Biomedical subjects

C A Vedeler

Publications and source records attributed to C A Vedeler.

At least 19 recordsLinked to original sources

PubMed2006

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

Adenocarcinoma↗

PubMed2006

Detection of autoantibodies to the BTB-kelch protein KLHL7 in cancer sera.

The aim of the study was to search for novel targets of autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against autoantigen(s) shared by the cancer cells and the nervous system. By serological screening of a rat cerebellum cDNA expression library using anti-Hu-positive sera from three patients with paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an isoform of the BTB-kelch protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7 protein is expressed in the nuclei of neurones, but not in other tissues including various cancers. However, the KLHL7 protein was detected in the nuclei of cancer cell lines. Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with multiple sclerosis were positive for KLHL7 antibodies. Sixteen patients with classical PNS and anti-Hu or anti-Yo antibodies were also negative for KLHL7 antibodies. Seven cancer patients with KLHL7 antibodies had various signs of neurological disease that could be related to cancer, whereas the remaining five seropositive cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7 antibodies are associated with various cancers, and in some patients also with neurological disease. Whether KLHL7 antibodies can be used as paraneoplastic markers for PNS remains to be determined.

Amino Acid Sequence↗

PubMed2006

Management of paraneoplastic neurological syndromes: report of an EFNS Task Force.

Paraneoplastic neurological syndromes (PNS) are remote effects of cancer on the nervous system. An overview of the management of classical PNS, i.e. paraneoplastic limbic encephalitis, subacute sensory neuronopathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome and paraneoplastic peripheral nerve hyperexcitability is given. Myasthenia gravis and paraproteinemic neuropathies are not included in this report. No evidence-based recommendations were possible, but good practice points were agreed by consensus. Urgent investigation is indicated, especially in central nervous system (CNS) syndromes, to allow tumour therapy to be started early and prevent progressive neuronal death and irreversible disability. Onconeural antibodies are of great importance in the investigation of PNS and can be used to focus tumour search. PDG-PET is useful if the initial radiological tumour screen is negative. Early detection and treatment of the tumour is the approach that seems to offer the greatest chance for PNS stabilization. Immune therapy usually has no or modest effect on the CNS syndromes, whereas such therapy is beneficial for PNS affecting the neuromuscular junction. Symptomatic therapy should be offered to all patients with PNS.

Advisory Committees↗

PubMed2006

FcgammaR and multiple sclerosis: an overview.

Receptors for the Fc domain of IgG (FcgammaR) play a key role in the immune system by linking the cellular and humoral immune systems. Despite extensive documentation of CNS-specific antibodies in cerebrospinal fluid and plaques in multiple sclerosis (MS) patients, the role of FcgammaR in this disease remains largely unexplored. Studies indicate however, that polymorphisms in some FcgammaR genes and treatment that induces FcgammaR on immune-competent cells could influence disease progression and treatment response.

Animals↗

PubMed2006

Autopsy findings in the nervous system and ovarian tumour of two patients with paraneoplastic cerebellar degeneration.

OBJECTIVES: To review autopsy findings in paraneoplastic cerebellar degeneration. MATERIALS AND METHODS: We report the autopsy results of two individuals with paraneoplastic cerebellar degeneration and ovarian cancer. RESULTS: Both patients had extensive loss of cerebellar Purkinje cells and general activation of microglia in the central nervous system, as well as signs of immunactivation in the medulla. CONCLUSION: The immunoactivation in PCD is widespread and involving more than the cerebellum.

Aged, 80 and over↗

PubMed2006

An immunoprecipitation assay for the detection of onconeural antibodies.

INTRODUCTION: Onconeural antibodies are found in some patients with cancer, and are associated with paraneoplastic neurological syndromes. METHOD: A multi-well adapted fluid-phase immunoassay using radiolabelled recombinant onconeural proteins for the detection of onconeural antibodies is described. RESULT AND CONCLUSION: This immunoprecipitation technique is more sensitive in detecting onconeural antibodies than immunohistochemistry and immune blots.

Antibodies, Neoplasm↗

PubMed2006

cDNA expression library screening for identification of novel onconeural antigens.

Paraneoplastic neurological disorders occur as a remote effect of cancer. Tumor cells expressing neuron-specific proteins elicit an autoimmune response, resulting in the production of various antibodies. The antibodies are usually associated with different syndromes, but the identity of many of the antigens is still unknown. Screening a cDNA expression library is a powerful technique that allows identification of previously uncharacterized antigens. By using patient sera containing antibodies, the antigens of interest can be isolated and further characterized.

Antibodies, Neoplasm↗

PubMed2005

High dose methylprednisolone induces FcgammaRI on granulocytes in MS-patients.

Immune complexes impinge on receptors for the Fc domain of IgG (FcgammaR) and may thus influence the disease course in multiple sclerosis (MS). We analyzed FcgammaR distribution on monocytes and granulocytes in twenty relapsing-remitting MS patients at baseline, immediately after a five day course of high dose intravenous methylprednisolone (IVMP) treatment and after two months. After a five day course of IVMP the proportion of granulocytes with FcgammaRI was increased, P=0,002. There was no change in FcgammaRII and FcgammaRIII expression. The effect of IVMP on FcgammaRI expression could be important for the clearance of immune complexes in MS.

Adult↗

PubMed2005

Ethnic variations of IL-10 polymorphisms in a Sami and Norwegian population.

Interleukin-10 (IL-10) production is genetically determined and influenced by different polymorphisms in the promoter region of IL-10. These polymorphisms may contribute to the risk and clinical outcome of various infectious and immunological-related diseases. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and are ethnically different from the Norwegians. Different distribution of various immune-related diseases among the Samis compared with Norwegians have been reported. This is the first study to evaluate the distribution of IL-10 polymorphisms in the Sami population. Two hundred healthy Samis were genotyped for polymorphisms in the promoter region of IL-10 at region -1082 (G/A), -819 (T/C) and -592 (A/C). The allele frequencies, genotypes and haplotypes were compared with 187 healthy Norwegians. A significantly higher number of the Samis than the Norwegians had the ATA/ATA genotype, whereas the Norwegians displayed a higher frequency of the GCC/GCC genotype (P=0.0057). There was a significant difference in haplotypes in the two populations with a P=0.0024. These findings may be important for the distribution and clinical outcome of various infectious and immune-related disorders in the two populations.

Aged↗

PubMed2005

IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

Adult↗

PubMed2005

IL-6: an early marker for outcome in acute ischemic stroke.

OBJECTIVES: Inflammation plays an important role in the pathophysiology of stroke. We correlated interleukin (IL)-6, IL-10, C-reactive protein (CRP) and T-lymphocyte subtype levels in acute ischemic stroke patients with stroke volume and clinical outcome. MATERIALS AND METHODS: Blood samples were obtained from 11 patients at defined intervals during 1 year. Nine healthy age-matched subjects served as controls. IL-6, IL-10 and CRP were quantified by enzyme-linked immunosorbent assay and T lymphocytes by flow cytometry. Volume measurement was carried out by computed tomography or magnetic resonance imaging and clinical outcome was scored by the European stroke scale (ESS) and Barthel index (BI). RESULTS: IL-6 levels were increased in the acute phase of stroke compared with healthy controls (P = 0.002) and correlated with larger stroke volume (P = 0.012) and less favorable prognosis after 1 year, measured by ESS (P = 0.014) and BI (P = 0.006). IL-10, CRP and T-lymphocyte subtypes in the acute phase were not correlated with stroke volume or clinical outcome. CONCLUSION: IL-6 seems to be a robust early marker for outcome in acute ischemic stroke.

Acute Disease↗

PubMed2004

Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous system.

Autoantibodies against many proteins are common in sera from patients with various types of cancer. These antibodies are sometimes involved in the development of conditions associated with cancer, such as paraneoplastic neurologic disorders. We used a human brain cDNA expression library and serum from a paraneoplastic neurologic disorder patient to search for new autoantigens in the nervous system. Pyridoxal phosphatase was identified as a novel autoantigen. Expression studies showed that pyridoxal phosphatase was strongly expressed in various parts of the central nervous system. Sera contained antibodies against pyridoxal phosphatase in 22 of 243 (9.1%) patients with lung cancer and eight of 113 (7.1%) with other forms of cancer vs two of 88 (2.3%) healthy control subjects. In addition, 2-4% of patients with different autoimmune diseases had autoantibodies against pyridoxal phosphatase. None of the antipyridoxal phosphatase-positive patients were known to have a paraneoplastic neurologic disorder. Hence, autoantibodies against pyridoxal phosphatase correlate with cancer but not necessarily with the subset of patients with paraneoplastic neurological disorders although serum from such a patient was used to screen the cDNA library. This study showed that yet another enzyme involved in pyridoxal 5'-phosphate metabolism is an autoantigen. Thus, pyridoxal 5'-phosphate seems to be a common denominator for autoantigens involved in autoimmune diseases.

Animals↗

PubMed2004

Hu and voltage-gated calcium channel (VGCC) antibodies related to the prognosis of small-cell lung cancer.

PURPOSE: Hu antibodies previously have been associated with longer survival of patients with small-cell lung cancer (SCLC). Voltage-gated calcium channel (VGCC) antibodies play a pathogenic role in Lambert Eaton myasthenic syndrome, which is also associated with SCLC. These antibodies may reduce tumor growth in patients with the neurologic disease, but it is not clear whether they provide prognostic information in those without neurologic symptoms. PATIENTS AND METHODS: Two hundred patients with SCLC (age 39 to 79 years; mean, 62.3 years; 129 males and 71 females) receiving chemotherapy were studied for the presence of Hu and VGCC antibodies. Sera were examined for Hu antibodies by an in vitro transcription-translation-based immunoprecipitation technique and by immunohistochemistry/dot blot. VGCC (P/Q subtype) antibodies were detected by radioimmunoassay. Survival analysis was used to analyze the data. Results Hu antibodies were detected in 51 of 200 patients (25.5%) by in vitro transcription-translation-based immunoprecipitation and in 37 of 200 patients (18.5%) by immunohistochemistry or dot blot, whereas VGCC antibodies were detected in only 10 of 200 patients (5%). The presence of Hu antibodies did not correlate with VGCC antibodies, and there was no association between Hu or VGCC antibodies and the extent of disease or survival. CONCLUSION: Hu and VGCC antibodies are found in a proportion of SCLC patients, irrespective of neurologic symptoms, but their presence does not correlate with the prognosis of the SCLC.

Adult↗

PubMed2004

Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay.

Patients with paraneoplastic encephalomyelitis(subacute sensory neuronopathy) (PEM/SSN), most commonly associated with small-cell lung cancer (SCLC), frequently harbor Hu antibodies, which are usually detected by indirect immunohistochemistry or immunoblot. We developed a new radioimmunobinding assay to detect Hu antibodies based on in vitro transcribed and translated (ITT) HuD. High levels of Hu antibodies were detected in all seven PEM/SSN patients tested, but not in any of 15 patients with other paraneoplastic syndromes, 20 patients with Sjögren's syndrome, 20 patients with miscellaneous tumors and 99 of 100 blood donors. One of the blood donors had low levels of Hu antibodies. The radiobinding assay detected Hu antibodies in 45 of 191 (24%) patients with SCLC, in comparison with immunofluorescence and immuno dot blot, where only 34 of 191 (18%) were detected. All patients with Hu antibodies detected by immunofluorescence and immuno dot-blot were also positive by the radioimmunobinding assay. The results demonstrate that this assay is very specific and sensitive for the detection of Hu antibodies.

Antibodies↗

PubMed2004

Systemic complement activation following human acute ischaemic stroke.

The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia-reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C-reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow-up period of 12 months. Nine healthy gender- and age-matched subjects served as controls. The terminal SC5b-9 complement complex (TCC), CRP, soluble adhesion molecules (L-, E- and P- selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0.54 to 0.74 AU/ml at 72 h (P = 0.032), reached maximum at 7 days (0.90 AU/ml, P < 0.001), was still significantly increased at 12 days (0.70 AU/ml, P = 0.009) and thereafter normalized. CRP increased significantly from 1.02 to 2.11 mg/l at 24 h (P = 0.023), remained significantly increased for 1 week (2.53-2.94 mg/l, P = 0.012-0.017) and thereafter normalized. TCC and C-reactive protein (CRP) correlated significantly (r = 0.36, P < 0.001). The increase in TCC and CRP correlated to the size of infarction (r = 0.80 and P = 0.017 for TCC; r = 0.72 and P = 0.043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.

Acute Disease↗

PubMed2003

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

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.

Adult↗

PubMed2003

Interleukin-10 promoter polymorphisms in patients with Guillain-Barré syndrome.

Interleukin-10 (IL-10) may have both pro- and anti-inflammatory effects in Guillain-Barré syndrome (GBS). The distribution of polymorphisms in the IL-10 gene (-1082 (G/A), -819 (T/C) and -592 (A/C)) was analysed to determine whether they could influence disease susceptibility or clinical course in GBS. The -592 CC and -819 CC genotypes associated with increased IL-10 response were more frequent in the GBS patients than in the controls (P=0.027), but the polymorphisms did not influence the clinical course of the disease.

DNA Mutational Analysis↗

PubMed2003

Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration.

The present study examined the extent and distribution of lymphocyte infiltration in demyelinated lesions in the cerebral cortex of multiple sclerosis (MS) patients. Tissue sections from the brain of 10 MS patients and five patients without neurological disease were double labeled for myelin basic protein and the lymphocyte markers CD3, CD4, CD8, CD45RO, and CD20. The highest density of CD3-positive T cells was found in MS white matter lesions (40.4/10 high power fields (hpf)). Fewer T cells were detected in cortical lesions that extended through both white and gray matter (12.1/10 hpf; P < 0.001). The lowest number of T cells was detected in intracortical demyelinated lesions (1.1/10 hpf). This was equal to the lymphocyte density in nondemyelinated cerebral cortex within the same tissue block (1.1/10 hpf) or cerebral cortex in control brains (1.8/10 hpf). A similar distribution was found using the CD4, CD8, and CD45RO markers. CD20-positive B cells were scarce in all specimens examined. These data indicate that areas of intracortical demyelination in chronic MS are not associated with an increased number of lymphocytes, or an altered distribution of lymphocyte subsets, when compared with control areas in MS and control patients. This finding indicates that the extent of lymphocyte infiltration in MS lesions is dependent on lesion location.

Adult↗