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Sample records for adult gm2 gangliosidosis

  1. Electroconvulsive therapy treatment of depression in a patient with adult GM2 gangliosidosis.

    PubMed

    Renshaw, P F; Stern, T A; Welch, C; Schouten, R; Kolodny, E H

    1992-03-01

    Adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underlying gangliosidosis. We report the successful use of electroconvulsive therapy for treatment of severe depression in a young man with adult GM2 gangliosidosis. PMID:1386210

  2. [Adult GM2 gangliosidosis: improvement of ataxia with GABAergic drugs].

    PubMed

    Gazulla Abío, J; Benavente Aguilar, I

    2002-03-01

    The authors present a case of adult GM2 gangliosidosis, B1 enzymatic type. The main clinical features found were cerebellar ataxia, proximal lower limb weakness and myokymia. The neurological examination, and the biochemical, electrophysiologic and imaging studies are all described. Decreased activity of the enzyme beta-hexosaminidase A in the metabolism of the sulfate substrate 4-MU-NAGS was found in serum. Global cerebellar atrophy was observed in a cranial nuclear magnetic resonance. The electrophysiologic study showed continuous spontaneous activity integrated by myokymia and neuromyotonic discharges in addition to signs of acute and chronic denervation. Disappearance of the myokymia and improvement in the ataxia were attained with the use of the GABAergic drugs gabapentin and tiagabine. The authors try to explain the clinical improvement obtained with the drugs by relating their mechanisms of action to the central nervous system neurotransmitter alterations proposed for this disease. PMID:11927106

  3. Post-partum psychosis in adult GM2 gangliosidosis. A case report.

    PubMed

    Lichtenberg, P; Navon, R; Wertman, E; Dasberg, H; Lerer, B

    1988-09-01

    Adult hexosaminidase A deficiency is a form of GM2 gangliosidosis with autosomal recessive inheritance. Only 35 cases (mostly among Ashkenazic Jews) have been reported worldwide. Symptoms include, in a third of the cases, psychosis. A 27-year-old sufferer with no prior psychiatric history, developed a post-partum psychosis, with affective and hebephrenic components, 3 days following her first delivery. She responded to lithium within 10 days of initiating treatment; the full episode lasted 1 month. We conclude that lithium is the preferred treatment for psychosis in such adult patients, especially in light of possible long-term neurological deterioration caused by phenothiazines. Ashkenazic Jews with atypical neurological syndromes presenting with psychosis should be tested for hexosaminidase A deficiency. PMID:2977954

  4. Natural History of Infantile GM2 Gangliosidosis

    PubMed Central

    Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.

    2011-01-01

    OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. PMID:22025593

  5. Late-onset GM2 gangliosidosis presenting as burning dysesthesias.

    PubMed

    Chow, G C; Clarke, J T; Banwell, B L

    2001-07-01

    Two brothers with a painful neuropathy as a component of late-onset GM2 gangliosidosis of the Sandhoff type are presented. A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis. PMID:11483398

  6. GM2 gangliosidosis in British Jacob sheep.

    PubMed

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

    2014-01-01

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

  7. Progressive dystonia symptomatic of juvenile GM2 gangliosidosis.

    PubMed

    Nardocci, N; Bertagnolio, B; Rumi, V; Angelini, L

    1992-01-01

    A 9-year-old boy showed a progressive generalized dystonia, with onset at the age of 4 years, combined with mental deterioration and behavioral disturbances. The values of beta-hexosaminidase activities studied in plasma, leukocytes, and fibroblasts obtained using two different substrates (MUG-NAc and MUG-NAc-6-S) were significantly reduced but higher than in Tay-Sachs disease and similar to those found in the juvenile chronic form of GM2 gangliosidosis. With anticholinergic therapy, for 1.5 years, the dystonic symptoms did not progress and the boy can still care for himself and attend school. The description of another case of the disease, clinically expressed as dystonia, corroborates the existence of a dystonic phenotype of GM2 gangliosidosis. PMID:1532632

  8. [Recent advances in molecular genetics of GM2 gangliosidosis].

    PubMed

    Wakamatsu, N

    1995-12-01

    Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2 gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two catalytically active forms of this enzyme: Hex A, composed of one alpha and one beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency, have been recognized according to whether the defect involves the alpha subunit, beta subunit, or GM2 activator protein, respectively. A number of gene abnormalities responsible for the disease have been identified and mutations specific for phenotypes and racial backgrounds are summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff disease have been produced. With the finding of dramatically clinical phenotypes in these mice, these models could be useful for research on the pathogenesis or therapy of these diseases. PMID:8577047

  9. Pathology of GM2 gangliosidosis in Jacob sheep.

    PubMed

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

    2011-07-01

    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

  10. Animal models of GM2 gangliosidosis: utility and limitations

    PubMed Central

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  11. Animal models of GM2 gangliosidosis: utility and limitations.

    PubMed

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  12. Substrate reduction therapy in juvenile GM2 gangliosidosis.

    PubMed

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

    2009-01-01

    Substrate reduction therapy (SRT) is considered to be a potential therapeutic option for juvenile GM2 gangliosidosis (jGM2g). We evaluated the efficacy of SRT in jGM2g, assessing neurological, neuropsychological and brain magnetic resonance imaging (MRI) outcomes over a 24-month period of treatment. In an open-label and single-center study, five jGM2g patients (mean age 14.6+/-4.5 years) received oral miglustat at doses of 100-200mg t.i.d. adjusted to body surface area. Patients underwent general and neurological examinations, neuropsychological, electrophysiological, and brain MRI studies. All patients showed neurological deterioration over the period of the study, with particularly notable worsening of gait, speech and coordination. One patient experienced acute psychosis, and another showed worsening of pre-existing epilepsy. Some neuropsychological tests showed no evidence of deterioration in the three patients with high enough cognitive functioning for reliable assessment. Profound cognitive impairment in two children precluded neuropsychological evaluation. In four patients, evaluation of brain MRI showed no changes in white matter signal abnormalities and cerebellar atrophy noted at baseline, while one patient showed progression of cerebellar and supratentorial brain atrophy. Transmission electron microscopy analysis of peripheral mononuclear cells showed reduction of intracytoplasmatic inclusions with treatment. SRT with miglustat of patients with jGM2g failed to ameliorate progressive neurological deterioration, but apparently no worsening of some areas of cognitive function tested and brain MRI lesions was noted over 24 months of treatment. The results must be interpreted with care owing to the small sample of patients and the lack of a control-arm. PMID:19595619

  13. Juvenile-onset G(M2)-gangliosidosis in an African-American child with nystagmus.

    PubMed

    Paciorkowski, Alex R; Sathe, Swati; Zeng, Bei-Jin; Torres, Paola; Rosengren, Sally S; Kolodny, Edwin

    2008-04-01

    G(M2)-gangliosidosis is a neurodegenerative lysosomal disease with several clinical variants. We describe a 2-year-old black child with juvenile-onset disease, who presented with abnormal eye movements and cherry-red spots of the maculae. Mutation analysis of the HEXA gene revealed the patient to be a compound heterozygote (M1V/Y37N). The M1V mutation was previously described in an African-American child with acute infantile G(M2)-gangliosidosis. The Y37N mutation is novel. This combination of mutations is consistent with juvenile-onset disease, and provides further evidence for the association of the M1V mutation with individuals of black ancestry. The presence of oculomotor abnormalities is an unusual finding in this form of G(M2)-gangliosidosis, and adds to the phenotypic spectrum. PMID:18358410

  14. Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.

    PubMed

    Kornfeld, M

    2008-01-01

    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

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

    PubMed

    Tsuji, Daisuke

    2013-01-01

    Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-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 (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ 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

  16. Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

    PubMed

    Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

    2013-09-25

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

  17. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.

    PubMed

    Kitakaze, Keisuke; Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi; Itoh, Kohji

    2016-05-01

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

  18. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

    PubMed Central

    Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi

    2016-01-01

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

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

    PubMed

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

    2011-06-01

    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

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

    PubMed

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

    2007-03-23

    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

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

    PubMed

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

    2009-08-01

    GM2 gangliosidosis (GM2g) is an inherited neurodegenerative disorder caused by deficiency of lysosomal beta-hexosaminidase A, resulting in accumulation of GM2 ganglioside, principally in the brain. Substrate reduction therapy is currently under investigation as a treatment. The study investigated the pharmacokinetics and safety of miglustat given as single and multiple doses in infantile and juvenile GM2g patients for 6- and 24-months, respectively. Eleven patients with infantile (n = 6) and juvenile (n = 5) GM2g received oral miglustat at 30-200 mg t.i.d. adjusted to the body surface area. Patients underwent pharmacokinetic assessments on day 1 and at month 3. The pharmacokinetics of miglustat were described by a 2-compartmental model with a lag time, median time to maximum concentration of 2.5 h, and terminal half-life of about 10 h. The pharmacokinetics were time-independent, and did not differ between infantile and juvenile cohorts. The accumulation index was 1.7. Among infantile GM2g patients, the major drug-related adverse events (DRAEs) were abdominal discomfort and flatulence. In the juvenile group, however, the major DRAEs observed were diarrhea and weight loss. One juvenile patient developed peripheral neuropathy, and others showed progression of already established neuropathy, which was judged to be part of the natural progression of the disease. Some mild laboratory abnormalities observed were either transient or attributable to concomitant medications. Miglustat showed similar pharmacokinetic parameters in all patients, with no specific difference between infantile and juvenile forms. Miglustat was shown to be a safe drug, with mild to moderate diarrhea, as an age-dependent DRAE, which was controlled by dietary modification. PMID:19447653

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

    PubMed

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

    2013-01-01

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

  3. Juvenile GM2 gangliosidosis (AMB variant): inability to activate hexosaminidase A by activator protein.

    PubMed Central

    Inui, K; Grebner, E E; Jackson, L G; Wenger, D A

    1983-01-01

    Two sibling from a consanguineous Puerto Rican marriage were found to have a juvenile-onset type of lipidosis first noted at age 2 1/2 by expressing difficulties with motor function and developmental delay. They continued to deteriorate, showing muscle atrophy, spasticity, and loss of speech, and death occurred at ages 7 and 8. Examination of the brains from these patients revealed that the concentration of GM2 ganglioside was about 56% of the total gangliosides. Hexosaminidase and percent hexosaminidase A (HEX A) and other lysosomal enzymes were normal in cultured skin fibroblasts, liver, and brain. The concentration of the activator protein required for the enzymatic hydrolysis of GM2 ganglioside was in high normal levels in the brain of the patient available. However, the HEX A from the patient's brain and liver as well as from skin fibroblast lysates could not be activated to hydrolyze GM2 ganglioside by the activator protein from a control or himself. The HEX A from a control could be activated by the activator protein from controls or this patient. These patients appear to have a defect in HEX A, which does not affect it heat stability, electrophoretic migration, and activity toward fluorogenic substrates, but may affect the binding of the activator protein required for GM2 ganglioside hydrolysis. We propose to call these patients the AMB variant of GM2 gangliosidosis to denote the mutation in HEX A but with normal levels of HEX A and B with synthetic substrates. This is to distinguish these patients from those missing the activator protein and normal HEX A and B levels. Images Fig. 1 Fig. 2 PMID:6224417

  4. PYRIMETHAMINE AS A POTENTIAL PHARMACOLOGICAL CHAPERONE FOR LATE-ONSET FORMS OF GM2 GANGLIOSIDOSIS

    PubMed Central

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

    2007-01-01

    Late-onset GM2-gangliosidosis (GM2) is composed of two related, autosomal recessive, neurodegenerative diseases, both resulting from deficiency of lysosomal, heterodimeric β-hexosaminidase A (Hex A, αβ). 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 ER. To date all successful PCs have also been competitive inhibitors. Screening for Hex A inhibitors in a library of 1040 FDA-approved compounds identified pyrimethamine (PYR) as the most potent inhibitor. Cell lines from 10 late-onset Tay-Sachs (11 α-mutations, 2 novel), and 7 Sandhoff (9 β-mutations, 4 novel) disease patients, were cultured with PYR at concentrations corresponding to therapeutic doses. Cells carrying the most common late-onset mutation, αG269S, showed significant increases in residual Hex A activity, as did all 7 of the β-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 α-subunit. PYR, which binds to the active site in domain II, was able to function as PC even to domain I β-mutants. We concluded that PYR functions as a mutation-specific PC, variably enhancing residual lysosomal Hex A levels in late-onset GM2 patient cells. PMID:17237499

  5. The AB-variant of GM2-gangliosidosis. Clinical, biochemical, and pathological studies of two patients.

    PubMed

    Goldman, J E; Yamanaka, T; Rapin, I; Adachi, M; Suzuki, K; Suzuki, K

    1980-01-01

    Clinical, neuropathological, and biochemical studies are reported in two children with the AB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1--1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-beta-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases. PMID:6255724

  6. Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up.

    PubMed

    Masciullo, Marcella; Santoro, Massimo; Modoni, Anna; Ricci, Enzo; Guitton, Jerome; Tonali, Pietro; Silvestri, Gabriella

    2010-12-01

    GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease. PMID:20821051

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

    PubMed

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

    2015-05-01

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

  8. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

    PubMed

    Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

    2016-04-01

    Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. PMID:26286102

  9. The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

    PubMed Central

    Maegawa, Gustavo H. B.; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T. R.

    2010-01-01

    OBJECTIVE Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. METHODS A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, β-hexosaminidase enzyme activity, and mutation analysis was collected. RESULTS In our cohort of patients, the mean (±SD) age of onset of symptoms was 5.3 ± 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 ± 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 ± 5.5 years. The mean age of onset of speech problems was 7.0 ± 5.6 years, with a mean time of progression to anarthria of 5.6 ± 5.3 years. Muscle wasting (10.6 ± 7.4 years), proximal weakness (11.1 ± 7.7 years), and incontinence of sphincters (14.6 ± 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence

  10. Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

    PubMed Central

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

    2011-01-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-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

  11. Mechanism of abnormal growth in astrocytes derived from a mouse model of GM2 gangliosidosis.

    PubMed

    Kawashima, Nagako; Tsuji, Daisuke; Okuda, Tetsuya; Itoh, Kohji; Nakayama, Ken-ichi

    2009-11-01

    Sandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes the beta-subunit of N-acetyl-beta-hexosaminidase A and B, resulting in the accumulation of the ganglioside GM2. We isolated astrocytes from the neonatal brain of Sandhoff disease model mice in which the N-acetyl-beta-hexosaminidase beta-subunit gene is genetically disrupted (ASD). Glycolipid profiles revealed that GM2/GA2 accumulated in the lysosomes and not on the cell surface of ASD astrocytes. In addition, GM3 was increased on the cell surface. We found remarkable differences in the cell proliferation of ASD astrocytes when compared with cells isolated from wild-type mice, with a faster growth rate of ASD cells. In addition, we observed increased extracellular, signal-regulated kinase (ERK) phosphorylation in ASD cells, but Akt phosphorylation was decreased. Furthermore, the phosphorylation of ERK in ASD cells was not dependent upon extracellular growth factors. Treatment of ASD astrocytes with recombinant N-acetyl-beta-hexosaminidase A resulted in a decrease of their growth rate and ERK phosphorylation. These results indicated that the up-regulation of ERK phosphorylation and the increase in proliferation of ASD astrocytes were dependent upon GM2/GA2 accumulation. These findings may represent a mechanism in linking the nerve cell death and reactive gliosis observed in Sandhoff disease. PMID:19765188

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

    PubMed

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

    2011-06-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-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

  13. Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

    PubMed

    Muldoon, L L; Neuwelt, E A; Pagel, M A; Weiss, D L

    1994-05-01

    The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy. PMID:8178934

  14. Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis.

    PubMed

    Jeyakumar, M; Thomas, R; Elliot-Smith, E; Smith, D A; van der Spoel, A C; d'Azzo, A; Perry, V Hugh; Butters, T D; Dwek, R A; Platt, F M

    2003-04-01

    Mouse models of the GM2 gangliosidoses [Tay-Sachs, late onset Tay-Sachs (LOTS), Sandhoff] and GM1 gangliosidosis have been studied to determine whether there is a common neuro-inflammatory component to these disorders. During the disease course, we have: (i) examined the expression of a number of inflammatory markers in the CNS, including MHC class II, CD68, CD11b (CR3), 7/4, F4/80, nitrotyrosine, CD4 and CD8; (ii) profiled cytokine production [tumour necrosis factor alpha (TNF alpha), transforming growth factor (TGF beta 1) and interleukin 1 beta (IL1 beta)]; and (iii) studied blood-brain barrier (BBB) integrity. The kinetics of apoptosis and the expression of Fas and TNF-R1 were also assessed. In all symptomatic mouse models, a progressive increase in local microglial activation/expansion and infiltration of inflammatory cells was noted. Altered BBB permeability was evident in Sandhoff and GM1 mice, but absent in LOTS mice. Progressive CNS inflammation coincided with the onset of clinical signs in these mouse models. Substrate reduction therapy in the Sandhoff mouse model slowed the rate of accumulation of glycosphingolipids in the CNS, thus delaying the onset of the inflammatory process and disease pathogenesis. These data suggest that inflammation may play an important role in the pathogenesis of the gangliosidoses. PMID:12615653

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

    PubMed

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

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-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 β-hexosaminidase α (HEXA) and β (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 β-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

  16. Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice.

    PubMed

    Osmon, Karlaina J L; Woodley, Evan; Thompson, Patrick; Ong, Katalina; Karumuthil-Melethil, Subha; Keimel, John G; Mark, Brian L; Mahuran, Don; Gray, Steven J; Walia, Jagdeep S

    2016-07-01

    GM2 gangliosidosis is a group of neurodegenerative diseases caused by β-hexosaminidase A (HexA) enzyme deficiency. There is currently no cure. HexA is composed of two similar, nonidentical subunits, α and β, which must interact with the GM2 activator protein (GM2AP), a substrate-specific cofactor, to hydrolyze GM2 ganglioside. Mutations in either subunit or the activator can result in the accumulation of GM2 ganglioside within neurons throughout the central nervous system. The resulting neuronal cell death induces the primary symptoms of the disease: motor impairment, seizures, and sensory impairments. This study assesses the long-term effects of gene transfer in a Sandhoff (β-subunit knockout) mouse model. The study utilized a modified human β-hexosaminidase α-subunit (μ-subunit) that contains critical sequences from the β-subunit that enables formation of a stable homodimer (HexM) and interaction with GM2AP to hydrolyze GM2 ganglioside. We investigated a self-complementary adeno-associated viral (scAAV) vector expressing HexM, through intravenous injections of the neonatal mice. We monitored one cohort for 8 weeks and another cohort long-term for survival benefit, behavioral, biochemical, and molecular analyses. Untreated Sandhoff disease (SD) control mice reached a humane endpoint at approximately 15 weeks, whereas treated mice had a median survival age of 40 weeks, an approximate 2.5-fold survival advantage. On behavioral tests, the treated mice outperformed their knockout age-matched controls and perform similarly to the heterozygous controls. Through the enzymatic and GM2 ganglioside analyses, we observed a significant decrease in the GM2 ganglioside level, even though the enzyme levels were not significantly increased. Molecular analyses revealed a global distribution of the vector between brain and spinal cord regions. In conclusion, the neonatal delivery of a novel viral vector expressing the human HexM enzyme is effective in ameliorating the SD

  17. 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

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Chaperone therapy for GM2 gangliosidosis: effects of pyrimethamine on β-hexosaminidase activity in Sandhoff fibroblasts.

    PubMed

    Chiricozzi, Elena; Niemir, Natalia; Aureli, Massimo; Magini, Alessandro; Loberto, Nicoletta; Prinetti, Alessandro; Bassi, Rosaria; Polchi, Alice; Emiliani, Carla; Caillaud, Catherine; Sonnino, Sandro

    2014-08-01

    Sphingolipidoses are inherited genetic diseases due to mutations in genes encoding proteins involved in the lysosomal catabolism of sphingolipids. Despite a low incidence of each individual disease, altogether, the number of patients involved is relatively high and resolutive approaches for treatment are still lacking. The chaperone therapy is one of the latest pharmacological approaches to these storage diseases. This therapy allows the mutated protein to escape its natural removal and to increase its quantity in lysosomes, thus partially restoring the metabolic functions. Sandhoff disease is an autosomal recessive inherited disorder resulting from β-hexosaminidase deficiency and characterized by large accumulation of GM2 ganglioside in brain. No enzymatic replacement therapy is currently available, and the use of inhibitors of glycosphingolipid biosynthesis for substrate reduction therapy, although very promising, is associated with serious side effects. The chaperone pyrimethamine has been proposed as a very promising drug in those cases characterized by a residual enzyme activity. In this review, we report the effect of pyrimethamine on the recovery of β-hexosaminidase activity in cultured fibroblasts from Sandhoff patients. PMID:24356898

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

    PubMed

    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

    2009-04-01

    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

  1. The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy.

    PubMed

    Regier, Debra S; Proia, Richard L; D'Azzo, Alessandra; Tifft, Cynthia J

    2016-06-01

    The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1 or GM2 gangliosides. GM1 gangliosidosis has both central nervous system and systemic findings; while, GM2 gangliosidosis is restricted primarily to the central nervous system. Both disorders have autosomal recessive modes of inheritance and a continuum of clinical presentations from a severe infantile form to a milder, chronic adult form. Both are devastating diseases without cure or specific treatment however, with the use of supportive aggressive medical management, the lifespan and quality of life has been extended for both diseases. Naturally occurring and engineered animal models that mimic the human diseases have enhanced our understanding of the pathogenesis of disease progression. Some models have shown significant improvement in symptoms and lifespan with enzyme replacement, substrate reduction, and anti-inflammatory treatments alone or in combination. More recently gene therapy has shown impressive results in large and small animal models. Treatment with FDA-approved glucose analogs to reduce the amount of ganglioside substrate is used as off-label treatments for some patients. Therapies also under clinical development include small molecule chaperones and gene therapy. PMID:27491214

  2. Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice.

    PubMed

    Denny, Christine A; Heinecke, Karie A; Kim, Youngho P; Baek, Rena C; Loh, Katrina S; Butters, Terry D; Bronson, Roderick T; Platt, Frances M; Seyfried, Thomas N

    2010-06-01

    Sandhoff disease is an autosomal recessive, neurodegenerative disease involving the storage of brain ganglioside GM2 and asialo-GM2. Previous studies showed that caloric restriction, which augments longevity, and N-butyldeoxynojirimycin (NB-DNJ, Miglustat), an imino sugar that hinders the glucosyltransferase catalyzing the first step in glycosphingolipid biosynthesis, both increase longevity and improve motor behavior in the beta-hexosaminidase (Hexb) knockout (-/-) murine model of Sandhoff disease. In this study, we used a restricted ketogenic diet (KD-R) and NB-DNJ to combat ganglioside accumulation. Adult Hexb-/- mice were placed into one of the following groups: (i) a standard diet (SD), (ii) a SD with NB-DNJ (SD + NB-DNJ), (iii) a KD-R, and (iv) a KD-R with NB-DNJ (KD-R + NB-DNJ). Forebrain GM2 content (mug sialic acid/100 mg dry wt) in the four groups was 375 +/- 15, 312 +/- 8, 340 +/- 28, and 279 +/- 26, respectively, indicating an additive interaction between NB-DNJ and the KD-R. Most interestingly, brain NB-DNJ content was 3.5-fold greater in the KD-R + NB-DNJ mice than in the SD + NB-DNJ mice. These data suggest that the KD-R and NB-DNJ may be a potential combinatorial therapy for Sandhoff disease by enhancing NB-DNJ delivery to the brain and may allow lower dosing to achieve the same degree of efficacy as high dose monotherapy. PMID:20374428

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2015-01-01

    GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease where GLB1 gene mutations result in a reduction or absence of lysosomal acid β-galactosidase (βgal) activity. βgal deficiency leads to accumulation of GM1-ganglioside in the central nervous system (CNS). GM1 is characterized by progressive neurological decline resulting in generalized paralysis, extreme emaciation and death. In this study, we assessed the therapeutic efficacy of an adeno-associated virus (AAV) 9-mβgal vector infused systemically in adult GM1 mice (βGal−/−) at 1 × 1011 or 3 × 1011 vector genomes (vg). Biochemical analysis of AAV9-treated GM1 mice showed high βGal activity in liver and serum. Moderate βGal levels throughout CNS resulted in a 36–76% reduction in GM1-ganglioside content in the brain and 75–86% in the spinal cord. Histological analyses of the CNS of animals treated with 3 × 1011 vg dose revealed increased presence of βgal and clearance of lysosomal storage throughout cortex, hippocampus, brainstem and spinal cord. Storage reduction in these regions was accompanied by a marked decrease in astrogliosis. AAV9 treatment resulted in improved performance in multiple tests of motor function and behavior. Also the majority of GM1 mice in the 3 × 1011 vg cohort retained ambulation and rearing despite reaching the humane endpoint due to weight loss. Importantly, the median survival of AAV9 treatment groups (316–576 days) was significantly increased over controls (250–264 days). This study shows that moderate widespread expression of βgal in the CNS of GM1 gangliosidosis mice is sufficient to achieve significant biochemical impact with phenotypic amelioration and extension in lifespan. PMID:25964428

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

    MedlinePlus

    ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

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

    PubMed

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

    2014-08-01

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

  7. Glycosphingolipid degradation and animal models of GM2-gangliosidoses.

    PubMed

    Kolter, T; Sandhoff, K

    1998-08-01

    Glycosphingolipids form cell type-specific patterns on the surface of eukaryotic cells. Degradation of glycosphingolipids requires endocytic membrane flow of plasma membrane-derived glycosphingolipids into the lysosomes as the digesting organelles. The inherited deficiencies of lysosomal hydrolases and of sphingolipid activator proteins both give rise to sphingolipid storage diseases. Recent research has focused on the mechanisms leading to selective membrane degradation in the lysosomes and on the mechanism and physiological function of sphingolipid activator proteins. The GM2-degrading system is a paradigm for activator protein-dependent lysosomal degradation. Three polypeptide chains contribute to the in vivo degradation of ganglioside GM2: the alpha- and beta-chains of the beta-hexosaminidases and the GM2 activator. Mouse models of Tay-Sachs disease (alpha-chain deficiency), Sandhoff disease (beta-chain deficiency) and GM2 activator deficiency have been described. While the phenotypes of these variants of GM2-gangliosidoses are only slightly different in humans, the animal models show drastic differences in severity and course of the diseases. The reason for this is the specificity of sialidase, which is different between mouse and human. A double-knockout mouse lacking beta-hexosaminidases A, B and S shows a phenotype of mucopolysaccharidosis and gangliosidosis. A substrate deprivation approach to therapy is discussed with respect to animal models of the GM2-gangliosidoses. PMID:9728335

  8. A nursing challenge: adult-onset Tay-Sachs disease.

    PubMed

    Hamilton, D

    1991-12-01

    Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort. PMID:1759864

  9. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease.

    PubMed

    MacQueen, G M; Rosebush, P I; Mazurek, M F

    1998-01-01

    Tay-Sachs disease (a GM2 gangliosidosis) is an inherited neuronal storage disease that can affect individuals across the age spectrum. Psychosis is reported in 30% to 50% of adult-onset patients, and many are misdiagnosed with schizophrenia. Mood disorders are present in more than 25% and cognitive impairment in more than 20%. Treatment of psychosis with neuroleptics may not have a favorable risk/benefit ratio, but treatment with benzodiazepines or electroconvulsive therapy may be efficacious. Metabolic diseases such as gangliosidosis are probably under-recognized as causes of neuropsychiatric illness. Increased awareness of these disorders will lead to accurate diagnosis, appropriate treatment selection, and genetic counseling. PMID:9547461

  10. Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome

    PubMed Central

    Salih, Mustafa A.; Seidahmed, Mohammed Z.; El Khashab, Heba Y.; Hamad, Muddathir H. A.; Bosley, Thomas M.; Burn, Sabrina; Myers, Angela; Landsverk, Megan L.; Crotwell, Patricia L.; Bilguvar, Kaya; Mane, Shrikant; Kruer, Michael C.

    2015-01-01

    Background The etiology of many cases of childhood-onset chorea remains undetermined, although advances in genomics are revealing both new disease-associated genes and variant phenotypes associated with known genes. Methods We report a Saudi family with a neurodegenerative course dominated by progressive chorea and dementia in whom we performed homozygosity mapping and whole exome sequencing. Results We identified a homozygous missense mutation in GM2A within a prominent block of homozygosity. This mutation is predicted to impair protein function. Discussion Although discovered more than two decades ago, to date, only five patients with this rare form of GM2 gangliosidosis have been reported. The phenotype of previously described GM2A patients has been typified by onset in infancy, profound hypotonia and impaired volitional movement, intractable seizures, hyperacusis, and a macular cherry red spot. Our findings expand the phenotypic spectrum of GM2A mutation-positive gangliosidosis to include generalized chorea without macular findings or hyperacusis and highlight how mutations in neurodegenerative disease genes may present in unexpected ways. PMID:26203402

  11. Biomedical genetics of the inherited metabolic diseases: the GM2-gangliosidoses.

    PubMed

    Kolodny, E H

    1984-03-01

    Many of the known gene defects result in inborn errors of metabolism that produce irreversible damage to the central nervous system. A variety of new clinical, morphologic, biochemical, and genetic techniques are being used to characterize these disorders more precisely. At the Shriver Center, the different genotypes of GM2-gangliosidosis are distinguished according to the ability of cells in culture to metabolize radioactively-labeled GM2-ganglioside. Large-scale screening for carriers of the trait for Tay-Sachs disease, the most common of the GM2-gangliosidoses, has dramatically reduced the incidence of this disease. Current efforts to isolate the genes for the alpha and beta chains of hexosaminidase A will lay the groundwork for better understanding of the molecular defects in these diseases and offers hope for a possible treatment. PMID:6428229

  12. Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.

    PubMed

    Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

    2015-09-01

    Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

  13. In Cellulo Examination of a Beta-Alpha Hybrid Construct of Beta-Hexosaminidase A Subunits, Reported to Interact with the GM2 Activator Protein and Hydrolyze GM2 Ganglioside

    PubMed Central

    Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J.; Samulski, R. Jude; Wakarchuk, Warren; Mark, Brian L.; Mahuran, Don J.

    2013-01-01

    The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

  14. In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

    PubMed

    Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J; Samulski, R Jude; Wakarchuk, Warren; Mark, Brian L; Mahuran, Don J

    2013-01-01

    The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

  15. Expression of the GM2-activator protein in the methylotrophic yeast Pichia pastoris, purification, isotopic labeling, and biophysical characterization.

    PubMed

    Wendeler, Michaela; Hoernschemeyer, Joerg; John, Michael; Werth, Norbert; Schoeniger, Maike; Lemm, Thorsten; Hartmann, Rudolf; Kessler, Horst; Sandhoff, Konrad

    2004-03-01

    The GM2-activator protein (GM2AP) belongs to a group of five small, nonenzymatic proteins that are essential cofactors for the degradation of glycosphingolipids in the lysosome. It mediates the interaction between the water-soluble enzyme beta-hexosaminidase A and its membrane-embedded substrate, ganglioside GM2, at the lipid-water interphase. Inherited defects in the gene encoding this glycoprotein cause a fatal neurological storage disorder, the AB variant of GM2 gangliosidosis. With the aim to establish a convenient eukaryotic system that allows the efficient production of functionally folded, glycosylated GM2AP and offers the potential of cost-efficient isotopic labeling for structural studies by NMR spectroscopy, we established the expression of recombinant GM2AP in the methylotrophic yeast Pichia pastoris. For the construction of expression plasmids, either the full cDNA encoding human GM2AP preproprotein was cloned in the expression vector pPIC3.5K, or the cDNA encoding only the mature form of GM2AP was inserted in the vector pPIC9K under control of the alcohol oxidase 1 promoter. Both plasmids led to the successful secretory expression of active, glycosylated GM2AP, which could easily be purified by Ni-NTA chromatography due to the hexahistidine tag introduced at the C-terminus. Remarkably, the expression of this membrane-active protein in P. pastoris was accompanied by two peculiarities which were not encountered in other expression systems for GM2AP: First, a significant fraction of the secreted protein existed in the form of aggregates, and second, considerable amounts of noncovalently bound lipids were associated with the recombinant protein. A three-step purification scheme was therefore devised consisting of Ni-NTA, reversed phase, and gel filtration chromatography, which finally yielded 10-12 mg of purified, monomeric GM2AP per liter of expression supernatant. MALDI- and ESI-TOF mass spectrometry were employed to assess the processing, homogeneity

  16. GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A.

    PubMed

    Peleg, L; Meltzer, F; Karpati, M; Goldman, B

    1995-04-01

    The biochemical properties of hexosaminidase A (HexA) and the coding sequence of the alpha-subunit were examined in a patient of Syrian ancestry with the B1 form of Tay-Sachs disease (TSD). The biochemical characteristics of the variant HexA suggest that both active sites are affected by the mutation(s). Kinetic studies with the beta-subunit specific substrate, 4-methylumbelliferyl-beta-D-N-acetylglucosamine (MUG), revealed a significant difference between the Km values. of normal and variant HexA, while no difference was found when the sulfated substrate MUG-6-sulfate (MUGS), which is specific for the alpha-subunit active site, was used. The Vmax values for both substrates were significantly lower in extracts from B1 variant cells than in control extracts, implying a reduced enzyme level in the variant cells. A noncompetitive inhibitor of the reaction with MUGS, N-acetylglucosamine (NAG), induced a significant inhibition (30%) in the mutant cells only. When MUG was used as substrate, variant HexA was found to be more heat stable (T50 = 170 min) than normal HexA (T50 = 65 min). Furthermore, the mutant cell preparation differed from control in the relation between Hex thermosensitivity and protein concentration in the reaction. Two new mutations were identified in exon 5 of the HexA gene: a C496 to G transversion, which produced an Arg166 -->Gly alteration and a deletion of C498 which generated a shift in the reading frame. The patient was a heterozygote for both mutations even though her parents are first cousins. There is no evidence as yet which of these mutations accounts for the B1 phenotype. PMID:8581357

  17. Modified beta-D-N-acetylhexosaminidase isozymes for enzyme replacement in GM2 gangliosidosis.

    PubMed

    Rattazzi, M C; Dobrenis, K; Joseph, A; Schwartz, P

    1987-01-01

    The therapeutic potential of enzyme replacement in lysosomal storage disorders has remained largely unfulfilled, perhaps because of negative reactions to the initial disappointing results. Despite the existence of several animal models that can be utilized to explore solutions to the problems of exogenous enzyme targeting, the interest in ERT prevalent during the 1970's seems to have subsided to be replaced by active interest in bone marrow transplantation (BMT, Krivit and Paul [1986]). This is a logical approach to enzyme replacement in storage disorders of the RE system, and indeed some encouraging results have been obtained. However, in addition to having high morbidity and mortality, in the ultimate analysis BMT presents the same targeting problems as conventional ERT. In our opinion, these problems can be solved more easily in the case of ERT by exploiting the existing cellular uptake mechanisms and infusing enzymes whose structure has been suitably modified by simple biochemical manipulations. Accordingly, we have explored a methodology that takes advantage of negative charges on the cell surface to obtain nonspecific but effective membrane binding of beta-hex coupled to the highly positively charged PLL, followed by internalization and routing to the lysosomes. This system increases uptake of exogenous enzyme by some neurons in vitro and possibly in vivo, but its efficiency depends on the cells' endocytic activity that, in the case of neuronal soma, apparently is low. Thus, we have chosen as recognition marker for specific neuronal uptake a nontoxic fragment of TTx that is efficiently taken up by these cells. The initial results are encouraging; they support our contention that effective enzyme replacement methodologies can be devised, and encourage us to continue our work in this direction. Finally, recombinant DNA techniques are now being applied to a number of LSD, and the genes for several of the pertinent enzymes have been or are being isolated. In addition to representing a first step towards gene replacement therapy, the results of this work will permit the generation of large amounts of human enzymes from bacteria by recombinant DNA methods, thus obviating the problem of enzyme supply for ERT. Since human lysosomal enzymes obtained from bacteria will be nonglycosylated, to obtain cell uptake it will be necessary to resort to the type of modifications that we are trying to develop at this time, i.e., covalent linkage to moieties that allow non-glycosyl-mediated cellular uptake. Thus, our work on beta-hex may provide a model for biochemical manipulations of bacterially produced enzymes applicable to several LSD. PMID:2956216

  18. Beta-hexosaminidase isozymes and replacement therapy in Gm2 gangliosidosis.

    PubMed

    Rattazzi, M C

    1983-01-01

    The problem of cell targeting of lysosomal enzymes is a critical one in the development of strategies for therapeutic enzyme replacement in lysosomal storage diseases. In principle, posttranscriptional isozymes with different carbohydrate-chain composition may be helpful in exploiting existing glycosyl-specific receptors on target cells, if the receptor specificities are known and match the glycosyl composition of available isozymes. In practice, however, the choice is limited to isozymes that can be obtained from tissues available in abundance, such as placenta or blood plasma. Our early experiments show that one can interfere with the interaction between hepatic (RES) receptor and enzyme glycosyl chain, to obtain extrahepatic targeting of beta-hexosaminidase, with catabolic effects. This approach, of course, does not have an immediate therapeutic application, as it involves injection of large amounts of foreign material in order to inhibit hepatic uptake. Modification of the glycosyl chain may be the method of choice in selected instances [Furbish et al. 1981], but is applicability again depends on the knowledge of receptor specificity on target cells and on composition of the glycosyl chain of the enzyme in question. Our recent experiments are a first step toward obtaining enzyme forms that can be endocytosed efficiently by mechanisms that are independent of glycosyl-specific receptors. Charge-mediated, absorptive endocytosis can be obtained by covalent coupling of cationic PLL to beta-hexosaminidase. Given the abundance of negative surface charges on most cell types [Weiss, 1969], this approach may be applicable to different target cells and organs, and possibly also to lysosomal enzymes other than beta-hexosaminidase. The existence of glycosyl recognition signals on beta-hexosaminidase can be obviated by simple chemical manipulations, such as Na-metaperiodate oxidation, which effectively prevents hepatic RES uptake [Rattazzi et al, 1982]. In combination with PLL conjugation, this may ultimately result in an enzyme form that escapes the undesired, preferential RES uptake and is efficiently endocytosed by most cells. It will remain to be seen if this artificially created isozyme (for which we propose the name "ersatzyme") is catabolically effective. This can easily be verified in our animal model, along the lines followed to demonstrate the catabolic effects of native Hex A. Finally, the recent developments in molecular genetics, which allows production of human proteins in bacterial systems by recombinant DNA techniques, make it very likely that abundant beta-hexosaminidase may be similarly obtained for therapeutic applications.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6227586

  19. Diagnosing Lysosomal Storage Disorders: The GM2 Gangliosidoses.

    PubMed

    Hall, Patricia; Minnich, Sara; Teigen, Claire; Raymond, Kimiyo

    2014-01-01

    The GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by defective β-hexosaminidase. There are three clinical conditions in this group: Tay-Sachs disease (TSD), Sandhoff disease (SD), and hexosaminidase activator deficiency. The three conditions are clinically indistinguishable. TSD and SD have been identified with infantile, juvenile, and adult onset forms. The activator deficiency is only known to present with infantile onset. Diagnosis of TSD and SD is based on decreased hexosaminidase activity and a change in the percentage of activity between isoforms. There are no biochemical tests currently available for activator deficiency. This unit provides a detailed procedure for identifying TSD and SD in affected individuals and carriers from leukocyte samples, the most robust sample type available. PMID:25271840

  20. GM1 and GM2 gangliosides: recent developments.

    PubMed

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

    2014-03-01

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

  1. Serial 1H-MRS in GM2 gangliosidoses.

    PubMed

    Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola

    2008-03-01

    GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations. PMID:17387512

  2. A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates.

    PubMed

    Tropak, Michael B; Bukovac, Scott W; Rigat, Brigitte A; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J

    2010-03-01

    Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is an attractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are also inhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Here we demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the beta-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant beta-hexosaminidase A and substrate-hydrolysis as compared to mock-treated cells. PMID:19917668

  3. Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

    PubMed

    Kitamura, K; Livingston, P O; Fortunato, S R; Stockert, E; Helling, F; Ritter, G; Oettgen, H F; Old, L J

    1995-03-28

    Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high

  4. Prenatal and postnatal studies of a late infantile GM2 gangliosidosis in a family of Syrian origin: a possible B1 variant.

    PubMed

    Shukry, A; Goldman, B; Shihab, S; Peleg, L

    1993-10-01

    We describe late infantile Tay-Sachs disease with high residual hexosaminidase A activity in two siblings of a Syrian Druze family. The patients' leukocytes had 26% of normal hexosaminidase A activity when tested with the conventional fluorogenic substrate 4-methyl-umbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (4-MUG) and only about 10% when assayed with the sulfated substrate, 4-methyl-umbelliferal- beta-N-acetyl-glucosamine-6-sulfate (4-MUGS). According to the standard procedure of the heterozygote screening program (employing 4-MUG and heat inactivation), the parents were not diagnosed as an at-risk couple since the father was classified as a noncarrier. However, both parents' levels were clearly within the carrier range on the basis of 4-MUGS. The unique catalytic characteristics of the patients' enzyme forward the assumption that the affected sibs are B1 variants. The parents' enzymatic levels, together with their known consanguinity, might indicate that these patients are homozygotes for the rare mutation and not genetic compounds as has been documented for most of the infantile B1 variants. To the best of our knowledge this is the first reported case of B1 variant in a child of that extraction. PMID:8244659

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

    PubMed

    Tropak, Michael B; Mahuran, Don

    2007-10-01

    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 3.2.1.52) 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

  6. Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

    PubMed Central

    Li, Qi; Wang, Wei; Machino, Yusuke; Yamada, Tadaaki; Kita, Kenji; Oshima, Masanobu; Sekido, Yoshitaka; Tsuchiya, Mami; Suzuki, Yui; Nan-ya, Ken-ichiro; Iida, Shigeru; Nakamura, Kazuyasu; Iwakiri, Shotaro; Itoi, Kazumi; Yano, Seiji

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. PMID:25421609

  7. Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease

    PubMed Central

    Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

    2011-01-01

    To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease. PMID:22205997

  8. Lyso-GM2 ganglioside: a possible biomarker of Tay-Sachs disease and Sandhoff disease.

    PubMed

    Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-Ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

    2011-01-01

    To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease. PMID:22205997

  9. The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus

    PubMed Central

    Liu, Yan; Blaum, Bärbel S.; Reiter, Dirk M.; Feizi, Ten; Dermody, Terence S.; Stehle, Thilo

    2012-01-01

    Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus. PMID:23236285

  10. Canine GM1-gangliosidosis. A clinical, morphologic, histochemical, and biochemical comparison of two different models.

    PubMed Central

    Alroy, J.; Orgad, U.; DeGasperi, R.; Richard, R.; Warren, C. D.; Knowles, K.; Thalhammer, J. G.; Raghavan, S. S.

    1992-01-01

    The clinical, morphologic, histochemical, and biochemical features of GM1-gangliosidosis in two canine models, English Springer Spaniel (ESS) and Portuguese Water Dog (PWD), have been compared. The disease onset, its clinical course, and survival period of the affected dogs were similar in both models. Skeletal dysplasia was noted radiographically at 2 months of age, whereas at 4 1/2 months of age there was progressive neurologic impairment. However, dwarfism and coarse facial features were seen only in ESS. Both models had similar deficiency in activity of lysosomal beta-galactosidase, but possessed a normal protein activator for GM1-beta-galactosidase. Both models stored GM1-ganglioside, asialo-GM1, and oligosaccharides in brain. Furthermore, only the PWD stored glycoproteins containing polylactosaminoglycans in visceral organs, and neither model stored them in the brain. Morphologically, both models demonstrated similar storage material in multiple tissues and cell types. The ultrastructure of the storage material was cell-type specific and identical in both models. However, some differences in the lectin staining pattern were noted. Our clinical, biochemical, and histochemical findings indicate that PWD and ESS may represent two different mutations of the beta-galactosidase gene. Moreover, the authors conclude that it is difficult, and inappropriate, to apply the human classification of GM1-gangliosidosis (i.e. infantile, juvenile, and adult forms) to these canine models. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1546746

  11. MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis.

    PubMed

    Regier, Debra S; Kwon, Hyuk Joon; Johnston, Jean; Golas, Gretchen; Yang, Sandra; Wiggs, Edythe; Latour, Yvonne; Thomas, Sarah; Portner, Cindy; Adams, David; Vezina, Gilbert; Baker, Eva H; Tifft, Cynthia J

    2016-03-01

    Background GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1, encoding β-galactosidase. The range of severity is from type I infantile disease, lethal in early childhood, to type III adult onset, resulting in gradually progressive neurological symtpoms in adulthood. The intermediate group of patients has been recently classified as having type II late infantile subtype with onset of symptoms at one to three years of age or type II juvenile subtype with symptom onset at 2-10 years. To characterize disease severity and progression, six Late infantile and nine juvenile patients were evaluated using magnetic resonance imaging (MRI), and MR spectroscopy (MRS). Since difficulties with ambulation (gross motor function) and speech (expressive language) are often the first reported symptoms in type II GM1, patients were also scored in these domains. Deterioration of expressive language and ambulation was more rapid in the late infantile patients. Fourteen MRI scans in six Late infantile patients identified progressive atrophy in the cerebrum and cerebellum. Twenty-six MRI scans in nine juvenile patients revealed greater variability in extent and progression of atrophy. Quantitative MRS demonstrated a deficit of N-acetylaspartate in both the late infantile and juvenile patients with greater in the late infantile patients. This correlates with clinical measures of ambulation and expressive language. The two subtypes of type II GM1 gangliosidosis have different clinical trajectories. MRI scoring, quantitative MRS and brain volume correlate with clinical disease progression and may serve as important minimally-invasive outcome measures for clinical trials. © 2015 Wiley Periodicals, Inc. PMID:26646981

  12. Sialidase-mediated depletion of GM2 ganglioside in Tay-Sachs neuroglia cells.

    PubMed

    Igdoura, S A; Mertineit, C; Trasler, J M; Gravel, R A

    1999-06-01

    Tay-Sachs disease is a severe, inherited disease of the nervous system caused by accumulation of the brain lipid GM2 ganglioside. Mouse models of Tay-Sachs disease have revealed a metabolic bypass of the genetic defect based on the more potent activity of the enzyme sialidase towards GM2. To determine whether increasing the level of sialidase would produce a similar effect in human Tay-Sachs cells, we introduced a human sialidase cDNA into neuroglia cells derived from a Tay-Sachs fetus and demonstrated a dramatic reduction in the accumulated GM2. This outcome confirmed the reversibility of GM2 accumulation and opens the way to pharmacological induction or activation of sialidase for the treatment of human Tay-Sachs disease. PMID:10332044

  13. Biology and potential strategies for the treatment of GM2 gangliosidoses.

    PubMed

    Chavany, C; Jendoubi, M

    1998-04-01

    The GM2 gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside GM2 owing to deficiency in beta-hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and beta subunits, respectively. The lack of treatment for GM2 gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of GM2 gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes. PMID:9572057

  14. Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

    PubMed

    Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

    2016-07-01

    The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. PMID:27066976

  15. Anti-GM2 ganglioside antibodies are a biomarker for acute canine polyradiculoneuritis

    PubMed Central

    Bianchi, Ezio; Dondi, Maurizio; Penderis, Jacques; Cappell, Joanna; Burgess, Karl; Matiasek, Kaspar; McGonigal, Rhona; Willison, Hugh J.

    2016-01-01

    Acute canine polyradiculoneuritis (ACP) is considered to be the canine equivalent of the human peripheral nerve disorder Guillain-Barré syndrome (GBS); an aetiological relationship, however, remains to be demonstrated. In GBS, anti-glycolipid antibodies (Abs) are considered as important disease mediators. To address the possibility of common Ab biomarkers, the sera of 25 ACP dogs, 19 non-neurological, and 15 epileptic control dogs were screened for IgG Abs to 10 glycolipids and their 1 : 1 heteromeric complexes using combinatorial glycoarrays. Anti-GM2 ganglioside Abs were detected in 14/25 ACP dogs, and anti-GA1 Abs in one further dog. All controls except for one were negative for anti-glycolipid Abs. In this cohort of cases and controls, the glycoarray screen reached a diagnostic sensitivity of 60% and a specificity of 97%; a lower sensitivity (32%) was reported using a conventional glycolipid ELISA. To address the possible pathogenic role for anti-GM2 Abs in ACP, we identified GM2 in canine sciatic nerve by both mass spectrometry and thin layer chromatography overlay. In immunohistological studies, GM2 was localized predominantly to the abaxonal Schwann cell membrane. The presence of anti-GM2 Abs in ACP suggests that it may share a similar pathophysiology with GBS, for which it could thus be considered a naturally occurring animal model. PMID:23521648

  16. Restoration of the GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay-Sachs disease animal model.

    PubMed

    Martino, S; Cavalieri, C; Emiliani, C; Dolcetta, D; Cusella De Angelis, M G; Chigorno, V; Severini, G M; Sandhoff, K; Bordignon, C; Sonnino, S; Orlacchio, A

    2002-08-01

    The therapeutic potential of bone marrow-derived stromal cells for the therapy of Tay-Sachs disease is primarily related to the restoration of their own GM2 ganglioside storage. With this aim, we produced bone marrow-derived stromal cells from the adult Tay-Sachs animal model and transduced them with a retroviral vector encoding for the alpha-subunit of the lysosomal enzyme beta-hexosaminidase A (E.C. 3.2.1.52). Our results demonstrate that transduced Tay-Sachs bone marrow-derived stromal cells have beta-hexosaminidase A comparable to that of bone marrow-derived stromal cells from wild-type mice. Moreover, beta-hexosaminidase A in transduced Tay-Sachs bone marrow-derived stromal cells was able to hydrolyze the GM2 ganglioside in a feeding experiment, thus demonstrating the correction of the altered phenotype. PMID:12374215

  17. Neuropsychiatric aspects of adult-onset Tay-Sachs disease: two case reports with several new findings.

    PubMed

    Hurowitz, G I; Silver, J M; Brin, M F; Williams, D T; Johnson, W G

    1993-01-01

    Deficiency of hexosaminidase A causes the GM2 gangliosidosis known as Tay-Sachs disease. It is now known that this condition has several late-onset variants that cause numerous neuropsychiatric disturbances. Early recognition is important because treatment with phenothiazines and heterocyclic antidepressants may worsen the course. The authors report two cases with several new findings, including prominent psychiatric symptoms without psychosis early in the course of the illness. PMID:8428133

  18. N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice.

    PubMed

    Baek, Rena C; Kasperzyk, Julie L; Platt, Frances M; Seyfried, Thomas N

    2008-05-01

    Sandhoff disease involves the CNS accumulation of ganglioside GM2 and asialo-GM2 (GA2) due to inherited defects in the beta-subunit gene of beta-hexosaminidase A and B (Hexb gene). Accumulation of these glycosphingolipids (GSLs) produces progressive neurodegeneration, ultimately leading to death. Substrate reduction therapy (SRT) aims to decrease the rate of glycosphingolipid (GSL) biosynthesis to compensate for the impaired rate of catabolism. The imino sugar, N-butyldeoxygalactonojirimycin (NB-DGJ) inhibits the first committed step in GSL biosynthesis. NB-DGJ treatment, administered from postnatal day 2 (p-2) to p-5 (600 mg/kg/day)), significantly reduced total brain ganglioside and GM2 content in the Sandhoff disease (Hexb(-/-)) mice, but did not reduce the content of GA2. We also found that NB-DGJ treatment caused a slight, but significant elevation in brain sialidase activity. The drug had no adverse effects on viability, body weight, brain weight, or brain water content in the mice. No significant alterations in neutral lipids or acidic phospholipids were observed in the NB-DGJ-treated Hexb(-/-) mice. Our results show that NB-DGJ is effective in reducing total brain ganglioside and GM2 content at early neonatal ages. PMID:18207611

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

    PubMed Central

    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

    2011-01-01

    GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000– 1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected 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. PMID:21497194

  20. Identification of ganglioside GM2 activator playing a role in cancer cell migration through proteomic analysis of breast cancer secretomes.

    PubMed

    Shin, Jihye; Kim, Gamin; Lee, Jong Won; Lee, Ji Eun; Kim, Yoo Seok; Yu, Jong-Han; Lee, Seung-Taek; Ahn, Sei Hyun; Kim, Hoguen; Lee, Cheolju

    2016-06-01

    Cancer cell secretomes are considered a potential source for the discovery of cancer markers. In this study, the secretomes of four breast cancer (BC) cell lines (Hs578T, MCF-7, MDA-MB-231, and SK-BR-3) were profiled with liquid chromatography-tandem mass spectrometry analysis. A total of 1410 proteins were identified with less than 1% false discovery rate, of which approximately 55% (796 proteins) were predicted to be secreted from cells. To find BC-specific proteins among the secreted proteins, data of immunohistochemical staining compiled in the Human Protein Atlas were investigated by comparing the data of BC tissues with those of normal tissues. By applying various criteria, including higher expression level in BC tissues, higher predicted potential of secretion, and sufficient number of tandem mass spectra, 12 biomarker candidate proteins including ganglioside GM2 activator (GM2A) were selected for confirmation. Western blot analysis and ELISA for plasma samples of healthy controls and BC patients revealed elevation of GM2A in BC patients, especially those who were estrogen receptor-negative. Additionally, siRNA-mediated knockdown of GM2A in BC cells decreased migration in vitro, whereas the overexpression of GM2A led to an increase in cell migration. Although GM2A as a diagnostic and prognostic marker in BC should be carefully verified further, this study has established the potential role of GM2A in BC progression. PMID:27002480

  1. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.

    PubMed

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

  2. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

    PubMed Central

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

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

    PubMed

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

    2012-07-01

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

  4. GM2Calc: precise MSSM prediction for (g-2) of the muon

    NASA Astrophysics Data System (ADS)

    Athron, Peter; Bach, Markus; Fargnoli, Helvecio G.; Gnendiger, Christoph; Greifenhagen, Robert; Park, Jae-hyeon; Paßehr, Sebastian; Stöckinger, Dominik; Stöckinger-Kim, Hyejung; Voigt, Alexander

    2016-02-01

    We present GM2Calc, a public C++ program for the calculation of MSSM contributions to the anomalous magnetic moment of the muon, (g-2)_μ . The code computes (g-2)_μ precisely, by taking into account the latest two-loop corrections and by performing the calculation in a physical on-shell renormalization scheme. In particular the program includes a tan β resummation so that it is valid for arbitrarily high values of tan β , as well as fermion/sfermion-loop corrections which lead to non-decoupling effects from heavy squarks. GM2Calc can be run with a standard SLHA input file, internally converting the input into on-shell parameters. Alternatively, input parameters may be specified directly in this on-shell scheme. In both cases the input file allows one to switch on/off individual contributions to study their relative impact. This paper also provides typical usage examples not only in conjunction with spectrum generators and plotting programs but also as C++ subroutines linked to other programs.

  5. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    PubMed

    Thomas, P K; Young, E; King, R H

    1989-09-01

    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. PMID:2795083

  6. Evidence for Lipid Packaging in the Crystal Structure of the GM2-Activator Complex with Platelet Activating Factor

    SciTech Connect

    Wright, Christine S.; Mi, Li-Zhi; Rastinejad, Fraydoon

    2010-11-16

    GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2 {angstrom} crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement of two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.

  7. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis

    PubMed Central

    Lehman, Anna; Chioza, Barry; Baple, Emma L.; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A.; Al-Turki, Saeed; McEntagart, Meriel E.; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P.; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Hurles, Matthew E.

    2013-01-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

  8. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis.

    PubMed

    Harlalka, Gaurav V; Lehman, Anna; Chioza, Barry; Baple, Emma L; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A; Al-Turki, Saeed; McEntagart, Meriel E; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Platt, Frances M; Hurles, Matthew E; Crosby, Andrew H

    2013-12-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

  9. Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain

    PubMed Central

    Arthur, Julian R.; Heinecke, Karie A.; Seyfried, Thomas N.

    2011-01-01

    Filipin is an antibiotic polyene widely used as a histochemical marker for cholesterol. We previously reported cholesterol/filipin-positive staining in brain of β-galactosidase (β-gal) knockout (−/−) mice (GM1 gangliosidosis). The content and distribution of cholesterol and gangliosides was analyzed in plasma membrane (PM) and microsomal (MS) fractions from whole-brain tissue of 15 week-old control (β-gal+/−) and GM1 gangliosidosis (β-gal−/−) mice. Total ganglioside content (μg sialic acid/mg protein) was 3-fold and 7-fold greater in the PM and MS fractions, respectively, in βgal−/− mice than in βgal+/− mice. GM1 content was 30-fold and 50-fold greater in the PM and MS fractions, respectively. In contrast, unesterified cholesterol content (μg/mg protein) was similar in the PM and the MS fractions of the βgal−/− and βgal+/− mice. Filipin is known to bind to various sterol derivatives and phospholipids on thin-layer chromatograms. Biochemical evidence is presented showing that filipin also binds to GM1 with an affinity similar to that for cholesterol, with a corresponding fluorescent reaction. Our data suggest that the GM1 storage seen in the β-gal−/− mouse contributes to the filipin ultraviolet fluorescence observed in GM1 gangliosidosis brain. The data indicate that in addition to cholesterol, filipin can also be useful for detecting GM1. PMID:21508255

  10. Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

    PubMed Central

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

    2012-01-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-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 β-hexosaminidase α (HEXA) and β (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 β-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

  11. Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses

    PubMed Central

    Yamaguchi, Akira; Katsuyama, Kayoko; Nagahama, Kiyotaka; Takai, Toshiyuki; Aoki, Ichiro; Yamanaka, Shoji

    2004-01-01

    Mice containing a disruption of the Hexb gene have provided a useful model system for the study of the human lysosomal storage disorder known as Sandhoff disease (SD). Hexb–/– mice rapidly develop a progressive neurologic disease of ganglioside GM2 and GA2 storage. Our study revealed that the disease states in this model are associated with the appearance of antiganglioside autoantibodies. Both elevation of serum antiganglioside autoantibodies and IgG deposition to CNS neurons were found in the advanced stages of the disease in Hexb–/– mice; serum transfer from these mice showed IgG binding to neurons. To determine the role of these autoantibodies, the Fc receptor γ gene (FcRγ) was additionally disrupted in Hexb–/– mice, as it plays a key role in immune complex–mediated autoimmune diseases. Clinical symptoms were improved and life spans were extended in the Hexb–/–FcRγ–/– mice; the number of apoptotic cells was also decreased. The level of ganglioside accumulation, however, did not change. IgG deposition was also confirmed in the brain of an autopsied SD patient. Taken together, these findings suggest that the production of autoantibodies plays an important role in the pathogenesis of neuropathy in SD and therefore provides a target for novel therapies. PMID:14722612

  12. A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

    PubMed

    Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

    2009-01-01

    Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons. PMID:18952610

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

    PubMed

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

    2013-03-01

    Lysosomal β-galactosidase (β-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 β-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 β-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human β-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 β-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 β-Gal mutants. PMID:23337983

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

    PubMed

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

    2006-05-01

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

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

    PubMed

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

    2012-01-01

    GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-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

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

    PubMed Central

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

    2012-01-01

    GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-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

  17. GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.

    PubMed

    Muthupalani, Sureshkumar; Torres, Paola A; Wang, Betty C; Zeng, Bai Jin; Eaton, Samuel; Erdelyi, Ildiko; Ducore, Rebecca; Maganti, Rajanikarath; Keating, John; Perry, Bain J; Tseng, Florina S; Waliszewski, Nicole; Pokras, Mark; Causey, Robert; Seger, Rita; March, Philip; Tidwell, Amy; Pfannl, Rolf; Seyfried, Thomas; Kolodny, Edwin H; Alroy, Joseph

    2014-04-01

    G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal β-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid β-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several

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

    PubMed Central

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

    2015-01-01

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

  19. Sequential proteolysis and high-field FTICR MS to determine disulfide connectivity and 4-maleimide TEMPO spin-label location in L126C GM2 activator protein.

    PubMed

    Tipton, Jeremiah D; Carter, Jeffrey D; Mathias, Jordan D; Emmett, Mark R; Fanucci, Gail E; Marshall, Alan G

    2009-09-15

    The GM2 activator protein (GM2AP) is an 18 kDa nonenzymatic accessory protein involved in the degradation of neuronal gangliosides. Genetic mutations of GM2AP can disrupt ganglioside catabolism and lead to deadly lysosomal storage disorders. Crystallography of wild-type GM2AP reveals 4 disulfide bonds and multiple conformations of a flexible loop region that is thought to be involved in lipid binding. To extend the crystallography results, a cysteine construct (L126C) was expressed and modified with 4-maleimide TEMPO for electron paramagnetic resonance (EPR) studies. However, because a ninth cysteine has been added by site-directed mutagenesis and the protein was expressed in E. coli in the form of inclusion bodies, the protein could misfold during expression. To verify correct protein folding and labeling, a sequential multiple-protease digestion, nano-liquid chromatograph (LC) electrospray ionization 14.5 T Fourier transform ion cyclotron resonance mass spectrometry assay was developed. High-magnetic field and robust automatic gain control results in subppm mass accuracy for location of the spin-labeled cysteine and verification of proper connectivity of the four disulfide bonds. The sequential multiple protease digestion strategy and ultrahigh mass accuracy provided by FTICR MS allow for rapid and unequivocal assignment of relevant peptides and provide a simple pipeline for analyzing other GM2AP constructs. PMID:19689113

  20. Enzyme replacement treatment for Tay-Sachs disease brain cells in culture utilizing concanavalin A-mediated hexosaminidase A uptake: biochemical and morphological evidence of GM2 mobilization.

    PubMed

    Brooks, S E; Hoffman, L M; Adachi, M; Amsterdam, D; Schneck, L

    1980-01-01

    When Concanavalin A (Con A) is bound to the cell membrane, it functions as an artificial enzyme receptor, mediating the binding and intracellular incorporation of significant amounts of exogenous hexosaminidase A (Hex A) into Tay-Sachs disease (TSD) glia cells. The treated cells retained almost 50% of incorporated Hex A activity after 3 days incubation in Hex A free medium. Hex A was released from Con A within the cell and was available as free enzyme. Biochemical analysis of gangliosides in Con A and Hex A treated cells depicted a greater than 50% reduction in stored GM2 ganglioside and a fourfold reduction in GM2 label (14C) when compared to controls. Ultrastructural evidence of GM2 breakdown is presented which supports the biochemical and labeling studies. PMID:7376831

  1. beta 1-4N-acetylgalactosaminyltransferase can synthesize both asialoglycosphingolipid GM2 and glycosphingolipid GM2 in vitro and in vivo: isolation and characterization of a beta 1-4N-acetylgalactosaminyltransferase cDNA clone from rat ascites hepatoma cell line AH7974F.

    PubMed Central

    Hidari, J K; Ichikawa, S; Furukawa, K; Yamasaki, M; Hirabayashi, Y

    1994-01-01

    We have cloned a cDNA encoding beta 1-4N-acetylgalactosaminyltransferase (EC 2.4.1.92) (GalNAc-T) from rat ascites hepatoma of the free-cell type AH7974F. The cell line only expressed asialo-series glycosphingolipids (GSLs) including asialo-GM2 [Taki, T., Hirabayashi, Y., Ishiwata, Y., Matsumoto, M., and Kojima, K. (1979) Biochim. Biophys. Acta 572, 113-120]. The cDNA, pGNA56, was isolated by screening AH7974F cDNA library in lambda gt10 with a probe. The probe was obtained from AH7974F cDNA by PCR using primers with the nucleotide sequence of the human GalNAc-T cDNA. The amino acid sequence deduced from the nucleotide sequence of pGNA56 exhibited 88% similarity to the human GalNAc-T sequence. The enzyme was a typical type II membrane protein, which consisted of a short N-terminal residue, a transmembrane region, and a long C-terminal residue, including the catalytic domain. The substrate specificity of rat GalNAc-T was determined using homogenates from cells into which the cDNA clone was transfected. The enzyme catalysed not only the formation of GM2 and GD2 from GM3 and GD3 respectively, but also asialo-GM2 from CDH. It also acted on GSL substrates, including GM1b, sialylparagloboside and GD1 alpha. On the other hand, the enzyme did not transfer GalNAc to soluble substrates such as glycoproteins and oligosaccharide. The GSL compositional and immunocytochemical analyses of stable transfectants obtained by transfection of the cDNA showed simultaneous expression of asialo-GM2 and GM2 on the plasma membrane. Therefore, we concluded that the formation of asialo-GM2, GM2 and GD2 was catalysed by the single GalNAc-T. Northern-blot hybridization showed that the GalNAc-T mRNA was strongly expressed in rat brain, testis, and spleen. The gene was also expressed in rat normal liver to a lesser extent. We found the GSLs in asialo- and alpha-pathways such as asialo-GM1 and GD1 alpha in the rat tissues by using a sensitive t.l.c.-immunostaining method. These observations also

  2. Refined mapping of the G[sub M2] activator protein (GM2A) locus to 5q31. 3-q33. 1, distal to the spinal muscular atrophy locus

    SciTech Connect

    Heng, H.H.Q.; Xie, B.; Shi, X.M.; Tsui, L.C.; Mahuran, D.J. )

    1993-11-01

    The G[sub M2] activator locus (GM2A) had previously been considered as a candidate gene for some forms of spinal muscular atrophy (SMA; mapped to 5q11.2-q13.3). It was eliminated as a possible candidate because PCR-based mapping failed to localize the gene to chromosome 5, as was previously reported using an ELISA-based methodology. However, the authors demonstrated that the PCR primers used preferentially amplified a processed pseudogene (GM2AP) that was mapped to chromosome 3 and that GM2A was located on chromosome 5. In this report, they reconsider the candidacy of GM2A by refining its localization on chromosome 5 using fluorescence in situ hybridization. They localize GM2A to 5q31.3-q33.1; thus, it is not a candidate gene for SMA. 11 refs., 2 figs.

  3. Increased Expression of Simple Ganglioside Species GM2 and GM3 Detected by MALDI Imaging Mass Spectrometry in a Combined Rat Model of Aβ Toxicity and Stroke

    PubMed Central

    Caughlin, Sarah; Hepburn, Jeffrey D.; Park, Dae Hee; Jurcic, Kristina; Yeung, Ken K.-C.; Cechetto, David F.; Whitehead, Shawn N.

    2015-01-01

    The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer’s disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain’s response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in the presence of beta-amyloid (Aβ) toxicity in addition to ischemic injury. To model a stroke, rats received a unilateral striatal injection of endothelin-1 (ET-1) (stroke alone group). To model Aβ toxicity, rats received intracerebralventricular (icv) injections of the toxic 25-35 fragment of the Aβ peptide (Aβ alone group). To model the combination of Aβ toxicity with stroke, rats received both the unilateral ET-1 injection and the bilateral icv injections of Aβ₂₅₋₃₅ (combined Aβ/ET-1 group). By 3 d, a significant increase in the simple ganglioside species GM2 was observed in the ischemic brain region of rats who received a stroke (ET-1), with or without Aβ. By 21 d, GM2 levels only remained elevated in the combined Aβ/ET-1 group. GM3 levels however demonstrated a different pattern of expression. By 3 d GM3 was elevated in the ischemic brain region only in the combined Aβ/ET-1 group. By 21 d, GM3 was elevated in the ischemic brain region in both stroke alone and Aβ/ET-1 groups. Overall, results indicate that the accumulation of simple ganglioside species GM2 and GM3 may be indicative of a mechanism of interaction between AD and stroke. PMID:26086081

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  6. GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients.

    PubMed

    Gort, Laura; de Olano, Natalia; Macías-Vidal, Judit; Coll, M A Josep

    2012-09-10

    The GM2 gangliosidoses are autosomal recessive lysosomal storage diseases caused by a deficiency of the β-hexosaminidase A enzyme. This enzyme is composed of two polypeptide chains designated the α- and β- subunits and it interacts with the GM2 activator protein. The HEXA and HEXB genes encode the α-subunit and the β-subunit, respectively. Mutations in these genes are causative of Tay-Sachs disease (HEXA) and Sandhoff disease (HEXB). We analyzed the complete HEXA gene in 34 Spanish patients with Tay-Sachs disease and the HEXB gene in 14 Spanish patients with Sandhoff disease. We identified 27 different mutations, 14 of which were novel, in the HEXA gene and 14 different mutations, 8 of which unreported until now, in the HEXB gene, and we attempted to correlate these mutations with the clinical presentation of the patients. We found a high frequency of c.459+5G>A (IVS4+5G>A) mutation in HEXA affected patients, 22 of 68 alleles, which represent the 32.4%. This is the highest percentage found of this mutation in a population. All patients homozygous for mutation c.459+5G>A presented with the infantile form of the disease and, as previously reported, patients carrying mutation p.R178H in at least one of the alleles presented with a milder form. In HEXB affected patients, the novel deletion c.171delG accounts for 21.4% of the mutant alleles (6/28). All patients with this deletion showed the infantile form of the disease. The Spanish GM2 gangliosidoses affected patients show a great mutational heterogeneity as seen in other inherited lisosomal diseases in this country. PMID:22789865

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

    PubMed Central

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

    2005-01-01

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

  8. [A case of multifocal motor neuropathy with IgM lambda anti-GM1 antibody and IgM kappa paraprotein reacting exclusively with GM2].

    PubMed

    Arai, Motomi; Kusunoki, Susumu

    2009-01-01

    A 57-year-old previously healthy woman visited our clinic complaining of frequent muscle cramps and progressive weakness in the hands and fingers for 3 years. On examination, cranial nerves were unremarkable. There were moderate weakness and mild muscle wasting with fasciculation in the left thumb flexor and interossei on both sides. Tendon reflexes were hypoactive. There were no pathologic reflexes or sensory deficit. The cerebrospinal fluid was unremarkable. Nerve conduction studies demonstrated conduction block in the right ulnar nerve. Compound muscle action potential in the left median nerve was low-normal. Distal motor latencies, motor and sensory nerve conduction velocities were normal in all nerves tested. A diagnosis of multifocal motor neuropathy was made. Two courses of intravenous immunoglobulin infusion gave no beneficial effects. The patient had IgM kappa monoclonal gammopathy of undetermined significance. Her serum IgM reacted with GM2, GM1, and GA1 but not with GD1a, GD1b, GD3, GalNAc-GD1a, GT1b, GQ1b, galactocerebroside, or sulfated glucuronyl paragloboside. IgM kappa paraprotein reacted exclusively with GM2. Only IgM lambda bound to GM1 and GA1, suggesting the possibility that another paraprotein, though undetectable by immunoelectrohoresis, had a reactivity with GM1 and GA1. This case showed previously unreported antigenic specificity of paraproteins in cases of MMN. PMID:19348179

  9. Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency

    PubMed Central

    2013-01-01

    Background Canine GM1 gangliosidosis is a fatal disease in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan and is maintained as a standard breed in many countries. Therefore, it is important to control and reduce the prevalence of GM1 gangliosidosis for maintaining the quality of this breed and to ensure supply of healthy dogs to prospective breeders and owners. This molecular epidemiological survey was performed to formulate an effective strategy for the control and prevention of this disease. Results The survey was carried out among 590 clinically unaffected Shiba Inu dogs from the 8 districts of Japan, and a genotyping test was used to determine nation-wide and regional carrier frequencies. The number and native district of affected dogs identified in 16 years from 1997 to June 2013 were also surveyed retrospectively. Of the 590 dogs examined, 6 dogs (1.02%, 6/590) were carriers: 3 dogs (2.27%, 3/132) from the Kinki district and the other 3 dogs from the Hokkaido, Kanto, and Shikoku districts. The retrospective survey revealed 23 affected dogs, among which, 19 dogs (82.6%) were born within the last 7 years. Of the 23 affected dogs, 12 dogs (52.2%) were from the Kinki district. Pedigree analysis demonstrated that all the affected dogs and carriers with the pedigree information have a close blood relationship. Conclusions Our results showed that the current carrier frequency for GM1 gangliosidosis is on the average 1.02% in Japan and rather high in the Kinki district, which may be related to the high prevalence observed over the past 16 years in this region. This observation suggests that carrier dogs are distributed all over Japan; however, kennels in the Kinki district may face an increased risk of GM1 gangliosidosis. Therefore, for effective control and prevention of this disease, it is necessary to examine as many breeding dogs as possible from all regions of Japan, especially from kennels located in areas with high prevalence

  10. iCataly-PseAAC: Identification of Enzymes Catalytic Sites Using Sequence Evolution Information with Grey Model GM (2,1).

    PubMed

    Xiao, Xuan; Hui, Meng-Juan; Liu, Zi; Qiu, Wang-Ren

    2015-12-01

    Enzymes play pivotal roles in most of the biological reaction. The catalytic residues of an enzyme are defined as the amino acids which are directly involved in chemical catalysis; the knowledge of these residues is important for understanding enzyme function. Given an enzyme, which residues are the catalytic sites, and which residues are not? This is the first important problem for in-depth understanding the catalytic mechanism and drug development. With the explosive of protein sequences generated during the post-genomic era, it is highly desirable for both basic research and drug design to develop fast and reliable method for identifying the catalytic sites of enzymes according to their sequences. To address this problem, we proposed a new predictor, called iCataly-PseAAC. In the prediction system, the peptide sample was formulated with sequence evolution information via grey system model GM(2,1). It was observed by the rigorous jackknife test and independent dataset test that iCataly-PseAAC was superior to exist predictions though its only use sequence information. As a user-friendly web server, iCataly-PseAAC is freely accessible at http://www.jci-bioinfo.cn/iCataly-PseAAC. A step-by-step guide has been provided on how to use the web server to get the desired results for the convenience of most experimental scientists. PMID:26077845

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

    PubMed Central

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

    2012-01-01

    Deficiencies of lysosomal β-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 β-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 β-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

  12. Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

    PubMed

    Thonhofer, Martin; Weber, Patrick; Santana, Andres Gonzalez; Fischer, Roland; Pabst, Bettina M; Paschke, Eduard; Schalli, Michael; Stütz, Arnold E; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G

    2016-03-01

    From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis. PMID:26838810

  13. Synthesis of C-5a-substituted derivatives of 4-epi-isofagomine: notable β-galactosidase inhibitors and activity promotors of GM1-gangliosidosis related human lysosomal β-galactosidase mutant R201C.

    PubMed

    Thonhofer, Martin; Weber, Patrick; Gonzalez Santana, Andres; Tysoe, Christina; Fischer, Roland; Pabst, Bettina M; Paschke, Eduard; Schalli, Michael; Stütz, Arnold E; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G

    2016-06-24

    From an easily available partially protected analog of 1-deoxy-L-gulo-nojirimycin, by chain-branching at C-4 and suitable modification, lipophilic analogs of the powerful β-D-galactosidase inhibitor 4-epi-isofagomine have been prepared. New compounds exhibit considerably improved inhibitory activities when compared with the unsubstituted parent compound and may serve as leads toward new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease. PMID:27063389

  14. Characterization of beta-galactosidase mutations Asp332-->Asn and Arg148-->Ser, and a polymorphism, Ser532-->Gly, in a case of GM1 gangliosidosis.

    PubMed Central

    Zhang, S; Bagshaw, R; Hilson, W; Oho, Y; Hinek, A; Clarke, J T; Callahan, J W

    2000-01-01

    We have identified and characterized three missense mutations in a patient with type 1 G(M1) gangliosidosis, namely a substitution of G for A at nucleotide position 1044 (G1044-->A; in exon 10) on one allele, which converts Asp(332) into asparagine, and both a mutation (C492-->A in exon 4, leading to the amino acid change of Arg(148)-->Ser) and a polymorphism (A1644-->G in exon 15, leading to a change of Ser(532)-->Gly) on the other allele. This patient had less than 1% residual beta-galactosidase activity and minimally detectable levels of immunoreactive beta-galactosidase protein in fibroblasts. To account for the above findings, a series of expression and immunolocalization studies were undertaken to assess the impact of each mutation. Transient overexpression in COS-1 cells of cDNAs encoding Asp(332)Asn, Arg(148)Ser and Ser(532)Gly mutant beta-galactosidases produced abundant amounts of precursor beta-galactosidase, with activities of 0, 84 and 81% compared with the cDNA clone for wild-type beta-galactosidase (GP8). Since the level of vector-driven expression is much less in Chinese hamster ovary (CHO) cells than in COS-1 cells, and we knew that exogenous beta-galactosidase undergoes lysosomal processing when expressed in these cells, transient expression studies were performed of Arg(148)Ser and Ser(532)Gly, which yielded active forms of the enzyme. In this case, the Arg(148)Ser and Ser(532)Gly products gave rise to 11% and 86% of the control activity respectively. These results were not unexpected, since the Arg(148)Ser mutation introduced a major conformational change into the protein, and we anticipated that it would be degraded in the endoplasmic reticulum (ER), whereas the polymorphism was expected to produce near-normal activity. To examine the effect of the Asp(332)Asn mutation on the catalytic activity, we isolated CHO clones permanently transfected with the Asp(332)Asn and Asp(332)Glu constructs, purified the enzymes by substrate

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

    SciTech Connect

    Petroulakis, E.; Cao, Z.; Salo, T.

    1994-09-01

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

  16. Reversibility of neuropathology in Tay–Sachs-related diseases

    PubMed Central

    Cachón-González, María-Begoña; Wang, Susan Z.; Ziegler, Robin; Cheng, Seng H.; Cox, Timothy M.

    2014-01-01

    The GM2 gangliosidoses are progressive neurodegenerative disorders due to defects in the lysosomal β-N-acetylhexosaminidase system. Accumulation of β-hexosaminidases A and B substrates is presumed to cause this fatal condition. An authentic mouse model of Sandhoff disease (SD) with pathological characteristics resembling those noted in infantile GM2 gangliosidosis has been described. We have shown that expression of β-hexosaminidase by intracranial delivery of recombinant adeno-associated viral vectors to young adult SD mice can prevent many features of the disease and extends lifespan. To investigate the nature of the neurological injury in GM2 gangliosidosis and the extent of its reversibility, we have examined the evolution of disease in the SD mouse; we have moreover explored the effects of gene transfer delivered at key times during the course of the illness. Here we report greatly increased survival only when the therapeutic genes are expressed either before the disease is apparent or during its early manifestations. However, irrespective of when treatment was administered, widespread and abundant expression of β-hexosaminidase with consequent clearance of glycoconjugates, α-synuclein and ubiquitinated proteins, and abrogation of inflammatory responses and neuronal loss was observed. We also show that defects in myelination occur in early life and cannot be easily resolved when treatment is given to the adult brain. These results indicate that there is a limited temporal opportunity in which function and survival can be improved—but regardless of resolution of the cardinal pathological features of GM2 gangliosidosis, a point is reached when functional deterioration and death cannot be prevented. PMID:24057669

  17. Reversibility of neuropathology in Tay-Sachs-related diseases.

    PubMed

    Cachón-González, María-Begoña; Wang, Susan Z; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2014-02-01

    The GM2 gangliosidoses are progressive neurodegenerative disorders due to defects in the lysosomal β-N-acetylhexosaminidase system. Accumulation of β-hexosaminidases A and B substrates is presumed to cause this fatal condition. An authentic mouse model of Sandhoff disease (SD) with pathological characteristics resembling those noted in infantile GM2 gangliosidosis has been described. We have shown that expression of β-hexosaminidase by intracranial delivery of recombinant adeno-associated viral vectors to young adult SD mice can prevent many features of the disease and extends lifespan. To investigate the nature of the neurological injury in GM2 gangliosidosis and the extent of its reversibility, we have examined the evolution of disease in the SD mouse; we have moreover explored the effects of gene transfer delivered at key times during the course of the illness. Here we report greatly increased survival only when the therapeutic genes are expressed either before the disease is apparent or during its early manifestations. However, irrespective of when treatment was administered, widespread and abundant expression of β-hexosaminidase with consequent clearance of glycoconjugates, α-synuclein and ubiquitinated proteins, and abrogation of inflammatory responses and neuronal loss was observed. We also show that defects in myelination occur in early life and cannot be easily resolved when treatment is given to the adult brain. These results indicate that there is a limited temporal opportunity in which function and survival can be improved-but regardless of resolution of the cardinal pathological features of GM2 gangliosidosis, a point is reached when functional deterioration and death cannot be prevented. PMID:24057669

  18. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase.

    PubMed

    Hofer, Doris; Paul, Karl; Fantur, Katrin; Beck, Michael; Bürger, Friederike; Caillaud, Catherine; Fumic, Ksenija; Ledvinova, Jana; Lugowska, Agnieszka; Michelakakis, Helen; Radeva, Briguita; Ramaswami, Uma; Plecko, Barbara; Paschke, Eduard

    2009-08-01

    Alterations in GLB1, the gene coding for acid beta-D-galactosidase (beta-Gal), can result in GM1 gangliosidosis (GM1), a neurodegenerative disorder, or in Morquio B disease (MBD), a phenotype with dysostosis multiplex and normal central nervous system (CNS) function. While most MBD patients carry a common allele, c.817TG>CT (p.W273L), only few of the >100 mutations known in GM1 can be related to a certain phenotype. In 25 multiethnic patients with GM1 or MBD, 11 missense mutations were found as well as one novel insertion and a transversion causing aberrant gene products. Except c.602G>A (p.R201H) and two novel alleles, c.592G>T (p.D198Y) and c.1189C>G (p.P397A), all mutants resulted in significantly reduced beta-Gal activities (<10% of normal) upon expression in COS-1 cells. Although c.997T>C (p.Y333H) expressed 3% of normal activity, the mutant protein was localized in the lysosomal-endosomal compartment. A homozygous case presented with late infantile GM1, while a heterozygous, juvenile case carried p.Y333H together with p.R201H. This allele, recently found in homozygous MBD, gives rise to rough endoplasmic reticulum (RER)-located beta-Gal precursors. Thus, unlike classical MBD, the phenotype of heterozygotes carrying p.R201H may rather be determined by poorly active, properly transported products of the counter allele than by the mislocalized p.R201H precursors. PMID:19472408

  19. Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients.

    PubMed

    Milone, Giuseppe; Leotta, Salvatore; Battiato, Katia; Murgano, Pamela; Mercurio, Salvatore; Strano, Aurora; Poidomani, Massimo; Coppoletta, Stefania; Mauro, Elisa; Avola, Giuseppe; Pinto, Valeria; Camuglia, Maria Grazia; Giustolisi, Rosario

    2007-10-01

    We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m(2) + G-CSF 10 microg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN) > 0.5 x 10(9)/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 microg/kg resulted in a maximum length of neutropenia (PMN < 0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment. PMID:17917963

  20. A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission.

    PubMed

    O'Cearbhaill, Roisin E; Ragupathi, Govind; Zhu, Jianglong; Wan, Qian; Mironov, Svetlana; Yang, Guangbin; Spassova, Maria K; Iasonos, Alexia; Kravetz, Sara; Ouerfelli, Ouathek; Spriggs, David R; Danishefsky, Samuel J; Sabbatini, Paul J

    2016-01-01

    We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011-Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient's pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36-68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2-39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability. PMID:27110823

  1. A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission

    PubMed Central

    O’Cearbhaill, Roisin E.; Ragupathi, Govind; Zhu, Jianglong; Wan, Qian; Mironov, Svetlana; Yang, Guangbin; Spassova, Maria K.; Iasonos, Alexia; Kravetz, Sara; Ouerfelli, Ouathek; Spriggs, David R.; Danishefsky, Samuel J.; Sabbatini, Paul J.

    2016-01-01

    We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011–Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient’s pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36–68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2–39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability. PMID:27110823

  2. Integrated multiplex ligation dependent probe amplification (MLPA) assays for the detection of alterations in the HEXB, GM2A and SMARCAL1 genes to support the diagnosis of Morbus Sandhoff, M. Tay-Sachs variant AB and Schimke immuno-osseous dysplasia in humans.

    PubMed

    Sobek, Anna K U; Evers, Christina; Dekomien, Gabriele

    2013-02-01

    Multiplex ligation dependent probe amplification (MLPA) assays were designed for the genes HEXB (OMIM: 606873), GM2A (OMIM: 613109) and SMARCAL1 (OMIM: 606622) of humans. Two sets of synthetic MLPA probes for these coding exons were tested. Changes in copy numbers were detected as well as single nucleotide polymorphisms (SNPs) by complementary DNA sequence analyses. The MLPA method was shown to be reliable for mutation detection and identified five published and 12 new mutations. In all cases from a Morbus Sandhoff cohort of patients, exclusively one variation in copy number was observed and linked to a nucleotide alteration called c.1614-14C>A. This deletion comprised exons 1-5. One of these cases is described in detail. Deletions were neither detected in the GM2A nor the SMARCAL1 genes. The MLPA assays complement routine diagnostics for M. Sandhoff (OMIM: 268800), M. Tay-Sachs variant AB (OMIM: 272750) and Schimke immuno-osseous dysplasia (OMIM: 242900). PMID:23010210

  3. The insecticidal effect of diatomaceous earth against adults and nymphs of Blattella germanica

    PubMed Central

    Hosseini, Seyyed Akbar; Bazrafkan, Sahar; Vatandoost, Hassan; Abaei, Mohammad Reza; Ahmadi, Mussa Soleimani; Tavassoli, Maryam; Shayeghi, Mansoreh

    2014-01-01

    Objective To evaluate the insecticidal effect of diatomaceous earth (DE) against adults and nymphs of Blattella germanica. Methods This cross sectional study has been done on the laboratory strain of German cockroaches. Two stages, nymph and adult, were exposed to six dose rates of the DE, 2.5, 5, 10, 15, 20 and 25 g/m2, at 24, 48 and 72 h exposure period. Mortality (number of dead cockroaches) was assessed after 24 h. Other exposed specimens were transferred to the beakers contained food and water for counting the retard mortality rate after 1 week. Results Increasing in dose rates of DE increased mortality rate, so that the lowest and highest mortality rates were observed in 2.5 and 25 g/m2, respectively. The results of the statistical analysis showed no significant difference in the lethality of 50% of DE plus water on the German cockroach nymphs. Conclusions Due to the resistance of German cockroach against organochloride, organophosphorus, carbamate and pyrethriodes insecticides, it is suggested to use DE for insect's control. PMID:25183087

  4. Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease.

    PubMed

    Karumuthil-Melethil, Subha; Nagabhushan Kalburgi, Sahana; Thompson, Patrick; Tropak, Michael; Kaytor, Michael D; Keimel, John G; Mark, Brian L; Mahuran, Don; Walia, Jagdeep S; Gray, Steven J

    2016-07-01

    GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 ganglioside (GM2) in neuronal tissue. Two of these are due to the deficiency of the heterodimeric (α-β), "A" isoenzyme of lysosomal β-hexosaminidase (HexA). Mutations in the α-subunit (encoded by HEXA) lead to Tay-Sachs disease (TSD), whereas mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). The third form results from a deficiency of the GM2 activator protein (GM2AP), a substrate-specific cofactor for HexA. In their infantile, acute forms, these diseases rapidly progress with mental and psychomotor deterioration resulting in death by approximately 4 years of age. After gene transfer that overexpresses one of the deficient subunits, the amount of HexA heterodimer formed would empirically be limited by the availability of the other endogenous Hex subunit. The present study used a new variant of the human HexA α-subunit, μ, incorporating critical sequences from the β-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP- GM2 complex. We report the design of a compact adeno-associated viral (AAV) genome using a synthetic promoter-intron combination to allow self-complementary (sc) packaging of the HEXM gene. Also, a previously published capsid mutant, AAV9.47, was used to deliver the gene to brain and spinal cord while having restricted biodistribution to the liver. The novel capsid and cassette design combination was characterized in vivo in TSD mice for its ability to efficiently transduce cells in the central nervous system when delivered intravenously in both adult and neonatal mice. This study demonstrates that the modified HexM is capable of degrading long-standing GM2 storage in mice, and it further demonstrates the potential of this novel scAAV vector design to facilitate widespread distribution of the HEXM gene or potentially other similar-sized genes to the nervous system

  5. IUE observations of RW Hydrae /gM2 + pec/

    NASA Technical Reports Server (NTRS)

    Kafatos, M.; Michalitsianos, A. G.; Hobbs, R. W.

    1980-01-01

    Analysis of the intense UV continuum observed between 1100 and 2000 A suggested that observations of the late type star RW Hya is a binary system in which the secondary is the central star of a planetary nebula. The UV spectrum is characterized by semiforbidden and allowed transition lines, of which the C IV doublet is particularly strong. Tidal interaction from the M giant is proposed as a method of forming a nebula with the characteristic densities inferred from the UV line analysis. RW Hya is suggested as a possible source of soft X-ray emission if material is accreting onto the surface of the secondary.

  6. Genetics Home Reference: GM1 gangliosidosis

    MedlinePlus

    ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  7. Adult Compacts.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    This bulletin focuses on adult compacts, three-way agreements among employers, potential employees, and trainers to provide the right kind of quality training to meet the employers' requirements. Part 1 is an executive summary of a report of the Adult Compacts Project, which studied three adult compacts in Birmingham and Loughborough, England, and…

  8. Urinary tract infection - adults

    MedlinePlus

    Bladder infection - adults; UTI - adults; Cystitis - bacterial - adults; Pyelonephritis - adults; Kidney infection - adults ... to the hospital if you: Are an older adult Have kidney stones or changes in the anatomy ...

  9. Adult Strabismus

    MedlinePlus

    ... will likely improve the double vision and depth perception. Also, strabismus affects adults in emotional, social, and ... muscle surgery is usually not severe. Headache, pulling sensation with eye movement and foreign body sensation in ...

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

    SciTech Connect

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. )

    1989-04-01

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

  11. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... the upper airway for obstructive sleep apnea in adults. Sleep . 2010;33:1408-1413. PMID: 21061864 www. ...

  12. Impact of prehypertension on left ventricular mass and QT dispersion in adult black Nigerians

    PubMed Central

    Ale, OK; Ajuluchukwu, JN; Oke, DA; Mbakwem, AC

    2014-01-01

    Summary Background Prehypertension has been associated with target-organ damage. This study sought to determine the impact of prehypertension (PHT) on QT dispersion and left ventricular hypertrophy (LVH) in adult black Nigerians. Methods One hundred and one subjects with office blood pressure (BP) < 140/90 mmHg were categorised according to their office BP into normotensive (BP < 120/80 mmHg, n = 57) and prehypertensive (BP 120–139/80–89 mmHg, n = 44) groups. Echocardiography and electrocardiography (ECG) were performed on the subjects. Results Thirty-four males aged 53.65 ± 16.33 years and 67 females aged 52.42 ± 12.00 years were studied. The mean QT interval dispersion (QTd) of the normotensive (38.96 ± 11.06 ms) and prehypertensive (38.41 ± 11.81 ms) groups were similar (p = 0.81). Prehypertensive subjects had higher left ventricular mass (LVM) (165.75 ± 33.21 vs 144.54 ± 35.55 g, p = 0.024), left ventricular mass index 1 (LVMI-1) (91.65 ± 16.84 vs 80.45 ± 18.65 g/m2, p = 0.021) and left ventricular mass index 2 (LVMI-2) (54.96 ± 10.84 vs 47.51 ± 12.00 g/m2.7, p = 0.017). QTd was independent of echocardiographic and electrocardiographic LVH (p > 0.05). Conclusion Compared with normotension, prehypertension is associated with higher LVM but similar QTd. This suggests that structural remodelling precedes electrical remodelling in prehypertension. PMID:24844553

  13. Adult Play.

    ERIC Educational Resources Information Center

    Charles, John M.

    In its broadest context, play can be interpreted as any pleasurable use of discretionary time. Playfulness is an intrinsic feature of being human, and should be viewed in the light of a total lifestyle, not as an occurrence in an isolated time of life. Adult play appears to be an indefinable and controversial concept. A holistic approach should be…

  14. CPR: Adult

    MedlinePlus Videos and Cool Tools

    Refresher Center Home FIRST AID, CPR and AED LIFEGUARDING Refresher Putting It All Together: CPR—Adult (2:03) Refresher videos only utilize this player QUICK LINKS Home RedCross.org Purchase Course Materials Shop Our Store ...

  15. [Neurological presentations of lysosomal diseases in adult patients].

    PubMed

    Sedel, F; Turpin, J-C; Baumann, N

    2007-10-01

    Lysosomal diseases represent a large group of genetic storage disorders characterized by a defect in the catabolism of complex molecules within the lysosome. Effective treatments are now possible for some of them given progresses in bone-marrow transplantation, enzyme replacement therapy and substrate reduction therapy. Neurologists and psychiatrists are concerned by these diseases because they can present in adolescence or adulthood with progressive neuropsychiatric signs. Here we focus on late-onset clinical forms which can be met in an adult neurology or psychiatric department. Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography. PMID:18033028

  16. ADULT EDUCATION OF MIGRANT ADULTS.

    ERIC Educational Resources Information Center

    BEAL, CATHERINE; AND OTHERS

    UNITS ON MIGRANT ADULT EDUCATION, AND A UNIT ON ORGANIZING INFORMAL GROUPS OF MIGRANT WOMEN TO DISCUSS MAINTAINING AND IMPROVING THEIR TEMPORARY HOMES, ARE PRESENTED. THE GOALS OF THE UNIT ON EDUCATION FOR MIGRANT MEN ARE ECONOMIC INDEPENDENCE, BETTER HEALTH AND WELL-BEING, AND BETTER HANDLING OF RESPONSIBILITIES. THE MAIN DIVISIONS OF THE…

  17. [Adult twins].

    PubMed

    Charlemaine, Christiane

    2006-12-31

    This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality. PMID:17352324

  18. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  19. Adult Development and Learning of Older Adults

    ERIC Educational Resources Information Center

    Roberson, Donald N., Jr.

    2005-01-01

    This summary of adult development covers a wide range of authors. Adult development is one way of understanding how the internal and external changes in our lives have an impact on learning. Of particular importance in this work are the developmental issues of older adults. I present various theories of adult development such as linear and…

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

    PubMed

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

    2010-09-01

    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

  1. Adults Need Vaccines, Too!

    MedlinePlus

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  2. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  3. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  4. Panic Disorder among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  5. Bipolar Disorder Among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  6. Major Depression Among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  7. Arizona Adult Education Standards

    ERIC Educational Resources Information Center

    Arizona Department of Education, 2006

    2006-01-01

    Adult education standards are the cornerstone for quality teaching, quality learning, and quality lives. The Arizona Adult Education Standards Initiative (Standards Initiative) represents a proactive effort by Arizona's adult education community to ensure rigor and consistency in program content and student outcomes for adult learners throughout…

  8. Adult Cancers in Adolescents and Young Adults.

    PubMed

    Laurence, Valérie; Marples, Maria; Stark, Daniel P

    2016-01-01

    The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials. Here, we discuss the management of AYAs with 3 of the most common cancers affecting adults, when they emerge in the AYA populations, and therefore are currently met by medical oncologists - breast cancer, colorectal cancer and melanoma. PMID:27595357

  9. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  10. [Factors affecting Diatomaceous earth effectiveness in the control of Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) adults].

    PubMed

    Alves, Luis F A; Oliveira, Daian G P; Neves, Pedro M O J

    2008-01-01

    Diatomaceous earth (DE) is a potential alternative to control the lesser mealworm of poultry farms Alphitobius diaperinus (Panzer). Our study aimed to understand the role of some of the environmental and insect behavioral factors play on DE effectiveness, such as the substrate (chicken food and poultry house litter), temperature and DE repellent activity on lesser mealworm adults. Mortality was higher at the highest temperature (32 masculineC), and it increased with DE concentration (53 and 84% respectively, for concentrations of 86 and 172 g/m(2)) (P < 0.05). The substrate also influenced DE effectiveness: 95% mortality was observed in the feed, against 4% in the poultry litter. Part of these results can be attributed to the removal of DE particles by the poultry bedding, as supported by scanning electron microscopy (SEM) observations and rhodamine concentration on the surface of the insects. As to insect behavior, DE had a repellent effect, since trap capture decreased nearly 50% in traps containing DE as opposed to those containing only food. Therefore, environmental factors do affect the DE effectiveness, and they must be taken into consideration when looking into developing control strategies in the field. PMID:19169561

  11. Patient Eye Examinations - Adults

    MedlinePlus

    ... Examinations, Adults Patient Eye Examinations, Children Refractive Errors Scientists in the Laboratory Visual Acuity Testing Patient Eye Examinations, Adults × Warning message Automatic fallback to the cURL connection method kicked in to handle the request. Result code ...

  12. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  13. Adult Congenital Heart Association

    MedlinePlus

    ... survivable, manageable, yet in the routine years between infancy and adulthood, sometimes forgettable. The Adult Congenital Heart ... understand the continuum of the disease from its infancy. The Adult Congential Heart Association brings together valuable ...

  14. Adult Congenital Heart Association

    MedlinePlus

    ... to ACHA Search The futures of adults with congenital heart disease made brighter by their pasts Get Involved 2016 ... conference theme is "The Changing Landscape of Adult Congenital Heart Disease." Join Us Help us improve the quality of ...

  15. Depression in Older Adults

    ERIC Educational Resources Information Center

    Stickle, Fred; Onedera, Jill D.

    2006-01-01

    The purpose of this article is to address selected aspects of depression in older adults. Specifically, symptoms, risk factors, diagnosis, and interventions for depression in older adults are reviewed.

  16. Adult Learning: A Reader.

    ERIC Educational Resources Information Center

    Sutherland, Peter, Ed.

    This book on adult learning is divided into six sections. Section 1, Cognitive Processes, includes the following chapters: "Cognitive Processes: Contemporary Paradigms of Learning" (Jack Mezirow); "Information Processing, Memory, Age and Adult Learning" (Gillian Boulton-Lewis); "Adult Learners' Metacognitive Behaviour in Higher Education" (Barry…

  17. Aspects of Adult Education.

    ERIC Educational Resources Information Center

    Chandrasekhar, Rajkumari

    This book presents an overview of and prescription for adult education in India. Following an introduction to the problem of illiteracy in India, the book's 14 chapters cover a broad spectrum of adult education issues. Topics discussed include adult education and national development; roles of voluntary organizations, universities, colleges, and…

  18. Dimensions of Adult Learning

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    2004-01-01

    This broad introduction to adult and postcompulsory education offers an overview of the field for students, adult educators and workplace trainers. The book establishes an analytical framework to emphasize the nature of learning and agency of learners; examines the core knowledge and skills that adult educators need; discusses policy, research and…

  19. Kids Who Outwit Adults.

    ERIC Educational Resources Information Center

    Seita, John R.; Brendtro, Larry K.

    Kids who distrust adults are highly skilled at hiding their real nature and resisting change. Most adults shun such youths or get mired in conflict with them. Punitive get tough practices as well as traditional flaw-fixing treatment are reactive strategies that often drive these youths further from adult bonds and reinforce oppositional and…

  20. Adult Learners in Universities.

    ERIC Educational Resources Information Center

    Baker, Janette, Ed.

    1981-01-01

    Theories on adult development and learning and some of the Ontario universities' programs and services for the adult learner are examined, and Athabasca University, Alberta's answer to the British Open University, is described. Peter O'Donnell discusses adult learners' needs and explains how Athabasca University serves this specific type of…

  1. Adult Competency Education Resources.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of brief descriptions of 20 current resources for Adult Performance Level (APL) and Adult Competency Education (ACE) programs, this guide was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are already involved with APL/ACE programs. Each citation contains information…

  2. Adult Competency Education Profile.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of abstracts of 120 current Adult Performance Level (APL) and Adult Competency Education (ACE) federally supported projects being conducted in 34 States and the District of Columbia, this project profile was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are currently…

  3. Adult Education in Turkey

    ERIC Educational Resources Information Center

    Miser, Rifat; Ural, Ozana; Ünlühisarýklý, Özlem

    2013-01-01

    This study investigates the situation and practices of adult education in Turkey in terms of (a) participants, (b) providers, and (c) program areas. The data were derived from published statistical data and one-to-one interaction with adult education providers when such data are unavailable. Turkey has a long tradition of adult education with…

  4. Navajo Adult Basic Education.

    ERIC Educational Resources Information Center

    Navajo Community Coll., Tsaile, AZ.

    The objectives of this Special Experimental Demonstration Project in Adult Basic Education for the Navajo were: (1) to raise the educational and social level of Navajo adult students who are unable to read, write, and speak English; (2) to assist the Navajo adult students to take advantage of occupational and vocational training programs; (3) to…

  5. The Adult Experience.

    ERIC Educational Resources Information Center

    Belsky, Janet

    The 14 chapters of this textbook chronicle adult development from youth through old age, emphasizing both research and interviews with adults at various stages in their lives. Topics covered include the following: (1) the academic field of adult development; (2) theories and research methods; (3) aging and disease prevention; (4) sexuality and…

  6. Adult Numeracy Core Curriculum.

    ERIC Educational Resources Information Center

    Steeds, Andrew, Ed.

    Designed primarily for adult literacy teachers and tutors, this curriculum describes the content of what should be taught in numeracy programs in order to meet the individual needs of adults through the selection and teaching of skills appropriate to those adults' needs. An introduction describes national standards and qualifications, learners,…

  7. Adults and GNVQs.

    ERIC Educational Resources Information Center

    Pettitt, Aidan

    1996-01-01

    This document is intended for further education colleges in the United Kingdom wishing to extend their General National Vocational Qualification (GNVQ) provision to adults, extend their adult students' options for accreditation, or review the suitability of different qualification routes for adults. It presents information about the development of…

  8. Canadian Adult Basic Education.

    ERIC Educational Resources Information Center

    Brooke, W. Michael, Comp.

    "Trends," a publication of the Canadian Association for Adult Education, is a collection of abstracts on selected subjects affecting adult education; this issue is on adult basic education (ABE). It covers teachers and teacher training, psychological factors relating to the ABE teacher and students, manuals for teachers, instructional materials,…

  9. Adult Survival Skills Assessment.

    ERIC Educational Resources Information Center

    Walsko, Gregory M.

    The purpose of this instrument is to supplement data from the Adult Basic Learning Examination in assessing the functional level of adults in daily situations. It may also be used as a teaching tool for adults requesting tutoring in specific concepts and skills presented in the instrument. This instrument is an informal assessment instrument and…

  10. Adults Role in Bullying

    ERIC Educational Resources Information Center

    Notar, Charles E.; Padgett, Sharon

    2013-01-01

    Do adults play a role in bullying? Do parents, teachers, school staff, and community adult leaders influence bullying behavior in children and teenagers? This article will focus on research regarding all adults who have almost daily contact with children and teens and their part in how bullying is identified, addressed, and prevented. This article…

  11. Adult Learning Assumptions

    ERIC Educational Resources Information Center

    Baskas, Richard S.

    2011-01-01

    The purpose of this study is to examine Knowles' theory of andragogy and his six assumptions of how adults learn while providing evidence to support two of his assumptions based on the theory of andragogy. As no single theory explains how adults learn, it can best be assumed that adults learn through the accumulation of formal and informal…

  12. Adult Education in Greece

    ERIC Educational Resources Information Center

    Kokkos, Alexios

    2008-01-01

    The central aim of this article is to analyse the current situation of adult education in Greece. The article focuses on the following points: (a) the degree of participation in programmes of continuing professional training and general adult education courses, (b) the quality and the outcomes of the adult education provision in Greece, and (c)…

  13. An Adult ESL Curriculum.

    ERIC Educational Resources Information Center

    South Carolina Literacy Resource Center, Columbia.

    This curriculum framework for adult literacy was written by 21 South Carolina adult English-as-a-Second-Language (ESL) instructors, as submitted to the South Carolina Literacy Resource Center. It is based on current theories in the fields of adult education and second language acquisition and is designed to be flexible so that it may be adapted to…

  14. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    PubMed Central

    Goláň, Lubor; Goker-Alpan, Ozlem; Holida, Myrl; Kantola, Ikka; Klopotowski, Mariusz; Kuusisto, Johanna; Linhart, Aleš; Musial, Jacek; Nicholls, Kathleen; Gonzalez-Rodriguez, Derlis; Sharma, Reena; Vujkovac, Bojan; Chang, Peter; Wijatyk, Anna

    2015-01-01

    Purpose Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. Patients and methods This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies. Results Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (−1.21 mL/min/1.73 m2 vs −3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (−1.05 nmol/mL vs −2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the

  15. Safeguarding vulnerable adults.

    PubMed

    Griffith, Richard

    Nurses have a professional duty to safeguard vulnerable adults from abuse under the provisions of the Nursing and Midwifery Council's (NMC) revised Code (2015). With adult abuse continuing to increase, all members of the nursing team are well placed to identify and take action to safeguard the vulnerable. This article sets out how the Care Act 2014 seeks to improve the safeguarding of vulnerable adults and the role of nurses in that process. PMID:26153813

  16. Characterization of Inducible Models of Tay-Sachs and Related Disease

    PubMed Central

    Sargeant, Timothy J.; Drage, Deborah J.; Wang, Susan; Apostolakis, Apostolos A.

    2012-01-01

    Tay-Sachs and Sandhoff diseases are lethal inborn errors of acid β-N-acetylhexosaminidase activity, characterized by lysosomal storage of GM2 ganglioside and related glycoconjugates in the nervous system. The molecular events that lead to irreversible neuronal injury accompanied by gliosis are unknown; but gene transfer, when undertaken before neurological signs are manifest, effectively rescues the acute neurodegenerative illness in Hexb−/− (Sandhoff) mice that lack β-hexosaminidases A and B. To define determinants of therapeutic efficacy and establish a dynamic experimental platform to systematically investigate cellular pathogenesis of GM2 gangliosidosis, we generated two inducible experimental models. Reversible transgenic expression of β-hexosaminidase directed by two promoters, mouse Hexb and human Synapsin 1 promoters, permitted progression of GM2 gangliosidosis in Sandhoff mice to be modified at pre-defined ages. A single auto-regulatory tetracycline-sensitive expression cassette controlled expression of transgenic Hexb in the brain of Hexb−/− mice and provided long-term rescue from the acute neuronopathic disorder, as well as the accompanying pathological storage of glycoconjugates and gliosis in most parts of the brain. Ultimately, late-onset brainstem and ventral spinal cord pathology occurred and was associated with increased tone in the limbs. Silencing transgenic Hexb expression in five-week-old mice induced stereotypic signs and progression of Sandhoff disease, including tremor, bradykinesia, and hind-limb paralysis. As in germline Hexb−/− mice, these neurodegenerative manifestations advanced rapidly, indicating that the pathogenesis and progression of GM2 gangliosidosis is not influenced by developmental events in the maturing nervous system. PMID:23028353

  17. Characterization of inducible models of Tay-Sachs and related disease.

    PubMed

    Sargeant, Timothy J; Drage, Deborah J; Wang, Susan; Apostolakis, Apostolos A; Cox, Timothy M; Cachón-González, M Begoña

    2012-09-01

    Tay-Sachs and Sandhoff diseases are lethal inborn errors of acid β-N-acetylhexosaminidase activity, characterized by lysosomal storage of GM2 ganglioside and related glycoconjugates in the nervous system. The molecular events that lead to irreversible neuronal injury accompanied by gliosis are unknown; but gene transfer, when undertaken before neurological signs are manifest, effectively rescues the acute neurodegenerative illness in Hexb-/- (Sandhoff) mice that lack β-hexosaminidases A and B. To define determinants of therapeutic efficacy and establish a dynamic experimental platform to systematically investigate cellular pathogenesis of GM2 gangliosidosis, we generated two inducible experimental models. Reversible transgenic expression of β-hexosaminidase directed by two promoters, mouse Hexb and human Synapsin 1 promoters, permitted progression of GM2 gangliosidosis in Sandhoff mice to be modified at pre-defined ages. A single auto-regulatory tetracycline-sensitive expression cassette controlled expression of transgenic Hexb in the brain of Hexb-/- mice and provided long-term rescue from the acute neuronopathic disorder, as well as the accompanying pathological storage of glycoconjugates and gliosis in most parts of the brain. Ultimately, late-onset brainstem and ventral spinal cord pathology occurred and was associated with increased tone in the limbs. Silencing transgenic Hexb expression in five-week-old mice induced stereotypic signs and progression of Sandhoff disease, including tremor, bradykinesia, and hind-limb paralysis. As in germline Hexb-/- mice, these neurodegenerative manifestations advanced rapidly, indicating that the pathogenesis and progression of GM2 gangliosidosis is not influenced by developmental events in the maturing nervous system. PMID:23028353

  18. Gangliosidoses.

    PubMed

    Patterson, Marc C

    2013-01-01

    The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-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

  19. Alternative Programming for Adults.

    ERIC Educational Resources Information Center

    Flint, Thomas A.; Frey, Ruth

    2003-01-01

    The Council for Adult and Experiential Learning is currently cataloguing alternative programming features that are most effective with adult students in a best practices inventory organized around a framework of high-level descriptive principles of effectiveness. This chapter identifies a few interesting features from a quick survey of this…

  20. Adult Education in Germany.

    ERIC Educational Resources Information Center

    Huddleston, John

    This study is limited essentially to adult education in West Germany, although the historical sections include references to earlier experiences and experiments in areas now Russian-occupied. The terms "adult edcuation" and "workers' education" are clarified. Both are presented as separate movements. Brief reference is made to political, social,…

  1. Adult Learning Matters

    ERIC Educational Resources Information Center

    Thomson, Rachel

    2009-01-01

    Adult Learners' Week--which is supported by the Department for Innovation, Universities and Skills and the European Social Fund, amongst a raft of other organisations--is all about raising demand for learning. At its core, the campaign is about encouraging under-represented groups--including low-skilled, unemployed and low-paid adults and those…

  2. Teachers of Adults Will...

    ERIC Educational Resources Information Center

    Pankowski, Mary L.

    1975-01-01

    The article lists the 12 competencies of adult education teachers that are considered essential to assist adults in achieving instructional goals and objectives. Following the listing a brief justification and examples of ways to evaluate teacher competencies are discussed. (Author/BP)

  3. Recruiting Adult Education Students.

    ERIC Educational Resources Information Center

    Learning Resources Network, Manhattan, KS.

    This document is the first nationwide compilation of successful recruiting techniques for students in adult basic education, literacy, General Educational Development classes, and adult high school degree programs. Information for the publication was gathered from a literature search and other sources, especially "Reaching the Least Educated," a…

  4. Counseling Adult Adoptees

    ERIC Educational Resources Information Center

    Corder, Kate

    2012-01-01

    This review presents various resources about working with adult adoptees in order to inform counselors in their practice. Topics covered include basics of adoption, including types of adoption and adoption statistics; possible issues adult adoptees may face; and suggestions and implications for counselors. The article addresses some of the serious…

  5. Adult Education and Development.

    ERIC Educational Resources Information Center

    Hinzen, Heribert, Ed.

    2002-01-01

    This document contains 19 papers on adult education and development worldwide. The following papers are included: "Editorial" (Heribert Hinzen); "Lifelong Learning in Europe: Moving towards EFA (Dakar Framework for Action on Education for All) Goals and the CONFINTEA V Agenda" (Sofia Conference on Adult Education); "Poverty and Schooling in the…

  6. Adult Day Services

    MedlinePlus

    A Smart Choice Adult Day Services Comparison At-a-Glance 1 Adult Day Services Assisted Living Home Care Nursing Homes Live at home with family ... supervision Nursing care available as needed during the day Flexibility to receive care only on days when ...

  7. Today's Adult Students

    ERIC Educational Resources Information Center

    Reese, Susan

    2012-01-01

    Who are the adult students in career and technical education (CTE) today? There is not one simple answer to that question. Some are young with little life experience, while others are returning to the workforce and learning new skills to reinvent themselves. Whatever the case, educating adult students is an integral part of ACTE's mission, and the…

  8. Adult Learning and Education

    ERIC Educational Resources Information Center

    Rubenson, Kjell, Ed.

    2011-01-01

    As individuals and societies try to respond to fundamental economic and social transformation, the field of adult learning and education is rapidly getting increased attention and new topics for research on adult learning have emerged. This collection of articles from the International Encyclopedia of Education 3e offers practitioners and…

  9. Dialogue and Adult Learning.

    ERIC Educational Resources Information Center

    Tarule, Jill Mattuck

    1992-01-01

    Discussion of the role of language and dialogue in adult learning looks at dialogue as epistemology and at talk as learning. It is proposed that the challenge in teaching and retaining adult learners is to create dialogue-rich classrooms, including many external speech opportunities, small-group discussion, and group projects. (MSE)

  10. Libraries and Adult Learners.

    ERIC Educational Resources Information Center

    Josey, E. J., Ed.

    1982-01-01

    Of the 13 essays presented in this special issue on libraries and adult education, 8 focus on programs and services from the public library for adult learners. These essays provide information on: (1) an Education Information Centers Program (EIC) designed to complement employment skills training provided under the Comprehensive Employment and…

  11. Adult Education in Finland

    ERIC Educational Resources Information Center

    Szekely, Radu

    2006-01-01

    Ever since the first ideas of national independence appeared in Finland, adult education has played an essential role in shaping the destiny of the Finns. With a history of almost 130 years, during which it has continuously increased in quality and quantity, the Finnish adult education system has ensured that Finland stays among the most…

  12. Adult Education Regional Planning

    ERIC Educational Resources Information Center

    California Community Colleges, Chancellor's Office, 2015

    2015-01-01

    For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

  13. Adult Education in Cohesion.

    ERIC Educational Resources Information Center

    Rubenson, Kjell

    2003-01-01

    International Adult Literacy Survey data show the average adult education participation in Nordic countries is 14% higher than in other industrialized nations. Public support for participation of the disadvantaged, an active labor market policy, and popular education are key characteristics. (Contains 37 references.) (Author/JOW)

  14. Young Adult Literature.

    ERIC Educational Resources Information Center

    Sewell, Ernestine P., Ed.

    1981-01-01

    The major articles in this journal issue deal with various aspects of young adult literature. Specific topics covered in the articles are (1) questions worth asking students about young adult novels, (2) the five major functions of adolescent literature in high school literature programs, (3) Southwestern literature for adolescents, (4) teaching…

  15. Adult Vocational Training.

    ERIC Educational Resources Information Center

    Ministry of Labour, Copenhagen (Denmark).

    Danish adult vocational training activities take the form of specifically targeted initial and continued training for employed and unemployed adults. Planning, development, and adaptation of vocational training programs (AMU programs) are characterized by tripartite cooperation among public authorities and organizations of employers and employees.…

  16. Adult Counseling Project.

    ERIC Educational Resources Information Center

    Perrone, Phil; Davis, Sandy A.

    In order to determine the specific counseling needs of the adult learner, staff of the Adult Counseling Project began by conducting a literature search pertaining to the problems of returning students and those considering a return to school. The review revealed that little is known about the educational and vocational needs of the returning…

  17. Toward Transpersonal Adult Development

    ERIC Educational Resources Information Center

    Boucouvalas, Marcie

    2016-01-01

    As a foundation for discussing transpersonal adult development, the author traces her trajectory, involvement in, and contribution to the modern transpersonal movement and her introduction of it to the adult learning literature, beginning during the early 1980s. Highlighted are the transpersonal domain and a differentiation between transpersonal…

  18. Adult Vocational Teacher Competencies.

    ERIC Educational Resources Information Center

    Hole, F. Marvin

    As part of a larger study to investigate the backgrounds and professional inservice needs of part-time adult vocational teachers in Pennsylvania, research was conducted to identify and assess adult vocational teacher competencies. Following a literature review, a survey instrument was devised which listed thirty-four competencies (basically…

  19. Adult Tech Prep.

    ERIC Educational Resources Information Center

    Schaad, Donna

    For over 2 years, Blak Hawk College (Illinois) has provided high school equivalency (GED) candidates and recipients, older returning students, and underprepared high school graduates with a Tech Prep curriculum to give them the skills to make the transition from adult basic education to college or work. The Adult Tech Prep (ATP) core curriculum…

  20. Financing of Adult Education

    ERIC Educational Resources Information Center

    Archer, David

    2007-01-01

    The 2008 EFA Global Monitoring Report recognises adult literacy as the most neglected of the EFA goals. It is neglected most obviously in respect of the financial allocations made by governments and donors. This shortage of financing creates a dangerous situation in which adult educators seek to convince politicians to invest, based on false…

  1. Authenticity in Adult Learning

    ERIC Educational Resources Information Center

    Ashton, Sam

    2010-01-01

    This paper is concerned with the relationship between authenticity and adult learning and prompted by some studies in which adult "authentic learning" is a central concept. The implication revealed by them is that real-worldness of learning contexts, learning content and learning tasks is perceived as conferring authenticity on learning. Here,…

  2. Gender Dysphoria in Adults.

    PubMed

    Zucker, Kenneth J; Lawrence, Anne A; Kreukels, Baudewijntje P C

    2016-03-28

    Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater client autonomy, and improved understanding of the benefits and limitations of current treatment modalities. PMID:26788901

  3. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.

    PubMed

    Karp, Judith E; Blackford, Amanda; Smith, B Douglas; Alino, Katrina; Seung, Amy Hatfield; Bolaños-Meade, Javier; Greer, Jacqueline M; Carraway, Hetty E; Gore, Steven D; Jones, Richard J; Levis, Mark J; McDevitt, Michael A; Doyle, L Austin; Wright, John J

    2010-07-01

    Flavopiridol, a cyclin-dependent kinase inhibitor, is cytotoxic to leukemic blasts. In a Phase II study, flavopiridol 50 mg/m(2) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9 (FLAM) to 45 adults with newly diagnosed acute myelogenous leukemia (AML) with multiple poor-risk features. Thirty patients (67%) achieved complete remission (CR) and 4 (9%) died. Twelve (40%) received myeloablative allogeneic bone marrow transplant (BMT) in first CR. Median OS and DFS are not reached (67% alive 12.5-31 months, 58% in CR 11.4-30 months), with median follow-up 22 months. Sixteen received FLAM in CR, with median OS and DFS 9 and 13.1 months, and 36% alive at 21-31 months. Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients. PMID:19962759

  4. Relation of components of the metabolic syndrome to left ventricular geometry in hispanic and non-hispanic black adults

    PubMed Central

    Apridonidze, Teimuraz; Shaqra, Hussein; Ktaich, Nessrine; Liu, Jennifer E; Bella, Jonathan N

    2011-01-01

    Background: Left ventricular (LV) hypertrophy is an independent predictor of increased cardiovascular morbidity and mortality. It remains unclear whether components of the metabolic syndrome are associated with LV hypertrophy. Methods and Results: Accordingly, we analyzed echocardiograms in 192 consecutive ambulatory patients referred for echocardiography from October to December 2004. Patients were excluded if they had atrial fibrillation, significant valvular heart disease or failed to cooperate for echocardiogram. Of these, 126 (66%) patients met Adult Treatment Panel (ATP) III diagnostic criteria for the metabolic syndrome. 29% had any 3 metabolic syndrome components, 18% had any 4 metabolic syndrome components and 17% had all 5 metabolic syndrome components. In analyses of variance adjusted for age and sex, LV mass and LV mass adjusted to its allometric relation to height2.7 (LV mass/height2.7) were higher in patients with metabolic syndrome compared to those without metabolic syndrome (237 g [228-239 95%CI] vs. 224 g [206-239 95%CI] p=0.005 and 62 g/m2.7 [59-65 95%CI] vs. 56 g/m2.7 [52-60 95%CI] p=0.014, respectively). The prevalence of LV hypertrophy using prognostically-validated gender-specific partition values for LV mass/height2.7 was significantly higher in metabolic syndrome patients than in those without metabolic syndrome (81 v. 58%, p<0.001). There was a step-wise increase in LV mass/height2.7 in those with no metabolic syndrome components to those with increasing number of metabolic syndrome components (Figure, p<0.001). In this study of high-risk patients, the significant independent predictors of LV hypertrophy were only high blood pressure (OR=3.2, p=0.008) and increased waist circumference (OR=2.8, p=0.006) with no interaction between blood pressure and waist circumference. Conclusion: Metabolic syndrome is associated with higher LV mass and prevalence of LV hypertrophy. Increasing number of metabolic syndrome components is associated with step

  5. Adult Education in the Seventies.

    ERIC Educational Resources Information Center

    Indian Adult Education Association, New Delhi.

    The proceedings of the 24th All India Adult Education Conference highlight two symposia, "Adult Education and Urban Development" and "Adult Education and Green Revolution." Commission Reports on the two symposia are given. (DB)

  6. Chemotherapy for bone sarcomas in adults: the MD anderson experience.

    PubMed

    Benjamin, Robert S; Wagner, Michael J; Livingston, J Andrew; Ravi, Vinod; Patel, Shreyaskumar R

    2015-01-01

    Increasing age is an adverse prognostic factor in the treatment of primary bone tumors. There are few published data on treatment of primary bone tumors in adults. This paper presents data from the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center, summarizing our treatment results. To treat primary osteosarcoma, we used 90 mg/m2 of doxorubicin as a continuous intravenous infusion over 48 to 96 hours and 120 to 160 mg/m2 of cisplatin intravenously or intra-arterially. Initially, we found a marked difference in postoperative continuous disease-free survival (CDFS) between those with 90% or greater (i.e., good response) tumor necrosis and those with less than 90% (i.e., poor response) tumor necrosis. The sequential addition of high-dose methotrexate and ifosfamide to patients with poorly responding disease improved their CDFS to that of patients with good response. Older patients and those who have tumors with variant histology have inferior outcomes. Evaluation of subsequent patients revealed similar outcomes for those with good or poor response to induction therapy, supporting our practice of adaptation of postoperative chemotherapy to the results of preoperative chemotherapy. PET-CT is the best imaging modality to screen for a response with tumors inside bone. To treat Ewing sarcoma, we have employed 2 mg of vincristine, 75 to 90 mg/m2 of doxorubicin as a 72-hour infusion, and 2.5 g/m2 of ifosfamide over 3 hours daily for 4 doses (i.e., vincristine, doxorubicin, and ifosfamide [VAI]). Preliminary analysis indicates a higher CDFS when adjusted for patient age than seen with the standard alternating regimen used in pediatrics. A screening MRI of the pelvis and spine can detect subtle metastatic disease in bone or bone marrow that is missed by other imaging modalities or blind biopsy. Chondrosarcoma is treated surgically or on investigational protocols. Giant cell tumor of bone is usually managed surgically, but multiple

  7. Young Adult Smoking Behavior

    PubMed Central

    Ling, Pamela M.; Neilands, Torsten B.; Glantz, Stanton A.

    2009-01-01

    Background Young adults have the highest smoking rate of any age group in the U.S., and new strategies to decrease young adult smoking are needed. The objective of the current study was to identify psychographic and demographic factors associated with current smoking and quitting behaviors among young adults. Methods Attitudes, social groups, and self-descriptors, including supporting action against the tobacco industry, advertising receptivity, depression, alcohol use, and other factors associated with smoking were tested for associations with smoking behaviors in a 2005 cross-sectional survey of 1528 young adults (aged 18–25 years) from a web-enabled panel. Analyses were conducted in 2007. Results Being older was associated with current smoking, whereas having some higher education and being African American or Hispanic were negatively associated with smoking. Supporting action against the tobacco industry was negatively associated with smoking (AOR=0.34 [95% CI=0.22, 0.52]). Perceived usefulness of smoking, exposure to smokers, increased perceived smoking prevalence, receptivity to tobacco advertising, binge drinking, and exposure to tobacco advertising in bars and clubs were associated with smoking. Supporting action against the tobacco industry was associated with intentions to quit smoking (AOR= 4.43 [95% CI=2.18, 8.60]). Conclusions Young adults are vulnerable to tobacco-industry advertising. Media campaigns that denormalize the tobacco industry and appeal to young adults appear to be a powerful intervention to decrease young adult smoking. PMID:19269128

  8. Depression in Older Adults

    PubMed Central

    Fiske, Amy; Wetherell, Julie Loebach; Gatz, Margaret

    2010-01-01

    Depression is less prevalent among older adults than among younger adults but can have serious consequences. Over half of cases represent a first onset in later life. Although suicide rates in the elderly are declining, they are still higher than in younger adults and more closely associated with depression. Depressed older adults are less likely to endorse affective symptoms and more likely to display cognitive changes, somatic symptoms, and loss of interest than are younger adults. Risk factors leading to the development of late life depression likely comprise complex interactions among genetic vulnerabilities, cognitive diathesis, age-associated neurobiological changes, and stressful events. Insomnia is an often overlooked risk factor for late life depression. We suggest that a common pathway to depression in older adults, regardless of which predisposing risks are most prominent, may be curtailment of daily activities. Accompanying self-critical thinking may exacerbate and maintain a depressed state. Offsetting the increasing prevalence of certain risk factors in late life are age-related increases in psychological resilience. Other protective factors include higher education and socioeconomic status, engagement in valued activities, and religious or spiritual involvement. Treatments including behavioral therapy, cognitive behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy, and life review/reminiscence therapy are effective but too infrequently used with older adults. Preventive interventions including education for individuals with chronic illness, behavioral activation, cognitive restructuring, problem-solving skills training, group support, and life review have also received support. PMID:19327033

  9. Obsessive Compulsive Disorder among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  10. Brainstem Glioma in Adults

    PubMed Central

    Hu, Jethro; Western, Stephen; Kesari, Santosh

    2016-01-01

    Brainstem gliomas are not nearly as common in adults as they are in children. They are likely the final common consequence not of a single disease process but of several. They can be difficult to diagnose, and are challenging to treat. Clinical studies of this diagnosis are few and generally small. Because of these factors, our understanding of the biology of adult brainstem glioma is incomplete. However, the knowledge base is growing and progress is being made. In this article, we review the current state of knowledge for brainstem glioma in adults and identify key areas for which additional information is required. PMID:27556016

  11. Older Adults and Drinking

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Rethinking Drinking Older Adults and Drinking Past Issues / Spring 2014 Table of Contents Generally, ... liver problems, osteoporosis, memory problems, and mood disorders. Drinking and Medications Many medications, such as the ones ...

  12. The Colonial Adult Educator

    ERIC Educational Resources Information Center

    Long, Huey B.

    1975-01-01

    The adult evening schools of colonial America served a mixed clientele and provided instruction in a variety of subjects. Although most historians have described evening schoolmasters as incompetent frauds, research indicates that such descriptions are generally unjust and unfounded. (NHM)

  13. Motivation and Adult Education.

    ERIC Educational Resources Information Center

    Taylor, J. Rodney

    1982-01-01

    The author reviews theories of human motivation: Lewin's force field analysis, Skinner's operant reinforcement theory, and Maslow's hierarchy of needs. He then extracts the implications of these theories for adult learning. SK)

  14. CPR - adult - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100219.htm CPR - adult - series To use the sharing features on ... A.M. Editorial team. Related MedlinePlus Health Topics CPR A.D.A.M., Inc. is accredited by ...

  15. Mosquito, adult (image)

    MedlinePlus

    This illustration shows an adult southern house mosquito. This mosquito feeds on blood and is the carrier of many diseases, such as encephalitis, West Nile, dengue fever, yellow fever, and others. ( ...

  16. About BMI for Adults

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs About Adult BMI Language: ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Language: English Español (Spanish) ...

  17. Pneumonia - adults - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000017.htm Pneumonia in adults - discharge To use the sharing features on this page, please enable JavaScript. You have pneumonia, which is an infection in your lungs. In ...

  18. Adult Neurogenesis in Fish.

    PubMed

    Ganz, Julia; Brand, Michael

    2016-01-01

    Teleost fish have a remarkable neurogenic and regenerative capacity in the adult throughout the rostrocaudal axis of the brain. The distribution of proliferation zones shows a remarkable conservation, even in distantly related teleost species, suggesting a common teleost ground plan of proliferation zones. There are different progenitor populations in the neurogenic niches-progenitors positive for radial glial markers (dorsal telencephalon, hypothalamus) and progenitors with neuroepithelial-like characteristics (ventral telencephalon, optic tectum, cerebellum). Definition of these progenitors has allowed studying their role in normal growth of the adult brain, but also when challenged following a lesion. From these studies, important roles have emerged for intrinsic mechanisms and extrinsic signals controlling the activation of adult neurogenesis that enable regeneration of the adult brain to occur, opening up new perspectives on rekindling regeneration also in the context of the mammalian brain. PMID:26747664

  19. Motivation and Adult Education

    ERIC Educational Resources Information Center

    Veeraraghavan, J.

    1974-01-01

    The paper examines the role of adult education and the contribution it can make to the solution of current problems in developing countries, particularly the problems of economic under-development and over-population. (Author/AG)

  20. Yoga and Older Adults

    MedlinePlus

    ... My Go4Life Get Free Stuff Be a Partner Yoga and Older Adults Yoga is a mind and body practice that typically ... breathing exercises, and relaxation. Researchers are studying how yoga may help improve health and to learn more ...

  1. Glycosidases: inborn errors of glycosphingolipid catabolism.

    PubMed

    Ashida, Hisashi; Li, Yu-Teh

    2014-01-01

    Glycosphingolipids (GSLs) are information-rich glycoconjugates that occur in nature mainly as constituents of biomembranes. Each GSL contains a complex carbohydrate chain linked to a ceramide moiety that anchors the molecule to biomembranes. In higher animals, catabolism of GSLs takes place in lysosomes where sugar chains in GSLs are hydrolyzed by exo-glycosidases to cleave a sugar residue from the non-reducing end of a sugar chain. Inborn errors of GSL-catabolism, collectively called sphingolipidoses or GSL-storage diseases, are caused by the deficiency of exo-glycosidases responsible for the degradation of the specific sugar residues at the non-reducing termini in GSLs. This chapter briefly discusses glycone, anomeric, linkage, and aglycone specificities of exo-glycosidases and some of the historical landmarks on their associations with the chemical pathology of the five best known sphingolipidoses: GM1 gangliosidosis, GM2 gangliosidosis (Tay-Sachs disease), Fabry disease, Gaucher disease, and Krabbe disease. PMID:25151392

  2. Profiling oligosaccharidurias by electrospray tandem mass spectrometry: quantifying reducing oligosaccharides.

    PubMed

    Ramsay, Steven L; Meikle, Peter J; Hopwood, John J; Clements, Peter R

    2005-10-01

    A method to semiquantify urinary oligosaccharides from patients suffering from oligosaccharidurias is presented. 1-Phenyl-3-methyl-5-pyrazolone has been used to derivatize urinary oligosaccharides prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and alpha-mannosidosis. The oligosaccharides were referenced against the internal standard, methyl lactose, to produce ratios for comparison with control samples. Elevations in specific urinary oligosaccharides were indicative of lysosomal disease and the defective catabolic enzyme. This method has been adapted to enable assay of large sample numbers and could readily be extended to other oligosaccharidurias and to monitor oligosaccharide levels in patients receiving treatment. It also has immediate potential for incorporation into a newborn screening program. PMID:16111643

  3. Pancreatoblastoma in an adult.

    PubMed

    Zhang, Di; Tang, Na; Liu, Yang; Wang, En-Hua

    2015-01-01

    Pancreatoblastoma is a malignant pancreatic tumor that rarely occurs in adults. We report a case of an adult female with pancreatoblastoma. A mass was detected in the pancreatic head using computed tomography and ultrasonography. The clinical diagnosis was a solid-pseudopapillary neoplasm of the pancreas. However, after the operation, the final diagnosis was pancreatoblastoma, which showed two lines of differentiation: Acinar differentiation and squamoid corpuscles. The patient is currently in good condition. PMID:25673604

  4. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  5. Adult educators' core competences

    NASA Astrophysics Data System (ADS)

    Wahlgren, Bjarne

    2016-05-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or "core" requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students' prior learning into account; (3) supporting a learning environment; and (4) the adult educator's reflection on his or her own performance. At the end of his analysis of different competence profiles, the author notes that adult educators' ability to train adult learners in a way which then enables them to apply and use what they have learned in practice (thus performing knowledge transfer) still seems to be overlooked.

  6. Adult educators' core competences

    NASA Astrophysics Data System (ADS)

    Wahlgren, Bjarne

    2016-06-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or "core" requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students' prior learning into account; (3) supporting a learning environment; and (4) the adult educator's reflection on his or her own performance. At the end of his analysis of different competence profiles, the author notes that adult educators' ability to train adult learners in a way which then enables them to apply and use what they have learned in practice (thus performing knowledge transfer) still seems to be overlooked.

  7. Adult Education in Israel V.

    ERIC Educational Resources Information Center

    Kirmayer, Paul, Ed.; Michaelson, Serena T., Ed.

    This fifth journal edition focuses on the didactics of adult education in Israel. Following a "Preface" (Meir Peretz) discussing the didactics of adult education, three major fields are examined: Learning for Adults; Hebrew Language and Culture for Immigrants; and Special Populations (adults with learning disabilities, senior citizens, and…

  8. The Adult Learner: Four Aspects.

    ERIC Educational Resources Information Center

    Lucas, John A., Ed.

    1986-01-01

    Topics concerning the adult learner that are relevant to institutional researchers are addressed in four articles: marketing, predicting success for adult students, enrollment projection, and follow-up studies of adult learners. In "Institutional Research in Support of Marketing the Adult Student," Lydia Jurand notes the importance of identifying…

  9. The ABC's of Adult Ed

    ERIC Educational Resources Information Center

    Roehrig, Lucy

    2010-01-01

    According to the 2003 National Assessment of Adult Literacy, it is estimated that 93 million adults in the United States have basic or below basic literacy skills. Those individuals found most lacking in literacy skills were adults living in poverty, adults lacking a high school diploma, seniors and the elderly aged 65 and older, the more than one…

  10. Rich Environments for Adult Learners

    ERIC Educational Resources Information Center

    Bentham, Renee

    2008-01-01

    Unaware of the messages a bare adult learning environment sends and its effect on adult learners, a trainer attends an intensive Reggio Emilia course and learns that the physical environment is the "third teacher"--for adults as well as for children. Using principles of Reggio, she offers suggestions for enhancing adult learning spaces and…

  11. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

    PubMed Central

    Akgoc, Zeynep; Sena-Esteves, Miguel; Martin, Douglas R.; Han, Xianlin; d’Azzo, Alessandra; Seyfried, Thomas N.

    2015-01-01

    Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1′ structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses. PMID:25795792

  12. [Evolutive neuroradiological alterations in Sandhoff's disease].

    PubMed

    Gutiérrez-Solana, L G; Ruiz-Falcó, M L; García-Peñas, J J; Chabás, A; Manzano-Blanco, S; Gómez-Mardones, G; López-Terradas, J M

    1996-10-01

    Sandhoff's disease is a severe form of gangliosidosis GM2 which presents in the first year of life, basically as progressive psychomotor retardation and/or a macular red cherry spot. Our patient presented the clinical picture characteristic of the disease. Diagnosis was confirmed by determining the activity of hexosaminidases A and B in serum and of beta-N-acetil hexosaminases in fibroblast culture. In view of the fatal prognosis of the disease, in 1991 a transplant of alogenic bone marrow (TMO) was carried out to try to replace the enzymes. This required exhaustive radiological follow-up to determine the possible neuro-radiological changes seen in this storage disease. Although treatment was not successful, the neuro-radiological findings may be of interest as perhaps being characteristic of the GM2 gangliosidosis: 1. Bilateral thalamic hyperecogenity in the cerebral ecography. 2. Differences between the thalamo-putamen densities due to bilateral homogeneous thalamic hyperdensity on the CT scan. 3. Thalamic hypointensity both on T2 sequences and in proton density on MR with the cerebral white matter being progressively affected. In conclusion, we suggest that bilateral symmetrical thalamic changes are an early finding which is probably specific to the GM2 gangliosidoses and may be useful from the point of view of carrying out more specific investigations in infants suspected of having a degenerative neurological disorder. PMID:8983726

  13. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses.

    PubMed

    Akgoc, Zeynep; Sena-Esteves, Miguel; Martin, Douglas R; Han, Xianlin; d'Azzo, Alessandra; Seyfried, Thomas N

    2015-05-01

    Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1' structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses. PMID:25795792

  14. Adult Brainstem Gliomas

    PubMed Central

    Reyes-Botero, German; Mokhtari, Karima; Martin-Duverneuil, Nadine; Delattre, Jean-Yves

    2012-01-01

    Brainstem gliomas are uncommon in adults and account for only 1%–2% of intracranial gliomas. They represent a heterogeneous group of tumors that differ from those found in their pediatric counterparts. In adults, a low-grade phenotype predominates, which is a feature that likely explains their better prognosis compared to that in children. Because biopsies are rarely performed, classifications based on the radiological aspect of magnetic resonance imaging results have been proposed to establish treatment strategies and to determine outcomes: (a) diffuse intrinsic low-grade, (b) enhancing malignant glioma, (c) focal tectal gliomas, and (d) exophytic gliomas. Despite significant advances in neuroradiology techniques, a purely radiological classification remains imperfect in the absence of a histological diagnosis. Whereas a biopsy may often be reasonably avoided in the diffuse nonenhancing forms, obtaining histological proof seems necessary in many contrast-enhanced brainstem lesions because of the wide variety of differential diagnoses in adults. Conventional radiotherapy is the standard treatment for diffuse intrinsic low-grade brainstem gliomas in adults (the median survival is 5 years). In malignant brainstem gliomas, radiotherapy is the standard treatment. However, the possible benefit of combined radiotherapy and chemotherapy (temozolomide or other agents) has not been thoroughly evaluated in adults. The role of anti-angiogenic therapies in brainstem gliomas remains to be defined. A better understanding of the biology of these tumors is of primary importance for identifying homogeneous subgroups and for improving therapy options and outcomes. PMID:22382458

  15. Adult onset retinoblastoma.

    PubMed

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-07-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  16. Adult Seborrheic Dermatitis

    PubMed Central

    2011-01-01

    Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal “device ”cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population. PMID:21607192

  17. Pharmacotherapy for adult ADHD.

    PubMed

    Adler, Lenard A

    2009-05-01

    The U.S. Food and Drug Administration has approved 3 medications, atomoxetine and the extended-release formulations of amphetamine salts and dexmethylphenidate, for the treatment of adult attention-deficit hyperactivity disorder (ADHD). Different formulations of the same drugs, as well as other agents and cognitive-behavioral therapy, have been tested to determine efficacy in ADHD alone and in ADHD with comorbid substance use disorders, mood disorders, and anxiety disorders. A deficit in research exists in regard to these comorbidities in adults with ADHD. PMID:19552859

  18. Tuberculosis in Older Adults.

    PubMed

    Rajagopalan, Shobita

    2016-08-01

    Tuberculosis (TB) remains one of the world's most lethal infectious diseases. Preventive and control strategies among other high-risk groups, such as the elderly population, continues to be a challenge. Clinical features of TB in older adults may be atypical and confused with age-related diseases. Diagnosis and management of TB in the elderly person can be difficult; treatment can be associated with adverse drug reactions. This article reviews the current global epidemiology, pathogenesis, clinical characteristics, diagnosis, management, and prevention of Mycobacterium tuberculosis infection in community-dwelling and institutionalized aging adults. PMID:27394018

  19. Back pain in adults.

    PubMed

    Becker, Jonathan A; Stumbo, Jessica R

    2013-06-01

    This article provides a summary of the many causes of back pain in adults. There is an overview of the history and physical examination with attention paid to red flags that alert the clinician to more worrisome causes of low back pain. An extensive differential diagnosis for back pain in adults is provided along with key historical and physical examination findings. The various therapeutic options are summarized with an emphasis on evidence-based findings. These reviewed treatments include medication, physical therapy, topical treatments, injections, and complementary and alternative medicine. The indications for surgery and specialty referral are also discussed. PMID:23668645

  20. Lectin histochemistry and ultrastructure of feline kidneys from six different storage diseases.

    PubMed

    Castagnaro, M; Alroy, J; Ucci, A A; Glew, R H

    1987-01-01

    We have compared the pattern of lectin staining with the ultrastructural features of kidneys from normal cats and 19 cats with 6 different lysosomal storage diseases. The diseases studied include GM1 and GM2 gangliosidosis, mucopolysaccharidosis (MPS)-I and MPS-VI, sphingomyelin-lipidosis (i.e., Niemann-Pick disease) and mannosidosis. Ten different biotinylated lectins were used as histochemical probes for carbohydrate residues and avidin-biotin-peroxidase complex as visualant. Concanavalia ensiformis agglutinin (Con A) stained mesangial cells in all storage diseases but GM1, epithelial cells in sphingomyelin-lipidosis and mannosidosis, endothelial cells in GM1 and mannosidosis and Bowman's capsule cells in all but GM2. Griffonia simplicifolia agglutinin I (GS-I) stained the glomerular endothelium in all six diseases, but not in control kidneys. Ricinus communis agglutinin-I (RCA-I) stained the glomerular epithelium only in GM1 and MPS-I. Succinylated wheat germ agglutinin (SWGA) stained the glomerular endothelium and epithelium in mannosidosis, and the glomerular epithelium and Bowman's capsule in MPS-I. Ultrastructure studies demonstrated an accumulation of oligosaccharides in cases of mannosidosis and GM1 gangliosidosis, a mixture of oligosaccharides and lipids in MPS-I, MPS-VI and GM2 gangliosidosis and only lipid storage in sphingomyelin lipidosis. These studies show that morphologic and histochemical changes are manifested in some kidney cell types in lysosomal storage diseases, even though the enzyme deficiency occurs in all cell types. Furthermore, we show that the nature of the undegraded stored material is complex and that other factors, such as rate of membrane turn over, membrane composition, and cell function may influence the amount and nature of the "stored" material. PMID:2892300

  1. The Adult Student Population.

    ERIC Educational Resources Information Center

    Snyder, Fred A.; Blocker, Clyde E.

    This study is concerned with the following topics on adult student attendance at Harrisburg Area Community College (HACC) during the 1969-70 academic year: student background, reason for attendance, enrollment in programs or courses, academic success, evidence of personal and occupational development. The report is based on the useable…

  2. Police and Adult Education.

    ERIC Educational Resources Information Center

    Sims, Vic

    The literature on adult education for police is reviewed and criticized. Among the publications that have been influential in debating the need for police education are Charles B. Saunder's "The Challenge of Crime in a Free Society" (1976), which endorses the Presidential Commission on Law Enforcement's recommendations regarding the vital…

  3. Helping Adults to Spell.

    ERIC Educational Resources Information Center

    Moorhouse, Catherine

    This book presents a range of strategies for adult literacy tutors and offers a wealth of practical advice on teaching spelling within the context of writing. Chapters 1-3 offer basic information on talking with the student about spelling, finding out how the student spells and helping the student to see himself/herself as a "good" speller, and…

  4. Adult Basic Education Curriculum.

    ERIC Educational Resources Information Center

    Massachusetts Career Development Inst., Springfield.

    This booklet, aimed at adult basic education students, pinpoints and summarizes a few common spelling rules to help make spelling easier, and includes a component on using the dictionary. In the text, each rule is presented with many examples. Exercises follow each spelling rule, allowing students the opportunity to apply the rule to specific…

  5. Helping Adults Learn

    ERIC Educational Resources Information Center

    Edmundson, Phyllis J.

    2007-01-01

    Increased attention to preparing addictions counselors and related professionals to use evidence-based practices has brought new attention to the preparation programs for addictions counselors. Research and theory about adult learning emphasizes the importance of students as active participants in problem and experience based learning. This paper…

  6. For Adult Audiences Only.

    ERIC Educational Resources Information Center

    Gallien, Kathryn J.

    1986-01-01

    Empire State College, a branch of the State University of New York, is a public institution designed for adults with 5,500 students at 40 locations. ESC's most successful student recruitment method is word of mouth. Suggestions on how to attract students are provided. (MLW)

  7. Bereavement in Older Adults.

    ERIC Educational Resources Information Center

    Morgan, James P.

    1994-01-01

    Factors that place older adults at risk for problems associated with the bereavement process are identified and discussed. Provides guidelines for distinguishing between normal bereavement depression and clinical depression, discusses the impact of different types of loss, describes three types of intervention, and explores countertransference.…

  8. Adult Religious Education

    ERIC Educational Resources Information Center

    Elias, John L.

    2012-01-01

    Most religious organizations exert their greatest effort in the religious education of children. This makes sense in terms of handing on the faith to the next generation. Historically, however, religious education of adults is the first endeavor of religious groups. Conducting education of children requires the previous religious education of…

  9. Adult Learning Matters

    ERIC Educational Resources Information Center

    Adults Learning, 2009

    2009-01-01

    The Campaigning Alliance for Lifelong Learning is to lobby parliament for the restoration of the 1.5 million adult learning places lost over the past two years. The campaign has attracted supporters from an astonishingly wide range of backgrounds. In this article, Gordon Marsden, Caroline Biggins, Beth Walker, Mike Chaney, Peter Davies, Sian…

  10. Individualized Adult Science Education.

    ERIC Educational Resources Information Center

    Lawrence, C. G.

    As the proceedings of a national seminar on individualized adult science education, a total of 13 articles is compiled in this volume concerning the theory and techniques of curriculum development and the individualization process in upgrading Canadian science courses. The topics include: The Characteristics and Formulation of Behavioral…

  11. Intelligence and Adult Learning.

    ERIC Educational Resources Information Center

    Fellenz, Robert A., Ed.; Conti, Gary J., Ed.

    "Understanding Adult Intelligence" (Robert Sternberg) focuses on the nature of intelligence. It explains Sternberg's triarchic theory, in which he posits three main aspects of intelligence: its relation to the internal or mental world of the learner, its relation to experience, and its relation to the surrounding world. "Strategies and Learning"…

  12. Adult Literacy Perspectives.

    ERIC Educational Resources Information Center

    Taylor, Maurice C., Ed.; Draper, James A., Ed.

    This book, intended to serve as a professional reference work, proposes to define the field of Adult Basic Education in its evolution, its contribution to professional education, and the principal problems and issues. The volume contains the following treatises: "Definitions and Evolution of the Concepts" (Thomas); "Selected Chronology of Literacy…

  13. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  14. Immigration and Adult Transitions

    ERIC Educational Resources Information Center

    Rumbaut, Ruben G.; Komaie, Golnaz

    2010-01-01

    Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Ruben Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage…

  15. Encyclopedia of Adult Development.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert, Ed.

    This encyclopedia contains 106 articles on adult development that were written by more than 75 specialists in such diverse fields as anthropology, communication, education, health sciences, history, and psychology. In a guide to related topics that is presented at the beginning of the encyclopedia, the 106 articles are grouped under the following…

  16. Dealing with Adult Illiteracy.

    ERIC Educational Resources Information Center

    USA Today, 1979

    1979-01-01

    Summarizes the findings of a recent study, "Adult Illiteracy in the United States: A Report to the Ford Foundation." Incidence of reading difficulties, effectiveness of literacy programs, and the relationship of reading ability to poverty are some of the topics discussed. New community-based literacy initiatives are recommended. (SJL)

  17. Adult Children of Alcoholics.

    ERIC Educational Resources Information Center

    Goodman, Ronald W.

    1987-01-01

    Presents analysis of adult children of alcoholics, their experience and adjustment in relation to the severity and type of alcoholism, age considerations and perceptions as a child, and existence and nature of significant others. Discusses alcoholics' and others' family issues, focusing on roles taken, and personality characteristics. Emphasizes…

  18. Profiles of Adult Learners.

    ERIC Educational Resources Information Center

    Illinois State Library, Springfield.

    Since January 1986, when the Illinois Secretary of State Literacy Grant Program began funding a wide variety of adult literacy programs, more than 30,000 students have sought help with reading. They have been matched with 25,000 tutors who have provided more than 2 million hours of volunteer instruction. The profiles in this booklet are stories of…

  19. Dance for Older Adults.

    ERIC Educational Resources Information Center

    Pruett, Diane Milhan, Ed.; And Others

    1983-01-01

    Dance programs for older adults that encourage exercise and socializing are described in six articles. Program guidelines of the American Alliance Committee on Aging are explained, and other articles emphasize a movement education approach that may involve intergenerational contact. A dance program held in a worship setting is also discussed. (PP)

  20. Adult Education in Sweden.

    ERIC Educational Resources Information Center

    Ministry of Education and Cultural Affairs, Stockholm (Sweden).

    The forms of adult education in Sweden discussed in this review include the courses provided by the Labour Market Board, the folk high schools, the national and local educational schemes, the Commission for TV and Radio in Education (TRU), and the training courses arranged by the employee organizations. Brief mention is also made of the courses…

  1. Individualized Mathematics for Adults.

    ERIC Educational Resources Information Center

    Yanosko, Barbara J.

    Adults who have chosen to interrupt their educational careers often face the problem of rusty academic skills. The Veterans Upward Bound Program at Humboldt State University developed a ten-week college preparatory program designed to help these people make the transition to college life with appropriate academic skills. Two different mathematics…

  2. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  3. Migration and Adult Education

    ERIC Educational Resources Information Center

    Gois, William

    2007-01-01

    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  4. Adult Education. Annual Report, National Advisory Council on Adult Education.

    ERIC Educational Resources Information Center

    National Advisory Council on Adult Education, Washington, DC.

    Recommendations of the President's National Advisory Council on Adult Education are the subject of this first annual report. The activities of the Council during its first year are listed. Recommendations for Action are: (1) a higher budget priority for adult education in Fiscal Year 1973, and the development of a Comprehensive Adult Education…

  5. Adult Development. What do Teachers of Adults Need To Know?

    ERIC Educational Resources Information Center

    Whiting, Susan; And Others

    The first part of this two-part paper provides a general review of adult development and is premised on an understanding of andragogy. Andragogy is the art and science of helping adults learn. It is based on the following four assumptions about adults: (1) as people mature they become less dependent and more self-directed; (2) experiences serve as…

  6. Teaching Nontraditional Adult Students: Adult Learning Theories in Practice

    ERIC Educational Resources Information Center

    Chen, Joseph C.

    2014-01-01

    As the USA experiences rapid growth of nontraditional adult students in higher education, educators and institutions will increasingly need to look beyond the traditional youth-centric educational models to better address adult learning needs. To date, no research has been conducted examining the learning experiences of adult students enrolled in…

  7. Utah Adult Education Services. Adult Education Report 1968-69.

    ERIC Educational Resources Information Center

    Utah State Board of Education, Salt Lake City.

    Major purposes for the preparation of this report on public school adult education in Utah were: to provide the public with a description of achievements, trends, and needs, and with meaningful cost accounting information; to make comparisons and analyses of adult education by program, school district, and year; and to provide the adult education…

  8. Adult Development and Adult Beginning Reading Behaviors: An Exploratory Study.

    ERIC Educational Resources Information Center

    Schumacher, Sally

    An ethnographic study investigated four adult beginning reading (ABR) classes in several adult learning centers in order to determine the effect of an adult's age and developmental phase on his or her behavior and attitudes in the learning-to-read process. For 9 months, a four-member research team conducted on-site observations, compiled extensive…

  9. Tay-Sachs disease: a case report.

    PubMed

    Arisoy, A E; Ozden, S; Ciliv, G; Ozalp, I

    1995-01-01

    Tay-Sachs disease (GM2 gangliosidosis I) is an autosomal recessive lysosomal-storage disorder confined to the central nervous system, resulting from deficiency of hexosaminidase A. The case presented is of a twelve-month-old girl brought to the hospital because of mental-motor deterioration and convulsions. She was the child of first cousins and had a history of the deaths of two siblings with the same manifestations. Generalized hypotonia, macrocephaly, hyperacusis and a retinal cherry red spot appearance were present. There was no organomegaly. The diagnosis of Tay-Sachs disease was made by means of absence of serum hexosaminidase A activity. PMID:7732608

  10. Hearing Loss and Older Adults

    MedlinePlus

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Hearing Loss and Older Adults On this page: What is ... about hearing loss and older adults? What is hearing loss? Hearing loss is a sudden or gradual decrease ...

  11. Alcohol Use and Older Adults

    MedlinePlus

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  12. Adults with Congenital Heart Defects

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Web Booklet: Adults With Congenital Heart Defects Updated:Apr ... topic from the list below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: ...

  13. Facts about Measles for Adults

    MedlinePlus

    ... as part of a combination vaccine, called the MMR vaccine that protects against measles, mumps, and rubella. Which adults should get vaccinated against measles with MMR vaccine? Adults born in 1957 or later who do ...

  14. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  15. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  16. Finding Your Adult Vaccination Record

    MedlinePlus

    ... Button Past Emails CDC Features Is Your Adult Vaccination Record Up-To-Date? Language: English Español (Spanish) ... next medical appointment. Staying Up-to-date on Vaccination is Important Every year thousands of adults in ...

  17. HIV Infection and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals HIV Infection and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... percentage is less than 15%. Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  18. Strategies in Aboriginal Adult Education

    ERIC Educational Resources Information Center

    Duncan, Alan T.

    1973-01-01

    Traditional Aboriginal practices render traditional adult education programs futile. Aboriginal adult education must be concerned with the growth and development of the total personality. Adopted strategies must motivate Aborigines as individuals and as members of the community. (AG)

  19. AIDS and the Older Adult.

    ERIC Educational Resources Information Center

    Allers, Christopher T.

    1990-01-01

    Older adults are finding themselves the neighbors of Acquired Immunodeficiency Syndrome (AIDS) patients as well as the primary caregivers of infected adult children. Focuses on roles, issues, and conflicts older adults face in dealing with relatives or neighbors with AIDS. Case management and educational intervention strategies are also offered.…

  20. Rural Education for Older Adults

    ERIC Educational Resources Information Center

    Mott, Vivian W.

    2008-01-01

    Meeting the learning needs of older adults in rural areas is a critical and growing concern for adult and continuing education. This chapter addresses learning in a rural context for older adults by examining several constructs. These include the definitions of "rural," the issues of the learners' ages, and the various structures and purposes…

  1. Act To Promote Adult Education.

    ERIC Educational Resources Information Center

    1970

    An act of the German Lower Saxony Parliament to promote adult education is presented. It has 24 general provisions relating to the following: purpose of adult education, principle for promotion, conditions for promotions of establishments, independence of adult education, prerequisites and form of acknowledgement of entitlement to promotion,…

  2. Adult Development and the Workplace.

    ERIC Educational Resources Information Center

    Heffernan, James M.

    Little attention has been given to how adults develop through their lifetimes and what roles their workplace environments play in that development. Research and theory regarding adult psychosocial development have confirmed the developmental life-cycle phases of adulthood. These are: leaving the family (ages 16-22), getting into the adult world…

  3. Philosophies of Adult Environmental Education

    ERIC Educational Resources Information Center

    Walter, Pierre

    2009-01-01

    This article offers a typology of philosophical traditions in environmental education for adults, based on five philosophical perspectives of adult education described by Elias and Merriam. These five traditions are liberal, progressive, behaviorist, humanist, and radical adult environmental education, respectively. A summary of each philosophy's…

  4. Adult Education and Development, 1994.

    ERIC Educational Resources Information Center

    Adult Education and Development, 1994

    1994-01-01

    The publication is a half-yearly journal for adult education in Africa, Asia, and Latin America. Issue 42 includes the following: "Adult Education for Self-Reliance in Community Health Education Programmes" (Kweka); "Promoting Good Nutrition" (Mangvwat); "Incorporating Health-Improvement Activities in Adult Education Programmes in Nigeria"…

  5. The Future of Adult Education

    ERIC Educational Resources Information Center

    Schmidt, Steven W.

    2013-01-01

    It is an interesting assignment to think about the future of adult education. In fact, it is an assignment the author has the graduate students in his "Introduction to Adult Education" class at East Carolina University consider during one of their course units. As a member of the Board of Directors for the American Association for Adult and…

  6. Achieving Adult Literacy. Fastback 330.

    ERIC Educational Resources Information Center

    Farris, Pamela J.

    Leaders in business and industry are demanding workers who not only can read and write but can think creatively and critically and solve problems. Federal- and state-funded programs and volunteer organizations are involved with adult literacy. Increasingly, corporations are funding adult literacy projects. Adults read for different reasons than…

  7. Policy Issues in Adult Education.

    ERIC Educational Resources Information Center

    Oliver, Leonard P.

    1983-01-01

    States that adult educators in the United States, unlike their counterparts abroad, have not been key actors in influencing policy with adult education overtones at the national, state, or local levels. Discusses how adult educators can become more influential by applying concepts used by Warren Bennis to describe organizational health: sense of…

  8. Transformative Dimensions of Adult Learning.

    ERIC Educational Resources Information Center

    Mezirow, Jack

    This book presents a theory of how adults learn by making meaning of their experiences. Chapter 1 gives an overview of an emerging transformation theory of adult learning, compares it with other theories of adult learning, and describes the dynamics of the process through which one makes meaning of one's experience. Chapter 2 examines the way…

  9. Visual Persistence and Adult Dyslexia.

    ERIC Educational Resources Information Center

    Winters, Roberta L.; And Others

    1989-01-01

    Visual persistence was investigated in adults with and without dyslexia in order to determine whether dyslexic adults demonstrate problems similar to those found in childhood dyslexia. Results showed that sensitivity of dyslexic adults was impaired when parts of a test stimulus were presented to adjacent retinal areas, suggesting that under…

  10. Adult Multiple Intelligences and Math.

    ERIC Educational Resources Information Center

    Costanzo, Meg Ryback

    In the Adult Multiple Intelligences (AMI) study, 10 teachers of adults from the northeastern region of the United States explored for 18 months the ways that multiple intelligences (MI) theory could support instruction and assessment in various adult learning contexts. The results of this research were published in a book by Julie Viens called MI…

  11. Adult Education in Western Germany.

    ERIC Educational Resources Information Center

    Knoll, Joachim H.; And Others

    Here are abstracts of three books on adult education in Western Germany, where the institutions and methods of continuing education have been nearly unknown. The first, ERWACHSENENBILDUNG IN DER BUNDESREPUBLIK (ADULT EDUCATION IN THE FEDERAL REPUBLIC), 167 pages, justifies regarding adult education today as a complete changeover from its forms in…

  12. Assessment Matters in Adult Learning.

    ERIC Educational Resources Information Center

    Donley, Jan; Napper, Rosemary

    This handbook was developed to give tutors of adult education information and ideas about assessing adult learning. It can be used as a reference for information about assessment and as a practical tool for tutors. Section 1, Introduction to Assessment in Adult Learning, includes information on these topics: what assessment is, how to assess, why…

  13. Literacy Proficiency of Older Adults

    ERIC Educational Resources Information Center

    van der Kamp, Max; Boudard, Emmanuel

    2003-01-01

    As a supplement to the International Adult Literacy Survey, the Netherlands devoted special attention to the literacy proficiency of older adults. A close look at the literacy skills of older adults and their use in daily life is relevant because demographic developments, individualisation, the position of older employees in the labour market and…

  14. Assessment Tools for Adult Education.

    ERIC Educational Resources Information Center

    Shefrin, Carol; Shafer, Dehra; Forlizzi, Lori

    The Assessment Tools for Adult Education project was designed to provide training and support to staff of the Pennsylvania Bureau of Adult Basic and Literacy Education (ABLE) funded programs to help them use assessment tools and procedures to document the learning gains of the adult students they serve. The following candidate assessment…

  15. Rural Adult Education: Current Status

    ERIC Educational Resources Information Center

    Ritchey, Jeffrey A.

    2008-01-01

    "Context". The word pervades the literature on adult and continuing education. For adult education practitioners and researchers alike, understanding the beliefs and actions of their educational place continues to be of significant concern, and rightfully so. That adults wish to have their histories, experiences, and abilities appreciated and…

  16. Teachers as Adult Learners: A New Perspective.

    ERIC Educational Resources Information Center

    Lawler, Patricia A.

    2003-01-01

    Presents the Adult Learning Model for Faculty Development of adult educators, which incorporates principles of adult learning and program planning concepts used in adult education. (Contains 20 references.) (SK)

  17. Diarrhoea in adults (acute)

    PubMed Central

    2008-01-01

    Introduction An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries traveling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, and oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution). PMID:19450323

  18. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  19. Rhinitis in Older Adults

    PubMed Central

    Nyenhuis, Sharmilee; Mathur, Sameer K.

    2013-01-01

    Rhinitis symptoms of rhinorrhea, congestion, sneezing, nasal/ocular pruritis, and postnasal drainage can significantly affect the quality of life for older adults. As the US population ages, it will be increasingly important for healthcare providers to effectively diagnose and manage rhinitis. Rhinitis is categorized broadly into allergic rhinitis and non-allergic rhinitis. Environmental changes and avoidance measures are a primary means of intervention. In addition, there are several topical therapies (nasal sprays) that can be effective for symptom control. PMID:23389558

  20. An Undergraduate Course in Adult Development: When the Virtual Adult Is an Adult

    ERIC Educational Resources Information Center

    Williams, Robert B.

    2014-01-01

    An aspect of an undergraduate psychology course on adult development was the preparation of case records on adults who consented to be studied. Participants (1) developed their abilities to observe and accurately record adult behavior across a variety of ages and contexts; (2) withheld judgments about behavior when evidence was lacking; (3)…

  1. Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB−/− mouse model of neurodegeneration

    PubMed Central

    Kyrkanides, Stephanos; Miller, Ann W.; Miller, Jen-nie H.; Tallents, Ross H.; Brouxhon, Sabine M.; Olschowka, Malory E.; O’Banion, M. Kerry; Olschowka, John A.

    2008-01-01

    Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB−/− mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB−/− mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFα and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM2 storage and pro-apoptotic activity or astrocyte activation in HexB−/−;Ccr2−/− double knockout mice, which eventually succumbed secondary to GM2 gangliosidosis. PMID:18657867

  2. Juvenile-onset motor neuron disease caused by novel mutations in β-hexosaminidase

    PubMed Central

    Pierson, Tyler Mark; Torres, Paola A.; Zeng, Bei-Jin; Glanzman, Allan M.; Adams, David; Finkel, Richard S.; Mahuran, Don J.; Pastores, Gregory M.; Tennekoon, Gihan I.; Kolodny, Edwin H.

    2013-01-01

    A 12 year-old female presented with a seven-year history of progressive muscle weakness, atrophy, tremor and fasciculations. Cognition was normal. Rectal biopsy revealed intracellular storage material and biochemical testing indicated low hexosaminidase activity consistent with juvenile-onset GM2-gangliosidosis. Genetic evaluation revealed compound heterozygosity with two novel mutations in the hexosaminidase β-subunit (c.512-3 C>A and c.1613+15_1613+18dup). Protein analysis was consistent with biochemical findings and indicated only a small portion of β-subunits were properly processed. These results provide additional insight into juvenile-onset GM2-gangliosidoses and further expand the number of β-hexosaminidase mutations associated with motor neuron disease. PMID:23158871

  3. Infantile Type Sandhoff Disease with Striking Brain MRI Findings and a Novel Mutation

    PubMed Central

    Beker-Acay, Mehtap; Elmas, Muhsin; Koken, Resit; Unlu, Ebru; Bukulmez, Aysegul

    2016-01-01

    Summary Background Sandhoff disease is an autosomal recessive disorder caused by β-hexosaminidase deficiency in which the ganglioside GM2 and other glycolipids accumulate intracellularly within lysosomes. This process results in progressive motor neuron manifestations, death from respiratory failure and infections in infantiles. Case Report This report presents a 22-month-old girl with infantile type Sandhoff disease that was hospitalized for generalized seizures and psychomotor retardation. She was diagnosed with a genetically proven novel mutation and by demonstrating it’s specific imaging findings. Conclusions Determination of spesific changes in neuroimaging which are initial findings for GM2 gangliosidosis is important from the point of diagnosis and follow-up in infants suspected of having a neurodegenerative disease. PMID:26985245

  4. [Intraosseous infusion for adults].

    PubMed

    Leidel, B A; Kirchhoff, C

    2008-04-01

    Intraosseous (IO) infusion methods have been common for emergency treatment in infants and children for years. The role of IO access in adults is however much less clear, but its importance in this patient group is increasing, and different devices are available today. Each device has strengths and weaknesses, but all achieve rapid vascular access even in challenging situations. The potential of IO access regarding both therapeutic and diagnostic options has been shown in several operational studies in and out of hospital. Insertion times require between 1 and 2 min in most cases, while insertion and handling of the IO access devices seem to be easy and reliable. The flow rates of IO access devices for adults are lower than those of large-bore peripheral intravenous catheters, but fluid resuscitation is possible in most cases at least with pressure bag infusion systems. Most drugs administered intravenously can be given intraosseously in equivalent dosages and with the same effects. Nevertheless the limitations and risks of IO access routes need to be considered for each application. Rapid IO access is now possible in all age groups, and the 2005 AHA Guidelines favor it over drug administration via the endotracheal tube. PMID:18250995

  5. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  6. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  7. Near Vision Test for Adults

    MedlinePlus

    ... Eyes Education Series Online Training and Certification Patient Education Materials Star Pupils ... Test for Adults Testing Near Vision and Distance Vision Prevent Blindness does NOT recommend that you ...

  8. Facts about Rubella for Adults

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  9. Facts about Mumps for Adults

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  10. Adult Literacy and Numeracy: Assessing Change. Adult Literacy Research Network.

    ERIC Educational Resources Information Center

    Cumming, J. Joy, Ed.; van Kraayenoord, Christina E., Ed.

    This document contains eight papers from an action research program to foster good practice in adult literacy provision and policy. "Introduction" (J. Joy Cumming, Christina E. van Kraayenoord) presents an overview of the action research project and individual reports. "Assessment: Making a Difference in Adult Literacy and Numeracy Learning" (J.…

  11. Evaluation of Adult Education Programs. California Adult Education.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    To assist adult educators in finding meaningful ways to measure the effectiveness of instruction, this monograph provides selected illustrations of specific methods used by adult education instructors to verify student learning. Obtained from teachers in the field, the examples are from programs in (1) dental assisting, (2) instrument pilot ground…

  12. Working with Young Adults. NIACE Lifelines in Adult Learning.

    ERIC Educational Resources Information Center

    Jackson, Carol

    This document explains how adult educators and others in the United Kingdom can increase levels of participation and achievement in learning for young adults by providing informal learning opportunities for those young people who are least inclined to participate in formal education and training programs. The guide outlines a step-by-step approach…

  13. Literacy of Older Adults in America. Adult Literacy Fact Sheet.

    ERIC Educational Resources Information Center

    Kent State Univ., OH. Ohio Literacy Resource Center.

    As part of the National Adult Literacy Survey (NALS) of 1992, the National Center for Education Statistics published a separate study that focuses on the literacy skills of older adults (aged 60 years and older) from a variety of perspectives, such as age, sex, amount of education, race or ethnic background, income, and geographic region. Some of…

  14. An Adult Education Program for Mentally Retarded Adults.

    ERIC Educational Resources Information Center

    Starnes, Jean; Damron, Imogene

    This curriculum guide is intended for use with mentally retarded adults who are enrolled in adult basic education classes. The curriculum provides guidelines to improve students' competencies in three main areas: general functioning skills and independence (transportation, interpersonal relationships, health and safety, goal setting, planning and…

  15. The Varieties of Adult Civic Engagement in Adult Learning

    ERIC Educational Resources Information Center

    Munoz, Linda; Wrigley, Heide Spruck

    2012-01-01

    Civic engagement, or the practice of democratic deliberation in adult education and learning, asks that adults use their experiences to cooperatively build solutions to the difficult social, economic, and political problems that affect their lives and communities now and into the future. The articles presented in this issue look at the…

  16. Atomoxetine Treatment for ADHD: Younger Adults Compared with Older Adults

    ERIC Educational Resources Information Center

    Durell, Todd; Adler, Lenard; Wilens, Timothy; Paczkowski, Martin; Schuh, Kory

    2010-01-01

    Objective: Atomoxetine is a nonstimulant medication for treating child, adolescent, and adult ADHD. This meta-analysis compared the effects in younger and older adults. Method: A post hoc analysis was conducted using data from two double-blind, placebo-controlled clinical trials. Data from patients aged 18-25 years were compared with data from…

  17. Adult Education in Australia: The Council of Adult Education.

    ERIC Educational Resources Information Center

    Randell, Shirley

    Liberal adult education in Victoria, Australia, takes its ideals, if not its form, from the pre-war university and Workers Education Association (WEA) partnerships: the university providing tutors and content, the WEA providing contact with unions and workers. Unique to Victoria is the level to which community-based adult education has been…

  18. Adults' conceptions of intelligence across the adult life span.

    PubMed

    Berg, C A; Sternberg, R J

    1992-06-01

    To examine whether young, middle-aged, and older adults view the concept of intelligent person as similar or different during adulthood, 140 adults of various ages rated how likely it would be for individuals of average and exceptional intelligence at 30, 50, and 70 years of age to be engaged in behaviors previously identified by adults as characterizing adult intelligence. Adults perceived more similarity between exceptionally intelligent prototypes of closer ages (i.e., 30 and 50 and 50 and 70). Intelligence was perceived to consist of interest and ability to deal with novelty, everyday competence, and verbal competence--dimensions that were perceived to be differentially important for different-aged prototypes and by individuals of different ages. Participants' conceptions also included the idea that intelligence is malleable and that abilities differentially increase or decrease across the life span. PMID:1610512

  19. [Adult celiac disease].

    PubMed

    Cellier, C; Grosdidier, E

    2001-05-15

    Celiac disease is much common than previously thought with a prevalence of 1/300, but most of cases are poorly symptomatic or silent. Fewer of half of patients report diarrhoea as a presenting symptom. In adults, the diagnosis should be considered, in case of isolated iron deficiency anaemia, neurological symptoms (ataxia, epilepsy), osteoporosis and arthralgia, infertility, dermatitis herpetiformis and abnormalities in liver tests. Characteristic histological features are total or subtotal villous atrophy associated with an increased number of intraepithelial lymphocytes. The most sensitive and specific circulating antibodies for the diagnosis are endomysial and transglutaminase IgA antibodies. The treatment of celiac disease requires a strict gluten free diet, but the observance to this diet is often difficult. In patients refractory to a strict gluten free diet, serious complications such as intestinal lymphoma or refractory sprue should be considered. PMID:11458609

  20. Secondary hypertension in adults

    PubMed Central

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-01-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. PMID:27211205

  1. Extravasation Injuries in Adults

    PubMed Central

    Al-Benna, S.; O'Boyle, C.; Holley, J.

    2013-01-01

    Insertion of an intravascular catheter is one of the most common invasive procedures in hospitals worldwide. These intravascular lines are crucial in resuscitation, allow vital medication to be administered, and can be used to monitor the patients' real-time vital parameters. There is, however, growing recognition of potential risks to life and limb associated with their use. Medical literature is now replete with isolated case reports of complications succinctly described by Garden and Laussen (2004) as “An unending supply of “unusual” complications from central venous catheters.” This paper reviews complications of venous and arterial catheters and discusses treatment approaches and methods to prevent complications, based on current evidence and endeavours to provide information and guidance that will enable practitioners to prevent, recognise, and successfully treat extravasation injuries in adults. PMID:23738141

  2. Adult Olfactory Bulb Neurogenesis.

    PubMed

    Lledo, Pierre-Marie; Valley, Matt

    2016-01-01

    Most organisms use their olfactory system to detect and analyze chemical cues from the external world to guide essential behaviors. From worms to vertebrates, chemicals are detected by odorant receptors expressed by olfactory sensory neurons, which in vertebrates send an axon to the primary processing center called the olfactory bulb (OB). Within the OB, sensory neurons form excitatory synapses with projection neurons and with inhibitory interneurons. Thus, because of complex synaptic interactions, the output of a given projection neuron is determined not only by the sensory input, but also by the activity of local inhibitory interneurons that are regenerated throughout life in the process of adult neurogenesis. Herein, we discuss how it is optimized and why. PMID:27235474

  3. The older adult driver.

    PubMed

    Carr, D B

    2000-01-01

    More adults aged 65 and older will be driving in the next few decades. Many older drivers are safe behind the wheel and do not need intensive testing for license renewal. Others, however, have physiologic or cognitive impairments that can affect their mobility and driving safety. When an older patient's driving competency is questioned, a comprehensive, step-by-step assessment is recommended. Many diseases that impair driving ability can be detected and treated effectively by family physicians. Physicians should take an active role in assessing and reducing the risk for injury in a motor vehicle and, when possible, prevent or delay driving cessation in their patients. Referral to other health care professionals, such as an occupational or physical therapist, may be helpful for evaluation and treatment. When an older patient is no longer permitted or able to drive, the physician should counsel the patient about using alternative methods of transportation. PMID:10643955

  4. Adult coeliac disease.

    PubMed

    Marmouz, F

    2007-01-01

    Coeliac disease is an auto-immune inflammatory reaction characterized by a partial or total villi's atrophy of the proximal small intestine occuring after ingestion of gluten in genetically predisposed patients. The classic form is much more frequent in children. Thereby there has been a misevaluation and improper treatment of coeliac disease in adults who suffer more from asymptomatica and atypical forms. Currently the only effective treatment is a strict gluten free diet for life. However recent researches brought a new light on the matter. Now oats as a causative factor is controvertial. The introduction of some moderate intestinal lesions (pre-atrophic with intra-epithelial hyperlymphocytosis qualified as "weak enteropathies") in the definition of coeliac disease might be possible. Moreover the way to diagnose has evolved as serological tests and markers are more used due to their efficiency. PMID:17375738

  5. Operation Bootstrap: Adult Education Program Responsibility.

    ERIC Educational Resources Information Center

    Johnston, Ella M.

    Adult educators need to ask themselves two basic questions: What are the problems which adults face today? What are the services which adult education can deliver to help adults individually, and collectively, resolve their problems? For many low-income adults, the problems of high death and unemployment rates, low life expectancy rates, limited…

  6. Segmenting the Adult Education Market.

    ERIC Educational Resources Information Center

    Aurand, Tim

    1994-01-01

    Describes market segmentation and how the principles of segmentation can be applied to the adult education market. Indicates that applying segmentation techniques to adult education programs results in programs that are educationally and financially satisfying and serve an appropriate population. (JOW)

  7. Adult Transition Program without Walls

    ERIC Educational Resources Information Center

    Moberg, Eric

    2010-01-01

    Best practices in adult transition special education for moderate to severe students suggest student-centered planning that maximizes independence in adult life. Based on the above sources, school districts and governing boards would best serve moderate to severe transition special education students with increasing integration into the community…

  8. Recall in Children and Adults

    ERIC Educational Resources Information Center

    Walen, Susan R.

    1970-01-01

    The learning and retention performances of children and adults were compared on free and serialized reproductions of meaningful words. Although the children took longer than the adults to reach the learning criterion, and short-term retention was equivalent for both groups, the children displayed a superior serial recall at 7-day retention.…

  9. Participation Training for Adult Education.

    ERIC Educational Resources Information Center

    Bergevin, Paul; McKinley, John

    Participation Training for Adult Education serves as a manual, guide, and resource for leaders and participants interested in establishing a program of adult learning called group-participation training. Goals emphasize participants learning about themselves as learners, how they relate to and can help others, and exploring the dynamics of a…

  10. Gangsta Rap and Adult Education

    ERIC Educational Resources Information Center

    Guy, Talmadge C.

    2004-01-01

    Adult education instructors and administrators, who typically are not members of the hip-hop generation, have little or no background, sensitivity, or understanding of the influence and significance of black popular culture and music for young African American and white adult learners. (Contains 1 note.)

  11. Focus on Young Adult Programming.

    ERIC Educational Resources Information Center

    Union, Bunni; Williams, Sheila

    1996-01-01

    Presents three library youth service programs which focus on "Pizza and Politicians," a public library pizza party which gave high school students and college-aged young adults a chance to meet and question politicians; a young adult "Reading to Seniors" program; "Making Books," a public library journal-making project for middle school students.…

  12. Native American Adult Reader I.

    ERIC Educational Resources Information Center

    King, Lovern Root, Ed.

    Aspects of Native American history and culture as well as issues and concerns of American Indians are presented in the twelve short articles in this reader for adults. Intended for use in an adult basic education/GED program, the reader features simply written stories (for grades 0-3), illustrations, vocabulary lists and student study questions.…

  13. Sibling Status Effects: Adult Expectations.

    ERIC Educational Resources Information Center

    Baskett, Linda Musun

    1985-01-01

    This study attempted to determine what expectations or beliefs adults might hold about a child based on his or her sibling status alone. Ratings on 50 adjective pairs for each of three sibling status types, only, oldest, and youngest child, were assessed in relation to adult expectations, birth order, and parental status of rater. (Author/DST)

  14. Understanding Adult Education and Training.

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    This book introduces readers to issues, debates and literatures related to a number of central areas of practice in adult education and training, especially in Australia. It is intended as a first attempt to define the field of adult education in Australia in an analytical and theoretical, as opposed to a theoretical and practical sense. Written…

  15. Predictive Modeling in Adult Education

    ERIC Educational Resources Information Center

    Lindner, Charles L.

    2011-01-01

    The current economic crisis, a growing workforce, the increasing lifespan of workers, and demanding, complex jobs have made organizations highly selective in employee recruitment and retention. It is therefore important, to the adult educator, to develop models of learning that better prepare adult learners for the workplace. The purpose of…

  16. Adult Academy Tutor Training Manual.

    ERIC Educational Resources Information Center

    Isserlis, Janet; And Others

    This handbook is for volunteer tutors, student interns, and VISTA volunteers working with adult basic education (ABE) and English-as-a-Second-Language (ESL) learners. The community-based handbook contains information about adult literacy and tutoring--what tutors do, who the learners are, and how the literacy learning process works. Introductory…

  17. Mass Media and Adult Education.

    ERIC Educational Resources Information Center

    Niemi, John A., Ed.

    Some important developments affecting the use of the mass media in adult education are described in this collection of papers. A paper by Dr. George Gordon accuses educators of lacking imagination in their whole approach to adult education, especially in their use of the media. Dr. Robert Carlson's paper delineates the history of educational…

  18. Examining Controversies in Adult Education.

    ERIC Educational Resources Information Center

    Kreitlow, Burton W.; And Others

    Controversies over adult education purposes, methods, audiences, and procedures are examined. After outlining a procedure for reviewing competing positions on controversial topics, the book pairs the contrasting views of two authors on each of 10 key issues facing adult education. Chapters cover: philosophies at issue (David L. Boggs); identifying…

  19. Adult Education in India & Abroad.

    ERIC Educational Resources Information Center

    Roy, Nikhil Ranjan

    A survey is made of various aspects of adult education in India since 1947, together with comparative accounts of the origin, development, and notable features of adult education in Denmark, Great Britain, the Soviet Union, and the United States. Needs and objectives in India, largely in the eradication of illiteracy, are set forth, and pertinent…

  20. Journey to International Adult Education

    ERIC Educational Resources Information Center

    Sun, Qi

    2005-01-01

    In this article, the author describes her journey to international adult education and shares some lessons learned from her journey. The author developed her interest in international adult education through the Scientific Research Institute of International and Comparative Education (SRIICE) at Beijing Normal University and discovered its…

  1. Travel and Adult Transformative Learning

    ERIC Educational Resources Information Center

    Lindstrom, Steven K.

    2011-01-01

    This phenomenological research study examines the lived experience of individual adult transformation in the context of travel. Adults throughout history have experienced profound personal and perception changes as a result of significant travel events. Transformative learning occurs through experience, crisis, and reflection, all of which are…

  2. Economic Essays on Adult Students

    ERIC Educational Resources Information Center

    Shetty, Sandeep

    2013-01-01

    Adult students are an important component of the current U.S education landscape. They account for over 40% of the degree-seeking fresh enrollees in the U.S. colleges and according to the U.S. Department of Education, their growth will soon outpace that of traditional students. Adult students have also received considerable attention in higher…

  3. Notes & Quotes on Adult Learning.

    ERIC Educational Resources Information Center

    Dobson, John R. A.

    This document is a review of literature on adult learning, assembled in a computer-printout format. It brings together brief statements made by authors on the various major aspects of individual and social (associational) learning, as well as information on planning and evaluation. The document also contains a glossary of adult education terms and…

  4. The Politics of Adult Education

    ERIC Educational Resources Information Center

    Ellison, Art

    2016-01-01

    Art Ellison is longtime advocate for adult education, having managed numerous advocacy campaigns over the past forty years on the state and national levels. Prior to his employment in 1980 as the NH State Director of Adult Education he worked for many years as a high school teacher and as a community organizer. In this article, Ellison offers some…

  5. Perceived Stress among Deaf Adults

    ERIC Educational Resources Information Center

    Jones, Elaine G.; Ouellette, Sue E.; Kang, Youngmi

    2006-01-01

    The Present Article describes the effectiveness of stress management classes in decreasing perceived stress among Deaf adults. Deaf adults may experience unique stressors, in addition to circumstances associated with increased stress in the general population. The Perceived Stress Scale (S. Cohen, Kamarck, & Mermelstein, 1983) was used as a…

  6. Recruiting and Retaining Adult Students.

    ERIC Educational Resources Information Center

    Hadfield, Janice

    2003-01-01

    Adult learners, long the stepchildren of colleges and universities, have nearly become the norm, and they spend billions of dollars each year on education. This chapter takes a customer-oriented approach to recruiting and retaining adult students in higher education. (GCP)

  7. Testing in Adult Basic Education.

    ERIC Educational Resources Information Center

    Ehringhaus, Carolyn

    1991-01-01

    Responses from 427 adult basic education teachers (51 percent response) indicated that (1) 84.8 percent use tests for placement; (2) the Tests of Adult Basic Education are overwhelmingly the most frequently used; and (3) 77.7 percent find their testing practices effective, although informal observation and assessment received the highest ranking.…

  8. Adult Education; State Demographic Data.

    ERIC Educational Resources Information Center

    National Advisory Council on Adult Education, Washington, DC.

    In order to clearly identify the target population of Federal activities in adult education, the Research Committee gathered State-by-State demographic information from the 1970 U.S. Census. This compilation of over 3,700 separate figures provides a profile of adults relating to an eligible population for a Federal-State-Local partnership program.…

  9. Senior Adult Consumer Advisory Manual,

    ERIC Educational Resources Information Center

    Ater, E. Carolyn, Ed.

    This manual is intended for use by senior adult peer advisors (age 60 and over) engaged in helping relationships in providing consumer education to other senior adults. The advisory procedures are based on a problem solving approach which incorporates the development of a self-help concept. Chapter 1 provides information on consumer advising. It…

  10. Adult Educator in Developing Countries

    ERIC Educational Resources Information Center

    Dutta, S. C.

    1973-01-01

    The role of adult education in developing countries is preparation of the people for accepting and inculcating change and helping to establish a pattern of social values enabling progress. Recommendations from the Asian Regional Seminar were a high degree of professionalism for adult educators and the establishing of a regional institute. (EA)

  11. Structuring an Adult Learning Environment.

    ERIC Educational Resources Information Center

    Frankel, Alan D.; Lindsey, William L.

    Mercy College in New York has devised a program that seeks to meet the special needs of returning adult students. To ease the restraints on the adult student's time and travel needs, the college holds classes in branches and extension centers throughout the urban area. It also offers eight-week courses that carry the same contact time requirements…

  12. Adult Learning Disorders: Contemporary Issues

    ERIC Educational Resources Information Center

    Wolf, Lorraine E., Ed.; Schreiber, Hope E., Ed.; Wasserstein, Jeanette, Ed.

    2008-01-01

    Recent advances in neuroimaging and genetics technologies have enhanced our understanding of neurodevelopmental disorders in adults. The authors in this volume not only discuss such advances as they apply to adults with learning disorders, but also address their translation into clinical practice. One cluster of chapters addresses developmental…

  13. Adult Functional Competency: A Summary.

    ERIC Educational Resources Information Center

    Texas Univ., Austin. Div. of Extension.

    The Adult Performance Level (APL) project summary specifies the competencies which are functional to economic and educational success in society and describes devices developed for assessing those competencies. The APL theory of functional competency identifies adult needs in general knowledge areas (consumer economics, occupational knowledge,…

  14. Adult Education Research in Finland.

    ERIC Educational Resources Information Center

    Niemi, John A.; Johnson, Arthur A.

    Finnish research in adult education falls into three categories: philosophical, historical, and empirical. (Philosophical research involves the analysis of the concept of adult education and its relationship to other levels of education. Empirical research embraces the psychological and sociological study of students, teachers, institutions, and…

  15. Neuropsychological Assessment of Adult Offenders

    ERIC Educational Resources Information Center

    Marceau, Roger; Meghani, Rehana; Reddon, John R.

    2008-01-01

    This report is primarily concerned with reporting on the normative results obtained on a large sample of serious adult offenders. An expanded Halstead-Reitan Neuropsychological Test Battery was administered to 584 adult offenders (OF), 132 normal controls (NC), and 494 acute psychiatric patients (PP). Subjects were between 18 and 44 years of age.…

  16. Obesity Prevention in Older Adults.

    PubMed

    Volpe, Stella Lucia; Sukumar, Deeptha; Milliron, Brandy-Joe

    2016-06-01

    The number of older adults living in the USA, 65 years of age and older, has been steadily increasing. Data from the National Health and Nutrition Examination Survey (NHANES), 2007-2010, indicate that more than one-third of older adults, 65 years of age and older, were obese. With the increased rate of obesity in older adults, the purpose of this paper is to present research on different methods to prevent or manage obesity in older adults, namely dietary interventions, physical activity interventions, and a combination of dietary and physical activity interventions. In addition, research on community assistance programs in the prevention of obesity with aging will be discussed. Finally, data on federal programs for older adults will also be presented. PMID:27107762

  17. Adult attachment and declining birthrates.

    PubMed

    Draper, Thomas W; Holman, Thomas B; White, Whitney; Grandy, Shannon

    2007-02-01

    Attachment scores for 658 young adults living in the U.S.A. were obtained using the Experiences in Close Relationships scale. The participants came from a subsample of the RELATE data set, who had also filled out the adult attachment measure. Those young adults living in Utah County, Utah, an area of the country with a higher than normal birthrate (88% members of the Church of Jesus Christ of Latter-day Saints), also had higher than average adult attachment scores. While the methodology was not sufficient to assess causal direction nor eliminate the possibility of unidentified influences, an undiscussed psychological factor, adult attachment, may play a role in the numerical declines observed among nonimmigrant communities in the USA and Europe. PMID:17450996

  18. Older adults challenged financially when adult children move home.

    PubMed

    Wallace, Steven P; Padilla-Frausto, D Imelda

    2014-02-01

    This policy brief looks at the financial burdens imposed on older Californians when adult children return home, often due to a crisis not of their own making, to live with their parents. The findings show that on average in California, the amount of money that older adults need in order to maintain a minimally decent standard of living while supporting one adult child in their home increases their expenses by a minimum of 50 percent. Low-income older adults are usually on fixed incomes, so helping an adult child can provide the child with a critical safety net but at the cost of the parents' own financial well-being. Policy approaches to assisting this vulnerable population of older adults include implementing reforms to increase Supplemental Security Income (SSI), improving the availability of affordable housing, assuring that all eligible nonelderly adults obtain health insurance through health care reform's expansion of Medi-Cal and subsidies, and increasing food assistance through SNAP and senior meal programs. PMID:24804354

  19. Coaching as a Strategy for Helping Adults

    ERIC Educational Resources Information Center

    Wax, Dorothy M.; Wertheim, Judith

    2015-01-01

    This chapter focuses on the use of coaching for adult learners, the specific characteristics adults bring to the learning environment, and strategies for dealing with the obstacles adult learners may face.

  20. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  1. General Information about Adult Hodgkin Lymphoma

    MedlinePlus

    ... Adult Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Adult Hodgkin Lymphoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  3. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  4. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  5. Just How Adult Is This Young Adult Book: Young Adult Books for the Junior High Readers.

    ERIC Educational Resources Information Center

    Decker, Charlotte

    1999-01-01

    Discusses young adult novels and presents a bibliography to acquaint librarians with titles and authors that are suitable for emerging young adult readers in grades five through nine. Subject categories include realistic fiction, in the news, historical fiction, short stories, legendary characters, mysteries, science fiction/fantasy/horror, and…

  6. Aspects of Adult Development. The Rossman Adult Learning Inventory: Creating Awareness of Adult Development.

    ERIC Educational Resources Information Center

    Romero, Frederick; And Others

    1990-01-01

    Romero's overview of adult developmental theory stresses the work of Erikson, Havighurst, Loevinger, Perry, Kohlberg, and Cross. Rossman and Rossman discuss the development of their Adult Learning Inventory with an extensive source summary for its 4 factors and a 62-item bibliography. (SK)

  7. Vitalistic thinking in adults.

    PubMed

    Wilson, Stuart

    2013-11-01

    Vitalistic thinking has traditionally been associated with reasoning about biological phenomena. The current research aimed to investigate a broader range of vitalistic thinking than previously studied. Esoteric notions of 'energy' are frequently used by individuals when making causal attributions for strange occurrences, and previous literature has linked such thinking with paranormal, magical, and superstitious beliefs. Two experiments are described that aim to investigate whether adults are vitalistic when asked to make causal judgments, and whether this can be predicted by thinking styles and prior paranormal belief. Experiment 1 asked participants to rate three causal options (one of which was vitalistic) for six vignettes. Scores on one dimension of paranormal belief (New Age Philosophy) and analytical thinking significantly predicted vitalism, but scores on intuitive thinking and Traditional Paranormal Beliefs did not. Experiment 2 extended the findings by asking participants to generate their own causal responses. Again, paranormal belief was found to be the best predictor of vitalism, but this time Traditional Paranormal Beliefs were associated with vitalistic responses whilst both intuitive and analytical thinking were unable to significantly predict classification. Results challenge previous findings, suggesting that vitalistic thinking may operate differently when applied to everyday causal reasoning. PMID:24094281

  8. [Prehospitale analgesia in adults].

    PubMed

    Hossfeld, Björn; Holsträter, Susanne; Bernhard, Michael; Lampl, Lorenz; Helm, Matthias; Kulla, Martin

    2016-02-01

    After securing vital function, treatment of pain is an important aspect in emergency medical care. Irrespective of the underlying disease or injury, pain is an important warning symptom of the body and the most common reason for an emergency alert notification. A patient assesses quality of care and success of prehospital care using the criteria of the extent of pain relief he experiences. Since mild pain does not usually lead to an emergency alert, the criteria apply mainly to treatment of severe and very severe pain. Pain perception varies from individual to individual. Accordingly, assessment of pain intensity is the very first step in pain therapy. The Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable) is suitable for pain assessment in adult emergency patients. Above a grade of 4, therapeutic intervention should be initiated with the goal of reducing pain to reach a value of <4, or at least to achieve a reduction by 3 points. The choice of analgesics that can be meaningfully used in pre-hospital emergency medicine is limited. The emergency physician should be aware of available drugs and administration routes. PMID:26949902

  9. Adult health checkup

    PubMed Central

    Ridley, Jane; Ischayek, Amanda; Dubey, Vinita; Iglar, Karl

    2016-01-01

    Abstract Objective To describe updates to the Preventive Care Checklist Form© to help family physicians stay up to date with current preventive health care recommendations. Quality of evidence The Ovid MEDLINE database was searched using specified key words and other terms relevant to the periodic health examination. Secondary sources, such as the Canadian Task Force on Preventive Health Care, the Public Health Agency of Canada, the Trip database, and the Canadian Medical Association Infobase, were also searched. Recommendations for preventive health care for average-risk adults were reviewed. Strong and weak recommendations are presented on the form in bold and italic text, respectively. Main message Updates were made to the form based on the Canadian Task Force on Preventive Health Care recommendations on screening for obesity (2015), cervical cancer (2013), depression (2013), osteoporosis (2013), hypertension (2012), diabetes (2012, 2013), and breast cancer (2011). Updates were made based on recommendations from other Canadian organizations on screening for HIV (2013), screening for sexually transmitted infections (2013), immunizations (2012 to 2014), screening for dyslipidemia (2012), fertility counseling for women (2011, 2012), and screening for colorectal cancer (2010). Some previous recommendations were removed and others lacking evidence were not included. Conclusion The Preventive Care Checklist Form has been updated with current recommendations to enable family physicians to provide comprehensive, evidence-based care to patients during periodic health examinations. PMID:27076540

  10. Clueless: Adult Mysteries with Young Adult Appeal 2002.

    ERIC Educational Resources Information Center

    Charles, John; Morrison, Joanna

    2002-01-01

    This annotated bibliography includes adult mysteries that appeal to teen readers under the categories of Sherlock Holmes; reference sources; private investigators; amateur sleuths; historical sleuths; suspense and thrillers; police procedurals; mystery blends; and anthologies. (LRW)

  11. La lecture et les adultes (Reading and Adults).

    ERIC Educational Resources Information Center

    Caceres, Benigno

    1980-01-01

    Discusses methods used to help adults improve their reading skills and read with more enjoyment. Particular attention is paid to the Reading Club method. An illustration is given of a particular exercise used at a center in Paris. (AMH)

  12. Computational models of adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Cecchi, Guillermo A.; Magnasco, Marcelo O.

    2005-10-01

    Experimental results in recent years have shown that adult neurogenesis is a significant phenomenon in the mammalian brain. Little is known, however, about the functional role played by the generation and destruction of neurons in the context of an adult brain. Here, we propose two models where new projection neurons are incorporated. We show that in both models, using incorporation and removal of neurons as a computational tool, it is possible to achieve a higher computational efficiency that in purely static, synapse-learning-driven networks. We also discuss the implication for understanding the role of adult neurogenesis in specific brain areas like the olfactory bulb and the dentate gyrus.

  13. Adult Hirschprung disease: radiographic findings.

    PubMed

    Mindelzun, R E; Hicks, S M

    1986-09-01

    Hirschprung disease is usually diagnosed in infancy. Occasionally patients reach adulthood without diagnosis or treatment. Four cases of adult Hirschprung disease are described. The principal radiographic findings are a markedly dilated, feces-filled colon above the zone of transition; a narrowed rectum; a cone- or funnel-shaped zone of transition; and a mosaic colonic pattern caused by collapsed redundant mucosa after colonic cleansing. In an adult, identification on a barium enema examination of an abrupt, smooth transition zone in the rectum with proximal colonic dilatation, in conjunction with an appropriate clinical history, should suggest the diagnosis of adult Hirschprung disease. PMID:3737900

  14. Thematic relations in adults' concepts.

    PubMed

    Lin, E L; Murphy, G L

    2001-03-01

    Concepts can be organized by their members' similarities, forming a kind (e.g., animal), or by their external relations within scenes or events (e.g., cake and candles). This latter type of relation, known as the thematic relation, is frequently found to be the basis of children's but not adults' classification. However, 10 experiments found that when thematic relations are meaningful and salient, they have significant influence on adults' category construction (sorting), inductive reasoning, and verification of category membership. The authors conclude that concepts function closely with knowledge of scenes and events and that this knowledge has a role in adults' conceptual representations. PMID:11293459

  15. Inservice Instructors: Adult Educator Competencies.

    ERIC Educational Resources Information Center

    Petersen, Mary Beth Harper

    1983-01-01

    Describes how fourteen principles of adult education provide the conceptual framework for performance competencies to guide the daily practice of instructors in the centralized inservice department of a large acute-care hospital. (JOW)

  16. Computer acceptance of older adults.

    PubMed

    Nägle, Sibylle; Schmidt, Ludger

    2012-01-01

    Even though computers play a massive role in everyday life of modern societies, older adults, and especially older women, are less likely to use a computer, and they perform fewer activities on it than younger adults. To get a better understanding of the factors affecting older adults' intention towards and usage of computers, the Unified Theory of Acceptance and Usage of Technology (UTAUT) was applied as part of a more extensive study with 52 users and non-users of computers, ranging in age from 50 to 90 years. The model covers various aspects of computer usage in old age via four key constructs, namely performance expectancy, effort expectancy, social influences, and facilitating conditions, as well as the variables gender, age, experience, and voluntariness it. Interestingly, next to performance expectancy, facilitating conditions showed the strongest correlation with use as well as with intention. Effort expectancy showed no significant correlation with the intention of older adults to use a computer. PMID:22317258

  17. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  18. Vaccinations for Adults with Diabetes

    MedlinePlus

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  19. Recommended Immunizations for Adults 50+

    MedlinePlus

    ... page please turn Javascript on. Health Screenings and Immunizations Recommended Immunizations For Adults 50+ The content in this section ... out more, visit How Vaccines Prevent Disease . Vaccines, Vaccinations, and Immunizations Understanding the difference between vaccines, vaccinations, ...

  20. Older Adults and Mental Health

    MedlinePlus

    ... is a widely underrecognized and undertreated medical illness. Depression often co-occurs with other serious illnesses, such as heart disease, stroke, diabetes, cancer, and Parkinson's disease. Because many older adults face these illnesses as well as various social and ...

  1. Osteoporosis: Unique to Older Adults

    MedlinePlus

    ... fractures if needed annual flu shots. Protein-Calorie Malnutrition Many older adults living at home eat poorly. ... serious that a condition known as protein-calorie malnutrition (PCM) develops. Sometimes, PCM occurs after a long ...

  2. Youths Transitioning as Adult Learners

    ERIC Educational Resources Information Center

    Davis, C. Amelia

    2014-01-01

    This chapter considers how transitions to adulthood have been historically represented and presents alternative ways of thinking about transitions to adulthood through the context of adult basic education programs.

  3. Adult-Onset Hypogonadism.

    PubMed

    Khera, Mohit; Broderick, Gregory A; Carson, Culley C; Dobs, Adrian S; Faraday, Martha M; Goldstein, Irwin; Hakim, Lawrence S; Hellstrom, Wayne J G; Kacker, Ravi; Köhler, Tobias S; Mills, Jesse N; Miner, Martin; Sadeghi-Nejad, Hossein; Seftel, Allen D; Sharlip, Ira D; Winters, Stephen J; Burnett, Arthur L

    2016-07-01

    In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up. PMID:27343020

  4. Asthma in adults (acute)

    PubMed Central

    2011-01-01

    Introduction About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild to moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 100 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (plus ipratropium bromide, pressured metered-dose inhalers, short-acting continuous nebulised, short-acting intermittent nebulised, short-acting iv, and inhaled formoterol); corticosteroids (inhaled); corticosteroids (single oral, combined inhaled, and short courses); education about acute asthma; generalist care; helium–oxygen mixture (heliox); magnesium sulphate (iv and adding isotonic nebulised magnesium to inhaled beta2 agonists); mechanical ventilation; oxygen supplementation (controlled 28% oxygen and controlled 100% oxygen); and specialist care. PMID:21463536

  5. What Does It Take to Be an Adult in Austria? Views of Adulthood in Austrian Adolescents, Emerging Adults, and Adults

    ERIC Educational Resources Information Center

    Sirsch, Ulrike; Dreher, Eva; Mayr, Eva; Willinger, Ulrike

    2009-01-01

    The present study examined the defining features of emerging adulthood, subjects' conceptions of the transition to adulthood, and the perceived adult status in Austria. The sample consisted of 775 subjects (226 adolescents, 317 emerging adults, 232 adults). Results showed that most Austrian emerging adults feel themselves to be between adolescence…

  6. [Epithelial hepatoblastomas in the adult].

    PubMed

    Mondragón Sánchez, R; Bernal Maldonado, R; Sada Navarro, L A; Hernández, A I; Hurtado Andrade, H; Cortés Espinoza, T; Sánchez Cisneros, R

    1994-01-01

    Hepatoblastoma is the most frequent primary malignant liver neoplasm in childhood; in adults it is extremely rare and only 27 cases have been published. The prognosis of this neoplasm is poor because it is usually discovered late. Surgery, chemotherapy and liver transplantation have been tried with poor results. We present two adult patients who were diagnosed with an epithelial hepatoblastoma. The pathogenesis, histologic features and current management is reviewed. PMID:7716366

  7. Root Caries in Older Adults.

    PubMed

    Gregory, Dick; Hyde, Susan

    2015-08-01

    Older adults are retaining an increasing number of natural teeth, and nearly half of all individuals aged 75 and older have experienced root caries. Root caries is a major cause of tooth loss in older adults, and tooth loss is the most significant negative impact on oral health-related quality of life for the elderly. The need for improved preventive efforts and treatment strategies for this population is acute. PMID:26357814

  8. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  9. Study Circle Guide: Adult Student Persistence

    ERIC Educational Resources Information Center

    National Center for the Study of Adult Learning and Literacy (NCSALL), 2006

    2006-01-01

    This study circle was created by the National Center for the Study of Adult Learning and Literacy (NCSALL). The study circle is part of NCSALL's efforts to help connect research and practice in the field of adult basic education and adult literacy. The Adult Student Persistence Study Circle is one of a series of study circles that NCSALL has…

  10. Dealing with Disruptive Behavior of Adult Learners

    ERIC Educational Resources Information Center

    Dobmeier, Robert; Moran, Joseph

    2008-01-01

    The adult education literature on disruptive behavior of adult learners was reviewed and a survey on disruptive behavior of adult learners was conducted with adult educators. The findings are synthesized in a conceptual framework for understanding the types and causes of disruptive behavior, which fall into the categories of inattention,…

  11. Adult Education in Israel, II-III.

    ERIC Educational Resources Information Center

    Kirmayer, Paul, Ed.; Pinnes, Noy, Ed.

    This is the second booklet in English that deals with adult education in Israel. The following papers are included: "Editors' Notes" (Paul Kirmayer, Noy Pinnes); "Introduction" (Meir Peretz); "Defining 'Adult Education'" (Yehezkel Cohen); "Planning Study Programs for Adults" (Rachel Tokatli); "The Role of Adult Education: Changing the Individual…

  12. Adults' Event Recall: Is Context Enough?

    ERIC Educational Resources Information Center

    Ratner, Hilary Horn; Padgett, Robert J.

    In studies of retention of verbal material adults have repeatedly remembered less than younger adults have. A study was conducted which asked older adults to remember an experienced event, retention of experiences being considered a better indicator of functioning ability than retention of word lists. In an initial study, older adults' recall was…

  13. Adult Education and Development, No. 47.

    ERIC Educational Resources Information Center

    Adult Education and Development, 1996

    1996-01-01

    This serial issue contains a total of 26 articles grouped under five headings: "Adult Learning: A Key for the Twenty-First Century (Fifth International Conference on Adult Education (Confintea V))"; "Trends in Adult Education Policy" (Belanger); "Adult Education in Modern Times" (Geissler); "From Criticism to Constructiveness" (Torres); "An…

  14. Competency-Based Adult Education Report.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    This resource guide for adult education personnel describes programs and publications on APL (Adult Performance Level) and Competency-Based Adult Education (CBAE). Includes: (1) Descriptions of APL examination programs developed by the American College Testing Program, (2) brief description of Missouri project on the identification of adult basic…

  15. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  16. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  17. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  18. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  19. Life Skills Curriculum for Senior Adult Learners.

    ERIC Educational Resources Information Center

    Leon County Schools, Tallahassee, FL.

    This life skills curriculum helps adult basic educators meet the needs of senior adult learners. An introduction contains the following sections: purpose statement; description of the senior adult learner; tips to remember on teaching senior adults; physiology of aging; teaching the hearing impaired; and teaching the visually impaired. The life…

  20. Engaging the Adult Learner Generational Mix

    ERIC Educational Resources Information Center

    Holyoke, Laura; Larson, Erick

    2009-01-01

    Educators and Trainers both focus on adult learning theory when teaching. In the workforce, as well as in higher education, current literature pertaining to adult learners tends to lump all adults into the same category. Scant research exists that reviews the adult learner through a generational lens. This paper examines the elements that engage…

  1. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  2. Adult Learners: Pathways to Progression. FEDA Paper.

    ERIC Educational Resources Information Center

    Reisenberger, Anna; Sanders, John

    1997-01-01

    A study focused on facilitating progression for adults from nonvocational adult education to qualification-bearing courses in further education (FE) and studied their patterns of progression and which factors helped or hindered such progress. Information was collected from adult learners in 10 adult and FE organizations in Britain through a…

  3. Methods in Adult Education, Third Edition.

    ERIC Educational Resources Information Center

    Morgan, Barton; And Others

    The adult education textbook is intended for persons preparing to teach adults as well as those already on the job. Following an introductory chapter, Chapter 2 is directed to the learning characteristics of adults. Chapter 3 focuses on steps of involving the potential participant in adult education programs, while Chapter 4 outlines various…

  4. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    PubMed Central

    de Gregorio, Cesare; Curtò, Lorenzo; Recupero, Antonino; Grimaldi, Patrizia; Almoto, Barbara; Venturino, Marilena; Cento, Domenico; Narbone, Maria Carola; Trimarchi, Francesco; Coglitore, Sebastiano; Cannavò, Salvatore

    2006-01-01

    Background Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. Methods Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8%) were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2) and relative wall thickness (cut-off 0.45) at echocardiography. Results There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD) and in 15% of controls (p = NS). Conclusion Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy), not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials. PMID:16507109

  5. Adults with ADHD. An overview.

    PubMed

    Wender, P H; Wolf, L E; Wasserstein, J

    2001-06-01

    Attention-Deficit Hyperactivity Disorder (ADHD) is a common, genetically transmitted neurological disorder, with onset in childhood, probably mediated by decreased brain dopaminergic functioning. The first author was one of the earliest to describe the persistence of symptoms into adulthood. Prevalence and natural history data suggest that of the 3 to 10% of children diagnosed with ADHD, one- to two-thirds (somewhere between 1 and 6% of the general population) continue to manifest appreciable ADHD symptoms into adult life. This paper describes how ADHD in adults can be readily diagnosed and treated, despite resembling or coexisting with other psychiatric disorders. The Wender Utah diagnostic criteria address adult characteristics of the disorder. Informant and patient interviews and rating scales are used to determine the psychiatric status of the patient as a child, make a retroactive diagnosis of childhood ADHD, and establish the current diagnosis of the adult. Stringent diagnosis is key to determining effective treatment. Dopamine agonist stimulant medications appear to be the most effective in treating ADHD. About 60% of patients receiving stimulant medication showed moderate-to-marked improvement, as compared with 10% of those receiving placebo. The core symptoms of hyperactivity, inattention, mood lability, temper, disorganization, stress sensitivity, and impulsivity have been shown to respond to treatment with stimulant medications. Non-dopaminergic medications, such as the tricyclic antidepressants and SSRIs have generally not been useful in adults with ADHD in the absence of depression or dysthymia. Pemoline is no longer approved for use in these patients, despite early favorable reports. Appropriate management of adult patients with ADHD is multimodal. Psychoeducation, counseling, supportive problem-directed therapy, behavioral intervention, coaching, cognitive remediation, and couples and family therapy are useful adjuncts to medication management

  6. Acute Psychiatric Hospital Admissions of Adults and Elderly Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1993-01-01

    Examination of the records of 240 inpatients with mental retardation and 7 with autism discharged from a university hospital indicated that elderly adults had more medical problems than did adults, more elderly adults were transferred to a state hospital, and the most common diagnosis in both adults and elderly adults was chronic schizophrenia,…

  7. Policy Review on Adult Learning: The Adult Non-Formal Education Policy of Mali, West Africa

    ERIC Educational Resources Information Center

    Gadio, Moussa

    2011-01-01

    This article focuses on the issue of policy development for adult learning in Mali, West Africa. On January 2007, the Malian government adopted the "Adult Non-formal Education Policy Document," which was intended to regulate the adult learning sector and federate the actions of policy makers, adult education providers, and adult learners. The…

  8. Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.

    PubMed

    Bolhuis, P A; Ponne, N J; Bikker, H; Baas, F; Vianney de Jong, J M

    1993-09-01

    Sandhoff disease is a lysosomal storage disorder characterized by accumulation of GM2 ganglioside due to mutations in the beta-chain of beta-hexosaminidase. Hexosaminidase activity is negligible in infantile Sandhoff disease whereas residual activity is present in juvenile and adult forms. Here we report the molecular basis of the first described adult form of Sandhoff disease. Southern analysis of chromosomal DNA indicated the absence of chromosomal deletions in the gene encoding the beta-chain. Northern analysis of RNA from cultured fibroblasts demonstrated that at least one of the beta-chain alleles was transcribed into normal-length mRNA. Sequence analysis of the entire cDNA prepared from poly-adenylated RNA showed that only one point mutation was present, consisting of a G-->A transition at nucleotide position 1514. This mutation changes the electric charge at amino acid position 505 by substitution of glutamine for arginine in a highly conserved part of the beta-chain, present even in the slime mold Dictyostelium discoideum. The nucleotide transition generated a new restriction site for DdeI, which was present in only one of the alleles of the patient. Reverse transcription of mRNA followed by restriction with DdeI resulted in complete digestion at the mutation site, demonstrating that the second allele was of an mRNA-negative type. Transfection of COS cells with a cDNA construct containing the mutation but otherwise the normal sequence resulted in the expression of a labile form of beta-hexosaminidase. These results show that the patient's is a genetic compound, and that the lability of beta-hexosaminidase found in this form of Sandhoff disease is based on a single nucleotide transition. PMID:8357844

  9. Psychological distress among homeless adults.

    PubMed

    Gelberg, L; Linn, L S

    1989-05-01

    Recent studies have reported a high prevalence of mental illness among the homeless. As part of a community-based survey of 529 homeless adults, we developed and tested a model to increase our understanding of the factors related to their psychological distress. Using a previously validated and reliable scale of perceived psychological distress, we found that homeless adults were more likely to report psychological distress than the general population (80% vs. 49%). Distress levels were not associated with most demographic or homeless characteristics or general appearance. However, distress was related to unemployment, greater cigarette and alcohol use, worse physical health, fewer social supports, and perceived barriers to obtaining needed medical care. Since mental, physical, and social health are strongly related among homeless adults, alleviating distress among them may be most effectively done by implementing a broad-based health services package coupled with employment programs provided in an accessible service delivery setting. PMID:2785158

  10. Adult Neurogenesis and Mental Illness

    PubMed Central

    Schoenfeld, Timothy J; Cameron, Heather A

    2015-01-01

    Several lines of evidence suggest that adult neurogenesis, the production of new neurons in adulthood, may play a role in psychiatric disorders, including depression, anxiety, and schizophrenia. Medications and other treatments for mental disorders often promote the proliferation of new neurons; the time course for maturation and integration of new neurons in circuitry parallels the delayed efficacy of psychiatric therapies; adverse and beneficial experiences similarly affect development of mental illness and neurogenesis; and ablation of new neurons in adulthood alters the behavioral impact of drugs in animal models. At present, the links between adult neurogenesis and depression seem stronger than those suggesting a relationship between new neurons and anxiety or schizophrenia. Yet, even in the case of depression there is currently no direct evidence for a causative role. This article reviews the data relating adult neurogenesis to mental illness and discusses where research needs to head in the future. PMID:25178407

  11. [Adult hepatoblastoma. A case report].

    PubMed

    Goikoetxea Urdiain, A; Sánchez Acedo, P; Mateo Retuerta, J; Tarifa Castilla, A; Zazpe Ripa, C; Herrera Cabezón, J

    Adult hepatoblastoma is a rare pathology. Its pathogeny is not well understood and prognosis is very bad. We pre-sent a case of adult hepatoblastoma treated in our centre. A 65 year-old male, without previous hepatopathy, who consulted due to right hypochondrial pain with a subacute evolution. The pathological diagnosis was adult epithelial hepatoblastoma, with free surgical margins. The patient recei-ved a second surgical intervention 5 months later due to early recurrence and died 10 months after the diagnosis due to a new massive recurrence. His definitive diagnosis is histological. Radical surgery is the only treatment that increases survival, but recurrence is frequent. There are no well-defined patterns of adjuvant chemotherapy nor is there any trans-plant experience. PMID:27599957

  12. Prenatal Famine and Adult Health

    PubMed Central

    Lumey, L.H.; Stein, Aryeh D.; Susser, Ezra

    2013-01-01

    We review human studies on the relation between acute exposures to prenatal famine and adult physical and mental health. These studies are observational and include exposures to a famine environment by natural or man-made causes or, more commonly, from the interplay between natural and human factors. These natural experiments provide an opportunity to examine long-term outcomes after famine exposures by comparing exposed and nonexposed individuals. The studies show consistent associations between prenatal famine and adult body size, diabetes, and schizophrenia. For other measures of adult health, findings are less robust. A relation between prenatal famine and some reported epigenetic changes may provide a potential mechanism to explain specific associations. Much progress can be made if current separate studies are further analyzed with comparable definitions of exposures and outcomes and using common analytic strategies. PMID:21219171

  13. Vaccinations for the Older Adult.

    PubMed

    Gnanasekaran, Gowrishankar; Biedenbender, Rex; Davidson, Harley Edward; Gravenstein, Stefan

    2016-08-01

    Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. PMID:27394026

  14. Water intoxication in adult cattle.

    PubMed

    Kawahara, Naoya; Ofuji, Sosuke; Abe, Sakae; Tanaka, Ai; Uematsu, Masami; Ogata, Yoshimi

    2016-05-01

    Water intoxication is a common disorder in calves and is usually characterized by transient hemoglobinuria. In contrast, the condition is very rare in adult cattle, with few reports on naturally occurring cases. In the present report, four female Japanese Black cattle, aged 16-25 months, showed neurological signs when they drank water following a water outage. Hemoglobinuria was not grossly observed, while severe hyponatremia was revealed by laboratory tests. Autopsy indicated cerebral edema with accumulation of serous fluid in expanded Virchow-Robin spaces. These results indicate the possibility of water intoxication associated with cerebral edema due to severe dilutional hyponatremia in adult cattle. PMID:27506091

  15. Adult Wilms tumor: Case report

    PubMed Central

    Morabito, V.; Guglielmo, N.; Melandro, F.; Mazzesi, G.; Alesini, F.; Bosco, S.; Berloco, P.B.

    2014-01-01

    Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis. PMID:25553532

  16. Adult Neurogenesis: An Evolutionary Perspective.

    PubMed

    Kempermann, Gerd

    2016-02-01

    When adult neurogenesis was discovered in the mammalian brain it was often considered an atavism and, even today, many people are convinced that there has been a "phylogenetic reduction" away from lifelong neurogenesis, favoring stability for complex brains. Adult neurogenesis is found throughout the animal kingdom but varies to a large extent. Mammals might have fewer neurogenic zones than, for example, fish, but within their remaining neurogenic zones, the new neurons are highly functional. Especially, humans have very substantial quantities of neurogenesis in their hippocampus. At least for the mammalian dentate gyrus, one can thus argue that there has been evolution toward neurogenesis-based plasticity rather than away from it. PMID:26684183

  17. Catastrophic events and older adults.

    PubMed

    Cloyd, Elizabeth; Dyer, Carmel B

    2010-12-01

    The plight of older adults during catastrophic events is a societal concern. Older persons have an increased prevalence of cognitive disorders, chronic illnesses, and mobility problems that limit their ability to cope. These disorders may result in a lack of mental capacity and the ability to discern when they should evacuate or resolve problems encountered during a catastrophe. Some older persons may have limited transportation options, and many of the elderly survivors are at increased risk for abuse, neglect, and exploitation. Recommendations for future catastrophic events include the development of a federal tracking system for elders and other vulnerable adults, the designation of separate shelter areas for elders and other vulnerable adults, and involvement of gerontological professionals in all aspects of emergency preparedness and care delivery, including training of frontline workers. Preparation through preevent planning that includes region-specific social services, medical and public health resources, volunteers, and facilities for elders and vulnerable adults is critical. Elders need to be protected from abuse and fraud during catastrophic events. A public health triage system for elders and other vulnerable populations in pre- and postdisaster situations is useful, and disaster preparedness is paramount. Communities and members of safety and rescue teams must address ethical issues before an event. When older adults are involved, consideration needs to be given to triage decision making, transporting those who are immobile, the care of older adults who receive palliative care, and the equitable distribution of resources. Nurses are perfectly equipped with the skills, knowledge, and training needed to plan and implement disaster preparedness programs. In keeping with the tradition of Florence Nightingale, nurses can assume several crucial roles in disaster preparedness for older adults. Nurses possess the ability to participate and lead community

  18. [Etiology of adult insomnia].

    PubMed

    Dollander, M

    2002-01-01

    In the article, the author develops an analysis of external and intrapsychic factors related to adults' insomnia. First she undertakes a literature review to describe semiological, evolutive and etiological levels of insomnia. From a semiological point of view, it is usual to differenciate initial insomnia (associated to the first phase of sleeping), intermittent insomnia (related to frequent awakenings) and final insomnia (related to early morning awakenings). From an evolutive point of view, we can identify transitory insomnia (characterized by frequent awakenings) and chronic insomnia. On the other hand, we are allowed to distinguish organic insomnia (disorder where an organic cerebral injury is demonstrated or suspected) from insomnias related to psychiatric or somatic disease or idiopathic one. Then, the author makes a literary review to identify various insomnia causes and points out. Social factors: insomnia rates are higher by divorced, separated or widowed people. Percentages are higher when scholastic level is weak, domestic income is less then 915 O a month, or by unemployed people. Besides, sleep quality is deteriorated by ageing. Sleeping and waking rhythm is able to loose its synchronization. Complaints about insomnia occur far frequently from women than men. Environmental factors: working constraints increase sleep disorders. It is possible to make the same conclusion when we have to face overcharge of external events, deep intrapsychic conflicts (related to grief, unemployment, damage or hospitalization) or interpersonal conflicts' situations where we are confronted to stress related to socio-affective environment, lack of social support or conjugal difficulties. Medical and physiologic causes: legs impatience syndrome, recurrent limbs shakings syndrome, breathe stop during sleep, narcolepsy, excessive medicine or hypnotic drugs use, some central nervous system injuries, every nocturnal awakening (related to aches.), surgical operation

  19. The Adult Literacy League and the Center for Adult Literacy.

    ERIC Educational Resources Information Center

    Hooks, William Michael; Nelson, Floride

    Since its foundation in 1968, the Adult Literacy League of Orlando, Florida, has dedicated itself to eradicating the educational handicaps of more than 2,575 local residents. The League, which in 1975 became part of the Open Campus of Valencia Community College (VCC), offers two courses: (1) a Literacy Tutor Training Workshop, a 10-hour program to…

  20. Miglustat therapy in juvenile Sandhoff disease.

    PubMed

    Tallaksen, C M E; Berg, J E

    2009-12-01

    GM(2)-gangliosidosis is a rare and heterogeneous inherited metabolic disorder caused by autosomal recessive mutations in genes encoding the lysosomal enzyme β-hexosaminidase, resulting in the accumulation of ganglioside GM(2) in various tissues, particularly the central nervous system. It is characterized by progressive neurological deterioration that mainly affects motor and spinocerebellar function. Several forms of GM(2)-gangliosidosis exist, including the Sandhoff variant. Currently there is no treatment for these conditions, except for palliative care. Miglustat (Zavesca) is a reversible inhibitor of glucosylceramide synthase, which catalyses the first committed step in the synthesis of glucose-based glycolipids. Miglustat has pharmacokinetic properties that allow it to cross the blood-brain barrier, and preclinical data suggest that it may benefit neuronopathic lysosomal storage diseases. Here we present a case report of a Norwegian patient with Sandhoff disease treated with miglustat at our centre in Norway. The patient initially presented with ataxia and dysarthria at 2-3 years of age, which progressed slowly during childhood. At age 14, he experienced episodes of depression and apathy, leading to weight loss. He was diagnosed with Sandhoff disease at age 16. Following 2.5 years of treatment with miglustat, his body weight was stabilized and disease progression appeared to have slowed, as evidenced by the lack of progressive brain atrophy. His depressive symptoms were managed using electroconvulsive treatment (ECT), which improved general functioning. These findings suggest that miglustat may provide beneficial effects in patients with juvenile Sandhoff disease, and that ECT may alleviate depressive symptoms. PMID:19898953

  1. Efficacy of Dinotefuran (Alpine® spray and dust) on six species of stored product insects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dinotefuran, an agonist of insect nicotinic acetylcholine receptors, was evaluated both as a 0.5% active ingredient aerosol spray and a dust combined with diatomaceous earth (DE), 5 g/m2 and 10g/m2), at 45% r.h. and 75% r.h. Target species were six adult stored product insect species: Tribolium cast...

  2. Personal Health Maintenance for Adults

    PubMed Central

    Holbrook, John H.

    1984-01-01

    The practice of adult medicine provides many opportunities to prolong life, prevent disease and disability and promote health. Essential steps in this process include establishing patient rapport, obtaining a comprehensive data base, providing periodic health examinations for both symptomatic and asymptomatic patients and helping patients change unhealthy behavior. PMID:6395497

  3. Adult Children and Aging Parents.

    ERIC Educational Resources Information Center

    Myers, Jane E.

    This book was developed to assist counselors and other caregivers in working with adult children and their aging parents. The first chapter addresses normative developmental issues in later life. This includes the demography of aging, theories of aging, and attitudes toward older persons, along with suggestions for identifying at-risk populations,…

  4. Cardiac Rehabilitation in Older Adults.

    PubMed

    Schopfer, David W; Forman, Daniel E

    2016-09-01

    The biology of aging and the pathophysiology of cardiovascular disease (CVD) overlap, with the effect that CVD is endemic in the growing population of older adults. Moreover, CVD in older adults is usually complicated by age-related complexities, including multimorbidity, polypharmacy, frailty, and other intricacies that add to the risks of ambiguous symptoms, deconditioning, iatrogenesis, falls, disability, and other challenges. Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with cardiovascular conditions. Although CR was originally designed primarily as an exercise training program for younger adults after a myocardial infarction or coronary artery bypass surgery, it has evolved as a comprehensive lifestyle program (promoting physical activity as well as education, diet, risk reduction, and adherence) for a broader range of CVD (coronary heart disease, heart failure, and valvular heart disease). It provides a valuable opportunity to address and moderate many of the challenges pertinent for the large and growing population of older adults with CVD. Cardiac rehabilitation promotes physical function (cardiorespiratory fitness as well as strength and balance) that helps overcome disease and deconditioning as well as related vulnerabilities such as disability, frailty, and falls. Similarly, CR facilitates education, monitoring, and guidance to reduce iatrogenesis and promote adherence. Furthermore, CR fosters cognition, socialization, and independence in older patients. Yet despite all its conceptual benefits, CR is significantly underused in older populations. This review discusses benefits and the paradoxical underuse of CR, as well as evolving models of care that may achieve greater application and efficacy. PMID:27297002

  5. New Directions in Adult Education

    ERIC Educational Resources Information Center

    McRainey, D. Lynn

    2008-01-01

    How are educators moving museums' interpretive goals beyond exhibition galleries? How are programs creating new relationships between a museum and its adult audiences? As plans for physical transformation at the Chicago History Museum took form, the education department launched a parallel process of planning to redefine the "look and feel" for…

  6. Behavior Theory and Adult Education.

    ERIC Educational Resources Information Center

    McLagan, Patricia A.

    The paper proposes that when behavior change is the major target of an adult education program, the designer must consider three factors: (1) the four basic targets for behavior change efforts (behavior goals and plans, basic knowledge and skills needed for successful performance, physical environment, reinforcers of behavior); (2) individual…

  7. Rural Adult Education in Australia.

    ERIC Educational Resources Information Center

    Roberts, Hew

    Adult education in rural areas in Australia provides a contrast both in its general mood and intentions and in its organization with that in the United States. Particularly in rural areas, there seems to be less of the compulsion to organize groups (there are usually no school boards, no chambers of commerce, no women's clubs, no youth centers)…

  8. The Economics of Adult Education

    ERIC Educational Resources Information Center

    Desjardins, Richard

    2013-01-01

    As the "Hamburg Declaration" makes clear, adult education (AE) is a key component of development strategies that seek to ensure the long-term well-being of nations. Yet, with few exceptions most countries systematically underinvest in AE. Of course, it is no easy task to achieve adequate investment levels that reflect an appropriate balance…

  9. Adult Education in Saudi Arabia.

    ERIC Educational Resources Information Center

    Griffin, Tim D.; Algren, Mark S.

    Religion pervades all aspects of Saudi Arabia, the conservative home of Islam, where the constitution is the Quran and law is interpreted by religious scholars. A formal adult basic education program was initiated in 1960. As part of the country's modernization since the early 1970s, the Saudi government has begun an enormous nation-building plan…

  10. Overcoming Exclusion through Adult Learning.

    ERIC Educational Resources Information Center

    Nash, Ian; Walshe, John

    Strategies for overcoming exclusion through adult learning were identified through case studies of 19 initiatives in the following countries: Belgium; Mexico; the Netherlands; Norway; Portugal; and the United Kingdom. The study programs involved a diverse array of formal, nonformal, and informal public sector, community, and enterprise-based…

  11. TRICARE Young Adult. Final rule.

    PubMed

    2013-05-29

    This final rule implements Section 702 of the Ike Skelton National Defense Authorization Act for Fiscal Year 2011 (NDAA for FY11). It establishes the TRICARE Young Adult (TYA) program to provide an extended TRICARE Program coverage opportunity to most unmarried children under the age of 26 of uniformed services sponsors. The TYA program is a premium-based program. PMID:23724426

  12. Adult Literacy Program Personnel Profile.

    ERIC Educational Resources Information Center

    Metis Associates, Inc., New York, NY.

    A study was conducted to find out about the people who conduct and work in adult literacy programs in New York City (NYC). Through a questionnaire distributed to NYC literacy practitioners working in programs operated by public libraries, the City University of New York, the New York City Board of Education, and community-based organizations, the…

  13. Group Access for Disabled Adults.

    ERIC Educational Resources Information Center

    Dale, Mark; Green, Pat

    1998-01-01

    Evaluation of a project to improve higher education access for adults with disabilities found students preferred separate over integrated provision. In integrated programs they felt isolated by teachers' lack of understanding and other students' reactions. In discrete programs they experienced shared understanding of disability, support, and work…

  14. ADVANCED ADULT EDUCATION IN ISRAEL.

    ERIC Educational Resources Information Center

    Ministry of Education and Culture, Jerusalem (Israel).

    ADULT EDUCATION IN ISRAEL IS UNDER THE SUPERVISION OF THE CULTURAL DEPARTMENT, WHICH RECOMMENDS TEACHERS AND LECTURERS AND IS RESPONSIBLE FOR INSPECTION AND FINANCIAL SUPPORT. STUDENT FEES ARE COLLECTED LOCALLY. PREVIOUSLY DEVOTED TO JEWISH TOPICS AND HEBREW LANGUAGE, THE PROGRAM HAS BEEN EXPANDED TO INCLUDE FORMAL SECONDARY EDUCATION, HUMANITIES,…

  15. Computer Technology in Adult Education.

    ERIC Educational Resources Information Center

    Slider, Patty; Hodges, Kathy; Carter, Cea; White, Barbara

    This publication provides materials to help adult educators use computer technology in their teaching. Section 1, Computer Basics, contains activities and materials on these topics: increasing computer literacy, computer glossary, parts of a computer, keyboard, disk care, highlighting text, scrolling and wrap-around text, setting up text,…

  16. Native American Adult Reader III.

    ERIC Educational Resources Information Center

    King, Lovern Root, Ed.

    This reader, one of three designed to provide adults in basic education/GED programs with meaningful material based on Native American cultures, includes selections appropriate for advanced reading ability (grade 7 and above). The twelve readings focus on culture, history, and contemporary concerns of Native Americans. Each selection includes a…

  17. Native American Adult Reader II.

    ERIC Educational Resources Information Center

    King, Lovern Root, Ed.

    This reader, one of three designed to provide adults in basic education/GED programs with meaningful materials based on Native American cultures, includes selections appropriate for intermediate reading ability (grades 4-6). The twelve readings focus on culture, history, and contemporary concerns of Native Americans. Each selection includes a…

  18. Adult Learning in the Workplace.

    ERIC Educational Resources Information Center

    1997

    This document contains four papers from a symposium on adult learning in the workplace. The first paper, "Measuring Critical Thinking: Is There a Single Instrument?" (Patricia K. Leitsch, Carol A. Lentz), examines two issues: the relationship between tests measuring critical thinking and those measuring readiness for self-directed learning and the…

  19. ADULT EDUCATION IN BRITISH COLUMBIA.

    ERIC Educational Resources Information Center

    VERNER, COOLIE, ED.

    PREPARED UNDER THE SPECIAL EDITORSHIP OF COOLIE VERNER, THIS JOURNAL ISSUE REVIEWS THE OVERALL DEVELOPMENT OF ADULT EDUCATION IN BRITISH COLUMBIA FROM THE LATE NINETEENTH CENTURY TO THE PRESENT, TRACES THE GROWTH OF UNIVERSITY EXTENSION DURING THE PERIOD 1915-63, DISCUSSES RECENT TRENDS AND ACTIVITIES IN VOCATIONAL AND NONVOCATIONAL PUBLIC SCHOOL…

  20. Quitting Smoking for Older Adults

    MedlinePlus

    ... Related Topics Alcohol Use and Older Adults COPD Lung Cancer The information in this topic was provided by the National Cancer Institute Topic last reviewed: June 2014 For an enhanced version of this page please turn Javascript on. Quitting Smoking for Older ...

  1. Death of an Adult Child

    MedlinePlus

    ... iGive.com Purchase Through AmazonSmile Contact Us Donate Death of an Adult Child The death of any child, regardless of cause or age, ... the situations that may have caused their child’s death. Judgmental statements from others indicating that the child ...

  2. COPD: Unique to Older Adults

    MedlinePlus

    ... Multiple Health Problems Prevention Join our e-newsletter! Aging & Health A to Z COPD Unique to Older Adults This section provides information ... not a weakness or a normal part of aging. Most people feel better with ... help you can, so that your COPD does not prevent you from living your life ...

  3. Visuomotor Binding in Older Adults

    ERIC Educational Resources Information Center

    Bloesch, Emily K.; Abrams, Richard A.

    2010-01-01

    Action integration is the process through which actions performed on a stimulus and perceptual aspects of the stimulus become bound as a unitary object. This process appears to be controlled by the dopaminergic system in the prefrontal cortex, an area that is known to decrease in volume and dopamine functioning in older adults. Although the…

  4. Sexual Assault of Adult Males.

    ERIC Educational Resources Information Center

    Stermac, Lana; And Others

    1996-01-01

    Examines the circumstances and characteristics of sexual assaults against adult males presenting to a crisis unit in a large metropolitan area. Most victims were young gay men, many of whom had physical or cognitive disabilities making them particularly vulnerable. Results suggest a need for increased awareness of acquaintance sexual assault in…

  5. Adult Students: A Priority Revisited

    ERIC Educational Resources Information Center

    Shugart, Sandy

    2008-01-01

    Many practices in higher education evolved significantly from 1985 to 2005. The presence of adult degree completion programs in colleges and universities of all types proliferated, with satellite campuses for this purpose in metropolitan areas often far removed from the "home campus." MBA programs multiplied during this same time, as did online…

  6. The Child and the Adult.

    ERIC Educational Resources Information Center

    Cavalletti, Sofia

    1994-01-01

    Discusses young children's relationship with God and the place of religion in their lives, focusing on the role of adults in proclaiming the essential elements of Christianity to children. Argues that even very young children can understand the essence of religion. (MDM)

  7. Is Adult Learning Demanding Enough?

    ERIC Educational Resources Information Center

    Hughes, David

    2012-01-01

    This is a fascinating time for adult learning in the UK. With a plethora of reviews reaching report stage alongside ongoing discussion about funding, qualifications and quality and the review of post-16 planning and funding in Wales, there is a real sense that things are about to change after a decade of well-meant but often misfocused reform.…

  8. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  9. Seven Things Adult Learners Dislike.

    ERIC Educational Resources Information Center

    Strzalka, Agnieszka

    1998-01-01

    A questionnaire was designed to elicit what adult learners disliked most about learning English. Seven dislikes were identified, including the following: textbooks in English only, role plays, drills, textbooks with no reading material or with artificial texts, homework, inflexible teachers, and audiotapes. (Author/VWL)

  10. Morphological Processing in Adult Dyslexia

    ERIC Educational Resources Information Center

    Leikin, Mark; Hagit, Even Zur

    2006-01-01

    This study employed the masked-priming paradigm [Forster and Davis (J Exp Psychol bearn Mem Cogn 10: 680-698, 1984).], along with traditional methods of evaluation of morphological awareness and phonological processing, to obtain a finer-grained picture of the relationship between morphological abilities and reading in adult dyslexic readers.…

  11. Essential English for Micronesian Adults.

    ERIC Educational Resources Information Center

    Conrad, Jo Ann; Reinecke, Hank

    This student workbook is designed to help Micronesian adults learn everyday English. Its ten chapters move from simple one-word picture labeling to more abstract ideas in a spiraled fashion, reiterating the essential elements of the English language in different, more complicated ways. Subjects covered include names for everyday objects and…

  12. Adult Vaccination--A Commentary

    ERIC Educational Resources Information Center

    Logan, Jennifer

    2008-01-01

    Traditionally, vaccines have been associated with childhood. Historically, many of the most-feared communicable diseases attacked infants and toddlers, and those who survived were generally protected from those diseases as adults. During the past century tremendous advances in vaccination spared millions the morbidity and mortality associated with…

  13. An Experiment in Adult Education

    ERIC Educational Resources Information Center

    Steele, Tom

    2009-01-01

    The Swarthmore Educational Settlement was founded in Leeds in 1909. Since then thousands of adult learners have benefited from its combinations of liberal, vocational and creative arts programmes, homely atmosphere and commitment to fellowship in learning. It has remained an independent centre, running its own affairs through its own council and…

  14. Boosting Adult Learning. Working Brief.

    ERIC Educational Resources Information Center

    Boyer, David

    Too many of Britain's workforce lack the skills needed for a knowledge-based economy. To remedy this will require the commitment, in time and resources, of individuals, employers, the education and training infrastructure and the state. Adults with the lowest qualifications have the least access to employer-funded training, especially in small…

  15. Socioeconomic Outcomes from Adult Education.

    ERIC Educational Resources Information Center

    Gooderham, Paul N.

    1991-01-01

    The degree to which age and gender influence completion of higher secondary education (HSE) and employment status was measured with a sample of 350 Norwegian adults. Application of a Status Attainment model revealed that post-HSE educational attainment is an important determinant of socioeconomic status for both men and women. (SK)

  16. Informal Helping Relationships Among Adults.

    ERIC Educational Resources Information Center

    Macdonald; Mairi St. John

    An exploratory study examined the informal helping relationship between adults seeking assistance with problems and the persons they selected as helpers. Fifteen men and 15 women were interviewed with an open ended questionnaire listing 50 possible reasons for selecting a helper and 35 possible ways in which a helper assisted with the problems.…

  17. National Adult Physical Fitness Survey.

    ERIC Educational Resources Information Center

    President's Council on Physical Fitness and Sports Newsletter, 1973

    1973-01-01

    This report of a personal interview research survey conducted for the President's Council on Physical Fitness and Sports in 1972 presents the following findings: (a) 45 percent of all adult Americans do not engage in any form of exercise; (b) walking is the most popular form of exercise, followed by bicycle riding, swimming, calisthenics, bowling,…

  18. Adult Learning. ARIS Information Sheet.

    ERIC Educational Resources Information Center

    Language Australia, Melbourne (Victoria). Adult Education Resource and Information Service.

    Adults may seek out learning at different times in their lives, for different reasons, and for vastly different purposes. Some of the reasons are to achieve pre-determined goals; to fill education gaps; to explore options and make choices; to develop personally; to perform a job or role better; or to enhance employment prospects. Learning itself…

  19. Adult Education and Worldview Construction.

    ERIC Educational Resources Information Center

    McKenzie, Leon

    This book frames the higher purposes of adult education in terms of worldview construction. Building on the work of Martin Heidegger, the first of the book's eight chapters defines worldview in two ways: as a vantage point in time and culture that conditions a person's experience of the world and as a person's understanding of the world. Chapter 2…

  20. Where Now for Adult Learning?

    ERIC Educational Resources Information Center

    Keep, Ewart; Rogers, David; Hunt, Sally; Walden, Christopher; Fryer, Bob; Gorard, Stephen; Williams, Ceri; Jones, Wendy; Hartley, Ralph

    2010-01-01

    With 6 billion British pounds of public spending reductions already on the table, and far deeper cuts inevitable, what are the prospects for adult learning in the new Parliament? Some of the regular contributors of this journal were asked what they expected and what they would like to see. Ewart Keep warns that the coalition parties' commitments…

  1. Algebraic Thinking in Adult Education

    ERIC Educational Resources Information Center

    Manly, Myrna; Ginsburg, Lynda

    2010-01-01

    In adult education, algebraic thinking can be a sense-making tool that introduces coherence among mathematical concepts for those who previously have had trouble learning math. Further, a modeling approach to algebra connects mathematics and the real world, demonstrating the usefulness of math to those who have seen it as just an academic…

  2. Adult Education and the Environment

    ERIC Educational Resources Information Center

    Field, John

    2008-01-01

    Due to the effects of global warming, writes Field, everyone now lives in times of plague, floods, and famine. While the UK government's track record on green issues is not all bad, still it is vulnerable to criticism. In this article, the author discusses what adult education has to offer to the environmental movement, despite existing…

  3. Adult Education and Development, 1993.

    ERIC Educational Resources Information Center

    Hinzen, Heribert, Ed.

    1993-01-01

    These two issues of a half-yearly journal for adult education cover Africa, Asia, and Latin America. Number 40 consists of 35 articles on 4 themes: Multicultural dimensions; environmental learning; cooperation and partnership with Eastern Europe; and women and training. Articles include: "It Is Time to Understand that the World Belongs to All of…

  4. The Older Adult and Learning.

    ERIC Educational Resources Information Center

    Hiemstra, Roger

    According to recent census figures, 10% of today's population are over 65 years old. It has often been stated that individual learning needs and capabilities decline with age. To challenge this idea, a study was conducted to gather information about older adults, their learning interests, activities, and obstacles. Four hypotheses were tested…

  5. Adult Learners' Week in Switzerland.

    ERIC Educational Resources Information Center

    Jermann, Ruth

    2002-01-01

    The slogan of International Adult Learners Week in Switzerland is "one hour a day for learning." Four goals of the lifelong learning agenda are government policies to promote access, public awareness campaigns, creation of public learning places, and development of networks for real and virtual learning. (SK)

  6. Adult Braille Instruction in Finland.

    ERIC Educational Resources Information Center

    Heikkila, M.

    1990-01-01

    A program of the Finnish Central Federation of the Visually Handicapped is described. The program's aim is to provide and develop teaching materials and instructional methods to help persons who lost their eyesight as adults to learn braille. Discussed are personal tutoring, correspondence studying, regional courses, and program plans. (Author/JDD)

  7. Counseling Adults for Life Transitions.

    ERIC Educational Resources Information Center

    Walz, Garry R.; Benjamin, Libby

    Adult counseling is assuming increasing importance in counselor education and training. Most important is the developmental aspect of growth all through life, since adulthood is not a static period but can be as fraught with conflict and choice as childhood or adolescence. Outlines describe some important differences between young people and…

  8. Reading Activities of American Adults.

    ERIC Educational Resources Information Center

    Sharon, Amiel T.

    A reading activities survey as part of the Targeted Research and Development Reading Program was done by interviewing 3,504 adults, aged 16 years or older, selected by area probability sampling. Among the preliminary findings was that the most frequent type of reading is newspaper reading. Seven out of 10 people read or look at a newspaper during…

  9. Adult Learning in the Workplace.

    ERIC Educational Resources Information Center

    1999

    This document contains four symposium papers on adult learning in the workplace. "The Relationship between Workplace Learning and Employee Satisfaction in Small Businesses" (Robert W. Rowden, Shamsuddin Ahmad) reports the results of a study of the nature and extent of HRD, level of job satisfaction among workers, and correlation between HRD…

  10. Adult Literacy Issues in Canada.

    ERIC Educational Resources Information Center

    Burnaby, Barbara

    1991-01-01

    Literacy issues are discussed that affect Canadians age 15 and older who are barely literate in any language. Topics include the following: definitions of literacy; policy overviews and surveys; the impact of literacy on Canadian institutions; access for literacy learners; adult learning and classroom practice; and the plain language movement. (76…

  11. Adult Reading Habits and Patterns.

    ERIC Educational Resources Information Center

    Scales, Alice M.; Rhee, Ock

    2001-01-01

    Examines the reading habits and patterns of White and Asian American adults. Hypothesizes that when grouped by demographic variables, participants' responses about their reading habits and patterns would not differ. Concludes that gender, race, and education were predictors for participants' reading habits; education and race were predictors for…

  12. Adult Literacy in Rural Pennsylvania.

    ERIC Educational Resources Information Center

    Askov, Eunice N.

    The rural work force has lower basic skills to supply labor for new jobs with higher literacy demands. At all levels of education the rural population is at a disadvantage compared with the urban population. One out of five rural adults in Pennsylvania has not continued education past the eighth grade. Among the costs to businesses from employee…

  13. Counseling Needs of Adult Students.

    ERIC Educational Resources Information Center

    Erickson, Mildred B.

    This study was undertaken to determine the needs of adults who had decided to return to school for higher education, the basic hypothesis being that their needs (which are different from those of younger students) are not being met. A questionnaire was sent to more than 1,100 men and women over 26 years of age who were attempting to complete an…

  14. Adult Height and Childhood Disease

    PubMed Central

    BOZZOLI, CARLOS; DEATON, ANGUS; QUINTANA-DOMEQUE, CLIMENT

    2009-01-01

    Taller populations are typically richer populations, and taller individuals live longer and earn more. In consequence, adult height has recently become a focus in understanding the relationship between health and wealth. We investigate the childhood determinants of population adult height, focusing on the respective roles of income and of disease. Across a range of European countries and the United States, we find a strong inverse relationship between postneonatal (ages 1 month to 1 year) mortality, interpreted as a measure of the disease and nutritional burden in childhood, and the mean height of those children as adults. Consistent with these findings, we develop a model of selection and stunting in which the early-life burden of undernutrition and disease not only is responsible for mortality in childhood but also leaves a residue of long-term health risks for survivors, risks that express themselves in adult height and in late-life disease. The model predicts that at sufficiently high mortality levels, selection can dominate scarring, leaving a taller population of survivors. We find evidence of this effect in the poorest and highest-mortality countries of the world, supplementing recent findings on the effects of the Great Chinese Famine. PMID:20084823

  15. CPR - adult and child 9 years and older

    MedlinePlus

    Cardiopulmonary resuscitation - adult; Rescue breathing and chest compressions - adult; Resuscitation - cardiopulmonary - adult; Cardiopulmonary resuscitation - child 9 years and older; Rescue breathing ...

  16. For a Socialising Type of Adult Education: Transforming Adult Education into an Autonomous System for the Continuous Resocialisation of Adults.

    ERIC Educational Resources Information Center

    Bogard, Gerald

    This report sets out to establish the need for and to define a type of adult education for the socialization of adults. It arises from the meeting of a steering group responsible for the "Adult Education and Social Change" project, which studied educational practices relating to the long-term unemployed and older people. The key points listed…

  17. Screening for Hepatitis C Infections in Adults

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of screening: (1) Adults at high risk for ... C Virus Infection in Adults Potential Benefits and Harms of Screening and Treatment The Task Force reviewed ...

  18. Senior Health: Older Adults and Newer Technology

    MedlinePlus

    ... Medical Director Senior Health: Older Adults and Newer Technology Volume 15 · Issue 6 · November/December 2005 Text ... adults who struggle to stand and walk. New technology includes knee units, shock-absorbing pylons, and other ...

  19. Rising Blood Sugar Hitting More Obese Adults

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159853.html Rising Blood Sugar Hitting More Obese Adults To curb diabetes, researchers ... HealthDay News) -- Among obese American adults, control of blood sugar is worsening, leading to more diabetes and heart ...

  20. General Information about Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  1. General Information about Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. General Information about Adult Soft Tissue Sarcoma

    MedlinePlus

    ... Soft Tissue Sarcoma Treatment (PDQ®)–Patient Version General Information About Adult Soft Tissue Sarcoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  4. Screening Pelvic Examination in Nonpregnant Adult Women

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening Pelvic Examination in Nonpregnant Adult Women: Recommendations From the American ... Physicians The full report is titled “Screening Pelvic Examination in Adult Women: A Clinical Practice Guideline From ...

  5. ERIC/RCS: Adult Performance Level Project

    ERIC Educational Resources Information Center

    Swiss, Thom

    1976-01-01

    This second article in a two-part series reviews the literature in the Educational Resources Information Center (ERIC) on the Adult Performance Level (APL) project and other programs for adult education. (See CS 710 176) (KS)

  6. Weakened Immune System and Adult Vaccination

    MedlinePlus

    ... for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... up to age 26 years Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  7. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  8. How Can Older Adults Prevent Falls?

    MedlinePlus

    ... Falls and Older Adults How Can Older Adults Prevent Falls? Past Issues / Winter 2014 Table of Contents ... healthy and happy. There are simple ways to prevent most falls. "Injuries from falls are a major ...

  9. Facts about Meningococcal Disease for Adults

    MedlinePlus

    ... Meningococcal Disease Facts about Meningococcal Disease for Adults Facts about Meningococcal Disease for Adults What is meningococcal ... risks associated with the vaccines. Disease and vaccine facts FACT: Quadrivalent meningococcal vaccine (A, C, W, and ...

  10. Sexuality in Older Adults: A Deconstructionist Perspective

    ERIC Educational Resources Information Center

    Huffstetler, Beverly

    2006-01-01

    Societal myths argue against active expression of sexuality in older adults, but these prejudices are unfounded. Using a deconstructionist framework, this article addresses issues surrounding sexuality in older adults. Implications for clinical practice are given.

  11. Anesthesia for Adults Having Eye Surgery

    MedlinePlus

    ... Condiciones Chinese Conditions Anesthesia for Adults Having Eye Surgery En Español What kinds of anesthesia are available for adults having eye surgery? A “general”, “local”, or “topical” anesthesia is necessary ...

  12. Personality Profiles of Physically Impaired Young Adults.

    ERIC Educational Resources Information Center

    Richman, Lynn C.; Harper, Dennis C.

    1980-01-01

    Different forms of chronic observable disability may have differing impacts on adult personality adjustment. Young adults with cleft lip/palate display fewer personality adjustment problems than those with orthopedic impairment. (Author)

  13. Essay Review: On the Instruction of Adults.

    ERIC Educational Resources Information Center

    Fulton, Rodney D.

    1992-01-01

    Organizing instruction for adults should begin by clarifying the relationship between educator and learner. Proper matching of their roles based on the needs and preferences of content, learner, educator, and organization along a continuum underlies successful adult education. (SK)

  14. [Generalized GM1 gangliosidosis. Report of a case and review of the literature].

    PubMed

    Pérez, R; Cuesta, J M; Haro de los Monteros, N; Hernando Mayor y Montes, J C

    1984-05-01

    Authors present the case of a child, daughter of non related parents with neurologic progressive affectation, retina and visceral implication with certain pseudogargolic clinical aspect without near familiar antecedents suggestive of this disease. Biochemistry and histologic studies revealed a B-galactosidase enzyme deficiency and lipidic intracellular increase in different viscera. Biochemistry, hystological and clinical aspects exposed are fundamentally differential of another causes of pseudo-Hurler syndrome. PMID:6433763

  15. Liver involvement in adults with measles.

    PubMed

    Dinh, Aurélien; Fleuret, Victoire; Hanslik, Thomas

    2013-12-01

    We retrospectively collected the characteristics of 80 consecutive adult patients with biologically confirmed measles during a recent epidemic in France. We report on the frequency and severity of liver involvement in adult patients with measles. In our experience, measles in adults was not severe and hepatitis was not correlated with severe cases or bacterial infection. Therefore, hepatitis should be regarded as a usual symptom rather than a complication of measles infection in adults. PMID:23938044

  16. Vocational and Adult Education in Europe.

    ERIC Educational Resources Information Center

    van Wieringen, Fons, Ed.; Attwell, Graham, Ed.

    This book contains 25 papers on vocational and adult education in Europe and the United States. The following papers are included: "Vocational and Adult Education in Europe: Introduction to the Volume" (Fons van Wieringen, Graham Attwell); "Introduction to Section 1: Markets and Institutions in Vocational and Adult Education" (Fons van Wieringen);…

  17. Leading Online Learning Initiatives in Adult Education

    ERIC Educational Resources Information Center

    Olesen-Tracey, Kathy

    2010-01-01

    Adult learners often face barriers to participation in traditional classroom instruction. As technology access grows and adults naturally incorporate technology into their daily lives, adult education programs are finding innovative ways to blend technology with instruction through quality online learning opportunities. This article highlights the…

  18. Children's Representation of Child and Adult Knowledge

    ERIC Educational Resources Information Center

    Fitneva, Stanka A.

    2010-01-01

    Do children think that adult knowledge subsumes or only partially overlaps child knowledge? Sixty-four 4- and 6-year-old children were asked either whether a child and an adult know the answers to questions tapping adult- and child-specific knowledge (Experiment 1) or to whom each question should be addressed (Experiment 2). Children were also…

  19. A European Vision for Adult Education

    ERIC Educational Resources Information Center

    Waddington, Sue; Tuckett, Alan; Boucher, Fiona

    2012-01-01

    The National Institute of Adult Continuing Education (NIACE) is the UK national coordinator for the European Agenda for Adult Learning, with the challenge of creating a coherent message across the four countries to inform European cooperation on adult learning. To start the debate, the journal staff asked Sue Waddington, Alan Tuckett, and Fiona…

  20. Educational Counseling of Adults: Where It's At.

    ERIC Educational Resources Information Center

    Grabowski, Stanley M.

    "Counseling adults is the most impoverished, depressed, but developing area in the entire area of adult education." This is due to: (1) a lack of serious commitment by the educational community, (2) a lack of adequate literature, and (3) a lack of clear-cut role distinctions. The limited number of research studies on counseling adults conclude…