda Dos Santos; Pereira, Camila Lino; Santana, Fabiana; de Souza Wyse, Angela Terezinha; Salbego, Christianne Gazzana; Trindade, Vera Maria Treis



The non-equal-interval direct new information Verhulst GM(1,1) model with two times fitting and its application to test data processing  

Microsoft Academic Search

The non-equal-interval direct Verhulst new information GM(1,1) model with two times fitting was built which extended equal interval to non-equal-interval and suited for general data modeling and estimating parameters of direct Verhulst GM(1,1). The new model chooses the nth component of X(0) as the starting conditions of the grey differential model. The new model need not pre-process the primitive data,

Youxin Luo; Zheming He



The research of reaction abilities and errors distributions for the model of GM(1,1) to simulate equal difference and geometric ratio sequence  

Microsoft Academic Search

The model of GM(1,1) is one of the most important sections in the gray system theories. The abilities of reaction, which the original sequence data are simulated by the GM(1,1), are always noticed by many scholars. However, it is stopped in evaluation of prediction errors in one or two examples that the problem is researched in the present. In this

Xuewen Tang; SiFeng Liu; ZhiGeng Fang; XiangMin Xu; YaoGuo Dang



The Ganglioside GM1 Enhances Microtubule Networks and Changes the Morphology of Neuro-2a Cells in Vitroby Altering the Distribution of MAP2  

Microsoft Academic Search

The effect of ganglioside GM1 on components of the neuronal cytoskeleton was studied in Neuro-2a neuroblastoma cells using immunofluorescent, immunogold-labeled, and Western blot analysis. Exposure of cells to GM1 for 24 h resulted in an increased microtubular network and level of tubulin, a redistribution of MAP2 immunoreactivity from perikarya to distal neuritic processes, and an increased MAP2 gold label in

Li-Juan Wang; Rita Colella; Glee Yorke; Fred J. Roisen



Opioid Receptor and Calcium Channel Regulation of Adenylyl Cyclase, Modulated By GM1, in NG108-15 Cells: Competitive Interactions  

Microsoft Academic Search

GM1 ganglioside was previously shown to function as a specific regulator of excitatory opioid activity in dorsal root ganglion neurons and F11 hybrid cells, as seen in its facilitation of opioid-induced activation of adenylyl cyclase and its ability to dramatically reduce the threshold opioid concentration required to prolong the action potential duration. The elevated levels of GM1 resulting from chronic

Gusheng Wu; Zi-Hua Lu; Peter Alfinito; Robert W. Ledeen



GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.  


The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. PMID:21567908

Kaya, Namik; Al-Owain, Mohammad; Abudheim, Nada; Al-Zahrani, Jawaher; Colak, Dilek; Al-Sayed, Moeen; Milanlioglu, Aysel; Ozand, Pinar T; Alkuraya, Fowzan S



The Mutations in Ashkenazi Jews with Adult GM2 Gangliosidosis, the Adult Form of Tay-Sachs Disease  

Microsoft Academic Search

The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive disorder that results from mutations in the alpha chain of beta -hexosaminidase A. This disorder, like infantile Tay-Sachs disease, is more frequent in the Ashkenazi Jewish population. A point mutation in the alpha -chain gene was identified that results in the substitution of Gly269 with Ser in

Ruth Navon; Richard L. Proia



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

SciTech Connect

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.

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



[Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].  


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

Tsuji, Daisuke



The restriction mechanism of Chinese university results efficiency based on the hybrid of VPRS and optimized GM(1,1)  

NASA Astrophysics Data System (ADS)

Grey system theory and rough set theory are two different mathematical tools which are used to deal with uncertain or incomplete information, and yet they are relevant and complementary to a certain degree. They both improve the generality of data presentation by reducing its accuracy. In the paper, based on the statistics of Chinese universities science and technology from 2002 year to 2011 year, the key factors which affect the transfer performance are figured out by applying variable precision rough set models, output performance and transfer performance are predicted by optimal GM(1,1) model. According to the above, the restriction mechanism of university R&D performance is analyzed from a whole view of operating model and key influencing factors, and the prospect model is suggested.

Jian, Lirong; Liu, Sifeng



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


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

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



Segregative clustering of Lo and Ld membrane microdomains induced by local pH gradients in GM1-containing giant vesicles: a lipid model for cellular polarization.  


Several cell polarization processes are coupled to local pH gradients at the membrane surface. We have investigated the involvement of a lipid-mediated effect in such coupling. The influence of lateral pH gradients along the membrane surface on lipid microdomain dynamics in giant unilamellar vesicles containing phosphatidylcholine, sphingomyelin, cholesterol, and the ganglioside GM1 was studied. Lo/Ld phase separation was generated by photosensitization. A lateral pH gradient was established along the external membrane surface by acid local microinjection. The gradient promotes the segregation of microdomains: Lo domains within an Ld phase move toward the higher pH side, whereas Ld domains within an Lo phase move toward the lower pH side. This results in a polarization of the vesicle membrane into Lo and Ld phases poles in the axis of the proton source. A secondary effect is inward tubulation in the Ld phase. None of these processes occurs without GM1 or with the analog asialo-GM1. These are therefore related to the acidic character of the GM1 headgroup. LAURDAN fluorescence experiments on large unilamellar vesicles indicated that, with GM1, an increase in lipid packing occurs with decreasing pH, attributed to the lowering of repulsion between GM1 molecules. Packing increase is much higher for Ld phase vesicles than for Lo phase vesicles. It is proposed that the driving forces for domain vectorial segregative clustering and vesicle polarization are related to such differences in packing variations with pH decrease between the Lo and Ld phases. Such pH-driven domain clustering might play a role in cellular membrane polarization processes in which local lateral pH gradients are known to be important, such as migrating cells and epithelial cells. PMID:23121205

Staneva, Galya; Puff, Nicolas; Seigneuret, Michel; Conjeaud, Hélène; Angelova, Miglena I



Selection of Escherichia coli heat-labile toxin (LT) inhibitors using both the GM1-ELISA and the cAMP vero cell assay.  


Weaned piglets are very susceptible to diarrhea caused by enterotoxigenic Escherichia coli. In the past, various natural components were proposed to have beneficial effects by reducing the effects of diarrheal infectious diseases in humans and animals, and thus may represent an alternative for the use of (prophylactic) antibiotics. Alternatives may inactivate enterotoxigenic Escherichia coli heat-labile toxin (LT) by interfering with toxin binding to the cellular receptor GM1. In this study, various plants and other natural substances were tested for inhibitory properties, in the GM1 binding assay, and in the LT-induced cAMP production in Vero cells. The toxic dose of each compound was determined in a cell viability assay, and the highest nontoxic concentrations were used in the GM1 and cAMP assays. Results demonstrated that only d-(+)-galactose, lactose, N-acetyl-d-galactosamine, and two tea extracts were able to inhibit the binding of LT to its GM1 receptor. In the cAMP assay, only the two tea extracts showed inhibitory activity. This shows that d-(+)-galactose, lactose, and N-acetyl-d-galactosamine can indeed inhibit LT binding to GM1 based on structural homology with GM1 in the absence of living cells. However, in the cAMP assay, d-(+)-galactose, and lactose, N-acetyl-d-galactosamine are apparently metabolized to below their effective inhibitory concentration, likely predicting limited practical applicability in vivo. Both tea extracts maintained their activity in the presence of cells. The active compounds in both are probably polyphenols, which are not easily metabolized, and most likely work by aggregating the toxin. In conclusion, the combination of methods used here is a convenient and fast method for preselecting natural substances containing potentially toxin-binding compounds. Furthermore, if antidiarrhea activity is attributed to compounds found inactive here, their activity is unlikely based on interference with toxin binding. PMID:23692076

Verhelst, Roderick; Schroyen, Martine; Buys, Nadine; Niewold, Theo



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

Microsoft Academic Search

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 naïve 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

Stanley M. Crain; Ke-Fei Shen



The relationship between the concentration of ganglioside GM1 and antitumor activity of edelfosine--the Langmuir monolayer study.  


One of the characteristic features of tumor membranes is altered concentration of gangliosides level and their over-expression in tumor progression. This fact should be considered when the mechanism of activity and selectivity of edelfosine (ED)--a membrane-active anticancer drug--is investigated. Strong affinity of this drug to ganglioside GM1, found in binary mixed monolayers, encouraged us for a deeper investigations on more complex model systems. In this work we have studied the influence of edelfosine on the interactions between molecules in model sphingomyelin/cholesterol monolayer, mimicking a tumor membrane, containing ganglioside in increasing proportion that is characteristic of cancer progression. It was found that edelfosine in very low concentration (1%) practically does not influence on model membrane system, independently of the proportion of ganglioside. On the other hand, at the increased ED concentration (10%), the interactions between the lipids in the mixed system become progressively stronger upon the increase of ganglioside concentration as compared to those in the model tumor membrane. The results of our investigations show that the affinity of edelfosine towards tumor cells may be correlated with over-expression of gangliosides in cancer cells. PMID:20692132

Hac-Wydro, Katarzyna; Dynarowicz-?atka, Patrycja



The New Non-Equidistant Optimum GM(1,1) with Modified the nth Components Taken as Initial Value and Its Application Research to Metal Cutting  

Microsoft Academic Search

Based on grey system theory, a new kind of nonequidistant optimum grey model GM(1,1) with optimizing modified the nth components taken as initial value of response function of grey differential equation and the background value to test data process was proposed, the method of precision inspection was introduced. The example was given. The method can be used for model establishing

Youxin Luo; Lingfang Li



[Effects of oxidative stress inducers, neurotoxins, and ganglioside GM1 on Na+, K+-ATPase in PC12 and brain synaptosomes].  


To elucidate mechanism of ganglioside neuroprotection, it is important to study their metabolic effects, specifically of action on Na+, K+ -ATPase. It has been shown that under effect of oxidative stress inductors and neurotoxins an oxidative inactivation of this enzyme takes place in PC12 cells and brain cortex synaptosomes, this inactivation being able to be prevented or decreased by ganglioside GM1. Thus, for instance, 24 h after action of 1 mM H2O2, activity of Na+, K+ -ATPase in PC12 cells decreased more than twice. However, in the case of preincubation of the cells with ganglioside GM1 prior to the H2O2 action this enzyme activity did not differ statistically significantly from control. Ganglioside GM1 also was able to increase significantly the enzyme activity decreased by action on the PC12 cells of amyloid beta-peptide (AP) causing lesion of neurons in Alzheimer's disease and at low H202 concentrations. Experiments on brain cortex synaptosomes have established that not only antioxidants--alpha-tocopherol and superoxide dismutase--but also ganglioside GM1 prevent the glutamateproduced Na+, K+ -ATPase oxidative inactivation. The obtained data agree with a suggestion that the ganglioside neuroprotective effect at action on nerve cells of such toxins as Abeta, glutamate or reactive oxygen species is due to their ability to inhibit the free-radical reactions. PMID:17674707

Zakharova, I O; Sokolova, T V; Furaev, V V; Rychkova, M P; Avrova, N F


GM (1,1) Model Gray Prediction for the Gold-Medal Result of Women's Put Shot in the 30th Olympic Games  

Microsoft Academic Search

Through the methods of document and mathematical statistics, this paper takes the gold-medal records of women's shot put in the Olympic Games from1992 to 2008 as the raw data and uses GM(1,1) prediction model in Gray System Theory to predict the gold-medal result of women's shot put in the 2012 London Olympic Games. After the residual test, correlation test and

Zhang Bo; Qin Chaoling; Xu Xiaoli; Zeng Fanbo



Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD\\/Shi-scid mice  

Microsoft Academic Search

The scid mutation was backcrossed on to the NOD\\/Shi mouse background, resulting in the development of NOD\\/Shi-scid mice, which showed lack of mature lymphocytes, macrophage dysfunction and absence of circulating complement, but were not as impaired in natural killer (NK) cell activity as NOD\\/LtSz-scid mice. We then examined the effect of recipient NK cell depletion by anti-asialo GM1 antiserum on

H Yoshino; T Ueda; M Kawahata; K Kobayashi; Y Ebihara; A Manabe; R Tanaka; M Ito; S Asano; T Nakahata; K Tsuji



Effects of the mono- and tetrasialogangliosides GM1 and GQ1b on ATP-induced long-term potentiation in hippocampal CA1 neurons  

Microsoft Academic Search

The effects of the mono- and tetrasialogangliosides, GM1 and GQ1b, on ATP-induced long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Application of 5 or 10 µM ATP for 10 min resulted in a transient depression followed by a slow augmentation of synaptic transmission, leading to LTP. LTP induced by treatment with 5 µM ATP was

Satoshi Fujii; Kotaro Igarashi; Hiroshi Sasaki; Hidekazu Furuse; Ken-ichi Ito; Hiroshi Kato; Jin-ichi Inokuchi; Hatsue Waki



Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition  

Microsoft Academic Search

Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition. J. Davies, A. Dewar, A. Bush, T. Pitt, D. Gruenert, D.M. Geddes, E.W.F.W. Alton. #ERS Journals Ltd 1999. ABSTRACT: The high incidence of colonization of the cystic fibrosis (CF) airway with Pseudomonas aeruginosa has been attributed to several mechanisms including increased numbers

J. Davies; A. dewar; A. Bush; T. Pitt; D. Gruenert; D. M. Geddes; E. W. F. W. Alton



Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation, electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS\\/MS  

Microsoft Academic Search

Gangliosides play important biological roles and structural characterization of both the carbohydrate and the lipid moieties\\u000a is important. The FT-ICR MS\\/MS techniques of electron capture dissociation (ECD), electron detachment dissociation (EDD),\\u000a and infrared multiphoton dissociation (IRMPD) provide extensive fragmentation of the protonated and deprotonated GM1 ganglioside.\\u000a ECD provides extensive structural information, including identification of both halves of the ceramide and

Melinda A. McFarland; Alan G. Marshall; Christopher L. Hendrickson; Carol L. Nilsson; Pam Fredman; Jan-Eric Månsson



Distribution of the attachment (G) glycoprotein and GM1 within the envelope of mature respiratory syncytial virus filaments revealed using field emission scanning electron microscopy  

Microsoft Academic Search

Field emission scanning electron microscopy (FE SEM) was used to visualize the distribution of virus-associated components, the virus-attachment (G) protein, and the host-cell-derived lipid, GM1, in respiratory syncytial virus (RSV) filaments. RSV-infected cells were labeled in situ with a G protein antibody (MAb30) whose presence was detected using a second antibody conjugated to colloidal gold. No bound MAb30 was detected

Chris E. Jeffree; Helen W. Mc. L Rixon; Gaie Brown; James Aitken; Richard J Sugrue



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

Microsoft Academic Search

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

Philip O. Livingston; Gerd Ritter; Michele Jones Calves



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

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

E. Petroulakis; Z. Cao; T. Salo



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

PubMed Central

Galectin-3 binding to cell surface glycoproteins, including branched N-glycans generated by N-acetylglucosaminyltransferase V (Mgat5) activity, forms a multivalent, heterogeneous, and dynamic lattice. This lattice has been shown to regulate integrin and receptor tyrosine kinase signaling promoting tumor cell migration. N-cadherin is a homotypic cell-cell adhesion receptor commonly overexpressed in tumor cells that contributes to cell motility. Here we show that galectin-3 and N-cadherin interact and colocalize with the lipid raft marker GM1 ganglioside in cell-cell junctions of mammary epithelial cancer cells. Disruption of the lattice by deletion of Mgat5, siRNA depletion of galectin-3, or competitive inhibition with lactose stabilizes cell-cell junctions. It also reduces, in a p120-catenin-dependent manner, the dynamic pool of junctional N-cadherin. Proteomic analysis of detergent-resistant membranes (DRMs) revealed that the galectin lattice opposes entry of many proteins into DRM rafts. N-cadherin and catenins are present in DRMs; however, their DRM distribution is not significantly affected by lattice disruption. Galectin lattice integrity increases the mobile fraction of the raft marker, GM1 ganglioside binding cholera toxin B subunit Ctb, at cell-cell contacts in a p120-catenin-independent manner, but does not affect the mobility of either Ctb-labeled GM1 or GFP-coupled N-cadherin in nonjunctional regions. Our results suggest that the galectin lattice independently enhances lateral molecular diffusion by direct interaction with specific glycoconjugates within the adherens junction. By promoting exchange between raft and non-raft microdomains as well as molecular dynamics within junction-specific raft microdomains, the lattice may enhance turnover of N-cadherin and other glycoconjugates that determine junctional stability and rates of cell migration.

Boscher, Cecile; Zheng, Yu Zi; Lakshminarayan, Ramya; Johannes, Ludger; Dennis, James W.; Foster, Leonard J.; Nabi, Ivan R.



Intracellular processing and maturation of mutant gene products in hereditary ?-galactosidase deficiency (?-galactosidosis)  

Microsoft Academic Search

Heterogeneous patterns of biosynthesis, post-translational processing, and degradation were demonstrated for mutant enzymes in three clinical forms of ß-galactosidase deficiency (ß-galactosidosis): juvenile GM1-gangliosidosis, adult GM1-gangliosidosis, and Morquio B disease. The precursor of the mutant enzyme in adult GM1-gangliosidosis was not phosphorylated, and only a small portion of the gene product reached the lysosomes. The enzyme in Morquio B disease was

Akihiro Oshima; Kunihiro Yoshida; Kohji Itoh; Ryoichi Kase; Hitoshi Sakuraba; Yoshiyuki Suzuki



Stem Cell Transplant for Inborn Errors of Metabolism

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



The down-modulation of CD4 induced by the GM1 ganglioside is regulated by phosphatases and kinases: evidence from enzyme inhibitors and anti-CD45 antibodies.  


The involvement of protein kinases and phosphatases in the down-modulation of expression of CD4 molecules on peripheral blood lymphocytes (PBL) by gangliosides was studied. Exposure of PBL either to genistein or to H7 practically abolished the down-modulation of CD4 induced by GM1 and diminished their susceptibility to CD4+ down-modulation by exposure to GD1a. Staurosporine had no effect on the down-modulation of CD4 by either GM1 or GD1a. Orthovanadate treatment drastically inhibited the down-regulation of CD4 induced by GM1 but had no effect on down-modulation of CD4 induced by GD1a. Exposure to monoclonal antibodies (mAbs) against CD45 and CD45RA but not against CD45RO abrogated the down-modulation of CD4 by GM1. The down-modulation of CD4 elicited by GD1a, GD1b, or GT1b was not inhibited by anti-CD45RA and anti-CD45RO mAbs. MAbs against CD3, CD2, or HLA-DR had no effect on the GM1-induced down-modulation of CD4. In view of the differences obtained between GM1 and GD1a it was of interest to check whether these gangliosides competed for cellular binding sites. When PBL were first treated with anti-CD45RA and GM1 or with orthovanadate and GM1, which had a negligible effect on CD4 expression, and subsequently treated with GD1a the expression of CD4 was down-modulated. This demonstrated that GD1a binds to sites on the cell membrane to which GM1 does not bind. The present study indicates that the capacity of GM1 to down-modulate CD4 depended on the CD45 and particularly CD45RA molecules, while other gangliosides may utilize different cell surface structures to down-modulate the expression of CD4. PMID:9682003

Krifuks, O; Bergelson, L D; Schlesinger, M



Systematic synthesis and MAG-binding activity of novel sulfated GM1b analogues as mimics of Chol1 (?-series) gangliosides: highly active ligands for neural siglecs  

Microsoft Academic Search

Systematic synthesis and myelin-associated glycoprotein (MAG)-binding activity of novel sulfated GM1b analogues structurally related to Chol-1 (?-series) gangliosides, high-affinity ligands for neural siglecs, are described. The suitably protected gangliotriose derivatives, 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6-O-levulinoyl-?-d-galactopyranosyl-(1?4)-2,3,6-tri-O-benzyl-?-d-galactopyranosyl-(1?4)-2,3,6-tri-O-benzyl-?-d-glucopyranoside and 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6-O-levulinoyl-?-d-galactopyranosyl-(1?4)-2,6-di-O-benzyl-3-O-levulinoyl-?-d-galactopyranosyl-(1?4)-2,3,6-tri-O-benzyl-?-d-glucopyranoside were each glycosylated with ?-NeuAc-(2?3)-galactose donor to give the corresponding pentasaccharides in 94% (?1,3 glycoside only) and 90% (?1,3:?1,4=2:1), respectively. After proper manipulation of the

Hiromi Ito; Hideharu Ishida; Brian E Collins; Susan E Fromholt; Ronald L Schnaar; Makoto Kiso



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


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

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



Chemoenzymatic synthesis of 2-azidoethyl-ganglio-oligosaccharides GD3, GT3, GM2, GD2, GT2, GM1, and GD1a.  


We have synthesized several ganglio-oligosaccharide structures using glycosyltransferases from Campylobacter jejuni. The enzymes, alpha-(2-->3/8)-sialyltransferase (Cst-II), beta-(1-->4)-N-acetylgalactosaminyltransferase (CgtA), and beta-(1-->3)-galactosyltransferase (CgtB), were produced in large-scale fermentation from Escherichia coli and further characterized based on their acceptor specificities. 2-Azidoethyl-glycosides corresponding to the oligosaccharides of GD3 (alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-), GT3 (alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-), GM2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), GD2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), GT2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), and GM1 (beta-D-Galp-(1-->3)-beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-) were synthesized in high yields (gram-scale). In addition, a mammalian alpha-(2-->3)-sialyltransferase (ST3Gal I) was used to sialylate GM1 and generate GD1a (alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->3)-beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-) oligosaccharide. We also cloned and expressed a rat UDP-N-acetylglucosamine-4'epimerase (GalNAcE) in E. coli AD202 cells for cost saving in situ conversion of less expensive UDP-GlcNAc to UDP-GalNAc. PMID:16005859

Blixt, Ola; Vasiliu, Daniela; Allin, Kirk; Jacobsen, Nathan; Warnock, Dawn; Razi, Nahid; Paulson, James C; Bernatchez, Stéphane; Gilbert, Michel; Wakarchuk, Warren



Electrokinetic and electrostatic properties of bilayers containing gangliosides GM1, GD1a, or GT1. Comparison with a nonlinear theory.  

PubMed Central

We formed vesicles from mixtures of egg phosphatidylcholine (PC) and the gangliosides GM1, GD1a, or GT1 to model the electrokinetic properties of biological membranes. The electrophoretic mobilities of the vesicles are similar in NaCl, CsCl, and TMACl solutions, suggesting that monovalent cations do not bind significantly to these gangliosides. If we assume the sialic acid groups on the gangliosides are located some distance from the surface of the vesicle and the sugar moieties exert hydrodynamic drag, we can describe the mobility data in 1, 10, and 100 mM monovalent salt solutions with a combination of the Navier-Stokes and nonlinear Poisson-Boltzmann equations. The values we assume for the thickness of the ganglioside head group and the location of the charge affect the theoretical predictions markedly, but the Stokes radius of each sugar and the location of the hydrodynamic shear plane do not. We obtain a reasonable fit to the mobility data by assuming that all ganglioside head groups project 2.5 nm from the bilayer and all fixed charges are in a plane 1 nm from the bilayer surface. We tested the latter assumption by estimating the surface potentials of PC/ganglioside bilayers using four techniques: we made 31P nuclear magnetic resonance, fluorescence, electron spin resonance, and conductance measurements. The results are qualitatively consistent with our assumption.

McDaniel, R V; Sharp, K; Brooks, D; McLaughlin, A C; Winiski, A P; Cafiso, D; McLaughlin, S



Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease  

Microsoft Academic Search

Primary deficiency of ?-galactosidase results in GM1 gangliosidosis and Morquio B disease. Of the more than 40 disease-causing mutations described in the Gal gene to date, about 75% are of the missense type and are scattered along the length of the gene. No single, major common mutation has been associated with GM1 gangliosidosis. However, a Trp 273 Leu mutation has

Richard D Bagshaw; Sunqu Zhang; Alina Hinek; Marie-Anne Skomorowski; Donald Whelan; Joe T. R Clarke; John W Callahan




EPA Science Inventory

Adult, male Fischer-344 rats were given bilateral injections of 2.5 microgram colchicine or artificial cerebrospinal fluid into caudal and rostral sites of the dentate gyrus of the hippocampus. One group of rats received 21 consecutive daily injections of 20 mg/kg GM1 ganglioside...


Additional biochemical findings in a patient and fetal sibling with a genetic defect in the sphingolipid activator protein (SAP) precursor, prosaposin. Evidence for a deficiency in SAP-1 and for a normal lysosomal neuraminidase.  

PubMed Central

It has been shown that sphingolipid activator proteins (SAPs) 1 and 2 are encoded on the same gene along with two other putative activator proteins [Fürst, Machleidt & Sandhoff (1988) Biol. Chem. Hoppe-Seyler 369, 317-328 and O'Brien, Kretz, Dewji, Wenger, Esch & Fluharty (1988) Science 241, 1098-1101]. We have undertaken further biochemical investigations on a patient and fetal sibling, who were previously shown to have a unique sphingolipid storage disorder associated with an SAP-2 deficiency [Harzer, Paton, Poulos, Kustermann-Kuhn, Roggendorf, Grisar & Popp (1989) Eur. J. Pediatr. 149, 31-39]. The severity of their disorder suggested that other products of the SAP precursor or prosaposin gene may also be deficient. The turnover of cerebroside sulphate and globotriaosylceramide were investigated and were both impaired in fibroblasts from the patient and fetus. However, the activities of cerebroside sulphate sulphatase and globotriaosylceramide alpha-galactosidase in vitro were normal in cells from the fetus and patient respectively. In addition, there was an increase in cerebroside sulphate concentration in the kidney of the affected fetus. These results indicate that, in addition to the SAP-2 deficiency, there was a defect in SAP-1 function in this disorder. Additional increases in the concentration of monohexosyl- and dihexosyl-ceramide in the fetal kidney probably reflect the deficiency of SAP-2 in the case of monohexosylceramides, and the combined activator deficiency in the case of dihexosylceramides. Lactosylceramide-loading studies confirmed that there was a defect in the turnover of this lipid in fibroblasts from the affected patient and fetus but not from a patient with an isolated SAP-1 deficiency, or from patients with Krabbe disease, GM1 gangliosidosis or galactosialidosis. It has been suggested [Potier, Lamontagne, Michaud & Tranchemontagne (1990) Biochem. Biophys. Res. Commun. 173, 449-456] that the prosaposin gene also codes for lysosomal neuroaminidase. However, we found normal neuraminidase activity in fibroblasts from our patient, using assay conditions which are diagnostic for sialidosis patients. The role of prosaposin gene products in sphingolipid metabolism is discussed in view of our biochemical findings in this genetic disorder. Images Fig. 1.

Paton, B C; Schmid, B; Kustermann-Kuhn, B; Poulos, A; Harzer, K



Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery  

SciTech Connect

Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. (Program Resources, Inc., Frederick, MD (USA))



Progressive mental regression in siblings with Morquio disease type B (mucopolysaccharidosis IV B).  


A brother and sister with clinical and radiological features of Morquio disease, but with atypical mental regression, are described. Leucocyte and fibroblast beta-galactosidase activity was deficient in the siblings, while N-acetylgalactosamine 6-sulphate sulphatase and neuraminidase were normal. Study of the residual fibroblast beta-galactosidase activity towards 4-methylumbelliferyl and p-nitrophenyl beta-D-galactosides indicated that the mutation resembles that in typical Morquio B disease (increased Km and similar pH maximum) rather than that in GM1-gangliosidosis. The patients have therefore been classified as having Morquio B disease with atypical mental regression rather than GM1-gangliosidosis variants with particularly severe bony abnormalities. The mutation was, however, distinct from that in Morquio B disease since residual activity towards the alternative artificial substrate 4-methylumbelliferyl-beta-D-fucoside was increased. The patients represent further examples of the heterogeneity that can result from mutation at the beta-galactosidase locus. PMID:3121219

Giugliani, R; Jackson, M; Skinner, S J; Vimal, C M; Fensom, A H; Fahmy, N; Sjövall, A; Benson, P F



Fibroblast screening for chaperone therapy in ?-galactosidosis  

Microsoft Academic Search

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

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



Galectin-1 Is a Major Receptor for Ganglioside GM1, a Product of the Growth-controlling Activity of a Cell Surface Ganglioside Sialidase, on Human Neuroblastoma Cells in Culture  

Microsoft Academic Search

Cell density-dependent inhibition of growth and neu- ral differentiation in the human neuroblastoma cell line SK-N-MC are associated with a ganglioside sialidase- mediated increase of GM1 and lactosylceramide at the cell surface. Because these glycolipids expose galactose residues, we have initiated the study of the potential role of galectins in such cellular events. Using specific antibodies, galectin-1 but not galectin-3

Jurgen Kopitz; Carolina von Reitzenstein; Maria Burchert; Michael Cantz; Hans-Joachim Gabius



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

PubMed Central

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 (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

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



Therapeutic potential of intracerebroventricular replacement of modified human ?-hexosaminidase B for GM2 gangliosidosis.  


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 (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

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



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


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

Suzuki, Yoshiyuki; Ogawa, Seiichiro; Sakakibara, Yasubumi



Chaperone Therapy for Neuronopathic Lysosomal Diseases: Competitive Inhibitors as Chemical Chaperones for Enhancement of Mutant Enzyme Activities  

PubMed Central

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-?-valienamine (NOEV) and N-octyl-?-valienamine (NOV), as promising therapeutic agents for human ?-galactosidase deficiency disorders (mainly GM1-gangliosidosis) and ?-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 GM1-gangliosidosis model mice were developed and useful for experimental studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced ?-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Furthermore, we executed computational analysis for prediction of molecular interactions between ?-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 ?-glucosidase gene mutations in Gaucher disease. We hope chaperone therapy will become available for some patients with GM1-gangliosidosis, Gaucher disease, and potentially other lysosomal storage diseases with central nervous system involvement.

Suzuki, Yoshiyuki; Ogawa, Seiichiro; Sakakibara, Yasubumi



Antiganglioside antibody in patients with Guillain-Barr? syndrome who show bulbar palsy as an initial symptom  

PubMed Central

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.??

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



Expression cloning of rat cDNA encoding UDP-galactose:GD2 beta1,3-galactosyltransferase that determines the expression of GD1b/GM1/GA1.  


Using an anti-GD1b monoclonal antibody, expression cloning of a cDNA for the beta1,3-galactosyltransferase gene (EC was performed. KF4C, mouse melanoma B16 transfected with polyoma T antigen gene, and GM2/GD2 synthase cDNA was used as a recipient cell line for the cDNA library transfection. A cDNA clone of GD3 synthase, pD3T-31 was co-transfected with a cDNA library prepared from rat brain RNA using the pcDNAI expression vector. The isolated cDNA clone pM1T-9 predicted a type II membrane protein with 4 amino acids of cytoplasmic domain, 21 amino acids of transmembrane region, and a large catalytic domain with 346 amino acids. Introduction of the cDNA clone into a mouse melanoma line B16 previously transfected with a GM2/GD2 synthase gene resulted in the neo-synthesis of GM1. Co-transfection of the cell line with pM1T-9 and a GD3 synthase cDNA resulted in the expression of GD1b as well as GM1. Moreover, introduction of pM1T-9 into L cell (lacking GM3 synthase), previously transfected with GM2/GD2 synthase gene, resulted in the definite expression of asialo-GM1. These results indicated that GD1b/GM1/GA1 synthases were identical, as previously suggested based on enzymological analysis. In Northern blots of the beta1, 3-galactosyltransferase gene with total RNA from various rat tissues, a 1.6-kilobase mRNA was strongly expressed in spleen, thymus, kidney, and testis. However, the expression level of the gene in the adult brain tissue was not especially high. On the other hand, this gene was expressed at high levels in the rat brain of embryonal day 12, and reached a peak at around birth, then fell to low level in the adult brain. PMID:9312075

Miyazaki, H; Fukumoto, S; Okada, M; Hasegawa, T; Furukawa, K



Evaluation of GMI ganglioside-mediated apoptosis in feline thymocytes  

Microsoft Academic Search

Cats with inherited GM1 gangliosidosis (GM1 mutant cats) have premature thymic involution characterized by decreased total thymocytes primarily affecting the CD4+ CD8+ subpopulation. While GM1 mutant cats have increased cell surface GM1 gangliosides, as determined by cholera toxin B binding, on both thymocytes and peripheral lymph node cells only thymocytes show increased apoptosis. To determine if GM1 gangliosides can increase

Jie Zhou; Nancy R Cox; Sandra J Ewald; Nancy E Morrison; Henry J Basker



Rapid and simple polymerase chain reaction-based diagnostic assays for GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japanese domestic cats.  


Polymerase chain reaction (PCR)-based assays combined with microchip electrophoresis were developed and evaluated for diagnosis and genotyping of GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japanese domestic cats. A preliminary genotyping survey was carried out in the population of Japanese domestic cats (1,015 cats in total) in southern Japan. Three kinds of assays including PCR primer-induced restriction analysis (PIRA) and mutagenically separated (MS)-PCR were carried out using blood-stained Flinders Technology Associates filter papers (FTA cards) as templates. The PCR products were analyzed by both agarose gel and microchip electrophoreses. All assays were sufficient to determine the genotypes of this disease, but MS-PCR offered the most rapid and simplest test, as it does not need the restriction enzyme step required in PCR-PIRA. The use of microchip electrophoresis in combination with FTA cards for sampling could shorten the time required for genotyping and simplify the procedure as well. The genotyping survey in the current study did not find any cats that possessed the mutant allele, suggesting that the prevalence of this allele is low (<0.1%) in southern Japan. PMID:21398459

Rahman, Mohammad M; Shoubudani, Tomoaki; Mizukami, Keijiro; Chang, Hye-Sook; Hossain, Mohammad A; Yabuki, Akira; Mitani, Sawane; Higo, Takashi; Arai, Toshiro; Yamato, Osamu



Antibody to Ga1NAc-GD1a and Ga1NAc-GM1b in Guillain—Barré syndrome subsequent to Campylobacter jejuni enteritis  

Microsoft Academic Search

N-Acetylgalactosaminyl GD1a (Ga1NAc-GD1a) is a proposed target molecule for serum antibody in some patients with Guillain-Barré syndrome (GBS) (Kusunoki et al., 1994). We examined autoantibody to Ga1NAc-GD1a in sera from 58 GBS patients. Eight GBS patients had high IgG anti-Ga1NAc-GD1a antibody titers, 3 of whom also had high IgM anti-Ga1NAc-GD1a antibody titers. These 8 patients had experienced gastrointestinal infection before

Nobuhiro Yuki; Takao Taki; Shizuo Handa



Making a tool of an artifact: the application of photoinduced Lo domains in giant unilamellar vesicles to the study of Lo/Ld phase spinodal decomposition and its modulation by the ganglioside GM1.  


Electroformed giant unilamellar vesicles containing liquid-ordered Lo domains are important tools for the modeling of the physicochemical properties and biological functions of lipid rafts. Lo domains are usually imaged using fluorescence microscopy of differentially phase-partionioning membrane-embedded probes. Recently, it has been shown that these probes also have a photosensitizing effect that leads to lipid chemical modification during the fluorescence microscopy experiments. Moreover, the lipid reaction products are able as such to promote Lo microdomain formation, leading to potential artifacts. We show here that this photoinduced effect can also purposely be used as a new approach to study Lo microdomain formation in giant unilamellar vesicles. Photosensitized lipid modification can promote Lo microdomain appearance and growth uniformly and on a faster time scale, thereby yielding new information on such processes. For instance, in egg phosphatidylcholine/egg sphingomyelin/cholesterol 50:30:20 (mol/mol) giant unilamellar vesicles, photoinduced Lo microdomain formation appears to occur by the rarely observed spinodal decomposition process rather than by the common nucleation process usually observed for Lo domain formation in bilayers. Moreover, temperature and the presence of the ganglioside GM1 have a profound effect on the morphological outcome of the photoinduced phase separation, eventually leading to features such as bicontinuous phases, phase percolation inversions, and patterns evoking double phase separations. GM1 also has the effect of destabilizing Lo microdomains. These properties may have consequences for Lo nanodomains stability and therefore for raft dynamics in biomembranes. Our data show that photoinduced Lo microdomains can be used to obtain new data on fast raft-mimicking processes in giant unilamellar vesicles. PMID:22026409

Staneva, Galya; Seigneuret, Michel; Conjeaud, Hélène; Puff, Nicolas; Angelova, Miglena I



Ganglioside-like epitopes of lipopolysaccharides from Campylobacter jejuni (PEN 19) in three isolates from patients with Guillain-Barré syndrome  

Microsoft Academic Search

Sera from patients with Guillain-Barré syndrome (GBS) frequently have anti-GM1 antibody. We earlier showed that an lipopolysaccharides (LPS) from Campylobacter jejuni (PEN 19) isolated from a GBS patient has a GM1 ganglioside-like structure. Aspinall et al. (Biochemistry, 61 (1994) 335–337) reported that OH 4382 has an LPS that bears a GD3 ganglioside-like structure and that OH 4384 has an LPS

Nobuhiro Yuki; Shizuo Handa; Tadashi Tai; Masaki Takahashi; Kahiko Saito; Yoshihiro Tsujino; Takao Taki



Sphingolipidoses in Turkey.  


During the last 5 years 2057 children under the age of 5 with various neurologic symptoms with the suspected diagnosis of lysosomal storage diseases were referred to our hospital from different universities and state hospitals. We were able to separate sphingolipidoses by lysosomal enzyme screening. A total of 300 patients (15%) with sphingolipidoses were diagnosed; there were deficiencies of arylsulfatase A [metachromatic leukodystrophy (MLD)] in 93 (31%), hexosaminidase [Sandhoff disease (SHD)] in 62 (20.7%), hexosaminidase A [Tay-Sachs disease (TSD)] in 15 (5%), beta-galactosidase (GM1 gangliosidosis) in 35 (11.7%), alpha-galactosidase (Fabry disease) in one (0.3%) cerebroside beta-galactosidase (Krabbe disease) in 65 (21.7%) and glucosylceramidase (Gaucher disease) in 29 (9.6%). SHD (20.7%), MLD (31%) and Krabbe disease (21.7%) were common. Prenatal enzymatic diagnosis was made in 70 at risk pregnancies, 64 for TSD and SHD, three for MLD and three for GM1 gangliosidosis by using chorionic villus biopsy in 54, cord blood samples in 12 and cultured amniotic fluid cells in four. Seventeen fetuses were found to be affected. We have calculated the relative frequency and minimum incidence of sphingolipidoses in Turkey. The combined incidence of sphingolipidoses is 4.615 per 100,000 live births. The calculated incidences are 1.43, 0.95, 1, 0.23, 0.54, 0.45, 0.015 per 100,000 live births for MLD, SHD, Krabbe, Gaucher, TSD, GM1 gangliosidosis and Fabry diseases, respectively. The real incidence, which covers all subtypes of this group of diseases, should be greater than this number. The results suggested that, as a group, sphingolipidoses are relatively common and represent an important health problem in Turkey and some rare autosomal recessive diseases of Turkey are due to 'founder effect' created by consanguineous marriages. PMID:15275696

Ozkara, Hatice Asuman; Topçu, Meral



Lending a helping hand, screening chemical libraries for compounds that enhance beta-hexosaminidase A activity in GM2 gangliosidosis cells.  


Enzyme enhancement therapy is an emerging therapeutic approach that has the potential to treat many genetic diseases. Candidate diseases are those associated with a mutant protein that has difficulty folding and/or assembling into active oligomers in the endoplasmic reticulum. Many lysosomal storage diseases are candidates for enzyme enhancement therapy and have the additional advantage of requiring only 5-10% of normal enzyme levels to reduce and/or prevent substrate accumulation. Our long experience in working with the beta-hexosaminidase (EC isozymes system and its associated deficiencies (Tay-Sachs and Sandhoff disease) lead us to search for possible enzyme enhancement therapy-agents that could treat the chronic forms of these diseases which express 2-5% residual activity. Pharmacological chaperones are enzyme enhancement therapy-agents that are competitive inhibitors of the target enzyme. Each of the known beta-hexosaminidase inhibitors (low microm IC50) increased mutant enzyme levels to >or= 10% in chronic Tay-Sachs fibroblasts and also attenuated the thermo-denaturation of beta-hexosaminidase. To expand the repertoire of pharmacological chaperones to more 'drug-like' compounds, we screened the Maybridge library of 50,000 compounds using a real-time assay for noncarbohydrate-based beta-hexosaminidase inhibitors and identified several that functioned as pharmacological chaperones in patient cells. Two of these inhibitors had derivatives that had been tested in humans for other purposes. These observations lead us to screen the NINDS library of 1040 Food and Drug Administration approved compounds for pharmacological chaperones. Pyrimethamine, an antimalarial drug with well documented pharmacokinetics, was confirmed as a beta-hexosaminidase pharmacological chaperone and compared favorably with our best carbohydrate-based pharmacological chaperone in patient cells with various mutant genotypes. PMID:17894780

Tropak, Michael B; Mahuran, Don



[Identification of Krabbe disease in 2 brothers from East Germany using a new fluorogenic substrate for galactocerebrosidase].  


Activity of several lysosomal hydrolases was studied in skin fibroblasts obtained from two brothers living in GDR. Both patients exhibited distinct clinical symptoms of severe neurovisceral disease. Analysis of the lysosomal enzymes activity enabled to exclude possible occurrence in the patients of such glycolipidoses as Gaucher's disease, Sandhoff's disease, GM1-gangliosidosis and metachromatic leukodystrophy. A new fluorogenic galactoside of lipid nature 6-hexadecanoylamine-4-hethylumbellipheryl-beta-D-galactoside used as a substrate of galactocerebrosidase enabled to detect in the patients distinct decrease in this enzymatic activity and to diagnose Krabb's disease. Biochemical diagnosis of Krabb's disease using the fluorogenic substrate was also confirmed by analysis with labelled galactocerebroside as a substrate. PMID:3369131

Vidersha?n, G Ia; Zschiesche, M; Seidlitz, G


Vacuolating megalencephalic leukoencephalopathy in 12 Israeli patients.  


Leukodystrophy with macrocephaly as the main features of infantile neurodegenerative disease are characteristics of Canavan's disease, L-2-hydroxyglutaric aciduria, type I glutaric aciduria, and Alexander's disease. Also occasionally described are occidental congenital muscular dystrophy, G(M)2-gangliosidosis, metachromatic leukodystrophy, Krabbe's disease, and mucopolysaccharidosis. Since 1995, over 60 patients with a new syndrome, vacuolating megalencephalic leukoencephalopathy, have been described. The syndrome is characterized by macrocephaly, a slowly progressive clinical course of ataxia, spastic paraparesis, and seizure disorder with relatively spared cognition. Unlike other leukodystrophies with macrocephaly (except Alexander's disease), no metabolic marker has been found. We describe a similar group of 12 patients from two different Jewish ethnic origins in whom consanguinity is prominent. These patients have neuroimaging features and magnetic resonance spectroscopy findings indicating that there is an initial increase in white-matter edema with subsequent cystic formation. Consistent with loss of tissue in these areas, brain metabolites are reduced. The familial incidence in this group of patients is suggestive of autosomal-recessive inheritance. PMID:11292232

Ben-Zeev, B; Gross, V; Kushnir, T; Shalev, R; Hoffman, C; Shinar, Y; Pras, E; Brand, N



STD-NMR used to elucidate the fine binding specificity of pathogenic anti-ganglioside antibodies directly in patient serum.  


High-resolution binding profiles were elucidated for anti-GM1 IgM autoantibodies from two patients with a progressive form of paraproteinemic polyneuropathy. Antibody-ligand interaction was characterized by generating STD-NMR signals in target ganglio-oligosaccharides added directly to patient sera, without the requirement of antibody fractionation. Both immunoglobulins were found to have similar binding modalities, with interaction confined to two distinct spatially separated regions of GM1: the terminal betaGal(1-3)betaGalNAc disaccharide unit and the sialic acid residue. We describe a unique and powerful biophysical technique applied to define the molecular interaction between autoimmune disease-causing antibodies and their ganglioside targets. PMID:19105626

Houliston, R Scott; Jacobs, Bart C; Tio-Gillen, Anne P; Verschuuren, Jan J; Khieu, Nam H; Gilbert, Michel; Jarrell, Harold C



A comparative study of cytoplasmic granules imaged by the real-time microscope, Nile Red and Filipin in fibroblasts from patients with lipid storage diseases.  


Cytoplasmic granules in fibroblasts, visualized without stains, or labelled with Nile red, Filipin, or anti-LAMP-1 (lysosome-associated membrane protein 1), were imaged using the real-time microscope (RTM). New advances in light microscope technology were applied to detect cytoplasmic granules (RTM-visible granules) and characterize them by imaging contrast, size, shape, cellular distribution, composition, motion dynamics and quantity. Appearing as solid spheroids or ring structures, the majority of the RTM-visible granules contained Nile-red labelled neutral lipids. A smaller subpopulation, appearing dimmer, with less imaging contrast, contained Filipin-labelled free cholesterol. Most lipid storage granules have a diameter ranging from 0.3 mum to 0.6 mum, with a small population measuring up to 1 mum. They typically clustered in the perinuclear region and displayed relatively small oscillatory motion. Immunofluorescence based on LAMP-1 labelling highlighted granular structures that were distinct and separate from RTM-visible granules and other structures in the light modality of the microscope. RTM-visible granules were associated with disease phenotypes that have increased cellular neutral lipid stores corresponding to the Nile red-labelled droplets (e.g. triacylglycerides, cholesterol esters). As predicted, the fibroblast strains with a defect resulting in Wolman disease, when compared to control samples, consistently had RTM-visible granules, higher in imaging contrast and with larger diameters, that were labelled with Nile red, and also an increased frequency of Filipin-cholesterol complexes. By comparison, in fibroblasts where the lipid storage is less evident (Gaucher and Farber diseases) or from GM(1) gangliosidosis, where the primary storage substances are oligosaccharides, fewer and smaller RTM-visible granules were observed. In some cases, changes in contrast and morphology in the unstained cytoplasmic compartments were more evident than in the labelled structures. In summary, applying the RTM imaging system to fibroblasts enables differences between the various disease types to be seen and, in specific examples, a unique phenotype can be readily discerned. PMID:16435192

Pham, N-A; Gal, M R; Bagshaw, R D; Mohr, A J; Chue, B; Richardson, T; Callahan, J W



Patient \\  

Microsoft Academic Search

Contemporary medical decision making has been characterized as a struggle be- tween patients who are reportedly making more demands for medical interventions such as diagnostic tests and prescription drugs and physicians who are encouraged to partner with patients and satisfy them while simultaneously keeping medical costs down. Understanding this dynamic requires attention to the interactional strategies whereby patients indicate what

Virginia Teas Gill



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

SciTech Connect

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.

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



Multifocal motor neuropathy with conduction block: a study of 24 patients.  

PubMed Central

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment. Images

Bouche, P; Moulonguet, A; Younes-Chennoufi, A B; Adams, D; Baumann, N; Meininger, V; Leger, J M; Said, G



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

PubMed Central

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.

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



Antibodies to Glycoproteins Shared by Human Peripheral Nerve and Campylobacter jejuni in Patients with Multifocal Motor Neuropathy  

PubMed Central

We have tested serum samples from 24 patients with multifocal motor neuropathy (MMN) for reactivity to ganglioside GM1 and to Gal(?1–3)GalNAc-bearing glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni (Cj) serotype O:19. IgM anti-GM1 antibodies were detected by ELISA in 11 patients (45.8%) with MMN and in only one subject (4%) from the control group. Western blots showed positive reactivity of sera from 6 patients (25%) with MMN to several Gal(?1–3)GalNAc-bearing glycoproteins from human peripheral nerve and from Cj O:19 isolates. Sera from three patients (12.5%) with MMN showed positively reactive bands with similar electrophoretic mobility in all isolates (60–62?kDa, 48–51?kDa, 42?kDa, and 38?kDa). All six patients showed positive reactivity to 48–52 kDa protein isolated from human peripheral nerve. Increased titer of IgG antibodies to 60–62?kDa protein isolated from Cj O:19 associated with Guillain-Barré syndrome was detected in three patients, and their serum showed also IgG positive reactivity to peripheral nerve antigen with the same electrophoretic mobility. One of these patients had a previous history of Cj infection which suggests the possibility that Cj may be also involved in the pathogenesis of MMN.

Poceva-Panovska, Ana; Knezevic Apostolski, Sladjana



Genetics Home Reference: GM2-gangliosidosis, AB variant  


... activator. This protein is required for the normal function of an enzyme called beta-hexosaminidase A, which plays a critical ... AB variant. Because the AB variant impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this ...


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

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.

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



Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barré syndrome  

Microsoft Academic Search

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular

Nobuhiro Yuki; Keiichiro Susuki; Michiaki Koga; Yukihiro Nishimoto; Masaaki Odaka; Koichi Hirata; Kyoji Taguchi; Tadashi Miyatake; Koichi Furukawa; Tetsuji Kobata; Mitsunori Yamada



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

Microsoft Academic Search

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,

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


The optimization of background value in non-equidistant GM (1, 1) power model  

Microsoft Academic Search

precision. This paper defines non-equidistant GM(l,l) power model and makes a series of researches about it. Based on the error analysis of the GM(l,l) power model, the discrete function with non-homogeneous exponential law is used to fit the accumulated sequence, which can propose a structure method of the background value in GM(l,l) power model. The example indicates that the precision

Zhao Yang; Zheng-hua Hu



The combined forecasting method of GM(1,1) with linear regression and its application  

Microsoft Academic Search

Linear regression analysis could get better results in a short-term forecast. However, when some aberrant points exist in a given raw data sequence, it will be difficult for the linear regression function to accurately predict the changing tendency of the data sequence. To solve the problem, firstly, the raw data sequence with some abnormal data is classified into two parts:

Li Bing-jun; He Chun-hua



Object detection and tracking based on adaptive canny operator and GM(1,1) model  

Microsoft Academic Search

A new method of moving object detection and tracking from dynamical image sequence is proposed in this paper. This method uses information entropy to achieve the adaptive selection of high threshold in Canny operator. The modified Canny operator is used to detect the object contour from difference images. And this detected contour is then used as the template of partial

Zhiyu Zhou; Jianxin Zhang



The research of time lag effect of productivity and GDPbased on GM(1,2) model  

Microsoft Academic Search

With the theory of physics and chemistry, the author constructs a calculating model of productivity which takes production factors as system input and GDP as output. The article puts forward the model about the relationship of productivity, input factors and GDP, and productive forces are activators which transmit all the production factors into GDP. With the calculating model, the article

Wu Xin; Fang Zhi-geng; Shi Hong-xing





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

Patterson, Marc C



Crystal Structure of Human ?-Galactosidase  

PubMed Central

GM1 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, GM1 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.

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



The interval forecasting method based on non-equidistant GM(1,1) with application to regional grain production  

Microsoft Academic Search

Based on a raw sequence with some aberrant data, it is difficult for any prediction technique to give out an accurate point forecasting value. However, an interval forecasting value obtained by one or more different techniques should be reasonable and acceptable. In this paper, a data sequence having a linear tendency with upper\\/positive and lower\\/negative aberrances is analyzed. Upon the

Li Bing-jun; He Chun-hua



A hybrid forecasting method for day-ahead electricity price based on GM(1,1) and ARMA  

Microsoft Academic Search

Under deregulated environment, accurate price forecasting provides crucial information for electricity market participants to make reasonable competing strategies. With comprehensive consideration of the changing rules of the day-ahead electricity price of the United States PJM electricity market, a day-ahead electricity price forecasting method based on grey system theory and time series analysis is developed, in which the equal-dimension and new-information

Ruiqing Wang; Lian Yao; Yuzeng Li



Determination of oligosaccharides and glycolipids in amniotic fluid by electrospray ionisation tandem mass spectrometry: in utero indicators of lysosomal storage diseases.  


Prenatal diagnosis is available for many lysosomal storage disorders (LSD) using chorionic villus samples or amniocytes. Such diagnoses can be problematical if sample transport and culture are required prior to analysis. The purpose of this study was to identify useful biochemical markers for the diagnosis of lysosomal storage disorders from amniotic fluid. Amniotic fluid samples from control (n=49) and LSD affected (n=36) pregnancies were analysed for the protein markers LAMP-1 and saposin C by ELISA, and for oligosaccharide and lipid metabolite markers by electrospray ionisation-tandem mass spectrometry. Lysosomal storage disorder samples include; aspartylglucosaminuria, galactosialidosis, Gaucher disease, GM1 gangliosidosis, mucopolysaccharidosis types I, II, IIIC, IVA, VI, and VII, mucolipidosis type II, multiple sulfatase deficiency, and sialidosis type II. Each disorder produced a unique signature metabolic profile of protein, oligosaccharide, and glycolipid markers. Some metabolite elevations directly related to the disorder whilst others appeared unrelated to the primary defect. Many lysosomal storage disorders were clearly distinguishable from control populations by the second trimester and in one case in the first trimester. Samples from GM1 gangliosidosis and mucopolysaccharidosis type VII displayed a correlation between gestational age and amount of stored metabolite. These preliminary results provide proof of principal for the use of biomarkers contained in amniotic fluid as clinical tests for some of the more frequent lysosomal storage disorders causal for hydrops fetalis. PMID:15542394

Ramsay, Steven L; Maire, Irene; Bindloss, Colleen; Fuller, Maria; Whitfield, Phillip D; Piraud, Monique; Hopwood, John J; Meikle, Peter J



Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients  

PubMed Central

During recent years, a rising incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic critically ill patients has been reported. Critically ill patients are prone to develop disturbances in immunoregulation during their stay in the ICU, which render them more vulnerable for fungal infections. Risk factors such as chronic obstructive pulmonary disease (COPD), prolonged use of steroids, advanced liver disease, chronic renal replacement therapy, near-drowning and diabetes mellitus have been described. Diagnosis of IPA may be difficult and obtaining histo- or cytopathological demonstration of the fungus in order to meet the gold standard for IPA is not always feasible in these patients. Laboratory markers used as a non-invasive diagnostic tool, such as the galactomannan antigen test (GM), 1,3-?-glucan, and Aspergillus PCR, show varying results. Antifungal therapy might be considered in patients with persistent pulmonary infection who exhibit risk factors together with positive cultures or sequentially positive GM and Aspergillus PCR in serum, in whom voriconazole is the drug of choice. The benefit of combination antifungal therapy lacks sufficient evidence so far, but this treatment might be considered in patients with breakthrough infections or refractory disease.

Beishuizen, A.; Debets-Ossenkopp, Y. J.; Girbes, A. R. J.; Groeneveld, A. B. J.



Glucosylceramide modulates endolysosomal pH in Gaucher disease.  


GlcCer accumulation causes Gaucher disease where GlcCer breakdown is inhibited due to a hereditary deficiency in glucocerebrosidase. Glycolipids are endocytosed and targeted to the Golgi apparatus in normal cells but in Gaucher disease they are mistargeted to lysosomes. To better understand the role of GlcCer in endocytic sorting RAW macrophages were treated with Conduritol B-epoxide to inhibit GlcCer breakdown. Lipid analysis found increases in GlcCer led to accumulation of both triacylglycerol and cholesterol consistent with increased lysosomal pH. Ratio imaging of macrophages using both acridine orange and lysosensor yellow/blue to measure endolysosomal pH revealed increases in Conduritol B-epoxide treated RAW macrophages and Gaucher patient lymphoblasts. Increased endolysosomal pH was restricted to Gaucher lymphoblasts as no significant increases in pH were seen in Fabry, Krabbe, Tay-Sachs and GM1-gangliosidosis lymphoblasts. Substrate reduction therapy utilises inhibitors of GlcCer synthase to reduce storage in Gaucher disease. The addition of inhibitors of GlcCer synthesis to RAW macrophages also led to increases in cholesterol and triacylglycerol and an endolysosomal pH increase of up to 1 pH unit. GlcCer modulation appears specific since glucosylsphingosine but not galactosylsphingosine reversed the effects of GlcCer depletion. Although no acute effects on glycolipid trafficking were observed using bafilomycin A the results are consistent with a multistep model whereby increases in pH lead to altered trafficking via cholesterol accumulation. GlcCer modulates endolysosomal pH in lymphocytes suggesting an important role in normal lysosomes which may be disrupted in Gaucher disease. PMID:23628459

Sillence, Dan J



A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis.  

PubMed Central

Paired cerebrospinal fluid and serum samples of patients with amyotrophic lateral sclerosis (n = 35) revealed no consistent abnormalities of CSF cell count, CSF albumin, CSF IgG, CSF IgM, IgG or IgM index, or oligoclonal immunoglobulin band formation in the CSF. Determination of IgG and IgM CSF and serum antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b, and GT1b showed a characteristic pattern which allowed the differentiation of amyotrophic lateral sclerosis from controls and from patients with other neurological disorders including multiple sclerosis. Specifically, patients with the disease had elevated CSF IgM antibodies to all gangliosides except AGM1. The lack of correlation between the CSF findings and corresponding serum antibodies suggests a chronic, compartmental, intrathecal immune response of low activity in amyotrophic lateral sclerosis. Whether this immune response is primary and of pathogenetic significance, or an epiphenomenon of neuronal degeneration, remains to be investigated.

Stevens, A; Weller, M; Wietholter, H



Correlation of Sonographic and Electrophysiological Findings in a Patient with Multifocal Motor Neuropathy.  


BACKGROUND AND PURPOSE: Multifocal motor neuropathy (MMN) is an acquired, immune mediated, and commonly associated with antiganglioside antibodies against GM1 lower motor neuropathy, with an incidence of 1 per 100,000. The usual age of onset is between 20 and 50 years and men appear to be more often affected than women. Patients usually present with multifocal weakness that can be localized to named nerve distributions. METHODS: The gold standard for the diagnosis is the electrophysiological detection of focal, partial conduction block of motor fibers without involvement of sensory fibers, at sites that are uncommon areas of compression. The diagnostic sonography of the peripheral nervous system is a rapidly evolving and constantly expanding imaging field in the last years, especially in patients presenting with signs of polyneuropathy. RESULTS: We report for the first time a correlation of the sonographic and electrophysiological findings in a patient with MMN. CONCLUSION: We draw the attention on the usefulness of ultrasonography for detecting and diagnosing segmental lesions of the peripheral nerves in MMN and other immune mediated neuropathies, especially in cases where a nervous segment cannot be easily explored in terms of inching technique. PMID:23253207

Kerasnoudis, Antonios



A new line immunoassay for the multiparametric detection of antiganglioside autoantibodies in patients with autoimmune peripheral neuropathies.  


A novel line immunoassay for the multiparametric detection of 11 antiganglioside autoantibodies (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, and GQ1b) was evaluated by comparing the reactivities in sera of 77 patients with suspected or definite autoimmune peripheral neuropathies (PNP), 60 blood donors, and 30 systemic lupus erythematodes (SLE) patients. At least one antiganglioside autoantibody was detectable in 97.4% of the patients with neuropathies compared to 12.2% in the control group. A broad spectrum of reactivities with more than two antiganglioside autoantibodies including all tested gangliosides except GD2 and GT1b was found in nearly one-third of the patients with neuropathies whereas in the control group autoantibody profiles with more than two reactivities were observed in two SLE patients only. For the first time anti-GM4 IgG and IgM antibodies were shown in PNP including Guillain-Barré syndrome (GBS), Miller-Fisher syndrome (MFS), and multifocal motor neuropathy (MMN). Different autoantibody profiles detectable by this multiparametric assay may help to diagnose different entities within the growing spectrum of autoimmune PNP. PMID:17785314

Conrad, Karsten; Schneider, Hauke; Ziemssen, Tjalf; Talaska, Thomas; Reinhold, Dirk; Humbel, Rene-Louis; Roggenbuck, Dirk



Gene Transfer Corrects Acute GM2 Gangliosidosis--Potential Therapeutic Contribution of Perivascular Enzyme Flow  

PubMed Central

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.

Cachon-Gonzalez, M Begona; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M



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


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

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



Lysosomal storage disease.  


We report a case of lysosomal storage disease diagnosed by lysosomal enzyme assay in a two year old boy with a history of gradual onset of weakness of body, poor vision, flaccid neck and spasticity in all four limbs with hyper-reflexia. On fundus examination cherry red spots were noted at macula. On performing lysosomal enzyme assay, beta-galactosidase level was considerably low. This indicates that the child is affected by lysosomal storage disease most likely GM1 gangliosidosis. The diagnosis is important because the disease is rare and it may be missed as the symptoms are similar to other neurological conditions and the diagnosis can help with future conception. PMID:20795466

Khatiwada, B; Pokharel, A


Effect of lacto-N-neotetraose, asialoganglioside-GM1 and neuraminidase on adherence of otitis media-associated serotypes of Streptococcus pneumoniae to chinchilla tracheal epithelium  

Microsoft Academic Search

The adherence ofStreptococcus pneumoniae(Spn) otitis media-associated serotypes 3, 6A and 14 to ciliated chinchilla respiratory epithelium was investigated using a whole organ perfusion technique. We demonstrated that Spn adhere to chinchilla tracheal epithelium within 30 min and exhibit saturation kinetics indicating that the effect being observed is receptor mediated. Inhibition of adherence was achieved by prior incubation of Spn with

H. H. Tong; M. A. McIver; L. M. Fisher; T. F. DeMaria



Enhanced analgesic potency and reduced tolerance of morphine in 129\\/SvEv mice: evidence for a deficiency in GM1 ganglioside-regulated excitatory opioid receptor functions  

Microsoft Academic Search

A recent study reported that chronic morphine treatment of the 129\\/SvEv strain of mice did not result in the usual development of tolerance observed in most other mouse strains. The authors' analyses suggested that the anomalous lack of tolerance in 129\\/SvEv mice might be due to a defect in NMDA receptor functions. However, our previous studies suggested that cellular signs

Stanley M. Crain; Ke-Fei Shen



Overproduction of the CFTR R Domain Leads to Increased Levels of AsialoGM1 and Increased Pseudomonas aeruginosa Binding by Epithelial Cells  

Microsoft Academic Search

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), particularly the common D F508 mutation, have been associated with alterations in glycolipid sialylation and the availability of re- ceptors for Pseudomonas aeruginosa binding. The surface properties of 9HTEo 2 tracheal epithelial cell lines transfected with plasmids that overproduce the regulatory (R) domain of CFTR (pCEP-R) and lack cyclic adenosine monophosphate-stimulated Cl

Ruth Bryan; Dianne Kube; Aura Perez; Pamela Davis; Alice Prince


Respiratory syncytial virus assembly occurs in GM1-rich regions of the host-cell membrane and alters the cellular distribution of tyrosine phosphorylated caveolin-1  

Microsoft Academic Search

We have previously shown that respiratory syncytial virus (RSV) assembly occurs within regions of the host-cell surface membrane that are enriched in the protein caveolin-1 (cav-1). In this report, we have employed immunofluorescence microscopy to further examine the RSV assembly process. Our results show that RSV matures at regions of the cell surface that, in addition to cav-1, are enriched

Gaie Brown; Richard J. Sugrue


Experimental immunization with Borrelia burgdorferi induces development of antibodies to gangliosides.  

PubMed Central

Patients with neuroborreliosis produce antibodies, mostly of the immunoglobulin M (IgM) class, to gangliosides, particularly to those with Gal(beta 1-3)GalNac terminal sequences. Lewis rats were immunized with a nonpathogenic strain of Borrelia burgdorferi and with a chloroform-methanol extract (nonprotein) of this organism (CM) to determine whether antibodies to B. burgdorferi also recognized gangliosides. Rats were also immunized with asialo-GM1 to determine whether the elicited antibodies recognized antigens in B. burgdorferi. Rats immunized with B. burgdorferi produced low levels of IgM antibodies that cross-reacted with asialo-GM1 and GM1. Rats immunized with CM had marked IgM reactivity to asialo-GM1 and GM1. Immunization with asialo-GM1 resulted in antibodies that cross-reacted with B. burgdorferi antigens. Although antibodies to B. burgdorferi were of both the IgM and IgG classes, those to CM and to asialo-GM1 and GM1 were predominantly in the IgM fraction. Reactivity of the IgM antibodies decreased after adsorption with the heterologous and the homologous antigens, indicating bidirectional cross-reactivity between CM, asialo-GM1, and GM1 and that immunization with one produces antibodies to the other. There was no in vivo deposition of Ig in peripheral nerves, nor was there nerve pathology as a result of immunizations, but IgM antibodies to asialo-GM1 and CM recognized homologous antigens in the nodes of Ranvier of peripheral nerves from nonimmunized rats. This immunization model suggests that antibodies to gangliosides in Lyme disease have a microbial origin and are potentially relevant in pathogenesis.

Garcia-Monco, J C; Seidman, R J; Benach, J L



Patient Empowerment  


... empowerment and increasing your odds of surviving. Self Advocacy Don’t Rush Do not rush into surgery ... a local cancer patient support group or patient advocacy meeting in your community and attend. You can ...


Patient Advocacy

CPTAC recognizes the important role that patients, patient advocates, and other members outside of the traditional science community play in advancing cancer research, and is actively involved in dialogue with such communities.  To this end the consortium


Patient Safety  


Patient safety is one of the nation's most pressing health care challenges. A 1999 report by the Institute ... each year as the result of lapses in patient safety. There are things you can do to help ...


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


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

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



Lipocalin-type prostaglandin D synthase is up-regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides.  


Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a dually functional protein, acting both as a PGD2-synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. L-PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up-regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease). We investigated whether up-regulation of L-PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann-Pick type C1 disease. Quantitative RT-PCR revealed that L-PGDS mRNA was up-regulated in the brains of all these mouse models. In addition, strong L-PGDS immunoreactivity was observed in OLs, but not in either astrocytes or microglia in these models. Thus, up-regulation of L-PGDS appears to be a common response of OLs in LSDs. Moreover, surface plasmon resonance analyses revealed that L-PGDS binds GM1 and GM2 gangliosides, accumulated in neurons in the course of LSD, with high affinities (KD = 65 and 210 nm, respectively). This suggests that L-PGDS may play a role in scavenging harmful lipophilic substrates in LSD. PMID:16515539

Mohri, Ikuko; Taniike, Masako; Okazaki, Issei; Kagitani-Shimono, Kuriko; Aritake, Kosuke; Kanekiyo, Takahisa; Yagi, Takashi; Takikita, Shoichi; Kim, Hyung-Suk; Urade, Yoshihiro; Suzuki, Kinuko



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

PubMed Central

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.

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



Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology.  


In this work we showed that genotype-related patterns of hexosaminidase activity, isoenzyme composition, gene expression and ganglioside metabolism observed during embryonic and postnatal brain development are recapitulated during the progressive stages of neural precursor cell (NPC) differentiation to mature glia and neurons in vitro. Further, by comparing NPCs and their differentiated progeny established from Tay-Sachs (TS) and Sandhoff (SD) animal models with the wild-type counterparts, we studied the events linking the accumulation of undegraded substrates to hexosaminidase activity. We showed that similarly to what observed in brain tissues in TS NPCs and progeny, the stored GM2 was partially converted by sialidase to GA2, which can be then degraded in the lysosomes to its components. The latter can be used in a salvage pathway for the formation of GM3. Interestingly, results obtained from ganglioside feeding assays and from measurement of lysosomal sialidase activity suggest that a similar pathway might work also in the SD model. PMID:19166507

Martino, Sabata; di Girolamo, Ilaria; Cavazzin, Chiara; Tiribuzi, Roberto; Galli, Rossella; Rivaroli, Anna; Valsecchi, Manuela; Sandhoff, Konrad; Sonnino, Sandro; Vescovi, Angelo; Gritti, Angela; Orlacchio, Aldo



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

Microsoft Academic Search

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

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



Frustrating patients  

Microsoft Academic Search

Objective:To identify differences between patients viewed as frustrating by their physicians and those considered typical and satisfying.\\u000a \\u000a Design:This cross-sectional observational study focused on psychologically distressed high users of medical services. Frustrating\\u000a patients were compared with typical and satisfying patients, using data from patient questionnaires, physician assessments,\\u000a structured psychiatric interviews, and computerized utilization records.\\u000a \\u000a \\u000a \\u000a Setting:Group Health Cooperative of Puget Sound, a

Elizabeth H. B. Lin; Wayne Katon; Michael Von Korff; Terry Bush; Patricia Lipscomb; Joan Russo; Ed Wagner



Neuro-ophthalmology of late-onset Tay-Sachs disease (LOTS)  

Microsoft Academic Search

Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells. Objective: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies. Methods: Fourteen patients with biochemically confirmed LOTS (8 men; age range 24

J. C. Rucker; B. E. Shapiro; Y. H. Han; A. N. Kumar; S. Garbutt; E. L. Keller; R. J. Leigh



Identification of Sandhoff disease in a Thai family: clinical and biochemical characterization.  


Sandhoff disease is a GM2 gangliosidosis that is rare in Thailand. The authors report a Thai family with two children known to have infantile form of Sandhoff disease. The index case exhibited mitral valve prolapse with mitral regurgitation as an early sign, which is a rare presentation in Sandhoff disease. Thereafter the patient had developmental regression, startle reaction, and cherry red spots. The diagnosis was confirmed by biochemical analysis. PMID:20873083

Sakpichaisakul, Kullasate; Taeranawich, Pairat; Nitiapinyasakul, Achara; Sirisopikun, Todsaporn



Distinct Immunoglobulin Class and Immunoglobulin G Subclass Patterns against Ganglioside GQ1b in Miller Fisher Syndrome following Different Types of Infection  

Microsoft Academic Search

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barresyndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G (IgG) > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed



Lipid Storage Diseases  


... result, various lipids and particularly cholesterol accumulate inside nerve cells and cause them to malfunction. Patients with types ... storage of acidic lipid materials particularly in the nerve cells in teh central and peripheral nervous systems. GM1 ...


Patient's perspective.  


An unknown, but significant subgroup (perhaps the majority), of patients who have undergone chemotherapy treatment for their cancer report a subsequent decline in cognitive performance (e.g., difficulty in balancing a checkbook; forgetting or mixing up names of friends or relatives, etc.). The condition has been termed chemo fog, chemo brain, or some similar term to reflect the fact that the symptoms are usually difficult to describe and involve domains of cognition such as attention, concentration, memory, speed of information processing, multitasking, or ability to organize information. The deficits are reported to persist. The magnitude of the negative impact on quality of life depends, as does the condition itself, on multiple and varied factors. This chapter relates the experience of one patient. PMID:20738000

Raffa, Robert B; Martin, Kathleen J



Overwhelmed Patients  

PubMed Central

OBJECTIVE Patients with diabetes may experience high burden of treatment (BOT), including treatment-related effects and self-care demands. We examined whether patients with type 2 diabetes and their clinicians discuss BOT, the characteristics of their discussions, and their attempts to address BOT during visits. RESEARCH DESIGN AND METHODS Two coders independently reviewed videos of 46 primary care visits obtained during a practice-based trial and identified utterances concerning BOT, classifying them by topic and by whether BOT was addressed (i.e., whether statements emerged aimed at alleviating BOT). RESULTS Of the 46 visits, 43 (93.5%) contained BOT discussions. Both coders identified 83 discussions: 12 involving monitoring, 28 treatment administration, 19 access, and 24 treatment effects. BOT was unambiguously addressed only 30% of the time. CONCLUSIONS BOT discussions usually arise during visits but rarely beget problem-solving efforts. These discussions represent missed opportunities for reducing treatment-related disruptions in the lives of patients with diabetes, which may affect adherence and well-being.

Bohlen, Krista; Scoville, Elizabeth; Shippee, Nathan D.; May, Carl R.; Montori, Victor M.



Atypical Miller Fisher syndrome with GQ1b antibodies  

Microsoft Academic Search

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

Mark A Paine; Geoff Keir; Gordon T Plant



Patient Safety Organizations  


... mail Updates Welcome to AHRQ's Patient Safety Organization Web Site The Patient Safety and Quality Improvement Act of 2005 (Patient Safety Act) authorized the creation of Patient Safety Organizations (PSOs) to improve the ...


Should patient safety be more patient centred?  


In a patient-centred health system the views, experiences and rights of the patient drive the way that care is delivered. There is now an increasing emphasis on patient-centredness as an essential characteristic of safe and high quality care, but to date the involvement of patients in patient safety activities has been limited. The views and priorities of patients are not always valued in safety and quality work, and their perspectives are rarely included in activities such as incident investigation. We propose six areas of action to make patient safety more patient centred and hypothesise that the replacement of industrial safety models with a patient-centred model of safety culture will improve clinicians' ability to engage with safety initiatives. PMID:20128754

Jorm, Christine M; Dunbar, Nicola; Sudano, Leena; Travaglia, Joanne F



Pharmacist-Patient Interaction and Patient Expectations  

ERIC Educational Resources Information Center

|The nature of the professional interaction between the pharmacist and the patient was explored, with data collected from 3,743 questions asked of 16 pharmacists during an 8-week period. Factors that might affect the nature of the pharmacist-patient interaction are identified along with a cognitive-based profile of patient wants. (LBH)|

DeSimone, Edward M.; And Others



[Patient education in France].  


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

Bertrand, Dominique



Reassessment of rectal approach to neuropathology in childhood  

PubMed Central

A series of 93 rectal biopsies performed for diagnosis of suspected progressive neurometabolic disease between 1967 and 1973 is reviewed, and the results of this and of two previously published series totalling 307 biopsies are analysed. In GM1 and GM2 gangliosidosis, Batten's disease, and certain other neuronal storage diseases rectal biopsy is a reliable diagnostic alternative to brain biopsy. However, the need for biopsy has diminished with improvement in other diagnostic methods, particularly enzyme assay, the availability of which should determine the extent to which biopsy is used. It is suggested that rectal biopsy is necessary in the various forms of Batten's disease and in the neurovisceral storage disease with supranuclear ophthalmoplegia described by Neville et al. (1973). In certain diseases its use is unjustified, either because the result would be negative or because other less traumatic, reliable investigations are available. On rare occasions it is justifiable to use rectal biopsy either as an `excluding investigation' to exclude Batten's disease for certain in a healthy sib of a known case with this disorder or to detect the disease before onset of clinical symptoms. The need for a full thickness biopsy and for a full range of staining methods is emphasized. Without these the investigation cannot be expected to give diagnostic information and may be misleading, giving `false negative' results. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6

Brett, E. M.; Lake, B. D.



Molecular mechanisms of pathogenesis in a glycosphingolipid and a glycoprotein storage disease.  


The lysosomal system comprises a specialized network of organelles crucial for the sorting, digestion, recycling and secretion of cellular components. With their content of hydrolytic enzymes, lysosomes regulate the degradation of a multitude of substrates that reach these organelles via the biosynthetic or the endocytic route. Gene defects that affect one or more of these hydrolases lead to LSDs (lysosomal storage diseases). This underscores the apparent lack of redundancy of these enzymes and the importance of the lysosomal system in cell and tissue homoeostasis. Some of the lysosomal enzymes may form multiprotein complexes, which usually work synergistically on substrates and, in this configuration, may respond more efficiently to changes in substrate load and composition. A well-characterized lysosomal multienzyme complex is the one comprising the glycosidases ?-gal (?-galactosidase) and NEU1 (neuramidase-1), and of the serine carboxypeptidase PPCA (protective protein/cathepsin A). Three neurodegenerative LSDs are caused by either single or combined deficiency of these lysosomal enzymes. Sialidosis (NEU1 deficiency) and galactosialidosis (combined NEU1 and ?-gal deficiency, secondary to a primary defect of PPCA) belong to the glycoprotein storage diseases, whereas GM1-gangliosidosis (?-gal deficiency) is a glycosphingolipid storage disease. Identification of novel molecular pathways that are deregulated because of loss of enzyme activity and/or accumulation of specific metabolites in various cell types has shed light on mechanisms of disease pathogenesis and may pave the way for future development of new therapies for these LSDs. PMID:21118106

d'Azzo, Alessandra; Bonten, Erik



Metabolic cardiomyopathies  

PubMed Central

The energy needed by cardiac muscle to maintain proper function is supplied by adenosine Ariphosphate primarily (ATP) production through breakdown of fatty acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism, for example diabetes mellitus, hypertrophy and heart failure or alcoholic cardiomyopathy. Deficiency in enzymes of the mitochondrial ?-oxidation show a varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to a wide variety of cardiac disorders, without any obvious correlation between genotype and phenotype. A completely different pathogenetic model comprises cardiac manifestation of systemic metabolic diseases caused by deficiencies of various enzymes in a variety of metabolic pathways. Examples of these disorders are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease, various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis, carbohydrate–deficient glycoprotein syndromes and Sandhoff's disease). There are some systemic diseases which can also affect the heart, for example triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect or propionic acidaemia.

Guertl, Barbara; Noehammer, Christa; Hoefler, Gerald



Educating patients: staff response to patient misunderstanding.  


Members of a dentist's staff may be the best allies in promptly identifying patient misunderstandings related to their dental care. The doctor and his team should discuss the various ways in which patients may indicate misunderstandings about the dental practice's clinical or business policies. A staff member's prompt and thoughtful response can go a long way toward preventing patients' suspicion, non-compliance, and dissatisfaction. PMID:18630849

Roman, Kathleen M


Improving patient safety culture  

Microsoft Academic Search

Purpose – Improving hospital patient safety means an open and stimulating culture is needed. This article aims to describe a patient safety culture improvement approach in five Belgian hospitals. Design\\/methodology\\/approach – Patient safety culture was measured using a validated Belgian adaptation of the Hospital Survey on Patient Safety Culture (HSOPSC) questionnaire. Studies before (autumn 2005) and after (spring 2007) the

Johan Hellings; Ward Schrooten; Niek S. Klazinga; Arthur Vleugels



National Patient Safety Foundation  


... by @theNPSF Like Us on Facebook Copyright © 2013 National Patient Safety Foundation. All Rights Reserved. The National Patient Safety Foundation has been pursuing one mission since its founding ...


Patient-Specific Dosimetry.  

National Technical Information Service (NTIS)

A patient-specific optimally effective radiation dose for administration of a radiopharmaceutical to a patient for treatment of a disease may be established by basing the calculation of the appropriate therapeutic dose on factors such as the desired total...

J. A. Siegal K. R. Zasadny R. L. Wahl S. M. Kroll



Wooing patients with technology.  


Technologies that can give healthcare organizations a marketing advantage with patients include: Registration kiosks that request payment automatically, in a more comfortable environment for both patients and registration staff. Emails that enable patients to schedule initial visits and follow-up care. Secure online messaging platforms that enable patients to obtain timely answers to questions they have for their providers both before and after receiving services. PMID:23596831

Myers, Michael



Decision Making: The Patient’s Perspective  

Microsoft Academic Search

\\u000a There are major gaps in the quality of decisions about treatment options that involve making tradeoffs between benefits and\\u000a harms.1 Following standard counseling, patients score ‘D’ on knowledge tests and ‘F’ on their understanding of the probabilities\\u000a of benefits and harms. Moreover, there is a mismatch between the benefits and harms that patients value most and the option\\u000a that is

Dawn Stacey


ESWL in Hemophiliac Patients  

Microsoft Academic Search

Objective: To assess ESWL treatment of urolithiasis in patients with hemophilia, the frequency of hemorrhagic complications, and to determine the treatment outline.Patients and Methods: From 1991 to 1997, eleven patients with hemophilia were treated by ESWL for urolithiasis. Substitution of deficient coagulation factors was started on the day of treatment. Ultrasound examination was performed in all cases on the 1st

Maciej Czaplicki; Tomasz Jakubczyk; Janusz Judycki; Andrzej Borkowski; Jan M. Ziemski; Romuald Scharf; Andrzej Misiak; Pawel Szalecki



Melanoma in Immunosuppressed Patients  

PubMed Central

The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (?1000 patients in organ transplant recipient studies; ?500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients.

Kubica, Agnieszka W.; Brewer, Jerry D.



Multicenter Patient Records Research  

PubMed Central

The expanding health information infrastructure offers the promise of new medical knowledge drawn from patient records. Such promise will never be fulfilled, however, unless researchers first address policy issues regarding the rights and interests of both the patients and the institutions who hold their records. In this article, the authors analyze the interests of patients and institutions in light of public policy and institutional needs. They conclude that the multicenter study, with Institutional Review Board approval of each study at each site, protects the interests of both. “Anonymity” is no panacea, since patient records are so rich in information that they can never be truly anonymous. Researchers must earn and respect the trust of the public, as responsible stewards of facts about patients' lives. The authors find that computer security tools are needed to administer multicenter patient records studies and describe simple approaches that can be implemented using commercial database products.

Behlen, Fred M.; Johnson, Stephen B.



Tracheostomies in burn patients.  

PubMed Central

The use of tracheostomies in burned patients with inhalation injuries is now reserved for specific indications rather than as prophylactic airway management. A 5-year burn center experience with tracheostomies used in this fashion is presented. Ninety-nine tracheostomies were performed in 3246 patients who had indications of prolonged respiratory failure or acute loss of airway. Although colonization of the sputum was universal, neither rates of pulmonary sepsis nor mortality were significantly increased in patients who underwent tracheostomies. Twenty-eight patients developed late upper airway sequelae, including tracheal stenosis (TS), tracheoesophageal fistula (TEF), and tracheoarterial fistula (TAF). Duration of intubation correlated only with development of TAF, whereas patients in whom TEF developed were significantly older and more likely to have evidence of tracheal necrosis at the time of tracheostomy. The pathogenesis of upper airway sequelae in these patients as divergent responses to the combined insults of inhalation injury, infection, and intubation is considered. Images Fig. 1. Fig. 2. Fig. 3.

Jones, W G; Madden, M; Finkelstein, J; Yurt, R W; Goodwin, C W



[Thromboprophylaxis in surgical patients].  


The thromboprophylaxis strategy varies across the surgery type and the patient characteristics. The thromboembolic risk depends on the surgery and the patient's characteristics. The bleeding risk depends on the surgery, the anticoagulant drug and the patient's characteristics. The low molecular weight heparins remain the main drugs used for thromboprophylaxis in surgery, except in major orthopaedic surgery, a situation in which some of the new oral anticoagulants may be preferred. PMID:23910563

Godier, Anne; Rosencher, Nadia; Samama, Charles-Marc



Physicians as Patient Teachers  

PubMed Central

Physicians have a central role in educating patients and the public in the elements of personal health maintenance. To be an effective teacher, one must recognize the learning needs of each patient and use methods of information transfer that will result in comprehension and compliance. To bring about a change in life-style, one must also have an understanding of a patient's health beliefs and the determinants of human behavior. Using this information together with behavior modification strategies, physicians can forge an effective partnership with patients working toward the goal of optimum health.

Brunton, Stephen A.



Thermoplastic Patient Fixation  

Microsoft Academic Search

\\u000a Background and Purpose:  Several methods have been developed to reduce tumor motions and patient movements during radiotherapy of lung cancer. In this\\u000a study, a multislice CT-based analysis was performed to examine the effect of a thermoplastic patient immobilization system\\u000a on the chest wall and tumor motions.\\u000a \\u000a \\u000a \\u000a Patients and Methods:  Ten patients with stage II–IV lung cancer were enrolled into the study. According

Arpad Kovacs; Janaki Hadjiev; Ferenc Lakosi; Marta Vallyon; Zsolt Cselik; Peter Bogner; Akos Horvath; Imre Repa



Helping Patients Manage Stress  

PubMed Central

Stress and worry are always a part of our patients' problems and frequently the sole cause of their symptoms. Ways of relieving anxiety in different types of patients are described, according to complexity and time required. The main principles are: adequate diagnosis; explanation of the stress symptom cycle; supportive reassurance; identification and reduction of stressors where possible, and varying degrees of personal development to bring patients' level of functioning and adjustment up to match his stresses. Objections and difficulties are discussed, together with benefits such as diminised use of anxiolytics; a healthier adjustment for the patient, and greater job satisfaction for the physician.

Rainham, David C.



The Anxious Patient  

PubMed Central

Anxiety appears in many disguises and mimics most other afflictions. Once the anxious patient has been recognized as such and a proper diagnosis is made, management of him is easily carried out within the framework of the medical transaction. Lack of awareness of underlying anxiety in a patient who presents with somatic complaints can lead to poor results for the patient and frustration for the physician. It is not the physician's role to remove all anxiety. Rather, it is his mission to manage the anxious patient so as to mediate the anxiety allowing for integrated adaptive function.

Mendel, Werner M.



Partners in our care: patient safety from a patient perspective  

Microsoft Academic Search

The voice and role of “patient” in patient safety were explored by the Calgary Health Region's Patient and Family Safety Council perspective and the Calgary Health Region, Calgary, Alberta, Canada—an important collaboration for enhanced patient safety. Insights into patient safety were shared and coauthored in this article by the Patient and Family Safety Council with members of the Calgary Health

R B Hovey; A Morck; S Nettleton; S Robin; D Bullis; A Findlay; H Massfeller



Promoting Patient Safety Through Preoperative Patient Verification  

Microsoft Academic Search

At Spectrum Health, Grand Rapids, Mich, a process to verify patient identification, procedure, and procedure side and site was developed and implemented to improve the current process. Focusing on risk-reduction strategies, an interdisciplinary task force revised the facility's surgical site identification policy and improved the surgical scheduling form to highlight information for sided procedures. Task force members also designed a

Becky Brown; Markay Riippa; Kathy Shaneberger



Patient Safety Threat - Syringe Reuse  


... Añadir en... Favorites Delicious Digg Google Bookmarks A Patient Safety Threat – Syringe Reuse Important Information! Please read this ... References Information for Patients FAQs for Patients A Patient Safety Threat - Syringe Reuse Preventing Unsafe Injection Practices Safe ...


Googling a patient.  


The twenty-six-year-old patient requested a prophylactic bilateral mastectomy with reconstruction because of an extensive family history of cancer. She reported that she had developed melanoma at twenty-five; that her mother, sister, aunts, and a cousin all had breast cancer; that a cousin had ovarian cancer at nineteen; and that a brother was treated for esophageal cancer at fifteen. The treating team was skeptical about this history, and they could find no documentation of the patient's reported melanoma. The surgeon wrote the patient's primary care physician, explaining that he had seen the patient and planned to proceed with the bilateral mastectomy and reconstruction. The primary care physician responded that he was unable to substantiate several of the patient's claims; some of his colleagues believed the family history to be fabricated. Trying to make sense of the discrepancies, the genetic counselor called a counselor colleague who had met with this patient. The colleague suggested that the in-house genetic counselor "google" the patient. The search revealed two Facebook pages linked to the patient. In one, apparently a personal profile, the patient stated that in addition to battling stage four melanoma, she had recently been diagnosed with breast cancer. She provided a link to a site where she solicited donations to attend a summit for young cancer patients. The other Facebook page featured numerous pictures of her with a bald head, as though she has been through chemotherapy. The genetic counselor showed the Facebook pages to the surgeon, who then decided not to operate. Should health care professionals "google" their patients? PMID:24092585

Volpe, Rebecca; Blackall, George; Green, Michael; George, Danny; Baker, Maria; Kauffman, Gordon


The Faith of Patients  

Microsoft Academic Search

Throughout my medical career I have been interested in the questions that patients ask about their illnesses. I work as a Liaison Psychiatrist and as an Honorary Consultant Palliative Care Physician in a local hospice. Many of my patients speak about suffering generally and some put their suffering into religious frameworks. I have found that religion and spirituality are prevalent

Simon Dein


Briefing of Orthodontic Patients  

Microsoft Academic Search

The aim of this study was to record the level of relevant knowledge among orthodontic patients and their parents in order to determine how they prepare for the first consultation and what level of orthodontic briefing is needed. The focus was on the response of young patients to briefing, with other objectives being to investigate what briefing media are used

Anastasia Chatziandroni-Frey; Christos Katsaros; Rolf Berg



[Mentality of cancer patients].  


Cancer ruins the patient's daily routine and causes anxiety thus affecting adaptation. An analysis of past conversations gives a glimpse of psychological problems tormenting cancer patients. The paper gives a glimpse in adaptation at the crux of a crisis and evaluates the role and potential of anxiety which can help go through it. PMID:20361623

Chulkova, V A; Pestereva, E V



SBAR for Patients  

Microsoft Academic Search

his article challenges caregivers to develop a new tool to improve communication between patients or families of patients and caregivers. Such a toolwould be a derivative of an enormously successful existing tool, developed by a leading health care quality executive, using principles established in naval training on nuclear submarines. The communication principles provide structured language, reduce authority gradient impact, and

Charles R. Denham



Mimivirus in Pneumonia Patients  

PubMed Central

Mimivirus, the largest virus known to date, is an amebal pathogen like Legionella spp. When mimivirus was used as an antigen in a migration inhibition factor assay, seroconversion was found in patients with both community- and hospital-acquired pneumonia. Mimivirus DNA was found in respiratory samples of patients with hospital-acquired pneumonia.

La Scola, Bernard; Marrie, Thomas J.; Auffray, Jean-Pierre



The somatic patient.  


A significant proportion of patients seen in the Emergency Department will present with somatic complaints for which there is no apparent physiologic cause. Such patients may be divided into two broad categories: (1) those with symptoms and signs consciously synthesized by the patient, either for obvious secondary gain (malingering) or as a result of more subtle and complex motivations (factitious disorders); and (2) those patients with symptoms that are the unconscious expression of psychological stress (somatoform disorders). The somatoform disorders include (1) somatization disorder (characterized by a chronic history of numerous and widely divergent somatic complaints), (2) psychogenic pain disorder (somatization expressed in terms of persistent pain), (3) hypochondriasis (a conviction that one is diseased and disabled in conjunction with a well-focused constellation of supporting symptoms), and (4) conversion disorder (a single, usually nonpainful neurologic symptom, often with identifiable coping value for the patient). The first three disorders have been aggregately termed the "common somatization syndrome." Management of the somatically focused patient includes the communication of a caring attitude to the patient in conjunction with a cautious and diligent search for treatable medical or psychiatric illness. Resocialization and development of patient links with ongoing, nurturing nonmedical as well as medical support systems is of benefit. PMID:2001663

Purcell, T B



Patient-controlled analgesia  

Microsoft Academic Search

Patient controlled analgesia (PCA) is any method of allowing a person in pain to administer their own pain relief. In a hospital setting PCA refers to an electronically controlled infusion pump that delivers a prescribed amount of intravenous analgesic to the patient when he or she activates a button. Opioids are the medication most often administered through PCAs.PCA was introduced

Italo Ciaralli



Malariotherapy for HIV patients  

Microsoft Academic Search

The objective of this study was to determine whether HIV patients who undergo malariotherapy experience beneficial immunological change without iatrogenic complications. In an approved, prospective study, asymptomatic, HIV-positive patients were inoculated with P. vivax malaria and the malaria infection was allowed to run a predetermined course according to standard malariotherapy protocols and was cured with chloroquine. After termination of the

Henry J Heimlich; Xiao Ping Chen; Bin Quan Xiao; Shu Gou Liu; Yue Hen Lu; Eric G Spletzer; Ji Li Yao



Patient Education Thesaurus.  

ERIC Educational Resources Information Center

|This thesaurus was compiled to make the materials in the Patient Education Room of the Donald J. Vincent Medical Library at Riverside Methodist Hospital, Columbus, Ohio, more accessible to patients. Subjects are grouped in fairly broad categories (e.g., Aging & Problems of Aging; Alcohol & Alcohol Abuse; Careers in the Medical Field; Childhood…

Cooper, Lynn


Withholding truth from patients.  


The issue of whether patients should always be told the truth regarding their diagnosis and prognosis has afforded much debate in healthcare literature. This article examines telling the truth from an ethical perspective. It puts forward arguments for and against being honest with patients, using a clinical example to illustrate each point. PMID:19753871

O'Sullivan, Elizabeth


Ending the patient relationship  

Microsoft Academic Search

practice in New Zealand1 states that the essential elements of a good doctor\\/patient relationship are communication, respect, professional honesty and trust. Whilst both practitioner and patient contribute to the relationship, Coles states that it is the responsibility of the practitioner to ensure that these essential elements are present. With the practitioner bearing this obligation, he or she will not be

Jonathan Coates


Gauging patient safety programs.  


In response to evidence that adverse medical events are widespread, patient safety programs have emerged and proliferated worldwide in recent years. Patient safety may be considered a new and distinct healthcare discipline. It emphasizes the reporting, analysis, and prevention of medical errors that can lead to adverse healthcare events. While this is a useful generic definition, it takes on different meanings for each healthcare discipline. When patient safety programs were studied, it was found that many are generic and may be inappropriately focused and researched. In planning a patient safety program, the basis of patient safety programs for all disciplines will have similarities. But each discipline will require nuances specific to the discipline since the goals, objectives, and requirements of each are unique. Furthermore, each discipline will have its own preferred outcomes that may change over time as new data become available and service providers become more knowledgeable of ways to increase the likelihood of desired outcomes. PMID:24013250

Montoya, Isaac D; Kimball, Olive M



A patient carrying HIV  

PubMed Central

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.

Adeela, Bashir



JAMA Patient Page: Concussion  


JAMA PATIENT PAGE Concussion C oncussion (or mild traumatic brain injury) is a brain injury caused by blunt head trauma. In the United States, concussion affects more than 1 million individuals each year. ...


JAMA Patient Page: Retinopathy  


... A Patient Page on causes of visual impairment was published in the October 15, 2003, issue. ... health problems that put them at risk for visual impairment should see an ophthalmologist (a doctor with specialized ...


Insurance Resources for Patients  


... in ensuring the health and safety of their employees. The ACA has developed resources to assist patients ... with management to determine who makes decisions regarding employee benefits. Resources to Educate Others about Chiropractic ACA ...


Communicating with patients  


... Concerns Readiness to learn Preferences Support Barriers and limitations (such as physical and mental capacity, and low ... support available to your patient. Identify barriers and limitations : You may perceive barriers to education, and your ...


JAMA Patient Page: Grief  


... of the American Medical Association JAMA PATIENT PAGE Grief G rief (bereavement) is the emotional and physical ... specifically to treat people with complicated grief. ABNORMAL GRIEF FOR MORE INFORMATION • National Mental Health Association 800/ ...


Proposed Patient Labeling  

Center for Biologics Evaluation and Research (CBER)

Text Version... patients who have a known allergic reaction to any of the components of the product or are allergic to yeast-derived products • near a resected or ... More results from


Lymphadenopathy in rheumatic patients.  

PubMed Central

Lymph node biopsy specimens from 22 patients with chronic inflammatory joint disease have been studied. The histology has been reviewed and immunoperoxidase staining carried out for the major immunoglobulin heavy and light chains, macrophage markers, and MT1, MB1 surface markers. Although two of these patients had been initially diagnosed and treated for malignant lymphoma, the clinical course has not substantiated the diagnosis, and on review malignancy could not be identified in any of the biopsy specimens. Careful attention to specific histological features, together with adequate clinical information, is therefore essential if the true nature of the lymph node enlargement is to be recognised. Clinical review of the 22 patients suggested that lymphadenopathy may, in some cases, be an early feature of inflammatory polyarthritis, and this was supported by the observation that 20% of patients with otherwise unexplained reactive lymphadenopathy developed an inflammatory polyarthropathy within one year of biopsy. Images

Kelly, C A; Malcolm, A J; Griffiths, I



Psychiatric patient and anaesthesia  

PubMed Central

Many patients with psychiatric illnesses are prescribed long-term drug treatment, and the anaesthesiologist must be aware of potential interactions with anaesthetic agents. Psychotropic drugs often given in combination with each other or with other non-psychiatric drugs generally exert profound effects on the central and peripheral neurotransmitter and ionic mechanisms. Hence, prior intake of these drugs is an important consideration in the management of the patient about to undergo anaesthesia and surgery. This article highlights the effects of anaesthetics on patients taking antipsychotics, tricyclic antidepressants, monoamine oxidase inhibitors and lithium carbonate. The risk that should be considered in the perioperative period are the extent of surgery, the patient's physical state, anaesthesia, the direct and indirect effects of psychotropics, risk of withdrawal symptoms and risk of psychiatric recurrence and relapse.

Attri, Joginder Pal; Bala, Neeru; Chatrath, Veena



[Rehabilitation for cancer patients].  


In Japan, the number of patients with cancer is increasing drastically with the increase in number of elderly people. Therefore, recently, the necessity of rehabilitation for cancer patients has been realized. Cancer rehabilitation can be classified as preventive, restorative, supportive, or palliative and is administered according to the degree of cancer progression. Rehabilitation is of great significance even for patients with progressive cancer as it helps maintain their quality of life. Various forms of impairment, disability, and handicap are associated with cancer rehabilitation. Examples of impairments that cancer patients experience are hemiplegia and higher brain dysfunction in brain tumor cases, paraplegia and quadriplegia in spinal or spinal cord tumor cases, neuropathy and radiculopathy in cases of tumor invasion, complications after surgery, peripheral neuropathy after chemotherapy, and dysphagia after radiotherapy. It is important to evaluate these impairments and the risks associated with rehabilitation. PMID:24047769

Tanuma, Akira



Care of Psychogeriatric Patients.  

National Technical Information Service (NTIS)

The provision of psychiatric services to elderly residents of a coastal region of Great Britain is discussed, with special attention to the services offered in the geriatric ward of the region's nearest psychiatric hospital. Laurel Ward, for patients over...

L. Roberts



Patient-Centered Research  

PubMed Central

LEARNING OBJECTIVE 1). To know drugs that decrease warfarin levels CASE A 66 year old woman, nursing home resident, with history of chronic atrial fibrillation, hemiplegia secondary to a stroke, congestive heart failure, hypertension and seizure disorder, presented to the hospital with worsening nausea and vomiting persisting for 3 weeks. Her medications included digoxin, warfarin and enalapril. The physical exam showed hemiplegia. Standard admission work up revealed an INR of 2.3 and a high serum phenytoin level of 42 mg/dl. The patient had phenytoin toxicity, so phenytoin was stopped and the patient observed. Two days later the patient developed generalized clonic-tonic seizures. At that time the phenytoin level was 22 mg/dl. It was decided to give the patient loading doses of carbamazepine oral suspension in order to prevent further seizures. The following evening the patient suddenly developed acute abdomen. The INR was 1.4. The patient developed mesenteric infarction secondary to embolism, as revealed by urgent exploratory laparotomy. The patient expired the next day. DISCUSSION The event was brought on by inadequate anticoagulation secondary to a drug-drug interaction between warfarin and carbamazepine that resulted in a drop in INR. This, in our patient with atrial fibrillation, allowed for cardiac thrombi formation and their embolisation to the mesenteric circulation. Drug-drug interactions with warfarin are among the most common interactions seen in clinical practice. The following drugs decrease warfarin level and predispose to thrombosis (remember the acronym "DECREASE"): Diuretics: spironolactone Estrogen containing oral contraceptives Carbamazepine, Corticosteroides, Rifampin Ethchlorvynol Alcoholism, Aminogluthethimide Sucralfate Etc: barbiturates, griseofulvin, and vitamin K (broccoli and bananas).

Karcic, E; Karcic, AA



Endocarditis in Oncology Patients  

Microsoft Academic Search

\\u000a Although relatively uncommon in the general population with an incidence of 2–7 cases per 100,000 person-years, infective\\u000a endocarditis (IE) is associated with significant morbidity and mortality. Recent studies suggest that the incidence of IE\\u000a in oncology patients overall has increased and that it is reasonable to maintain a baseline suspicion in patients who present\\u000a with the appropriate clinical scenario. An

Sara E. Cosgrove; Aruna Subramanian


Patient care in radiography  

SciTech Connect

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.

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



An Electronic Patient Record \\  

Microsoft Academic Search

By nature, an electronic patient record (EPR) [9] consists of many pieces owned and managed by dif-ferent entities: yourself as a patient, your referring doctor, the various specialists you are dealing with (e. g. gynecologist, optometrist, physical therapist), the pharmacist(s) you shop from, the various hospi-tals you go to for surgery or special examination, the insurance company (private or state-owned)

Serge Abiteboul; Bogdan Alexe; Omar Benjelloun; Bogdan Cautis; Irini Fundulaki; Tova Milo; Arnaud Sahuguet




Microsoft Academic Search

Objective: To measure the frequency of depression and its risk factors in patients under going hemodialysis. Methodology: It is a cross-sectional prospective study conducted at Hemodialysis unit of Shalamar Hospital and Shaikh Zayed Hospital, Lahore from 1st January 2006 to 30th April 2006. All patients getting regular hemodialysis for more than three months were included. Beck's Depression Inventory- II (BDI-II;

Muhammad Anees; Haris Barki; Mahrukh Masood; Muhammad Ibrahim; Asim Mumtaz



Keeping the patient happy.  


Customer service is the catch word for the 90s and hospitals are constantly looking for ways to make their customer--the patient--happier. In a section of the country where fried chicken, grits and gravy are home-cooking staples, an unlikely marriage between Southern hospitals and a European food preparation process may be the key to many hospitals' ability to cater to the patient by offering gourmet meals on a regular basis. PMID:10120396

Bomar, F


Depression in Cancer Patients  

Microsoft Academic Search

Oncologists commonly encounter patients with depressive symptoms. It is important for the clinician to recognize and treat\\u000a these symptoms in cancer patients, since they can occur for both physical and psychological reasons. This chapter describes\\u000a assessment of depression, differentiating between types and causes of depressive disorders, and treatment interventions. Risk\\u000a factors for suicide, assessment and management of suicide are also

Yesne Alici-Evcimen



PubMed Central

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.

Stoller, Robert J.; Rosen, Alexander C.



[Jehovah's Witness patients].  


There are still legal and ethical problems relating to the refusal of blood transfusion due to religious belief of Jehovah's Witness patients. Since general consensus about the anesthetic management of these patients has not been established, the "Guidelines for refusal of blood transfusion on religious grounds" was proposed by the joint committee including Japanese Society of Anesthesiologists in February 2008. The principle of the guideline is that if a patient, who refuses blood transfusion even at cost of life, is 18 years old or above and competent to understand the medical treatment and the adverse effects due to bloodless medicine, doctors may plan and complete bloodless surgery. The same policy is allowed if the patient is 15 years old or above and he/she as well as all the parental authorities refuse blood transfusion. In other cases, the policy of life-saving blood transfusion should be explained to the patients. If a bloodless surgery is planned, precise perioperative strategies to avoid blood loss have to be carried out with the cooperation of all the physicians who care the patient. Anesthesiologists should be carefully prepared for the possible law suits that might lead to unexpected outcomes. PMID:20857672

Yorozu, Tomoko



Rehabilitating elderly cardiac patients.  

PubMed Central

The aging cardiovascular system undergoes many anatomic and physiologic changes. Increased vascular resistance, myocardial "stiffness," abnormalities of rhythmicity of the sinoatrial node, irregular cardiac rhythms, and alterations in heart rate and blood pressure responses are all seen more frequently in older patients. These changes are likely to impair these patients' ability to make the rapid adjustments necessary to maintain cardiac output during exercise and activity. When cardiovascular disease processes are superimposed on the "normal" concomitants of aging, greater alterations in hemodynamic response to exercise activity are noted than usually occur in younger cardiac patients. Exercise testing of older cardiac patients is safe and is usually needed to prescribe an appropriate intensity of exercise activity. The choice of the exercise protocol, the timing of the exercise test in relation to taking prescribed cardiac medication, the choice of exercise equipment, and special considerations for devices such as pacemakers and automatic implantable cardiodefibrillators must be considered before the exercise test is done. Many of these factors and the presence of either silent or overt cardiac symptoms or untoward hemodynamic events will also affect the exercise prescription. Elderly patients usually show substantial functional improvement when participating in a cardiac rehabilitation program and comply well with prescribed exercise. Early educational intervention may be crucial to reducing disability in these patients.

Anderson, J. M.



Patient Education: An Annotated Bibliography.  

National Technical Information Service (NTIS)

The topics included are: (1) Background on development of patient education programs; (2) Patient education interventions; (3) References for health professionals; and (4) Research and evaluation in patient education.

J. J. Simmons



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

Microsoft Academic Search

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

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



Biomarkers in hemodialysis patients.  


Patients with chronic kidney disease (CKD) are, compared to the general population, at higher risk of cardiovascular disease (CVD), including sudden death, coronary artery disease (CAD), congestive heart failure (HF), stroke, and peripheral artery disease. The presence of CVD is independently associated with kidney function decline. Renal insufficiency is a strong and independent predictor of mortality in patients with different CKD stages. The interplay of traditional and nontraditional risk factors is complex such that risk factor profiles are different in CKD patients. Seemingly, paradoxical associations between traditional risk factors and cardiovascular outcome complicate efforts to identify real cardiovascular etiology in these patients. Additional tools are often required to aid clinical assessment of cardiovascular risk. Recently, a number of cardiovascular biomarkers were identified as predictors of outcome in CVD. These may be used to guide early diagnosis and therapy for CVD or may predict outcome in CKD. This review focuses on the potential diagnostic and prognostic use of some important new biomarkers including brain natriuretic peptide (BNP), cardiac troponins (cTns), inflammatory markers, adhesion molecules, and asymmetric dimethylarginine (ADMA) in CKD as well as those patients with end-stage renal failure. PMID:22870586

Hojs, Radovan; Bevc, Sebastjan; Ekart, Robert



Galen and his patients.  


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

Horstmanshoff, H F



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.



Are orthognathic patients different?  


This questionnaire-based study investigated the psychological profile of orthognathic patients prior to starting treatment and compared the findings with a control group of non-patients. Comparison of the data used multivariate multiple regression analysis where outcome variables and independent variables were studied simultaneously. Some differences were found in the psychological profile of the orthognathic patient. They displayed higher levels of state anxiety (P < 0.001), higher numbers of individuals in their social support network (P < 0.05), and lower body image and facial body image (P < 0.001). Self-esteem was also found to be lower, but only at borderline levels of significance (P = 0.052). PMID:10822893

Cunningham, S J; Gilthorpe, M S; Hunt, N P



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.


How patients manage asthma  

PubMed Central

In this paper we discuss how patients cope with asthma and suggest that individuals use medical advice selectively in a manner they consider appropriate to their personal and social circumstances. Use of medical services is influenced by patients' perception of the effectiveness of medical therapies, concern about the long-term use of drugs, access to alternative therapies, support and advice from others and the need to make particular sense of living with a chronic disease. Some people are reluctant to use medical services under any circumstances.

Harding, Jenny M.; Modell, Michael



The patient as sufferer.  


The use of the term sufferer to replace patient has become increasingly common. This paper examines the varied meanings implicit in the word sufferer from the Judaeo-Christian perspective. This includes the biblical themes of suffering as human nature, as punishment, as a test, as atonement and as liberation and deliverance. The consequences of these themes for the sufferer's role are examined, particularly the sufferer as accepting and the sufferer as victim. It is argued that replacing the medical model, implied by 'patient' with a theological model, implied by 'sufferer' does not free the person from the constraints of a damaging label. PMID:8353105

Atkinson, J M



Communicator styles of hospital patients during nurse–patient counseling  

Microsoft Academic Search

This article describes nurse–patient communication during counseling sessions. It focuses on the patient as a participant in a discussion and aims at a description of patients’ communicator styles, which were observed on videotape based on 38 counseling sessions transcribed word by word. Interviews of the participating nurses and patients were used for partial support of the interpretations. The analytic method

Tarja Kettunen; Marita Poskiparta; Leena Liimatainen



The Chronic Patient, Palliative Care Settings, and the Dying Patient  

Microsoft Academic Search

Chronic patients, patients with permanent disability, and the terminal patients all have in common the fact that their medical\\u000a condition cannot usually be reversed. Such patients often engender a feeling of helplessness in the physician. Physicians\\u000a are trained to seek out the cause of the illness and cure it, and patients who do not fit this model are frustrating indeed.

Hoyle Leigh


A Patient's Best Friend.  

ERIC Educational Resources Information Center

|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)|

Haggard, Ann



[Patients' rights in 2011].  


Patients' rights have progressed thanks to pressure from associations and the introduction of new laws. They were fully recognised by the law of 4th March 2002 which confirms the existence of the individual and collective rights of users of the healthcare system, thereby laying the basis for health democracy. PMID:21574312

Le Voyer, Anne-Claude



The patient with anemia  

Microsoft Academic Search

Anemia is not a diagnosis but usually a sign of a systemic illness. The clinical manifestations of anemia depend on its rate of development and severity. This paper presents a simple pathophysiologic classification of the various types of anemia based on the patient's medical history, physical findings, peripheral blood morphology, and signs of bone marrow activity as reflected in the

Fred Rosner; Hans W Grünwald



Nutrition in cancer patients  

Microsoft Academic Search

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

Sebastiano Mercadante



The Adolescent Patient.  

ERIC Educational Resources Information Center

|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…

Daniel, William A., Jr.


[Rehabilitation of hemiplegic patients].  


The multifactorial aspects of rehabilitation of hemiplegic patients are reported. Medical and neuropsychological aspects as well as the significance of therapies, such as occupational and language training, physiotherapy and recreation therapy, are discussed. The importance of the role of the family, the architectonic aspects, institutional placement, an early start to rehabilitation and the limits are emphasized. PMID:1947540

Ketz, E; Blanco, J; Gonser, A



Patient Participation: Current Knowledge and Applicability to Patient Safety  

PubMed Central

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.

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



Hospital Patients Are Adult Learners.  

ERIC Educational Resources Information Center

|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…

Caffarella, Rosemary S.


Training Patient and Family Storytellers and Patient and Family Faculty  

PubMed Central

Narrative medicine has become a prominent method of developing more empathetic relationships between medical clinicians and patients, on the basis of a deeper understanding of the patient experience. Beyond its usefulness during clinical encounters, patient storytelling can inform processes and procedures in Advisory Councils, Committee Meetings, and Family as Faculty settings, leading to improved quality and safety in health care. Armed with a better understanding of the patient experience, clinicians and administrators can make decisions, hopefully in collaboration with patients, that will enrich the patient experience and increase satisfaction among patients, families, and staff. Patient and family storytelling is a key component of the collaboration that is ideal when an organization seeks to deliver patient- and family-centered care. Providing patients and families with training will make the narratives they share more powerful. Health care organizations will find that purposeful storytelling can be an invaluable aspect of a patient- and family-centered culture. Well-delivered storytelling will support quality- and safety-improvement efforts and contribute to improved patient satisfaction. This article provides instruction for teaching patients and families how to tell stories with purpose and offers advice about how to support patients, families, and clinicians participating in this effort.

Morrise, Lisa; Stevens, Katy Jo



Patient satisfaction with healthcare in asthmatics and patients with COPD before and after patient education  

Microsoft Academic Search

Patient satisfaction with general practitioners (GP) and pulmonary outpatient clinics has not been previously compared in patients with asthma and chronic obstructive pulmonary disease (COPD) in addition to the effect of patient education on this satisfaction.We randomly allocated 78 asthmatics and 62 patients with COPD after ordinary outpatient management to a control or an intervention group. Intervention consisted of educational




[A dissociative patient].  


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

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



Evaluating respiratory patient disability.  


The evaluation of the disabilities of patients with respiratory disease is regulated by the Spanish Ministry of Labor and Social Security, as are disabilities of any other type. We believe, however, that in respiratory pathologies this evaluation is especially complicated because, as they are chronic processes, they inter-relate with other systems. Furthermore, they tend to have occasional exacerbations; therefore, normal periods may alternate with other periods of important functional limitations. The present document arises from the desire of SEPAR to update this topic and to respond to the requests of respiratory disease patient associations who have asked us to do so. In this paper, we analyze the current situation of work disability legislation as well as the determination of degrees and percentages, including the current criteria for assigning disabilities due to respiratory tract deficiencies. Lastly, we propose work guidelines that would improve the existing scenario and outline this evaluation for specific pathologies. PMID:22341300

Ruiz Manzano, Juan; Alfageme Michavila, Inmaculada; Chiner Vives, Eusebi; Martínez González, Cristina



Visualising patient flow.  


We describe the development of a method to distil routinely collected clinical data into patient flow information to aid hospital bed management. Using data from state-wide emergency department and inpatient clinical information systems, a user-friendly interface was developed to visualise patient flow conditions for a particular hospital. The historical snapshots employ a variable time scale, allowing flow to be visualised across a day, week, month or year. Flow information includes occupancy, arrival and departure rates, length-of-stay and access block observations, which can be filtered by age, departure status, diagnosis, elective status, triage category, and admission unit. The tool may be helpful in supporting hospital bed managers in their daily decision making. PMID:22797023

Jensen, Andrew; Boyle, Justin; Khanna, Sankalp



Pseudocyesis in infertile patients.  


In the African population, pseudocyesis is not an uncommon gynecologic disorder. The high premium on childbearing, as well as the deep-rooted cultural belief that children are a "security of old age" and continuation of the family, exposes the infertile woman to constant stress. The social and psychological satisfaction of parenthood is very important in this culture; while, for some patients, perception of the economic implication of children enhances the desire to have children. PMID:35415

Ladipo, O A


The patient with allergies.  


Allergic disease affects a sizeable percentage of the general population, has a significant impact on patient quality of life, and exerts a significant financial burden on society. Atopic symptoms from inhalant allergens are among the most frequent complaints in outpatient medical visits. Key history and physical examination findings help to distinguish allergic rhinitis from other forms of chronic rhinosinusitis. Diagnostic testing may not be necessary unless immunotherapy is contemplated. PMID:20736101

Franzese, Christine B; Burkhalter, Neal W



Patient Safety in Surgery  

PubMed Central

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.

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



Leptospirosis in elderly patients.  


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

Gancheva, Galya Ivanova



[Coping in transplantated patients].  


The theoretical model of coping mechanisms (CM), is based on a discussion between it's main determinant factors: individual and situational (related to the 2 approaches of coping: dispositional and constitutional). Actually the most used classification of CM is based on the division of CM in two main dimensions: coping focused on emotions and coping focused on problem resolution. It is essential that classification methods of CM have in consideration the coexistence of stable dispositional elements with a situational variability. Some instruments to evaluate CM are introduced, based on different theories. Coping can influence health threw different mechanisms (neuroendocrine system, health threatening behaviours and adherence) and is included in two of the more important theoretical models applied to health (Moos & Schafer's and Leventhal's). Based on a systematic literature review we concluded that the most prevalent CM in pre transplantation period are acceptance, active coping, seeking support, and the less used are self-blame and avoidance. In post transplantation period the more prevalent CM continue to be active coping and seeking support associated to confrontation, selfconfidence, religion and coping focused in the problem. Evasive, emotive and fatalistic CM are associated to less control sensed by patients. Confrontation is associated to a better quality of life and avoidance to a reduction of quality of life and higher depression levels and denial to non-adherence increase. Control sensed by patients, CM related to the expression of emotions and denial change threw clinical evolution of transplanted patients. PMID:18625093

Telles-Correia, Diogo; Mega, Inês; Barbosa, António; Barroso, Eduardo; Monteiro, Estela



[Sport for pacemaker patients].  


Sport activity is an important issue in many patients with a pacemaker either because they performed sport activities before pacemaker implantation to reduce the cardiovascular risk or to improve the course of an underlying cardiovascular disease (e.g. coronary artery disease, heart failure) by sports. Compared to patients with an implantable cardioverter defibrillator (ICD) the risks from underlying cardiovascular disease (e.g. ischemia, heart failure), arrhythmia, lead dysfunction or inappropriate therapy are less important or absent. Sport is contraindicated in dyspnea at rest, acute heart failure, new complex arrhythmia, acute myocarditis and acute myocardial infarction, valvular disease with indications for intervention and surgery and comorbidities which prevent physical activity. Patients with underlying cardiovascular disease (including hypertension) should preferably perform types and levels of physical activity that are aerobic (with dynamic exercise) such as running, swimming, cycling instead of sport with high anaerobic demands and high muscular workload. In heart failure, studies demonstrated advantages of isometric sport that increases the amount of muscle, thereby preventing cardiac cachexia. Sport with a risk of blows to the chest or physical contact (e.g. boxing, rugby, martial arts) should be avoided. Implantation, programming and follow-up should respect specific precautions to allow optimal physical activity with a pacemaker including implantation of bipolar leads on the side contralateral to the dominant hand, individual programming of the upper sensor and tracking rate and regular exercise testing. PMID:22854824

Israel, C W



Patients' Perspectives on Pain  

PubMed Central

Nociceptive and neuropathic pain (NP) are common consequences following spinal cord injury (SCI), with large impact on sleep, mood, work, and quality of life. NP affects 40% to 50% of individuals with SCI and is sometimes considered the major problem following SCI. Current treatment recommendations for SCI-NP primarily focus on pharmacological strategies suggesting the use of anticonvulsant and antidepressant drugs, followed by tramadol and opioid medications. Unfortunately, these are only partly successful in relieving pain. Qualitative studies report that individuals with SCI-related long-lasting pain seek alternatives to medication due to the limited efficacy, unwanted side effects, and perceived risk of dependency. They spend time and money searching for additional treatments. Many have learned coping strategies on their own, including various forms of warmth, relaxation, massage, stretching, distraction, and physical activity. Studies indicate that many individuals with SCI are dissatisfied with their pain management and with the information given to them about their pain, and they want to know more about causes and strategies to manage pain. They express a desire to improve communication with their physicians and learn about reliable alternative sources for obtaining information about their pain and pain management. The discrepancy between treatment algorithms and patient expectations is significant. Clinicians will benefit from hearing the patient´s voice.

Norrbrink, Cecilia; Lofgren, Monika; Hunter, Judith P.; Ellis, Jaqueline



Impact of patient obesity on the patient-provider relationship  

PubMed Central

Objective Health professionals’ weight bias may impair obese patients’ interactions with providers. However, few studies have examined how negative provider attitudes affect the patient-provider relationship for obese patients. We hypothesized that higher patient body mass index (BMI) would be negatively associated with patient-provider relationship quality. Methods We analyzed data from the 2007 Health Tracking Household Survey. BMI was the independent variable, and patient-perceived quality of the patient-provider relationship was the outcome. We performed log-binominal regression analyses accounting for complex survey design to examine the association of BMI with the patient-provider relationship. Results Of the 15,197 adult survey respondents, the 6,427 who answered the quality of care questions were eligible for analysis. Overall, 29% had a normal range BMI, 34% were overweight, and 37% were obese. We found few differences in ratings of the patient-provider relationship for overweight and obese respondents when compared to respondents with a normal range BMI. Conclusion These unexpected findings may have occurred due to patients’ inability to perceive providers’ weight bias, measurement error in questionnaire items, or decreasing weight bias among health professionals. Practice implications Patient’s positive perceptions of providers may indicate promise for health professionals acting as motivators of behavior change in obese patients.

Gudzune, Kimberly A.; Huizinga, Mary Margaret; Cooper, Lisa A.



Patient (customer) expectations in hospitals.  


The expectations of patient are one of the determining factors of healthcare service. The purpose of this study is to measure the Patients' Expectations, based on Patient's Rights. This study was done with Likert-Survey in Trabzon population. The analyses showed that the level of the expectations of the patient was high on the factor of receiving information and at an acceptable level on the other factors. Statistical meaningfulness was determined between age, sex, education, health insurance, and the income of the family and the expectations of the patients (p<0.05). According to this study, the current legal regulations have higher standards than the expectations of the patients. The reason that the satisfaction of the patients high level is interpreted due to the fact that the level of the expectation is low. It is suggested that the educational and public awareness studies on the patients' rights must be done in order to increase the expectations of the patients. PMID:17028043

Bostan, Sedat; Acuner, Taner; Yilmaz, Gökhan



Brainstem involvement in a child with ophthalmoplegia, ataxia, areflexia syndrome  

Microsoft Academic Search

The anatomic location and pathogenesis of the ophthalmoplegia, ataxia, areflexia syndrome, which includes both the Miller-Fisher syndrome and Bickerstaff's brainstem encephalitis, continues to be a matter for debate. A patient with this syndrome is reported, and the brainstem location of the lesion and elevated titers of anti-GM1 antibodies in serum are demonstrated.

Arnau Fargas; Manuel Roig; Elida Vazquez; Angel Fitó



Patient health questionnaire. Using a patient-focused assessment tool.  

PubMed Central

A patient health questionnaire was developed for use in family practice to help identify lifestyle risk factors, assess health care needs, and better understand patients. This article discusses the questionnaire's development and practical application. Images Figure 3

Mitchell, J. D.



Patient Education Strategies in Dermatology  

PubMed Central

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 individually evaluates several patient-education strategies: verbal education, written information, group-based learning, audiotapes, videotapes, computer-assisted education, and the internet. The review presents the strengths and limitations of each strategy based on recognized barriers to effective patient education that were discussed in Part 1. Additionally, a summary of recommendations for effective patient education is provided.

Holder, Jessica L.



Is patient-controlled analgesia controlled by the patient?  

Microsoft Academic Search

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.

Neil Taylor; George M. Hall; Peter Salmon



Patient Care Coordination of Adult Oncology Patients in Home Health  

Microsoft Academic Search

This article illustrates several key components regarding caring for adult oncology patients at home, such as focusing on the oncology nurse as the patient care coordinator (PCC) instead of utilizing today's terminology as the case manager. Oncology nurses are of a rare breed. They must have extensive skill, knowledge, compassion, and insight to manage patients with devastating diseases, which sets

Rita R. Callahan



Discharge advice in cancer patients: posttreatment patients' report  

Microsoft Academic Search

BACKGROUND: Cancer patients are presented with advice and instructions during treatment and at discharge. Most recommendations aim at relief of physical problems, psychosocial well-being, and patients' health care behaviors. Patients often struggle to incorporate advice into daily life, and this influences symptom relief, quality of life, and even longevity. OBJECTIVE: The aim of this study was to gain insight into

J. De Leeuw; J. B. Prins; M. A. W. Merkx; H. A. M. Marres; T. van Achterberg



Angle closure in younger patients.  

PubMed Central

PURPOSE: Angle-closure glaucoma is rare in children and young adults. Only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients in our database aged 40 or younger with angle closure. METHODS: Our database was searched for patients with angle closure who were 40 years old or younger. Data recorded included age at initial consultation; age at the time of diagnosis; gender; results of slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (from 1993 onward); clinical diagnosis; and therapy. Patients with previous incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age (+/- SD) at the time of consultation was 34.4 +/- 9.4 years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients), iridociliary cysts (8 patients), retinopathy of prematurity (7 patients), uveitis (5 patients), isolated nanophthalmos (3 patients), relative pupillary block (2 patients), Weill-Marchesani syndrome (3 patients), and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSION: The etiology of angle closure in young persons is different from that in the older population and is typically associated with structural or developmental ocular anomalies rather than relative pupillary block. Following laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention.

Chang, Brian M; Liebmann, Jeffrey M; Ritch, Robert



Lysosomal dysfunction in a mouse model of Sandhoff disease leads to accumulation of ganglioside-bound amyloid-? peptide.  


Alterations in the lipid composition of endosomal-lysosomal membranes may constitute an early event in Alzheimer's disease (AD) pathogenesis. In this study, we investigated the possibility that GM2 ganglioside accumulation in a mouse model of Sandhoff disease might be associated with the accumulation of intraneuronal and extracellular proteins commonly observed in AD. Our results show intraneuronal accumulation of amyloid-? peptide (A?)-like, ?-synuclein-like, and phospho-tau-like immunoreactivity in the brains of ?-hexosaminidase knock-out (HEXB KO) mice. Biochemical and immunohistochemical analyses confirmed that at least some of the intraneuronal A?-like immunoreactivity (iA?-LIR) represents amyloid precursor protein C-terminal fragments (APP-CTFs) and/or A?. In addition, we observed increased levels of A?40 and A?42 peptides in the lipid-associated fraction of HEXB KO mouse brains, and intraneuronal accumulation of ganglioside-bound A? (GA?) immunoreactivity in a brain region-specific manner. Furthermore, ?-synuclein and APP-CTFs and/or A? were found to accumulate in different regions of the substantia nigra, indicating different mechanisms of accumulation or turnover pathways. Based on the localization of the accumulated iA?-LIR to endosomes, lysosomes, and autophagosomes, we conclude that a significant accumulation of iA?-LIR may be associated with the lysosomal-autophagic turnover of A? and fragments of APP-containing A? epitopes. Importantly, intraneuronal GA? immunoreactivity, a proposed prefibrillar aggregate found in AD, was found to accumulate throughout the frontal cortices of postmortem human GM1 gangliosidosis, Sandhoff disease, and Tay-Sachs disease brains. Together, these results establish an association between the accumulation of gangliosides, autophagic vacuoles, and the intraneuronal accumulation of proteins associated with AD. PMID:22496568

Keilani, Serene; Lun, Yi; Stevens, Anthony C; Williams, Hadis N; Sjoberg, Eric R; Khanna, Richie; Valenzano, Kenneth J; Checler, Frederic; Buxbaum, Joseph D; Yanagisawa, Katsuhiko; Lockhart, David J; Wustman, Brandon A; Gandy, Sam



JAMA Patient Page: Mechanical Ventilation  


... produce unconsciousness to ensure the patient’s comfort. In emergency situations (such as cardiac arrest or during cardiopulmonary ... like all other mechanical devices, can malfunction. Sophisticated alarms and system checks are built into the machines ...


Patient selection in outpatient surgery.  


Ambulatory surgery is commonplace for a multitude of procedures and a wide range of patients. The types of procedures performed in the ambulatory setting are becoming more work-intensive, and patients with comorbidities make for a challenging environment. For a safe environment for surgery in ambulatory facilities, the complex task of patient selection is necessary. Until an algorithm is created that includes provider, procedure, facility, and patient comorbidites, clinicians must rely on general guidelines rather than precise recommendations. PMID:23830745

Kataria, Tripti; Cutter, Thomas W; Apfelbaum, Jeffrey L



What makes a patient unhappy.  


The best way to avoid an unhappy postoperative patient is to do everything one can to optimize the preoperative consultation and select patients carefully. This article draws on the judgment of a cosmetic surgeon with years of experience. By focusing on the individual unique needs of each patient, and by not being afraid to say no, the wise surgeon can expect a very high satisfaction rate from patients. PMID:18355697

Tobin, Howard A



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


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

Schneider, Udo; Ulrich, Volker



Respecting the dying patient's rights.  


Patients who are dying have unique needs and special rights. This article discusses eight basic rights for dying patients. It also gives examples of how hospice and home care providers can focus care to respect the dying patient's rights. PMID:14665971

Pitorak, Elizabeth Ford



[Education of heart failure patients].  


Therapeutic patient education (TPE) has proved to be beneficial in a number of chronic diseases such as diabetes, asthma, chronic kidney failure. A TPE unit has been set up in Marie-Madeleine hospital in Forbach. In order to improve the actions carried out with patients with heart failure undergoing treatment, a satisfaction survey was carried out with this group of patients. PMID:22641945

Giroux, Valerie



Weather conditions and spine patients  

Microsoft Academic Search

Purpose of study: To evaluate the effects of various weather conditions on reported health status in a large group of patients seen by spine care practitioners.Methods used: Initial visit patient data from 23 centers across the United States that participate in the National Spine Network were obtained. These data included various patient demographic information, including age and gender, and Short

John Glaser; Valerie Keffala; Kevin Spratt



Strategies for enhancing patient compliance  

Microsoft Academic Search

Patient noncompliance is a substantial obstacle to the achievement of therapeutic goals. This paper reviews a number of practical interventions with demonstrated efficacy in enhancing patient adherence, including (1) improving patients' levels of information concerning the specifics of their regimens, reinforcing essential points with review, discussion, and written instruction, and emphasizing the importance of the therapeutic plan, (2) taking clinically

Marshall H. Becker; Lois A. Maiman



Hyperpyrexia in spinal injury patients  

Microsoft Academic Search

We studied 13 spinal injury patients who had hyperpyrexia during an 18 month period (September 1984—March 1986) to discover if differences existed in the core temperature of patients with tetraplegia and those with paraplegia, and the contribution of these differences to the final outcome. Children were excluded from this study as well as patients with any sign of infection on

A Essiet; O Onuba



Caring for Latino patients.  


Latinos comprise nearly 16 percent of the U.S. population, and this proportion is anticipated to increase to 30 percent by 2050. Latinos are a diverse ethnic group that includes many different cultures, races, and nationalities. Barriers to care have resulted in striking disparities in quality of health care for these patients. These barriers include language, lack of insurance, different cultural beliefs, and in some cases, illegal immigration status, mistrust, and illiteracy. The National Standards for Culturally and Linguistically Appropriate Services address these concerns with recommendations for culturally competent care, language services, and organizational support. Latinos have disproportionately higher rates of obesity and diabetes mellitus. Other health problems include stress, neurocysticercosis, and tuberculosis. It is important to explore the use of alternative therapies and belief in traditional folk illnesses, recognizing that health beliefs are dependent on education, socioeconomic status, and degree of acculturation. Many-but not all-folk and herbal treatments can be safely accommodated with conventional therapy. Physicians must be sensitive to Latino cultural values of simpatia (kindness), personalismo (relationship), respeto (respect), and modestia (modesty). The LEARN technique can facilitate cross-cultural interviews. Some cultural barriers may be overcome by using the "teach back" technique to ensure that directions are correctly understood and by creating a welcoming health care environment for Latino patients. PMID:23317025

Juckett, Gregory



The Patient Who Falls  

PubMed Central

Falls are common health events that cause discomfort and disability for older adults and stress for caregivers. Using the case of an older man who has experienced multiple falls and a hip fracture, this article, which focuses on community-living older adults, addresses the consequences and etiology of falls; summarizes the evidence on predisposing factors and effective interventions; and discusses how to translate this evidence into patient care. Previous falls; strength, gait, and balance impairments; and medications are the strongest risk factors for falling. Effective single interventions include exercise and physical therapy, cataract surgery, and medication reduction. Evidence suggests that the most effective strategy for reducing the rate of falling in community-living older adults may be intervening on multiple risk factors. Vitamin D has the strongest clinical trial evidence of benefit for preventing fractures among older men at risk. Issues involved in incorporating these evidence-based fall prevention interventions into outpatient practice are discussed, as are the trade-offs inherent in managing older patients at risk of falling. While challenges and barriers exist, fall prevention strategies can be incorporated into clinical practice.

Tinetti, Mary E.; Kumar, Chandrika



Candida infections in surgical patients.  

PubMed Central

Serious Candida infections were seen in 55 surgical patients from January 1977 through December 1980. Most of the patients had compromising underlying conditions and many were elderly. Broad-spectrum antibiotics and total parenteral nutrition (TPN) appeared to predispose patients to Candida infections. Mortality rate from Candida was 38%. A high percentage of patients with positive blood or bile cultures died as a result of Candida infection. Therapy with intravenous amphotericin B was highly effective if given in adequate dosage. No patient receiving more than 200 mg of amphotericin B died, but the mortality rate was 56% in those receiving lower doses.

Marsh, P K; Tally, F P; Kellum, J; Callow, A; Gorbach, S L



Patient involvement in patient safety: How willing are patients to participate?  

Microsoft Academic Search

BackgroundDespite growing recognition internationally that patients can help to promote their own safety, little evidence exists on how willing patients are to take on an active role.ObjectivesTo investigate medical and surgical patients' perceived willingness to participate in different safety-related behaviours and the potential impact of doctors'\\/nurses' encouragement on patients' willingness levels.DesignCross-sectional exploratory study using a survey that addressed willingness to

R E Davis; N Sevdalis; C A Vincent



Patients Postoperatively Forget Aspects of Preoperative Patient Education  

Microsoft Academic Search

Background: Preoperative patient education is critically important to the success of any bariatric operation. In our clinic,\\u000a we perform extensive preoperative education and informed consent. Part of the informed consent process includes a preoperative\\u000a true\\/false quiz. This study tests the hypothesis that postoperative patients do not recall key components of their preoperative\\u000a education. Methods: Preoperatively, all patients were required to

Atul K. Madan; David S. Tichansky



Tremor in hemifacial spasm patients.  


Tremor often accompanies dystonia and some other movement disorders. There are no reports describing tremor in patients with hemifacial spasm (HFS). The aim of the study was to assess the occurrence, type and parameters of tremor in HFS patients. The study included 47 HFS patients (mean age: 58.6 ± 10.7-years-old) and 48 healthy volunteers matched by sex and age. Tremor was assessed clinically and objectively using a triaxial accelerometer and EMG. A load test with 500 g weight was performed in order to identify physiological tremor. The Clinical Global Impression-Severity scale (CGI-S) was used to assess the severity of HFS. Neurological examination revealed tremor in 19 patients and 5 control subjects, and the objective methods postural and kinetic hand tremor was confirmed. Among the patients we identified: one case of psychogenic tremor, two patients were diagnosed with essential tremor, six patients had essential tremor in one hand and enhanced physiologic tremor in the other, seven patients had essential tremor in both hands and three patients had physiological tremor in both hands. Five control subjects revealed enhanced the physiological tremor type. The occurrence of hand tremor was associated with higher severity of HFS, as assessed by CGI score. Tremor accompanies HFS in 40% of cases and 10% of control subjects. The aetiology of hand tremor in patients with HFS is unknown. However, it may be associated with compression of the tremor oscillator located in the medulla. PMID:21161713

Rudzi?ska, Monika; Wójcik, Magdalena; Hartel, Marcin; Szczudlik, Andrzej



Patient education in Dutch hospitals.  


Studies among patients, nurses, and doctors in Dutch hospitals reveal the need for health education. Patients are dissatisfied with the information received and feel that nurses and doctors fail to meet their expectations regarding health education. More attention needs to be given to older, alienated, and low socioeconomic-status patients. The exclusive use of health-education media (like booklets and videotapes) is limited. It is recommended that hospitals and nursing departments pay greater attention to the in-service training of personnel, appoint specialized health educators, and organize efforts at ward level to create a positive climate for educating patients about various diseases. The policy of the Dutch government and the activities of private organizations (eg, patient movements, radio and TV broadcasts) support the development of patient education in Dutch hospitals. PMID:10299840

Visser, A P



Prioritization strategies for patient evacuations.  


Evacuation from a health care facility is considered last resort, and in the event of a complete evacuation, a standard planning assumption is that all patients will be evacuated. A literature review of the suggested prioritization strategies for evacuation planning-as well as the transportation priorities used in actual facility evacuations-shows a lack of consensus about whether critical or non-critical care patients should be transferred first. In addition, it is implied that these policies are "greedy" in that one patient group is given priority, and patients from that group are chosen to be completely evacuated before any patients are evacuated from the other group. The purpose of this paper is to present a dynamic programming model for emergency patient evacuations and show that a greedy, "all-or-nothing" policy is not always optimal as well as discuss insights of the resulting optimal prioritization strategies for unit- or floor-level evacuations. PMID:23666434

Childers, Ashley Kay; Mayorga, Maria E; Taaffe, Kevin M



[Management of the drunken patient].  


Acute ethanol intoxication is frequent in emergency departments. The clinical presentation is highly variable and ranges from an inebriety to a coma and sometimes an agitated patient. You have to examine completely the patient and to do complementary exams with a capillary glycemia as the minimal standard. We must keep in mind that an acute ethanol intoxication is a diagnosis of exclusion. With trauma patients, we have to keep a low threshold for asking radiological advanced imaging, like cerebro-cervical CT scan. The patient should be reexamined frequently. The treatment is a supportive one. If the patient is agitated, you can give him haloperidol or a benzodiazepine. Before discharge, the patient should see the alcohologic team. PMID:24024390

Wolter, L; Della Santa, V



Diaries written for ICU patients.  


Diaries are written for critically ill patients, to help them understand their intensive care stay and come to terms with their illness. The aim of this content analysis of eight such diaries is to understand the potential benefits for patients and families of this care intervention. A main category emerged: Sharing throughout the ICU time. Four themes were identified: (a) Sharing the story, (b) Sharing the presence, (c) Sharing feelings, and (d) Sharing through support. The first theme reflects the narration of daily events. The second is the perceived presence of health professionals and family at the patient's bedside and the presence of the patient as a person through the diary entries. The third theme describes the expression of feelings as written throughout the text. The last theme refers to the support offered to the patient. The diaries reflect the commitment and care of contributors to the patients' welfare. PMID:17724101

Roulin, Marie-José; Hurst, Samia; Spirig, Rebecca



Patient centric identification and association.  


Increased technological complexity of medical devices and systems coupled with increased workloads and reduced staffing, have created difficulties and discontinuities in the management of patient information. These issues have directly impacted and contributed to a rise in equipment-related errors, patient dissatisfaction, a potential for patient injury and resulting overall increased concern for patient safety. In response these concerns a variety of new devices, systems and applications have been developed to share information, provide cross checks along with verified delivery of critical information to the point of care. These applications include biomedical information systems, medication administration, sample collection, and electronic medical records. The deployment of these new integrated and networked devices, systems and applications are dependent on an accurate and consistent patient identification and association methodology which dynamically manages the relationship between patients, staff and equipment. Since the association information is common to many applications and utilizes a variety of technologies, (i.e. active and passive radio frequency identification (RFID), barcodes, etc.) an institutional approach is necessary to mange these processes in a consistent manor utilizing a common set of identification hardware. Implementation of a "Patient Centric Identification and Association Platform" represents a significant advance in the management of clinical patient information. The implementation of a Biomedical Device Information Network at Memorial Sloan-Kettering Cancer Center (MSKCC) integrates the identification and association of patients with devices and care providers and provides the methodologies to manage alarms, providing the ability to filter low priority or nuisance alarms. This implementation enables critical information to be distributed directly to care providers utilizing dedicated communications devices. Patient Centric Identification and Association is the enabling technology providing precise identification and association establishing an enhanced environment of care, increased patient safety, and a clear proactive response to the regulatory requirements of the Joint Commission (JCAHO) national patient safety initiatives. PMID:19964258

Frisch, P; Miodownik, S; Booth, P; Carragee, P; Dowling, M



Characterizing Anxiety in Melanoma Patients  

Microsoft Academic Search

Background: Over half of melanoma patients experience significantly elevated anxiety levels leading to psychological distress and delays in diagnosis and treatment. Objective: To identify melanoma patients likely to experience high levels of anxiety, we characterized the contributing factors and coping strategies and investigated potential anxiety-alleviating interventions. Method: Surveys were sent to 94 melanoma patients at Women’s College Hospital’s Pigmented Lesion

Sharif B. Missiha; Nowell Solish



Antithrombotic Therapy in Cancer Patients  

Microsoft Academic Search

\\u000a A complex relationship exists between the coagulation system and tumour cells, with common mechanisms linking haemostasis\\u000a and malignancy. Venous thromboembolism (VTE) is the second most common cause of death in cancer patients and it is estimated\\u000a that about 1 in 7 patients die of avoidable pulmonary embolism (PE), rather than the cancer itself. Treating a patient with\\u000a cancer requires a

Ajay K. Kakkar


Patient education: compliance or emancipation?  


What is patient education? How do nurses teach? What is the meaning of patient education in the secondary care setting to people who have a chronic illness such as asthma? What is the meaning of patient education to nurses in the secondary care setting? How do the political, economic, social and cultural contexts of secondary care and nursing education influence education of people with a chronic illness? PMID:8634502

Parmee, R



Patient Understanding of Food Labels  

Microsoft Academic Search

Results: Most patients (89%) reported using food labels. While 75% of patients reported at least a high school education and 77% had 9th-grade literacy skills, only 37% had 9th-grade math skills. On average, patients answered 69% (standard deviation, 21%) of the food-label questions correctly. Common reasons for incorrect responses included misapplication of the serving size, confusion due to extraneous material

Russell L. Rothman; Ryan Housam; Hilary Weiss; Dianne Davis; Rebecca Gregory; Tebeb Gebretsadik; Ayumi Shintani; Tom A. Elasy



Diarrhea in patients with AIDS  

Microsoft Academic Search

Opinion statement  Diarrhea in patients with AIDS is a worldwide problem that can have a devastating impact on quality of life for the patient.\\u000a Chronic diarrhea, usually defined as at least 4 weeks’ duration, is more common in patients with low CD4-positive T-lymphocyte\\u000a counts, signaling advanced immunosuppression. Some organisms, such as Microsporidia, usually cause diarrhea only in the immunosuppressed;\\u000a others, such

Susan C. Morpeth; Nathan M. Thielman



[Erythrocyte filterability of angina patients].  


Erythrocyte filterability and its relation to erythrocyte volume, hemoglobin level and cholesterol/phospholipid ratio were studied in anginal patients. A 25% decrease in filterability and elevated erythrocyte cholesterol/phospholipid ratios were found in anginal patients, as compared to normal subjects. A close inverse correlation (r = -0.623) was demonstrated between erythrocyte filterability and cholesterol/phospholipid ratio. Mean erythrocyte volume and Hb levels were similar in anginal patients to those of normal subjects. PMID:3586485

Razumov, V B; Redchits, E G; Vinogradova, I V; Deev, A I; Khrennikov, V P



[Cytomegalovirus disease in immunocompromised patients].  


Human Cytomegalovirus are a ubiquitous herpesvirus establishing virus-infections which are usually asymptomatic in immunocompetent individuals. In patients with Acquired Immunodeficiency Syndrome (AIDS) and immunocompromised hosts, the virus causes primary, latent or chronic persistent infection. Primary CMV infection is very severe in immunocompromised patients as well as among healthy population. Among patients with AIDS Cytomegalovirus (CMV) is usually isolated from patients specimen in association with other pathogens (Pneumocystis carinii, Candida albicans). The prevalence of serious CMV (chorioretinitis, gastrointestinal disease, interstitial pneumonia and central nervous system disease), in AIDS population are respectable. PMID:10872268

Zvizdi?, S; Beslagi?, E; Kapi?, E; Zvizdi?-Karahodzi?, M



Patient Transport via Commercial Airlines  

PubMed Central

Because the frequency of patient transport from one hospital to another is increasing and the popularity of air travel continues to rise, physicians should be aware of the procedures for patient transport by commercial airlines. Major airlines in Canada have experienced personnel and established procedures that facilitate the transportation of patients with special medical needs. By working with the airline medical health officers and using up-to-date equipment, physicians can achieve safe, cost-effective transport of appropriate patients via commercial aircraft.

Macnab, Andrew John



Cardiac evaluation of stroke patients.  


There are two potential purposes for cardiac evaluation in patients with cerebrovascular disease: to identify possible cardioembolic pathophysiology for ischemic symptoms and to identify concomitant coronary artery disease. Both have important implications for patient prognosis and treatment, and testing therefore appears to be warranted. On the other hand, the cost conservation movement in medicine dictates that physicians limit unnecessary, costly, possibly risky testing when the diagnostic yield is low. For example, the overall yield of cardiac testing in "usual stroke patients" who have no suggestive history or findings on examination, chest X-ray, or electrocardiogram is less than 10% and may not be indicated routinely. Conversely, young patients with stroke of unknown cause are likely to benefit from aggressive cardiac testing. Many reported series and clinical trials have demonstrated that patients with cerebrovascular disease are more likely to die in follow-up from cardiovascular than from cerebrovascular causes. This risk is best defined and may be highest in patients with carotid disease, in whom the 5-year cardiac mortality rate may be as high as 40 to 50%. Studies have shown that such patients are also likely to have abnormal tests for cardiac ischemia, even when a history of cardiovascular events or symptoms or electrocardiographic abnormalities are lacking. These results, combined with further investigations into which cerebrovascular patients are at highest risk for cardiovascular disease and what testing best identifies underlying, treatable cardiovascular disease, are needed to direct the care and improve the cardiovascular prognosis of patients with cerebrovascular disease. PMID:9744828

Wilterdink, J L; Furie, K L; Easton, J D



Monitoring patients with multiple nevi.  


Early recognition is the most effective intervention to improve melanoma mortality. Early diagnosis of melanoma in atypical mole syndrome patients, however, may be challenging. Skin self-examination and periodic physician-based total-body skin examinations are recommended in atypical mole patients but dermoscopy, total-body photography, and digital dermatoscopy have been proved to improve accuracy in early detection of melanoma in these high-risk patients. Digital follow-up in atypical mole syndrome patients allows detection of new lesions and changes in preexisting lesions. PMID:24075545

Puig, Susana; Malvehy, Josep



Connecting Patients With Specialty Products  

PubMed Central

Previously, this series described distribution channels through which specialty drugs move to patients. This installment discusses changes and challenges that lie ahead, especially at the dispensing end.




Medical Cannabis Patients: Patient Profiles and Health Care Utilization Patterns  

Microsoft Academic Search

The possible medicinal uses of cannabis are growing, yet research on how patients use medical cannabis facility services remains scarce. This article reports on the Cannabis Care Study, in which 130 medical cannabis patients at seven facilities in the San Francisco Bay Area were surveyed to gather information about demographics, personal health practices, health outcomes, service use, and satisfaction with

Amanda Reiman



Expanding patient involvement in care. Effects on patient outcomes  

Microsoft Academic Search

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

Sheldon Greenfield; Sherrie H. Kaplan; Ware John E. Jr



Patient Education Leads to Better Care for Heart Patients.  

ERIC Educational Resources Information Center

|The staff of a heart and circulatory disease program of a State department of health conducted a special project at a city hospital which showed that a well-organized treatment and education program for patients with congestive heart failure increased the patient's knowledge of his disease, medication, and diet as well as his adherence to a…

Rosenberg, Stanley G.


Disciplined care for disciplined patients: experience of hospitalized blind patients.  


Blindness is a permanent condition that alters daily life of blind people. Interpretive phenomenology was used to understand lived experiences of the hospitalized blind people. "Disciplined care for disciplined patients" was one of the themes that emerged from the data. Provision of disciplined care can help health care professionals provide a holistic and comprehensive competent care for blind patients. PMID:24121699

Shamshiri, Mahmood; Mohammadi, Nooredin; Cheraghi, Mohammad Ali; Vehviläinen-Julkunen, Katri; Sadeghi, Tahereh


The virtual standardized patient. Simulated patient-practitioner dialog for patient interview training.  


We describe the Virtual Standardized Patient (VSP) application, having a computerized virtual person who interacts with medical practitioners in much the same way as actors hired to teach and evaluate patient assessment, diagnosis, and interviewing skills. The VSP integrates technologies from two successful research projects conducted at Research Triangle Institute. AVATALK provides natural language processing, emotion and behavior modeling, and composite facial expression and lip-shape modeling for a natural patient-practitioner dialog. Trauma Patient Simulator provides case-based patient history and trauma casualty data, real-time physiological modeling, interactive patient assessment, 3-D scenario simulation, and instructional record-keeping capabilities. The VSP offers training benefits that include enhanced adaptability, availability, and assessment. PMID:10977526

Hubal, R C; Kizakevich, P N; Guinn, C I; Merino, K D; West, S L



Patient Perspectives on Spirituality and the Patient-physician Relationship  

PubMed Central

OBJECTIVE To identify the preferences and concerns of seriously ill patients about discussing religious and spiritual beliefs with physicians. DESIGN Three focus group discussions with patients who had experienced a recent life-threatening illness. Discussions were audiotaped, transcribed verbatim, and reviewed independently by two investigators to identify discrete comments for grouping into domains. A third investigator adjudicated differences in opinion. Comments were then independently reviewed for relevance and consistency by a health services researcher and a pastoral counselor. SETTING Academic medical center. PARTICIPANTS Referred sample of 22 patients hospitalized with a recent life-threatening illness. MEASUREMENTS AND MAIN RESULTS Almost all of the 562 comments could be grouped into one of five broad domains: 1) religiosity/spirituality, 2) prayer, 3) patient-physician relationship, 4) religious/spiritual conversations, and 5) recommendations to physicians. God, prayer, and spiritual beliefs were often mentioned as sources of comfort, support, and healing. All participants stressed the importance of physician empathy. Willingness to participate in spiritual discussions with doctors was closely tied to the patient-physician relationship. Although divided on the proper context, patients agreed that physicians must have strong interpersonal skills for discussions to be fruitful. Physician-initiated conversation without a strong patient-physician relationship was viewed as inappropriate and as implying a poor prognosis. CONCLUSION Religion and spirituality are a source of comfort for many patients. Although not necessarily expecting physicians to discuss spirituality, patients want physicians to ask about coping and support mechanisms. This exploratory study suggests that if patients then disclose the importance of spiritual beliefs in their lives, they would like physicians to respect these values.

Hebert, Randy S; Jenckes, Mollie W; Ford, Daniel E; O'Connor, Debra R; Cooper, Lisa A



Adequacy of dialysis: the patient's role and patient concerns.  


The patient's role in adequacy of hemodialysis is demanding and complex. It requires meticulous attention to initiating, accepting, and maintaining extraordinary behavioral change. This includes the following: (1) major alteration of dietary habits, often contrary to a patient's familial and cultural customs; (2) compliance with a new, voluminous medication routine, often straining personal finances; (3) reallocation of time for transportation, treatment, and partial recovery, frequently consuming a minimum of 6 to 8 hours 3 days each week; (4) psychologic adjustment to unaccustomed chronic dependency on, and accountability to, an array of variably experienced and competent renal care staff; (5) skills, seldom taught, required to communicate clearly and regularly with overworked medical professionals who are often much younger with less life experience; and (6) additional commitment to compensating for the physical fatigue that routinely accompanies hemodialysis. Reasonable behavioral modification in these 6 categories is likely to increase the chances of a patient fulfilling his role in adequacy of dialysis. Some patients, however committed the staff have been in assisting them, may show little interest in dialysis adequacy and the patient's role. Other patients periodically may fail in their role unless the renal care team recognizes the patient as an individual who is included as an important team member. The patient requires consistent and repeated education about their disease, treatment, and risks and benefits of adherence. The unique, unnatural requirements of adequate chronic hemodialysis require this patient support from the renal staff, enhanced by continuous sensitive attention, empathy, and persuasion. This will help the patient achieve success in their role. PMID:15791563

Newmann, John M; Litchfield, William E



Calcimimetics in peritoneal dialysis patients.  


Though the prevalence of secondary hyperparathyroidism (SHP) and the related mineral metabolism (MM) changes have been reported at almost the same rate in peritoneal dialysis (PD) as in hemodialysis (HD) patients, PD patients have a higher prevalence of adynamic bone disease (ABD), suggesting that their bone is less sensitive for a given level of PTH. Furthermore, the phosphorus control seems to be better and vitamin D deficiency is more common in PD patients than in HD patients. So, the therapeutic approach to SHP and MM changes in PD patients might be different from the one applied to HD patients. Vitamin D metabolites and phosphate binders, though effective in controlling SHP of CKD patients, are not equally effective in controlling at the same extent calcium and/or phosphorus levels. Recently, a new drug (Cinacalcet) has been introduced in the clinical practice which significantly increased the chance of obtaining a simultaneous control of both PTH and MM parameters. However, only scanty data are present in the literature regarding the use of Cinacalcet in PD patients. The few studies produced in PD retraced the results obtained in hemodialysis patients, confirming that both in the short- and long-term Cinacalcet induced a more pronounced reduction of PTH in a larger percentage of patients as compared with standard therapy (ST), and this effect was associated with a decrease in both calcium and phosphorus concentrations, though the extent of the percentage decrease of phosphorus was lower than in HD patients. The safety/tolerability profile was again the same as in HD patients, with gastrointestinal symptoms representing the more frequently reported side effects. In our experience, given that a severe form of SHP is less frequent, the control of phosphate is usually better and vitamin D deficiency is more frequent in PD than in HD patients, making the former patients more prone to hypo- rather than hypercalcemia, the need for the use of the most recent and potent drugs for the control of SHP, including Cinacalcet, is usually lower in PD than in HD patients. PMID:22652729

Messa, Piergiorgio; Castelnovo, Claudia; Scalamogna, Antonio



Immunoglobulin GM and KM Allotypes and Prevalence of Anti-LKM1 Autoantibodies in Patients with Hepatitis C Virus Infection  

PubMed Central

GM and KM allotypes—genetic markers of immunoglobulin (Ig) ? and ? chains, respectively—are associated with humoral immunity to several infection- and autoimmunity-related epitopes. We hypothesized that GM and KM allotypes contribute to the generation of autoantibodies to liver/kidney microsomal antigen 1 (LKM1) in hepatitis C virus (HCV)-infected persons. To test this hypothesis, we characterized 129 persons with persistent HCV infection for several GM and KM markers and for anti-LKM1 antibodies. The heterozygous GM 1,3,17 23 5,13,21 phenotype was significantly associated with the prevalence of anti-LKM1 antibodies (odds ratio, 5.13; P = 0.002), suggesting its involvement in this autoimmune phenomenon in HCV infection.

Muratori, Paolo; Sutherland, Susan E.; Muratori, Luigi; Granito, Alessandro; Guidi, Marcello; Pappas, Georges; Lenzi, Marco; Bianchi, Francesco B.; Pandey, Janardan P.



Suicide in psychiatric patients: A comparative study  

Microsoft Academic Search

Many factors held to be associated with suicide also apply to mental illness in general. An important question is whether psychiatric patients who commit suicide are distinguishable from other psychiatric patients. — In this study, a comparison was made between suicide psychiatric patients and randomly selected psychiatric patients from the same original patient group. The patients were compared concerning factors

Birgitta Rorsman



Locomotor training in paraplegic patients  

Microsoft Academic Search

Based on observations of the locomotor capacity of spinalized cat, recent studies indicate that spinal locomotor centres can also be activated and trained in complete and incomplete paraplegic patients. Patients with incomplete paraplegia profit from the training program so that their walking ability on a stationary surface improved. This article reviews the training effects on the locomotor pattern underlying this

V. Dietz; G. Colombo; L. Jensen



[Pyomyositis in an immunocompetent patient].  


We report a case of pyomyositis in a 59 year-old immunocompetent male patient caused by methicillin-susceptible Staphylococcus aureus. A CT scan of the chest demonstrated a lesion of the pectoral muscles. The patient was treated with surgical drainage and cephalexin. Pyomyositis is a rare and potentially serious infection that requires early recognition and prompt treatment. PMID:22689040

Baran, Ezequiel; Aguilera, Karina; Lorenzi, Luciana M; Simoneto, Raúl; Valuntas, Laura; Basso, Gabriel



Assessing Psychiatric Patients for Violence  

Microsoft Academic Search

Managing violent patients is a dilemma that every clinician faces. This article reviews the current literature and assesses the evidence on the management of violent patients in the clinical setting. Risk factors (dispositional, historical, contextual and clinical) and early warning signs of violence will be outlined. Understanding these issues will facilitate the short-term prediction and prevention of violence in clinical

Tanya R. Anderson; Carl C. Bell; Traci E. Powell; Johnny L. Williamson



Patient Relations and Workplace Communication.  

ERIC Educational Resources Information Center

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…

Career Resources Development Center, Inc., San Francisco, CA.


Patient education in pain control  

Microsoft Academic Search

Patients' concerns about reporting pain and using analgesics have been cited as major contributors to the problem of inadequate pain management. The purpose of this paper is to describe a program of research in which we have focused on these patient concerns, or as we refer to them, \\

S. Ward; S. Hughes; H. Donovan; R. Serlin



Marketing with a patient focus.  


Marketing is not a dirty word. It's a process that enables you to better understand the needs and wants of your patients. It's about listening and learning from your patients as a way to improve the care you provide. PMID:9415762

Wintersteen, L



Patient involvement in enhanced recovery.  


There are proven benefits of encouraging patients to play a more active role and take responsibility for their recuperation after all surgical procedures. This article explores the concept of enhanced recovery and the development of tools to support patients and health professionals in using an enhanced recovery pathway. PMID:23621082

Cottle, Sue; Wendy, Lewis


Dental Surgery in Anticoagulated Patients  

Microsoft Academic Search

ontinuous oral anticoagulant therapy has been used to decrease the risk of thrombo- embolism for more than half a century, prolonging the lives of thousands of patients. Many physicians recommend interrupting continuous anticoagulant therapy for den- tal surgery to prevent hemorrhage. In reviewing the available literature, there are no well-documented cases of serious bleeding problems from dental surgery in patients

Michael J. Wahl



Heart failure in elderly patients  

Microsoft Academic Search

Several structural and functional changes contribute to heart failure in elderly patients: an age dependent increase in sympathetic nervous activity, left ventricular wall diameter, myocardial fibrosis and apoptosis, micro- and macrovascular coronary sclerosis, aortic stiffness. As a consequence, diastolic, but also systolic heart failure is a frequent finding in elderly patients. The relation of systolic to diastolic heart failure is

Martin Spiecker



Virtual Patients in Geriatric Education  

ERIC Educational Resources Information Center

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…

Tan, Zaldy S.; Mulhausen, Paul L.; Smith, Stephen R.; Ruiz, Jorge G.



Industrial Robots for Patient Support  

NASA Astrophysics Data System (ADS)

Flexibility, precision, and capability to support the clinical workflow make robots the ideal choice for ion beam therapy (IBT) facilities for use in patient positioning. To fulfill the clinical needs in IBT, an industrial robot patient positioner needs to be carefully designed regarding applications and safety issues as well as precision and handling.

Sommer, Andres


Radiosensitivity in Fanconi's anemia patients  

Microsoft Academic Search

The risks of radiation therapy in patients with Fanconi's anemia who have cancer are not clear. Possible toxicity was reported in six of 14 patients: 1\\/1 with vaginal cancer, 4\\/10 with head and neck or esophageal cancer, and 1\\/3 with oral cancer following bone marrow transplant.

Blanche P Alter



Work design and patient safety  

Microsoft Academic Search

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

P. Carayon; C. J. Alvarado; A. Schoofs Hundt



Care of the AIDS patient  

Microsoft Academic Search

Treatment of the person dying from AIDS requires attention to the biological, psychological, and social aspects of the patient. Diagnostic and therapeutic interventions must be appropriate for the stage of the illness, the wishes of the patient, and the risk-benefit ratio of each particular situation.Symptom management requires familiarity with the multiple problems seen in persons with AIDS (PWA). Optimal treatment

Jerome Schofferman



Taste testing in renal patients  

Microsoft Academic Search

Taste is an important component of food palatability and thus influences appetite and food consumption. Decreased taste acuity has been reported to occur in patients with chronic uremia and may be one of the factors of poor nutrition. The present review focuses on both the methodology and publications of studies researching taste acuity in renal patients. The four qualities distinguished

Ingrid van der Eijk; Margaret A Allman Farinelli



Liver fibrosis in overweight patients  

Microsoft Academic Search

Background & Aims: A common clinical issue is whether overweight patients with abnormal liver function test results should undergo liver biopsy. Although serious liver injury can occur, its prevalence and risk factors are not well known. Methods: Ninety-three consecutive patients with abnormal liver function tests (but without overt liver disease), body mass index (BMI) > 25 kg\\/m2, and no alcoholic,

Vlad Ratziu; Philippe Giral; Frederic Charlotte; Eric Bruckert; Vincent Thibault; Ioannis Theodorou; Lina Khalil; Gérard Turpin; Pierre Opolon; Thierry Poynard



Patient Disclosure of Medical Misdeeds  

ERIC Educational Resources Information Center

|Modern patients walk a tightrope between respecting medical authority and acting as knowledgeable advocates regarding health issues, with the agency and responsibilities that come with this. This article uses conversation analysis to explore this balance in relation to patient disclosures of medical misdeeds in video-recorded primary care medical…

Bergen, Clara; Stivers, Tanya



JAMA Patient Page: Robotic Surgery  


... surgeon sits at a console and operates the robot’s arms, which in turn move tiny tools inside the patient’s body. ... or her hands and wrists more naturally. The robot can reduce tremors in the surgeon’s movements and is helpful for surgery ...


JAMA Patient Page: Medical Specialties  


... diseases of the nervous system) • Neurosurgery (surgery of the brain and nervous system) • Nuclear medicine (use of nuclear ... this and previous JAMA Patient Pages, go to the Patient Page link on JAMA ’s ... Janet M. Torpy, MD, Writer Alison E. Burke, MA, Illustrator Richard M. Glass, ...


Respite Use in Dementia Patients  

Microsoft Academic Search

Caregivers of dementia patients often find themselves physically and emotionally exhausted. Respite care can lend the primary caregiver support. However, utilization of such service has been low. This prospective study explored patterns of institutional respite utilization over a one year time period. Fifty-eight caregivers of dementia patients treated in an outpatient memory loss clinic participated. Forty percent used respite care

Geri Adler; Michael A. Kuskowski; James Mortimer



[Butyrylcholinesterase activity in schizophrenic patients].  


Butyrylcholinesterase (BChE) is an enzyme that has been investigated for its putative role in neurodegenerative and neuropsychiatric disorders. The aim of our work was to study BChE activity variations in schizophrenic patients and to investigate the involvement of this enzyme in schizophrenia and the importance of determining its activity in this disease. This cross-sectional study was carried out 131 (104 males and 27 females, mean age? = 38.0? ±? 11.4 years) patients with chronic schizophrenia according DSM-IV criteria and 90 (64 males and 26 females, mean age? = 37.1? ± ?15.9 years) healthy controls. Plasma BChE activity was determined by a kinetic method on Integra 400plus(TM) (Roche Diagnostics). Patients with schizophrenia had higher plasma BChE activity than controls (P?patients had higher BChE activity and smokers had lower BChE activity than non-smokers either in patients and controls. In patients with schizophrenia, BChE activity was not differed with age, alcohol status and clinical sub-types, and was not correlated to duration of illness. Concerning therapeutic features, BChE activity was higher in patients treated with antipsychotics monotherapy than those treated with an association of antipsychotic and anticholinergic drugs, without significant difference (P? = 0.196). Schizophrenic patients showed an increase BChE activity, which could be related to the pathophysiology of schizophrenia. PMID:22123563

Mabrouk, Hajer; Mechria, Haithem; Mechri, Anouar; Rahali, Houda; Douki, Wahiba; Gaha, Lotfi; Fadhel Najjar, Mohamed


Psychodynamics in medically ill patients.  


This article explores the role of psychodynamics as it applies to the understanding and treatment of medically ill patients in the consultation-liaison psychiatry setting. It provides historical background that spans the eras from Antiquity (Hippocrates and Galen) to nineteenth-century studies of hysteria (Charcot, Janet, and Freud) and into the twentieth century (Flanders Dunbar, Alexander, Engle, and the DSM). The article then discusses the effects of personality on medical illness, treatment, and patients' ability to cope by reviewing the works of Bibring, Kahana, and others. The important contribution of attachment theory is reviewed as it pertains the patient-physician relationship and the health behavior of physically ill patients. A discussion of conversion disorder is offered as an example of psychodynamics in action. This article highlights the important impact of countertransference, especially in terms of how it relates to patients who are extremely difficult and "hateful," and explores the dynamics surrounding the topic of physician-assisted suicide, as it pertains to the understanding of a patient's request to die. Some attention is also given to the challenges surrounding the unique experience of residents learning how to treat medically ill patients on the consultation-liaison service. Ultimately, this article concludes that the use and understanding of psychodynamics and psychodynamic theory allows consultation-liaison psychiatrists the opportunity to interpret the life narratives of medically ill patients in a meaningful way that contributes importantly to treatment. PMID:19968453

Nash, Sara Siris; Kent, Laura K; Muskin, Philip R



Carotid endarterectomy in conscious patient  

Microsoft Academic Search

Objective: To evaluate morbidity and mortality of carotid endarterectomy performed under regional cervical block, taking into account duration of surgery, use of shunt, conversion to general anesthesia, surgical complications, stay of patients in the intensive care unit (ICU) and in the hospital, and patients' evolution over one year. Methods: From June 1998 to January 2004, 67 operations were performed on

Paulo César SANTOS; Hélio Antônio FABRI; Cláudio Ribeiro da CUNHA; Carlos Alberto da Cunha; Jullyanna S. M. Shinosaki; Morais SHINOSAKI; Adriano Silva; Alexandre Menezes RODRIGUES



Interventions related to patient safety.  


Patient safety is a growing priority in today's increasingly complex, highly technologic, and business-oriented health care system. This increasing emphasis is being fueled by issues such as cost containment, risk management, quality assurance, health care consumer activism, and legal accountability for practice. In such an environment, it is important that nursing be able to quantify and communicate what it does to promote and maintain patient safety. A standardized language of patient safety interventions provides nursing with the tool to do this. It provides a common language to use when dealing with patient safety issues in the practice, education, research, and administrative arenas. It also allows nurses to package and market the "product" of nursing care to health care consumers, other health care professionals, hospital administrators, and politicians, all of whom share an interest in ensuring that patient safety is maintained and promoted in the most comprehensive yet cost-efficient manner possible. PMID:1584696

Kanak, M F



Mediating consolation with suicidal patients.  


Psychiatric nurses frequently encounter suicidal patients. Caring for such patients often raises ethical questions and dilemmas. The research question for this study was: 'What understandings are revealed in texts about consolation and psychiatric nurses' responses to suicidal patients?' A Gadamerian approach guided re-interpretation of published texts. Through synthesizing four interpretive phases, a comprehensive interpretation emerged. This revealed being 'at home' with self, or an ethical way of being, as a hermeneutic understanding of a way to become ready to mediate consolation with suicidal patients. Trustworthiness was addressed by means of the qualities of auditability, credibility and confirmability. This re-interpretation adds to nursing knowledge, enhances understanding of previous research findings, provides pre-understanding for further research and reveals the value of hermeneutic inquiry in nursing. It also deepens understanding of a published model of consolation. These understandings may help to guide nurses who are struggling with suicidal patients. PMID:17562733

Gilje, Fredricka; Talseth, Anne-Grethe



Lung Cancer in Younger Patients  

PubMed Central

Carcinoma of the lung is rare in younger patients, but occasional reports of this condition have appeared in the literature. This article reviews the clinical and pathological patterns of bronchogenic carcinoma in 96 patients, 40 years old or younger seen at UCLA (University of California, Los Angeles) Hospital between 1956 and 1976. This review confirms the finding in other reports of a higher proportion of women among younger patients with lung cancer as well as a relatively low incidence of squamous cell carcinoma. Using comparative data from the UCLA and California tumor registries, we could find no significant difference in survival of the younger patients when compared with the general population of patients with lung cancer.

Ganz, Patricia A.; Vernon, Stephen E.; Preston, Dale; Coulson, Walter F.



Orthostatic Intolerance Ambulation in Patients Using Patient Controlled Analgesia  

PubMed Central

Background Opioid analgesics are widely used to reduce postoperative pain and to enhance post-operative recovery. However, orthostatic intolerance (OI) induced by opioid containing intravenous patient controlled analgesia (IPCA) may hinder postoperative recovery. This study investigated factors that affect OI in patients receiving IPCA for postoperative pain control. Methods OI was instantly evaluated at the time of first ambulation in 175 patients taking opioid containing IPCA after open and laparoscopic subtotal gastrectomies. Patients were classified as having OI if they experienced dizziness, nausea/vomiting, blurred vision, headache, somnolence and syncope. Factors contributing to OI were assessed with logistic regression analysis. Results Out of 175 patients, 61 (52.6%) male and 44 (74.6%) female patients experienced OI at the time of first ambulation. The frequency of OI related symptoms were dizziness (97, 55.4%), nausea (46, 26.3%), headache (9, 5.1%), blurred vision (3, 1.7%) and vomiting (2, 1.1%). Significant risk factors for OI were gender (P=0.002) and total amount of opioids administered (P=0.033). Conclusions The incidence of OI is significantly higher in male than in female patients and is influenced by the opioid dose.

Park, Kwang Ok



Electronic reminders to patients within an interactive patient health record.  


Keeping patients with complex medical illnesses up to date with their preventive care and chronic disease management services, such as lipid testing and retinal exam in patients with diabetes, is challenging. Within a commercially available electronic health record (EHR) with a secure personal health record (PHR), we developed a system that sends up to three weekly reminders to patients who will soon be due for preventive care services. The reminder messages reside within the secure PHR, which is linked to the EHR, and are displayed on a screen where patients can also send to the physician's office an electronic message to request appointments for the needed services. The reminder messages stop when the patient logs on to review the reminders. The system, designed with patient input, groups together all services that will be due in the next 3 months to avoid repeatedly messaging the patient. After 2 months, the cycle of reminders begins again. This system, which is feasible and economical to build, has the potential to improve care and compliance with quality measures. PMID:23611639

Fischer, Gary S; Hess, Rachel; Landeen, Babette M; Weimer, Melissa; Zieth, Caroline R; Dong, Xinxin; Clark, Sunday; Roberts, Mark S



Heart failure in elderly patients.  


Several structural and functional changes contribute to heart failure in elderly patients: an age dependent increase in sympathetic nervous activity, left ventricular wall diameter, myocardial fibrosis and apoptosis, micro- and macrovascular coronary sclerosis, aortic stiffness. As a consequence, diastolic, but also systolic heart failure is a frequent finding in elderly patients. The relation of systolic to diastolic heart failure is clearly shifted towards diastolic heart failure in elderly patients, especially in women. Mortality is increased with systolic dysfunction in elderly patients compared to younger heart failure patients. Mortality is less with diastolic dysfunction, but still higher compared to elderly without heart failure. In addition, morbidity is increased both with diastolic and systolic heart failure in elderly patients. Cognitive dysfunction is a frequent finding. After exclusion of specific cardiac and extracardiac reasons for dyspnoea, drug therapy of systolic heart failure in elderly is similar to younger patients. However, the physiological decrease of renal function and the more frequent renal impairment in elderly patients with heart failure needs to be considered. Guideline recommendations for drug therapy are based in most cases on studies conducted in younger systolic heart failure patients. A recent meta-analysis of randomized beta-blocker trials suggests improved survival with beta-blockers even in the elderly subgroup. Guidelines for the treatment of diastolic heart failure are available only recently. The term heart failure with normal left ventricular ejection fraction (LVEF) has been proposed instead of diastolic heart failure. Given the increased morbidity and mortality in elderly patients with heart failure and normal LVEF, therapy should include general measures, such as physical activity, weight reduction, volume restriction. Specific therapy includes optimal control of systolic and diastolic blood pressure, diuretics, nitrates, and frequency-control. However, randomized trials evaluating the efficacy of specific therapies in heart failure with normal LVEF are still missing. PMID:16621389

Spiecker, Martin



Depression in iraqi hemodialysis patients.  


Introduction: Affective disorders, particularly depression, are the commonest and probably the most important psychopathological complication of end stage renal disease (ESRD). Depression has the potential to alter adversely the medical outcome of ESRD patients and the psychological stress can affect patient's adherence to medication regimen. In Iraq as well as many other Arab countries, the true prevalence of depression among ESRD patients is unknown. The objective of this study was to determine the prevalence of depression among a cohort of Iraqi hemodialysis (HD) patients and relate it to their socio-demographic characteristics. Methods: We recruited patients from two HD centers in Baghdad, excluding patients with history of depression or other psychiatric disorders prior to the initiation of HD. The Arabic version of diagnostic and statistical manual of mental disorders fourth edition (DSM-IV) was used to diagnose depression. Beck's Depression Inventory was used to grade its severity. Clinical and laboratory data of the study group were documented and related to the diagnosis of depression. Results: Seventy-five Iraqi patients on maintenance HD were included in the study. Patients' duration on HD ranged from six months to five years. The prevalence of depression among this cohort of HD patients was 80%. The prevalence of severe, moderate and mild depression was 25%, 50% and 25% respectively. The mean depression score was 17.1. Female gender, unemployment, and marital status had statistically significant associations with depression. Conclusion: Depression is common in this group of Iraqi HD patients and its prevalence is comparable to the results of similar studies in other societies. Keyword: Depression; ESRD; Hemodialysis; Iraq. PMID:24053743

Hamody, Abdul Raheem Taha; Kareem, Ali Kadhim; Al-Yasri, Abdul Rasoul Sultan; Sh Ali, Ala Abdul-Hussein



Helping patients discuss CINV management: development of a Patient Charter.  


In April 2012, an Expert Group of specialist cancer nurses working in a variety of settings (e.g. chemotherapy delivery, chemotherapy service design, research, nurse leadership and patient information/advocacy) participated in telephone/web-based meetings, with the aim of sharing current experience of chemotherapy-induced nausea and vomiting (CINV) management, and reaching a consensus on the development of a Patient Charter, designed to help patients understand CINV management, and setting out key questions they may wish to ask their healthcare professionals. PMID:23593098

Young, Annie; Dielenseger, Pascale; Fernandez Ortega, Paz; Fernandez Perez, Dolores; Jones, Philippa; Lennan, Elaine; O'Donovan, Eileen; Sharp, Sue; Whiteford, Alison; Wiles, Lilian



Celebrity Patients, VIPs, and Potentates  

PubMed Central

Background: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of “difficult” (personality-disordered) patients. Similar problems, however, surround other types of “special” patients. Method: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. Results: Three types of “special” patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. Conclusion: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are “special”—and by caregivers mending their own vulnerable self-esteem.

Groves, James E.; Dunderdale, Barbara A.; Stern, Theodore A.



Character traits of malodor patients.  


Many patients visit oral malodor clinics because of malodors which are brought to their attention by friends and family, or because they note the behavior of people around them, they suspect a problem and develop a fear of having an oral malodor. However, only around 30% of such patients actually have levels of malodor high enough to bother other people. Many patients exhibit halitophobia symptoms, which present as self-perception of malodor, and thus have a strong obsession about their smell which results in distress. Here, we carried out a study on 300 outpatients who visited the Tokyo Dental College Chiba Hospital Odor Clinic. We used the Tokyo University Egogram (TEG) to elucidate character traits of affected outpatients and compared the occurrence of TEG types in these patients with those of normal individuals. We discovered that 10.4% of patients were A-dominant type, which was 10.6% lower than the 21.0% of normal individuals. On the other hand, 18.4% of patients were N-type (NP high, FC low), which was 9.9% higher than the 8.5% of normal individuals. Results revealed that very few of the malodor outpatients exhibited the trait that shows intelligence, calm judgment, and self-affirmation, and as a result enjoy their life. Instead, many of these patients tended to show high levels of kindness and appeared to be holding themselves back and exercising patience. PMID:21986393

Sugiyama, Toshiko; Kameyama, Atsushi; Yamakura, Daiki; Morinaga, Kazuki; Tsunoda, Masatake



Intralobar sequestration in adult patients.  


We examined retrospectively the characteristics and the outcomes of intralobar sequestrations (ILS). We reviewed data we obtained from the medical records of patients with ILS who underwent surgery at Laennec, Georges Pompidou European, and Amiens South Hospital. From 1985 to 2010, 26 consecutive adults patients underwent surgery for ILS. There were 14 males and 12 females. The average age was 37.3 years. The ILS was right-sided in 11 patients (42.3%) and left-sided in 15 patients (57.7%). A systemic artery supply was found during the preoperative period in 11. Surgery consisted of lobectomy (n=20), bilobectomy (n=1), segmentectomy (n=4), and pneumonectomy (n=1). There were no postoperative deaths, and the postoperative course was uneventful in 20 patients. All patients were alive and faring well at long-term follow-up (mean follow-up 36.5 ± 7.2 months). Surgery consisted of lobectomy in most cases. The arterial supply came from the descending thoracic and abdominal aorta. Hemoptysis and/or recurrent infections were present in 14/26 (54%) of patients. These are the same symptoms as those leading to the diagnosis of bronchectasis. This suggests, for similar reasons, that ILS in adults should be nosologically very similar to acquired lesions, such as bronchectasis. PMID:21362733

Berna, Pascal; Cazes, Aurélie; Bagan, Patrick; Riquet, Marc



Mining time-dependent patient outcomes from hospital patient records.  


We describe REMIND, a data mining framework that accurately infers missing clinical information by reasoning over the entire patient record. Hospitals collect computerized patient records (CPR's) in structured (database tables) and unstructured (free text) formats. Structured clinical data in the CPR's is often poorly recorded, and information may be missing about key outcomes and processes. For instance, for a population of 344 colon cancer patients, important clinical outcomes, such as disease state and its evolution, are stored only as unstructured data (doctors' dictations) in the CPR. Raw evidence (extracted directly from the CPR) is not a good predictor of disease state. Yet by combining this evidence in a principled fashion (using methods from uncertain and temporal reasoning), REMIND accurately infers disease state sequences for recurrence, a complex time-varying outcome, for these patients. These outcomes can now be added back into the CPR in structured form. PMID:12463900

Rao, Bharat R; Sandilya, Sathyakama; Niculescu, Radu; Germond, Colin; Goel, A



Shader Lamps Virtual Patients: the physical manifestation of virtual patients.  


We introduce the notion of Shader Lamps Virtual Patients (SLVP) - the combination of projector-based Shader Lamps Avatars and interactive virtual humans. This paradigm uses Shader Lamps Avatars technology to give a 3D physical presence to conversational virtual humans, improving their social interactivity and enabling them to share the physical space with the user. The paradigm scales naturally to multiple viewers, allowing for scenarios where an instructor and multiple students are involved in the training. We have developed a physical-virtual patient for medical students to conduct ophthalmic exams, in an interactive training experience. In this experience, the trainee practices multiple skills simultaneously, including using a surrogate optical instrument in front of a physical head, conversing with the patient about his fears, observing realistic head motion, and practicing patient safety. Here we present a prototype system and results from a preliminary formative evaluation of the system. PMID:22357021

Rivera-Gutierrez, Diego; Welch, Greg; Lincoln, Peter; Whitton, Mary; Cendan, Juan; Chesnutt, David A; Fuchs, Henry; Lok, Benjamin



Patient Opinions Regarding 'Pay for Performance for Patients'  

PubMed Central

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.

Helweg-Larsen, Marie; Volpp, Kevin G.



Efficacy of patient-controlled analgesia in women cholecystectomy patients  

Microsoft Academic Search

The purpose of this comparative study was to examine differences in pain intensity, sleep disturbance, sleep effectiveness, fatigue, and vigor between patients undergoing cholecystectomy who received either patient-controlled analgesia (PCA) or intramuscular (IM) injections of narcotics for postoperative pain. The PCA group consisted of 16 women, aged 22–58; the IM group consisted of 10 women, aged 22–60. Data were collected

Adela Yarcheski



Older patients’ aversion to antidepressants  

Microsoft Academic Search

BACKGROUND: Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known\\u000a to affect treatment initiation and adherence, but are often not expressed in clinical settings.\\u000a \\u000a \\u000a OBJECTIVE: To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment.\\u000a \\u000a \\u000a \\u000a \\u000a DESIGN. Cross-sectional, qualitative study utilizing semi-structured interviews.\\u000a \\u000a \\u000a \\u000a \\u000a PARTICIPANTS: Primary care patients

Catherine J. Datto; Katy Ruckdeschel; Kathryn Knott; Cynthia Zubritsky; David W. Oslin; Soumya Nyshadham; Poornima Vanguri; Frances K. Barg



[Psychotherapeutic treatment of borderline patients].  


The author gives in this paper an overview of current psychodynamic psychotherapy of patients with Borderline personality organization. Parallel to his own concept different treatment strategies by Adler, Volkan and Searles within the psychoanalytic framework are discussed. Finally recent developments of his own group are described. Emphasis lies on structuring the psychodynamic psychotherapeutic process of Borderline patients according to the developmental level the patient presents in each session and to treat symptoms belonging to so-called earlier levels (e.g primitive aggression, psychotic or paranoid transferences) before working through of more advanced conflicts. PMID:7761569

Kernberg, O F


Do turf wars kill patients?  


While physicians are often heard to complain that they are overworked with a heavy patient burden, so-called turf wars lurk under the surface, wherein physicians wrangle for the ability to perform what are generally highly-remunerated and quickly-performed procedures and interventions with excellent patient outcomes. It is very possible that within such turf wars, one specialty is consistently more skilled at performing the procedure than another, and therefore patient lives may be unnecessarily lost. This article hypothesizes that such differences in skills do exist between specialties and proposes a study to determine this. PMID:17521053

Baerlocher, Mark O



Alprazolam dependence in seven patients.  


The authors report on seven patients who met the DSM-III-R criteria for psychoactive substance (alprazolam) dependence. All had withdrawal symptoms, six demonstrated tolerance, and at least four had substantial social or occupational impairment secondary to drug use. All seven patients had begun taking alprazolam as treatment for anxiety or depression. Six patients abused other drugs or alcohol, either in the past or concurrently. Doses of alprazolam ranged from 2 to 12 mg/day, and duration of use was 6 months to 3 years. The potential for dependence should be considered when prescribing alprazolam. PMID:3258735

Juergens, S M; Morse, R M



Enteral Nutrition in Surgical Patients  

Microsoft Academic Search

.\\u000a Abstract.  \\u000a \\u000a \\u000a Purpose:   Malnutrition is well-recognized as a potential cause of increased morbidity and mortality in surgical patients; however,\\u000a enteral and parenteral nutritional support given pre- and postoperatively have been shown to decrease these rates. We conducted\\u000a a prospective study to assess the short-term efficacy of oral dietary supplementation in malnourished patients undergoing\\u000a major abdominal surgery.\\u000a \\u000a \\u000a \\u000a Methods:   Sixty patients undergoing

Sundeep Singh Saluja; Navneet Kaur; Upendra Kumar Shrivastava



Patient Navigation for Underserved Patients Diagnosed with Breast Cancer  

PubMed Central

The elimination of cancer disparities is critically important for lessening the burden of breast cancer (BC). Patient navigator programs (PNPs) have been shown to improve rates of BC screening in underserved communities, but there is a dearth of evidence regarding their benefits after the actual diagnosis of BC. We retrospectively examined sociodemographic characteristics, disease characteristics, and concordance to quality measures (QMs) of BC care among women participating in a PNP that services disadvantaged minority communities in the greater Boston area. Of the 186 PNP patients diagnosed with BC in 2001–2011 in three neighborhood community health centers, treatment data was available for 158 (85%) and race and disease stage information was available for 149 (80%). Regarding stage, 25% were diagnosed with in situ cancer, 32% had stage 1, 25% had stage 2, 13% had stage 3, and 5% had stage 4 BC. Guideline-indicated care was received by 70 of 74 patients (95%) for the hormonal therapy QM, 15 of 17 (88%) patients for the chemotherapy QM, and 65 of 71 (92%) patients for the radiation QM, all similar to published concordance rates at elite National Comprehensive Cancer Network institutions. These findings suggest that PNPs may facilitate evidence-based quality care for vulnerable populations. Future research should prospectively analyze quality metrics to assess measures to improve the process and outcomes of patient navigation in diverse underserved settings, compared with control non-navigated populations.

Raj, Aparna; Ko, Naomi; Battaglia, Tracy A.; Chabner, Bruce A.



Infection and the Burn Patient.  

National Technical Information Service (NTIS)

Burn patient survival has significantly increased during the past four decades as hypovolaemic shock, acute renal failure, invasive bacterial burn wound infection, Curling's ulcer, and metabolic wasting have been controlled by timely adequate resuscitatio...

B. A. Pruitt



Corneal Protection for Burn Patients.  

National Technical Information Service (NTIS)

The overall goal of this research is to preserve vision of patients recovering from severe facial burns by providing an improved method to reduce development of corneal defects, inflammation, infection and opacification. Scope: To further improve and unde...

I. E. Kochevar



Fluconazole Pharmacokinetics in Burn Patients  

PubMed Central

The pharmacokinetics of fluconazole in nine adult patients with severe (30 to 95% total body surface area) burns were studied. There was no significant difference in half-life (t1/2), clearance (CL), or volume of distribution (V) over time in five patients on days 3 and 8 of the study (P > 0.05). Combined parameter estimates (means ± standard deviations) for all nine patients for the two study periods were as follows: t1/2, 24.4 ± 5.8 h; CL, 0.36 ± 0.09 ml/min/kg; and V, 0.72 ± 0.12 liters/kg. These estimates of t1/2 and CL in burn patients were approximately 13% shorter and 30% more rapid, respectively, than the most extreme estimates reported for other populations.

Boucher, Bradley A.; King, Stephen R.; Wandschneider, Heidi L.; Hickerson, William L.; Hanes, Scott D.; Herring, Vanessa L.; Canada, Todd W.; Hess, Mary M.



There are No Routine Patients.  

National Technical Information Service (NTIS)

The importance of examining behavioral-response patterns of elderly and / or chronically ill patients on an individualized basis is stressed in a discussion concerned with the application of nursing skills and knowledge in skilled nursing care facilities....

G. J. Alfano



Transfusion medicine in trauma patients  

PubMed Central

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.

Murthi, Sarah B; Dutton, Richard P; Edelman, Bennett B; Scalea, Thomas M; Hess, John R



JAMA Patient Page: Aortic Aneurysms  


... of the American Medical Association JAMA PATIENT PAGE Aortic Aneurysms T he aorta is the body’s largest artery ... wall that may stretch and bulge outwards. An aortic aneurysm is a stretched and bulging section in the ...


Neurocognitive dysfunction in cancer patients.  


Many cancer patients experience impairments of neurocognitive function, including memory loss, distractibility, difficulty in performing multiple tasks (multitasking), and a myriad of other symptoms. Patients may also concurrently suffer from mood disturbance and symptoms that compromise their ability to function adequately, including fatigue and pain. The etiologies of these problems are diverse and include the direct effects of cancer within the central nervous system (CNS), indirect effects of certain cancers (e.g., paraneoplastic brain disorders), and both diffuse and highly specific effects of cancer treatments on the brain. In addition to these cancer-related causes, patients may have coexisting neurologic or psychiatric disorders that affect their cognition and mood. Careful assessment of patients complaining of neurocognitive or behavioral problems is essential to providing appropriate interventions and maximizing their ability to carry out usual activities. PMID:10680150

Meyers, C A




Microsoft Academic Search

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.

Gunter Janetschek; Jorg Seibold; Christian Radmayr; Georg Bartsch



JAMA Patient Page: Lung Cancer  


... of the American Medical Association JAMA PATIENT PAGE Lung Cancer L ung cancer is the leading cause of ... CT) screening for lung cancer. RISK FACTORS FOR LUNG CANCER FOR MORE INFORMATION • American Cancer Society www.cancer. ...


JAMA Patient Page: Bed Bugs  


... of the American Medical Association JAMA PATIENT PAGE Bed Bugs B ed bugs, Cimex lectularius , have been around ... which thrives in temperate and tropical regions worldwide. Bed bugs are exclusively hematophagous (they feed only on blood). ...


Angle closure in younger patients  

Microsoft Academic Search

PurposeAngle-closure glaucoma is rare in children and young adults; only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients aged 40 or younger with angle closure in our database.

Robert Ritch; Brian M Chang; Jeffrey M Liebmann



Herpesvirus Infection in Burned Patients.  

National Technical Information Service (NTIS)

Herpesvirus hominis infection of healing partial-thickness burns occurred in six patients. Two of these died with disseminated herpetic infection. They had necrotizing hepatic and adrenal lesions, similar to those that have been described in herpetic infe...

F. D. Foley K. A. Greenawald G. Nash B. A. Pruitt



JAMA Patient Page: Brain Death  


... the American Medical Association JAMA PATIENT PAGE Brain Death A person dies when brain function ceases, the ... techniques that can maintain some bodily functions. Brain death, as understood in US law and medical practice, ...


JAMA Patient Page: Myocardial Infarction  


... of the American Medical Association JAMA PATIENT PAGE Myocardial Infarction M yocardial infarction , also known as a heart attack, can strike without warning. A myocardial infarction occurs when blood supply to a part of ...


JAMA Patient Page: Cystic Fibrosis  


... the American Medical Association JAMA PATIENT PAGE Cystic Fibrosis C ystic fibrosis (CF) is a genetic (inherited) disease that affects ... the CF gene, that child will develop cystic fibrosis and can also pass the CF gene on ...


Examination of the adolescent patient.  


Adolescent patients need knowledge and motivation to practice a healthy lifestyle. The provider of adolescent health care is uniquely qualified to provide factual health information and practical advice. Enlisting parental support for confidential adolescent health services usually is not problematic when parents and health care providers share common goals and responsibility. The health care provider must develop rapport to foster high-risk health behavior disclosure and must promote health messages that are stronger than those received from peers, television, movies, and magazines. Adolescents who elect to abstain from sexual activity need as much support as sexually active patients. Depression, substance abuse, and eating disorders must be recognized and treated. Preventative health care services for adolescents can be optimized when office staff understand the special needs of these young women. The physician's concerns regarding the health of adolescent patients will be welcomed by patients, their parents, and the community. PMID:10693179

Hampton, H L



Patients, physicians, and the Internet.  


The Internet will have a profound effect on the practice and business of medicine. Physicians, eager to provide high-quality care and forced by competition to offer online services, will introduce e-mail and patient-friendly Web sites to improve administrative services and manage common medical conditions. Patients will identify more health information online and will take more responsibility for their care. The doctor/patient relationship will be altered: Some aspects of electronic communication will enhance the bond, and others will threaten it. Patients will have access to vast information sources of variable validity. Many physician organizations are preparing for the electronic transformation, but most physicians are unprepared, and many are resistant. PMID:11192394

Kassirer, J P


JAMA Patient Page: Periodontal Disease  


... into the gum tissue itself. FOR MORE INFORMATION American Dental Association National Institute of Dental ... Sources: National Institute of Dental and Craniofacial Research, American Dental Association, American Heart Association The JAMA Patient Page is ...


Corneal Protection for Burn Patients.  

National Technical Information Service (NTIS)

The overall goal of this research is to preserve vision of patients recovering from severe facial burns by providing an improved method to reduce development of corneal defects, inflammation, infection and opacification. Scope: To further improve and unde...

A. J. Johnson



Corneal Protection for Burn Patients.  

National Technical Information Service (NTIS)

Purpose: The overall goal of this research is to preserve vision of patients recovering from severe facial burns by providing an improved method to reduce development of corneal defects, inflammation, infection and opacification. Scope: In this reporting ...

I. E. Kochevar



JAMA Patient Page: Achilles Tendinopathy  


... the American Medical Association JAMA PATIENT PAGE Achilles Tendinopathy A tendon is a tough band of tissue ... come to mean a person’s principal weakness. Achilles tendinopathy is a common overuse injury, accounting for 11% ...


Repetition blindness in schizophrenic patients.  


Repetition blindness is the failure to report the detection of repeated items in rapid visually presented lists. It can be explained in terms of either a processing limitation or an active inhibitory process. In two studies conducted in either English or German language we set out to induce repetition blindness under various conditions in a total of 47 control subjects and 30 schizophrenic patients. The patients displayed the phenomenon to at least the same degree as normal control subjects. These results render unlikely accounts of repetition blindness which involve processes known to be dysfunctional in schizophrenic patients. Moreover, the study provides an example of how the performance of schizophrenic patients can constrain theories of normal cognition. PMID:9728732

Kammer, T; Saleh, F; Oepen, G; ManschreckT; Seyyedi, S; Kanwisher, N; Furmanski, C; Spitzer, M



JAMA Patient Page: Pulmonary Hypertension  


... the American Medical Association JAMA PATIENT PAGE Pulmonary Hypertension T he pulmonary artery is the main vessel ... mercury (mm Hg). In an individual with pulmonary hypertension , the average pressure in the pulmonary artery can ...


JAMA Patient Page: General Anesthesia  


... is provided by anesthesiologists (medical doctors with specialized education in the evaluation and care of patients before, during, and after surgery, including pain management), certified registered nurse anesthetists ... in the administration of anesthesia), and anesthesiologist assistants ( ...


From Test Tube To Patient  

Center for Drug Evaluation (CDER)

Text VersionPage 1. FDA Home Page | Search FDA Site | FDA AZ Index | Contact FDA From Test Tube To Patient From Test Tube To ... More results from


Processing Requests for Patient Data

This document describes general policies of the NCI funded cancer Cooperative Groups on providing individual patient data to investigators for use in research projects. Each group will have a more detailed set of procedures implementing the general policy.


How patients make treatment choices.  


The medical field has undergone a quiet revolution during the past three decades. Patients have been brought into the treatment decision process as never before. Gone are the days when the patient was delivered the diagnosis and simply told how their disorder was to be treated. Rather, widespread use of shared decision making has changed the way that patients and their physicians interact. The development of best clinical practices from concepts of evidence-based medicine has shown that, for many disorders, the various treatment options result in near-equivalent outcomes. More recently, the democratization of medical information by the internet has made the patient a much better informed consumer, and thus a more active participant in his or her own care. PMID:18682718

Hellenthal, Nicholas; Ellison, Lars



Psychotherapy with terminally ill patients  

Microsoft Academic Search

This study investigated the effectiveness of a psychotherapeutic technique, logotherapy, with terminally ill patients. Twenty male Veterans Administration volunteers were randomly assigned to one of two possible treatment conditions: (a) treatment group or (b) delayed-treatment, control group. Patients participating in the original treatment group received eight forty-five-minute sessions of psychotherapy over a two-week interval. Pre- and post-treatment measures were taken

Terry E. Zuehlke; John T. Watkins



Elderly patients also have rights  

Microsoft Academic Search

Background:Sharing information with relatives of elderly patients in primary care and in hospital has to fit into the complex set of obligations, justifications and pressures concerning the provision of information, and the results of some studies point to the need for further empirical studies exploring issues of patient autonomy, privacy and informed consent in the day-to-day care of older people.Objectives:To

M D Pérez-Cárceles; M D Lorenzo; A Luna; E Osuna



Strategic interventions with involuntary patients.  


For successful treatment of involuntary patients who resist change, therapists from all schools of thought use numerous interventions. A variety of interventions, from the general strategic therapy approach to tactics for dealing with specific behavioral symptoms, are described. Strong emphasis in applying interventions is placed on the therapist's controlling the therapeutic relationship and establishing the patient's responsibility for his behaviors. Guidelines are also given for the effective use of interventions and the precautions in applying them. PMID:7419178

Wathney, S; Baldridge, B



Alexithymia in chronic urticaria patients  

Microsoft Academic Search

Alexithymia has been described as an important dimension in several medical and psychiatric diseases. Chronic urticaria (CU) is a chronic condition, in which treatment is difficult. Our aim is to determine the prevalence of alexithymia traits in patients with CU, and to identify the relationships between alexithymia and psychological variables and quality-of-life dimensions. Fifty-five sequential CU patients in a faculty

Filipe Barbosa; João Freitas; Antonio Barbosa