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Find video protocols related to scientific articles indexed in Pubmed.
Paraneoplastic CDR2 and CDR2L antibodies affect Purkinje cell calcium homeostasis.
Acta Neuropathol.
PUBLISHED: 07-09-2014
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Paraneoplastic cerebellar degeneration (PCD) is characterized by loss of Purkinje cells (PCs) associated with progressive pancerebellar dysfunction in the presence of onconeural Yo antibodies. These antibodies recognize the cerebellar degeneration-related antigens CDR2 and CDR2L. Response to PCD therapy is disappointing due to limited understanding of the neuropathological mechanisms. Here, we report the pathological role of CDR antibodies on the calcium homeostasis in PCs. We developed an antibody-mediated PCD model based on co-incubation of cerebellar organotypic slice culture with human patient serum or rabbit CDR2 and CDR2L antibodies. The CDR antibody-induced pathology was investigated by high-resolution multiphoton imaging and biochemical analysis. Both human and rabbit CDR antibodies were rapidly internalized by PCs and led to reduced immunoreactivity of calbindin D28K (CB) and L7/Pcp-2 as well as reduced dendritic arborizations in the remaining PCs. Washout of the CDR antibodies partially recovered CB immunoreactivity, suggesting a transient structural change in CB calcium-binding site. We discovered that CDR2 and CB co-immunoprecipitate. Furthermore, the expression levels of voltage-gated calcium channel Cav2.1, protein kinase C gamma and calcium-dependent protease, calpain-2, were increased after CDR antibody internalization. Inhibition of these signaling pathways prevented or attenuated CDR antibody-induced CB and L7/Pcp-2 immunoreactivity loss, morphological changes and increased protein expression. These results signify that CDR antibody internalization causes dysregulation of cell calcium homeostasis. Hence, drugs that modulate these events may represent novel neuroprotective therapies that limit the damaging effects of CDR antibodies and prevent PC neurodegeneration.
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Paraneoplastic Hu and CRMP5 antibodies are present in smokers without cancer or neurological disease.
Respirology
PUBLISHED: 02-03-2014
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We investigated if the paraneoplastic Hu and collapsin response mediator protein 5 (CRMP5) antibodies could be used as early markers for lung cancer in smokers with or without chronic obstructive pulmonary disease (COPD).
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Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study.
Mult. Scler.
PUBLISHED: 01-16-2014
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The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory treatment is not well studied.
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Deficient phosphorylation of Stat1 in leukocytes identifies neutralizing antibodies in multiple sclerosis patients treated with interferon-beta.
PLoS ONE
PUBLISHED: 01-01-2014
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Anti interferon-beta (IFN-?) neutralizing antibodies (NAb) affect efficacy of treatment of multiple sclerosis patients, but exactly when the detrimental effects of NAbs offset therapeutic efficacy is debated. Quantification of intracellular pathway-specific phosphorylation by phospho-specific flow cytometry (phosphoflow) is a promising tool for evaluation of these effects in primary immune cells from treated patients at the single-cell level.
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[Neuromyelitis optica].
Tidsskr. Nor. Laegeforen.
PUBLISHED: 10-17-2013
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Neuromyelitis optica (NMO) is a rare autoimmune inflammatory disease of the central nervous system that is characterized mainly by recurrent optic neuritis and longitudinally extensive transverse myelitis. The aim of this article is to present current knowledge on the clinical features, diagnosis, pathogenesis and treatment of the condition.
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Progressive striatal necrosis associated with anti-NMDA receptor antibodies.
BMC Neurol
PUBLISHED: 05-30-2013
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We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity.
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Avidity of onconeural antibodies is of clinical relevance.
Cancer Immunol. Immunother.
PUBLISHED: 05-20-2013
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Onconeural antibodies are important in the detection of paraneoplastic neurological syndromes (PNS). The avidity of Hu, Yo, and CRMP5 antibodies from 100 patients was determined by immunoprecipitation (IP), and 13 of the Yo positive sera were also tested by surface plasmon resonance (SPR). There was a significant association between the results from IP and SPR. Yo antibodies had higher avidity than Hu and CRMP5 antibodies, and both high- and low-avidity antibodies were associated with tumors and PNS. High-avidity Yo antibodies were mainly associated with ovarian cancer, whereas high-avidity Hu and CRMP5 antibodies were mainly associated with small-cell lung cancer. Low-avidity CRMP5 and Yo antibodies were less often detected by a commercial line blot than high-avidity antibodies. The failure to detect low-avidity onconeural antibodies may result in under diagnosis of PNS.
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The Norwegian Stroke in the Young Study (NOR-SYS): rationale and design.
BMC Neurol
PUBLISHED: 02-13-2013
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Ischemic stroke in young adults is a major health problem being associated with a higher vascular morbidity and mortality compared to controls, and a stroke recurrence rate of 25% during the first decade. The assumed cause of infarction and the detected risk factors determine the early- and long-term treatment. However, for many patients the cause of stroke remains unknown. Risk factor profile and etiology differ in young and elderly ischemic stroke patients, and atherosclerosis is the determined underlying condition in 10 to 15%. However, subclinical atherosclerosis is probably more prevalent and may go unrecognized.Ultrasound imaging is a sensitive method for the detection of arterial disease and for measurement of adipose tissue. The relationship between intima-media thickness (IMT), plaques, cardiovascular risk factors including visceral adipose tissue (VAT) and ischemic events has repeatedly been shown.We have established The Norwegian Stroke in the Young Study (NOR-SYS) as a three-generation research program with the goal to increase our knowledge on heredity and the development of arterial disease and ischemic stroke. Extended standardized ultrasound examinations are done in order to find subclinical vessel disease for early and better prophylaxis.Methods/design: NOR-SYS is a prospective long-term research program. Standardized methods are used for anamnestic, clinical, laboratory, imaging, and ultrasound data collection in ischemic stroke patients aged <=60 years, their partners and joint adult offspring. The ultrasound protocol includes the assessment of intracranial, carotid and femoral arteries, abdominal aorta, and the estimation of VAT. To date, the study is a single centre study with approximately 400 patients, 250 partners and 350 adult offspring expected to be recruited at our site.
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CDR2L Antibodies: A New Player in Paraneoplastic Cerebellar Degeneration.
PLoS ONE
PUBLISHED: 01-01-2013
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Yo antibodies are associated with paraneoplastic cerebellar degeneration (PCD). We have characterized Yo sera by measuring CDR2 and CDR2L antibodies and the localization of their antigens.
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Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab.
Mult. Scler.
PUBLISHED: 04-20-2011
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In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy.
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[Intravenous IgG for treatment of neuromuscular diseases].
Tidsskr. Nor. Laegeforen.
PUBLISHED: 09-14-2010
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Highly purified IgG administered intravenously (IVIG) is used to treat many neurological diseases.
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Onconeural antibodies: improved detection and clinical correlations.
J. Neuroimmunol.
PUBLISHED: 06-25-2010
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Onconeural antibodies are found in many patients with paraneoplastic neurological syndromes (PNS) and define the disease as paraneoplastic. The study describes the presence of onconeural antibodies and PNS in 555 patients with neurological symptoms and confirmed cancer within five years, and compares the diagnostic accuracy of different antibody assays (immunoprecipitation, immunofluorescence and immunoblot). Onconeural antibodies were found in 11.9% of the patients by immunoprecipitation, in 7.0% by immunofluorescence and in 6.3% by immunoblot. PNS were present in 81.8% of the cancer patients that were seropositive by immunoprecipitation. Immunofluorescence and immunoblot failed to detect onconeural antibodies in almost one third of the PNS cases.
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CDR2 antigen and Yo antibodies.
Cancer Immunol. Immunother.
PUBLISHED: 06-03-2010
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Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients without PCD. We studied if there was an association between Yo antibody production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in ovarian cancers. We found similar CDR2 cDNA sequence, mRNA and protein levels in primary ovarian cancers, with or without associated Yo antibodies. CDR2 was also present in other cancers, as well as in normal ovary tissue. The results suggest that Yo antibodies are not only related to the expression of CDR2 alone, but also to immune dysregulation.
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A multivariate approach to reveal biomarker signatures for disease classification: application to mass spectral profiles of cerebrospinal fluid from patients with multiple sclerosis.
J. Proteome Res.
PUBLISHED: 05-27-2010
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Mass spectral profiles from cerebrospinal fluid (CSF) are used as input to a novel multivariate approach to select features responsible for the separation of patients with multiple sclerosis (MS) from control groups. Our targeted statistical approach makes it possible to systematically remove features in the spectral fingerprints masking the components expressing the disease pattern. The low molecular weight CSF proteome from 54 patients with MS and a range of other neurological diseases (OND), as well as neurological healthy controls (NHC), is analyzed in replicates using mass spectral profiling. Statistically validated partial least-squares discriminant analysis (PLS-DA) models are created as a first step to separate the groups. Using the group membership as a target, the most discriminatory projection in the multivariate space spanned by the spectral profiles is revealed. From the resulting target-projected component, the spectral regions most significantly contributing to group separation are identified using the nonparametric discriminating variable (DIVA) test together with the so-called selectivity ratio (SR) plot. Our approach is general and can be applied for other diseases and instrumental techniques as well.
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Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism.
Am. J. Hum. Genet.
PUBLISHED: 05-22-2010
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Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects.
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Neurofilament ELISA validation.
J. Immunol. Methods
PUBLISHED: 05-03-2009
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Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.
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Antibodies against interferon-beta in multiple sclerosis.
J. Neuroimmunol.
PUBLISHED: 04-20-2009
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We measured the frequency of binding antibody (BAB) and neutralizing antibody (NAB) against interferon-beta (IFN-beta) in sera from 827 patients with relapsing-remitting multiple sclerosis (RRMS) using various IFN-beta medications. Of the 827 patients, 363 (43.9%) had serum BAB after more than 12 months of IFN-beta treatment. Of the 363 BAB-positive sera, we analyzed 137 for BAB using a myxovirus-resistant protein A (MxA) protein induction assay (ELISA) and an MxA messenger RNA (mRNA) induction assay (real-time polymerase chain reaction (PCR)). We obtained similar results for each serum in both NAB assays, indicating a good correlation between transcription and translation of MxA. We tested all 363 sera by real-time PCR, and NAB was present in 70.8% of BAB-positive sera, or 31.1% of the 827 patients with relapsing-remitting multiple sclerosis (RRMS). Real-time PCR offers several advantages for measuring NAB compared with the MxA protein induction enzyme-linked immunosorbent assay and should be used routinely for NAB among patients with MS using IFN-beta treatment.
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[Paraneoplastic neurological syndromes].
Tidsskr. Nor. Laegeforen.
PUBLISHED: 03-14-2009
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Paraneoplastic neurological syndromes constitute a heterogenous group of diseases, which often cause severe neurological symptoms. Extensive research during the last 20 years has led to identification of new antigenic targets and inclusion of additional clinical conditions into this group of syndromes.
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Fatigue, pain and muscle weakness are frequent after Guillain-Barré syndrome and poliomyelitis.
J. Neurol.
PUBLISHED: 03-06-2009
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Guillain- Barré syndrome (GBS) and poliomyelitis may cause life-long health problems. We studied fatigue, pain and muscular weakness in both conditions to define possible interactions between these symptoms and their influence on residual disability and daily functioning.
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Onconeural antibodies in sera from patients with various types of tumours.
Cancer Immunol. Immunother.
PUBLISHED: 02-23-2009
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We assessed the frequency and levels of onconeural antibodies in 974 patients with various types of tumours, but without apparent paraneoplastic neurological syndromes (PNS).
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Treatment for paraneoplastic neuropathies.
Cochrane Database Syst Rev
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It is not unusual to observe peripheral nervous system involvement in people with tumours outside the nervous system. Any part of the peripheral nervous system can be involved, from sensory and motor neurons to nerve roots and plexuses, from distal trunks to neuromuscular junctions. Pathogenesis also varies from direct infiltration by cancer cells, to treatment toxicity, to metabolic derangement, cachexia, infections and paraneoplastic syndromes.Paraneoplastic neurological syndromes are symptoms or signs resulting from damage to organs or tissues that are remote from the site of the malignancy or its metastases. The pathogenesis is thought to be immune-mediated as a result of a cross-reaction against antigens shared by the tumour and nervous system cells.Paraneoplastic neuropathies are the most frequently reported paraneoplastic syndromes. They are, however, heterogeneous and require several therapeutic approaches. This review was undertaken to systematically assess any data available from randomised controlled trials (RCTs) on the treatment of paraneoplastic syndromes of the peripheral nervous system and not the whole range of paraneoplastic neurological syndromes.
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Discovery and initial verification of differentially abundant proteins between multiple sclerosis patients and controls using iTRAQ and SID-SRM.
J Proteomics
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In the present study, we aimed to discover cerebrospinal fluid (CSF) proteins with significant abundance difference between early multiple sclerosis patients and controls, and do an initial verification of these proteins using selected reaction monitoring (SRM). iTRAQ and Orbitrap MS were used to compare the CSF proteome of patients with clinically isolated syndrome (CIS) (n=5), patients with relapsing-remitting multiple sclerosis that had CIS at the time of lumbar puncture (n=5), and controls with other inflammatory neurological disease (n=5). Of more than 1200 identified proteins, five proteins were identified with significant abundance difference between the patients and controls. In the initial verification using SRM we analyzed a larger patient and control cohort (n=132) and also included proteins reported as differentially abundant in multiple sclerosis in the literature. We found significant abundance difference for 11 proteins after verification, of which the five proteins alpha-1-antichymotrypsin, contactin-1, apolipoprotein D, clusterin, and kallikrein-6 were significantly differentially abundant in several of the group comparisons. This initial study form the basis for further biomarker verification studies in even larger sample cohorts, to determine if these proteins have relevance as diagnostic or prognostic biomarkers for multiple sclerosis.
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[Baby with respiratory problems and cardiac arrest].
Tidsskr. Nor. Laegeforen.
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A ten-month-old girl was admitted to hospital with respiratory and gastrointestinal symptoms. Her condition deteriorated the following day, and she presented with symptoms of inspiratory stridor, facial palsy and ventricular fibrillation. She was resuscitated and intubated, and a normal spinal puncture was performed. Further investigation revealed areflexia, general hypotonia and reduced ejection fraction. Neurophysiological investigation showed long F-response, and renewed cerebrospinal fluid testing showed albuminocytologic dissociation, both typical signs of acute inflammatory demyelinating polyneuropathy (AIDP). Antitoxin was administered to the baby on suspicion of botulism, but immunological and microbiological testing ruled out infectious aetiology. She showed rapid improvement after i.v. immunoglobulin therapy, and was completely restituted/recovered 6 months after the incident.
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Identification of continuous epitopes of HuD antibodies related to paraneoplastic diseases/small cell lung cancer.
J. Neuroimmunol.
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HuD antibodies are associated with small cell lung cancer. To identify relevant epitopes of HuD antibodies, patient sera and a monoclonal antibody were analyzed for their reactivity to linear 20mer peptides spanning the human HuD protein. The HuD monoclonal antibody recognized a single fragment located in the first RNA recognition motif. Thorough analysis identified VRDKITQGSL as the actual epitope. Screening of anti-HuD positive patients and healthy controls identified eight peptides as potential subdominant epitopes. The majority of these peptides were located in the N-terminal end as well as in the linker region between the second and third RNA recognition motifs.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.