The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
John E. Greenlee - One of the best experts on this subject based on the ideXlab platform.
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neuronal uptake of anti Hu Antibody but not anti ri Antibody leads to cell death in brain slice cultures
Journal of Neuroinflammation, 2014Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Stacey L ClardyAbstract:Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu Antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri Antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal Antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu Antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) Antibody uptake occurred in living neurons and was not an artifact of Antibody diffusion into dead cells; 3) intracellular binding of anti-Hu Antibody produced neuronal cell death, whereas uptake of anti-Ri Antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of Antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this Antibody response. Our results raise questions as to whether anti-Ri Antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.
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comparative neuronal uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar and hippocampal slice cultures
Journal of the Neurological Sciences, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Noel G. CarlsonAbstract:WCN 2013 No: 1897 Topic: 36 — Other Topic Comparative neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in rat cerebellar and hippocampal slice cultures J.E. Greenlee, S.A. Clawson, B. Wood, K.E. Hill, N.G. Carlson. Neurology Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurology, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Research Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, USA; Center on Aging, University of Utah School of Medicine, Salt Lake City, UT, USA Background: Anti-Hu and anti-Ri are paraneoplastic autoantibodies recognizing intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. We have demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate intracellularly in cerebellar Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation is followed by cell death. The present study was conducted to determine whether anti-Hu and anti-Ri antibodies are also taken up by neurons and whether uptake of either Antibody is cytotoxic. Objective: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in slice cultures of rat cerebellum and hippocampus. Materials and methods: Rat cerebellar and hippocampal slice cultures were incubated with anti-Hu or anti-Ri antibodies and evaluated over time for Antibody uptake and for cell death. Specificity of anti-Hu cytotoxicity was confirmed by adsorbing anti-Hu IgGwith recombinant HuD protein. Results: Anti-Hu and anti-Ri antibodies accumulated in cerebellar and hippocampal neurons. Anti-Hu antibodies produced cell death which was significantly reduced by adsorption of anti-Hu IgG with recombinant HuD protein. In contrast, neurons accumulating anti-Ri antibodies showed no evidence of cell death as compared to controls. Conclusions: Anti-Hu and anti-Ri antibodies entered and accumulated in cerebellar and hippocampal neurons. Anti-Hu Antibody associated neuronal death involved reactivity with HuD protein. Anti-Ri Antibody did not affect neuronal viability and may cause neuronal dysfunction rather than cell death. doi:10.1016/j.jns.2013.07.2239 Abstract — WCN 2013 No: 1902 Topic: 36 — Other Topic An evaluation of the risks involved in ischemic encephalopathy among Mongolian children T. Sosorburam, B. Batbayar. Anesthesiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Children Hospital, Ulan-Bator, Mongolia Background: Ischemic encephalopathy is one of the emerging issues among third world countries. Hypoxia seems to be the main cause of this problem, but many risk factors are associated in causation of hypoxic ischemic encephalopathy (HIE). The aim of our study was to evaluate these risk factors among Mongolian children. Methods: This study was carried out at 3 children's hospitals, 85 neonates diagnosed with HIE over a year. Efforts were made to evaluate the questionnaire including details on parity, pre and postnatal histories, and specially the events of birth from labour till delivery of placenta. Results: There was a remarkable decreased antenatal hospital visits and almost 52% reported that they visited just once or twice during the whole pregnancy period. In 21%, there was history of increased mother age above 40 years while 62% reported that some incidents of hypoxia occurred at the time of birth. 20% used drugs or medication during the course of pregnancy without the consultation of the physician.31 % had a history of prolonged 2nd stage of labour. 49% were delivered by unskilled birth attendants. Conclusion: The data clearly showed that there are risks that can be avoided easily and a leading cause of mental retardation can be prevented. Lack of health awareness and decreased consultation from physicians on time seems to be the bulk of the problem in addition to lack of trained birth staff and health facilities. Efforts should be made to educate the mothers of child bearing ages, and counsel them to make the antenatal hospital visits more frequent as possible. doi:10.1016/j.jns.2013.07.2240 Abstract — WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? C.V.D.S. Vilharba, A.J. Godoy. Marketing, University Sao Judas, Sao Paulo, Brazil; Neurology, University City of Sao Paulo, Sao Paulo, Brazil Our understanding of the way the brain makes a decision is still incomplete. We decided to analyze the relationships between color and different emotions and sound and different emotions and their influences to make a choice. Forty-eight undergraduate students of marketing courses were interviewed. We presented 7 objects with different colors while they were listening to a “sad” song and again while listening to a “happy” song. In each case they had to choose one of them. Then we presented six identical objects associated with different sounds while listening to those songs. Forty-six percent of the students selected the red color during the sad moment (SM) and 40% during the happy moment (HM). None of them chose white during SM (however 10% selected white during HM). During HM the “forgotten” color was orange (2% of the students). Twenty-nine percent of the volunteers chose the object associated with the sound of a bomb during SM (the same sound was selected only by 12% during HM). Only 2% selected the sound of the wind (during SM or HM). Our results suggest that strong stimuli (visual or auditory) activate many neural circuits, making someone choose a red object or one associated with the sound of a bomb. Nevertheless a so called Abstracts / Journal of the Neurological Sciences e629 (2013) e629–e678 e645
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comparative uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar slice cultures p02 161
Neurology, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Ikuo Tsunoda, Noel G. CarlsonAbstract:OBJECTIVE: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in organotypic cultures of rat cerebellum. BACKGROUND: The paraneoplastic autoantibodies, anti-Hu and anti-Ri, recognize intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. The role of antibodies in causing paraneoplastic neurological injury has not been defined. However, we have previously demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate in Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation was followed by cell death. The present study was conducted to determine 1) whether anti-Hu and anti-Ri antibodies are also taken up by neurons in this culture system; 2) whether uptake is restricted to Purkinje cells, and 3) whether uptake of either Antibody is followed by cell death. DESIGN/METHODS: Rat cerebellar slice cultures were incubated with either anti-Hu or anti-Ri antibodies and were followed over time. TUNEL and FLICA methods were used to detect apoptosis. The dead cell stain, SYTOX green, was used to detect non-apoptotic cell death. RESULTS: Anti-Hu and anti-Ri antibodies accumulated not only in Purkinje cells but also in multiple other neuronal populations. Accumulation of anti-Hu Antibody was followed by apoptosis involving multiple neuronal populations: this became detectable within 72-96 hours. In contrast, as compared to controls, cells accumulating anti-Ri antibodies showed no evidence of apoptosis or necrotic cell death over a period of 200 hours. CONCLUSIONS: Uptake of anti-Hu and anti-Ri antibodies was observed in viable neurons throughout the cerebellum and was not restricted to Purkinje cells. While anti-Hu Antibody appears to be specifically cytotoxic, anti-Ri Antibody did not affect neuronal viability and may predominantly cause neuronal dysfunction rather than death. Supported by: United States Department of Veterans Affairs. Disclosure: Dr. Greenlee has received personal compensation for activities with American Academy of Neurology and Oliver Maner LLP. Dr. Greenlee has received personal compensation in an editorial capacity for Medlink. Dr. Clawson has nothing to disclose. Dr. Wood has nothing to disclose. Dr. Hill has nothing to disclose. Dr. Tsunoda has nothing to disclose. Dr. Carlson has nothing to disclose.
Yingyi Wang - One of the best experts on this subject based on the ideXlab platform.
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small cell lung cancer accompanied by tonsillar metastasis and anti Hu Antibody associated paraneoplastic neuropathy a rare case report with long term survival
Medicine, 2015Co-Authors: Jianjiao Ni, Linqian Weng, Hua Yang, Yingyi WangAbstract:AbstractTonsillar metastatic small cell lung cancer (SCLC) is rare, while anti-Hu antibodies are frequently found in SCLC.A 66-year-old man was admitted to our hospital with painful dysesthesia and muscle weakness in the distal extremities for over 1 year, progressive dysphagia for over 1 month, and
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small cell lung cancer accompanied by tonsillar metastasis and anti Hu Antibody associated paraneoplastic neuropathy a rare case report with long term survival
Medicine, 2015Co-Authors: Linqian Weng, Hua Yang, Mingsheng Liu, Yingyi WangAbstract:Tonsillar metastatic small cell lung cancer (SCLC) is rare, while anti-Hu antibodies are frequently found in SCLC. A 66-year-old man was admitted to our hospital with painful dysesthesia and muscle weakness in the distal extremities for over 1 year, progressive dysphagia for over 1 month, and severe cough and dyspnea for over 1 week. He was diagnosed with SCLC accompanied by tonsillar metastasis and anti-Hu Antibody-associated paraneoplastic sensory neuropathy (PSN). The patient tolerated 6 cycles of sequential chemoradiotherapy and gradually recovered. The patient's disease remained in remission 2 years after the diagnosis with a remarkable reduction of tumor burden and a persisting high titer of anti-Hu antibodies. To our knowledge, this is the first case of tonsillar metastatic SCLC accompanied by anti-Hu Antibody-associated PSN, whereby the anticancer immune response was presumed to play a vital role in disease control. Unilateral tonsillar metastasis of SCLC accompanied by anti-Hu Antibody-associated PSN can occur and in certain circumstances, may have a favorable prognosis.
Stacey L Clardy - One of the best experts on this subject based on the ideXlab platform.
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neuronal uptake of anti Hu Antibody but not anti ri Antibody leads to cell death in brain slice cultures
Journal of Neuroinflammation, 2014Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Stacey L ClardyAbstract:Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu Antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri Antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal Antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu Antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) Antibody uptake occurred in living neurons and was not an artifact of Antibody diffusion into dead cells; 3) intracellular binding of anti-Hu Antibody produced neuronal cell death, whereas uptake of anti-Ri Antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of Antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this Antibody response. Our results raise questions as to whether anti-Ri Antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.
Kenneth E. Hill - One of the best experts on this subject based on the ideXlab platform.
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neuronal uptake of anti Hu Antibody but not anti ri Antibody leads to cell death in brain slice cultures
Journal of Neuroinflammation, 2014Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Stacey L ClardyAbstract:Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu Antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri Antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal Antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu Antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) Antibody uptake occurred in living neurons and was not an artifact of Antibody diffusion into dead cells; 3) intracellular binding of anti-Hu Antibody produced neuronal cell death, whereas uptake of anti-Ri Antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of Antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this Antibody response. Our results raise questions as to whether anti-Ri Antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.
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comparative neuronal uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar and hippocampal slice cultures
Journal of the Neurological Sciences, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Noel G. CarlsonAbstract:WCN 2013 No: 1897 Topic: 36 — Other Topic Comparative neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in rat cerebellar and hippocampal slice cultures J.E. Greenlee, S.A. Clawson, B. Wood, K.E. Hill, N.G. Carlson. Neurology Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurology, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Research Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, USA; Center on Aging, University of Utah School of Medicine, Salt Lake City, UT, USA Background: Anti-Hu and anti-Ri are paraneoplastic autoantibodies recognizing intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. We have demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate intracellularly in cerebellar Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation is followed by cell death. The present study was conducted to determine whether anti-Hu and anti-Ri antibodies are also taken up by neurons and whether uptake of either Antibody is cytotoxic. Objective: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in slice cultures of rat cerebellum and hippocampus. Materials and methods: Rat cerebellar and hippocampal slice cultures were incubated with anti-Hu or anti-Ri antibodies and evaluated over time for Antibody uptake and for cell death. Specificity of anti-Hu cytotoxicity was confirmed by adsorbing anti-Hu IgGwith recombinant HuD protein. Results: Anti-Hu and anti-Ri antibodies accumulated in cerebellar and hippocampal neurons. Anti-Hu antibodies produced cell death which was significantly reduced by adsorption of anti-Hu IgG with recombinant HuD protein. In contrast, neurons accumulating anti-Ri antibodies showed no evidence of cell death as compared to controls. Conclusions: Anti-Hu and anti-Ri antibodies entered and accumulated in cerebellar and hippocampal neurons. Anti-Hu Antibody associated neuronal death involved reactivity with HuD protein. Anti-Ri Antibody did not affect neuronal viability and may cause neuronal dysfunction rather than cell death. doi:10.1016/j.jns.2013.07.2239 Abstract — WCN 2013 No: 1902 Topic: 36 — Other Topic An evaluation of the risks involved in ischemic encephalopathy among Mongolian children T. Sosorburam, B. Batbayar. Anesthesiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Children Hospital, Ulan-Bator, Mongolia Background: Ischemic encephalopathy is one of the emerging issues among third world countries. Hypoxia seems to be the main cause of this problem, but many risk factors are associated in causation of hypoxic ischemic encephalopathy (HIE). The aim of our study was to evaluate these risk factors among Mongolian children. Methods: This study was carried out at 3 children's hospitals, 85 neonates diagnosed with HIE over a year. Efforts were made to evaluate the questionnaire including details on parity, pre and postnatal histories, and specially the events of birth from labour till delivery of placenta. Results: There was a remarkable decreased antenatal hospital visits and almost 52% reported that they visited just once or twice during the whole pregnancy period. In 21%, there was history of increased mother age above 40 years while 62% reported that some incidents of hypoxia occurred at the time of birth. 20% used drugs or medication during the course of pregnancy without the consultation of the physician.31 % had a history of prolonged 2nd stage of labour. 49% were delivered by unskilled birth attendants. Conclusion: The data clearly showed that there are risks that can be avoided easily and a leading cause of mental retardation can be prevented. Lack of health awareness and decreased consultation from physicians on time seems to be the bulk of the problem in addition to lack of trained birth staff and health facilities. Efforts should be made to educate the mothers of child bearing ages, and counsel them to make the antenatal hospital visits more frequent as possible. doi:10.1016/j.jns.2013.07.2240 Abstract — WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? C.V.D.S. Vilharba, A.J. Godoy. Marketing, University Sao Judas, Sao Paulo, Brazil; Neurology, University City of Sao Paulo, Sao Paulo, Brazil Our understanding of the way the brain makes a decision is still incomplete. We decided to analyze the relationships between color and different emotions and sound and different emotions and their influences to make a choice. Forty-eight undergraduate students of marketing courses were interviewed. We presented 7 objects with different colors while they were listening to a “sad” song and again while listening to a “happy” song. In each case they had to choose one of them. Then we presented six identical objects associated with different sounds while listening to those songs. Forty-six percent of the students selected the red color during the sad moment (SM) and 40% during the happy moment (HM). None of them chose white during SM (however 10% selected white during HM). During HM the “forgotten” color was orange (2% of the students). Twenty-nine percent of the volunteers chose the object associated with the sound of a bomb during SM (the same sound was selected only by 12% during HM). Only 2% selected the sound of the wind (during SM or HM). Our results suggest that strong stimuli (visual or auditory) activate many neural circuits, making someone choose a red object or one associated with the sound of a bomb. Nevertheless a so called Abstracts / Journal of the Neurological Sciences e629 (2013) e629–e678 e645
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comparative uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar slice cultures p02 161
Neurology, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Ikuo Tsunoda, Noel G. CarlsonAbstract:OBJECTIVE: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in organotypic cultures of rat cerebellum. BACKGROUND: The paraneoplastic autoantibodies, anti-Hu and anti-Ri, recognize intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. The role of antibodies in causing paraneoplastic neurological injury has not been defined. However, we have previously demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate in Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation was followed by cell death. The present study was conducted to determine 1) whether anti-Hu and anti-Ri antibodies are also taken up by neurons in this culture system; 2) whether uptake is restricted to Purkinje cells, and 3) whether uptake of either Antibody is followed by cell death. DESIGN/METHODS: Rat cerebellar slice cultures were incubated with either anti-Hu or anti-Ri antibodies and were followed over time. TUNEL and FLICA methods were used to detect apoptosis. The dead cell stain, SYTOX green, was used to detect non-apoptotic cell death. RESULTS: Anti-Hu and anti-Ri antibodies accumulated not only in Purkinje cells but also in multiple other neuronal populations. Accumulation of anti-Hu Antibody was followed by apoptosis involving multiple neuronal populations: this became detectable within 72-96 hours. In contrast, as compared to controls, cells accumulating anti-Ri antibodies showed no evidence of apoptosis or necrotic cell death over a period of 200 hours. CONCLUSIONS: Uptake of anti-Hu and anti-Ri antibodies was observed in viable neurons throughout the cerebellum and was not restricted to Purkinje cells. While anti-Hu Antibody appears to be specifically cytotoxic, anti-Ri Antibody did not affect neuronal viability and may predominantly cause neuronal dysfunction rather than death. Supported by: United States Department of Veterans Affairs. Disclosure: Dr. Greenlee has received personal compensation for activities with American Academy of Neurology and Oliver Maner LLP. Dr. Greenlee has received personal compensation in an editorial capacity for Medlink. Dr. Clawson has nothing to disclose. Dr. Wood has nothing to disclose. Dr. Hill has nothing to disclose. Dr. Tsunoda has nothing to disclose. Dr. Carlson has nothing to disclose.
Susan A. Clawson - One of the best experts on this subject based on the ideXlab platform.
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neuronal uptake of anti Hu Antibody but not anti ri Antibody leads to cell death in brain slice cultures
Journal of Neuroinflammation, 2014Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Stacey L ClardyAbstract:Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu Antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri Antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal Antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu Antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) Antibody uptake occurred in living neurons and was not an artifact of Antibody diffusion into dead cells; 3) intracellular binding of anti-Hu Antibody produced neuronal cell death, whereas uptake of anti-Ri Antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of Antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this Antibody response. Our results raise questions as to whether anti-Ri Antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.
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comparative neuronal uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar and hippocampal slice cultures
Journal of the Neurological Sciences, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Noel G. CarlsonAbstract:WCN 2013 No: 1897 Topic: 36 — Other Topic Comparative neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in rat cerebellar and hippocampal slice cultures J.E. Greenlee, S.A. Clawson, B. Wood, K.E. Hill, N.G. Carlson. Neurology Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurology, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Research Service, Veterans Affairs Medical Center, Salt Lake City, UT, USA; Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, USA; Center on Aging, University of Utah School of Medicine, Salt Lake City, UT, USA Background: Anti-Hu and anti-Ri are paraneoplastic autoantibodies recognizing intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. We have demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate intracellularly in cerebellar Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation is followed by cell death. The present study was conducted to determine whether anti-Hu and anti-Ri antibodies are also taken up by neurons and whether uptake of either Antibody is cytotoxic. Objective: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in slice cultures of rat cerebellum and hippocampus. Materials and methods: Rat cerebellar and hippocampal slice cultures were incubated with anti-Hu or anti-Ri antibodies and evaluated over time for Antibody uptake and for cell death. Specificity of anti-Hu cytotoxicity was confirmed by adsorbing anti-Hu IgGwith recombinant HuD protein. Results: Anti-Hu and anti-Ri antibodies accumulated in cerebellar and hippocampal neurons. Anti-Hu antibodies produced cell death which was significantly reduced by adsorption of anti-Hu IgG with recombinant HuD protein. In contrast, neurons accumulating anti-Ri antibodies showed no evidence of cell death as compared to controls. Conclusions: Anti-Hu and anti-Ri antibodies entered and accumulated in cerebellar and hippocampal neurons. Anti-Hu Antibody associated neuronal death involved reactivity with HuD protein. Anti-Ri Antibody did not affect neuronal viability and may cause neuronal dysfunction rather than cell death. doi:10.1016/j.jns.2013.07.2239 Abstract — WCN 2013 No: 1902 Topic: 36 — Other Topic An evaluation of the risks involved in ischemic encephalopathy among Mongolian children T. Sosorburam, B. Batbayar. Anesthesiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Children Hospital, Ulan-Bator, Mongolia Background: Ischemic encephalopathy is one of the emerging issues among third world countries. Hypoxia seems to be the main cause of this problem, but many risk factors are associated in causation of hypoxic ischemic encephalopathy (HIE). The aim of our study was to evaluate these risk factors among Mongolian children. Methods: This study was carried out at 3 children's hospitals, 85 neonates diagnosed with HIE over a year. Efforts were made to evaluate the questionnaire including details on parity, pre and postnatal histories, and specially the events of birth from labour till delivery of placenta. Results: There was a remarkable decreased antenatal hospital visits and almost 52% reported that they visited just once or twice during the whole pregnancy period. In 21%, there was history of increased mother age above 40 years while 62% reported that some incidents of hypoxia occurred at the time of birth. 20% used drugs or medication during the course of pregnancy without the consultation of the physician.31 % had a history of prolonged 2nd stage of labour. 49% were delivered by unskilled birth attendants. Conclusion: The data clearly showed that there are risks that can be avoided easily and a leading cause of mental retardation can be prevented. Lack of health awareness and decreased consultation from physicians on time seems to be the bulk of the problem in addition to lack of trained birth staff and health facilities. Efforts should be made to educate the mothers of child bearing ages, and counsel them to make the antenatal hospital visits more frequent as possible. doi:10.1016/j.jns.2013.07.2240 Abstract — WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? WCN 2013 No: 1907 Topic: 36 — Other Topic Different emotions and strong stimuli: How do we make choices? C.V.D.S. Vilharba, A.J. Godoy. Marketing, University Sao Judas, Sao Paulo, Brazil; Neurology, University City of Sao Paulo, Sao Paulo, Brazil Our understanding of the way the brain makes a decision is still incomplete. We decided to analyze the relationships between color and different emotions and sound and different emotions and their influences to make a choice. Forty-eight undergraduate students of marketing courses were interviewed. We presented 7 objects with different colors while they were listening to a “sad” song and again while listening to a “happy” song. In each case they had to choose one of them. Then we presented six identical objects associated with different sounds while listening to those songs. Forty-six percent of the students selected the red color during the sad moment (SM) and 40% during the happy moment (HM). None of them chose white during SM (however 10% selected white during HM). During HM the “forgotten” color was orange (2% of the students). Twenty-nine percent of the volunteers chose the object associated with the sound of a bomb during SM (the same sound was selected only by 12% during HM). Only 2% selected the sound of the wind (during SM or HM). Our results suggest that strong stimuli (visual or auditory) activate many neural circuits, making someone choose a red object or one associated with the sound of a bomb. Nevertheless a so called Abstracts / Journal of the Neurological Sciences e629 (2013) e629–e678 e645
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comparative uptake and cytotoxicity of anti Hu and anti ri antibodies in rat cerebellar slice cultures p02 161
Neurology, 2013Co-Authors: John E. Greenlee, Susan A. Clawson, Kenneth E. Hill, Blair Wood, Ikuo Tsunoda, Noel G. CarlsonAbstract:OBJECTIVE: To evaluate neuronal uptake and cytotoxicity of anti-Hu and anti-Ri antibodies in organotypic cultures of rat cerebellum. BACKGROUND: The paraneoplastic autoantibodies, anti-Hu and anti-Ri, recognize intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu Antibody show neuronal destruction. In contrast, anti-Ri Antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. The role of antibodies in causing paraneoplastic neurological injury has not been defined. However, we have previously demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate in Purkinje cells in slice cultures of rat cerebellum and that Antibody accumulation was followed by cell death. The present study was conducted to determine 1) whether anti-Hu and anti-Ri antibodies are also taken up by neurons in this culture system; 2) whether uptake is restricted to Purkinje cells, and 3) whether uptake of either Antibody is followed by cell death. DESIGN/METHODS: Rat cerebellar slice cultures were incubated with either anti-Hu or anti-Ri antibodies and were followed over time. TUNEL and FLICA methods were used to detect apoptosis. The dead cell stain, SYTOX green, was used to detect non-apoptotic cell death. RESULTS: Anti-Hu and anti-Ri antibodies accumulated not only in Purkinje cells but also in multiple other neuronal populations. Accumulation of anti-Hu Antibody was followed by apoptosis involving multiple neuronal populations: this became detectable within 72-96 hours. In contrast, as compared to controls, cells accumulating anti-Ri antibodies showed no evidence of apoptosis or necrotic cell death over a period of 200 hours. CONCLUSIONS: Uptake of anti-Hu and anti-Ri antibodies was observed in viable neurons throughout the cerebellum and was not restricted to Purkinje cells. While anti-Hu Antibody appears to be specifically cytotoxic, anti-Ri Antibody did not affect neuronal viability and may predominantly cause neuronal dysfunction rather than death. Supported by: United States Department of Veterans Affairs. Disclosure: Dr. Greenlee has received personal compensation for activities with American Academy of Neurology and Oliver Maner LLP. Dr. Greenlee has received personal compensation in an editorial capacity for Medlink. Dr. Clawson has nothing to disclose. Dr. Wood has nothing to disclose. Dr. Hill has nothing to disclose. Dr. Tsunoda has nothing to disclose. Dr. Carlson has nothing to disclose.