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The type, distribution pattern and time course of spontaneous muscular activity are important for the diagnostics of neuromuscular diseases in the clinical practice. In neurogenic lesions with motor axonal involvement, pathologic spontaneous activity (PSA) is usually reliably detectable by needle electromyography (EMG) 2-4 weeks after occurrence of the lesion. The distribution pattern correlates with the lesion location. The focus of the present work is the description of the different forms of PSA in myogenic diseases.
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Electromiografía , Músculo Esquelético , Humanos , Músculo Esquelético/fisiopatología , Enfermedades Neuromusculares/fisiopatología , Enfermedades Neuromusculares/diagnóstico , Contracción Muscular/fisiologíaRESUMEN
The immune pathogenesis of multiple sclerosis (MS) is thought to be triggered by environmental factors in individuals with an unfavorable genetic predisposition. Epstein-Barr virus (EBV) infection is a major risk factor for subsequent development of MS. Human endogenous retroviruses (HERVs) can be activated by EBV, and might be a missing link between an initial EBV infection and the later onset of MS. In this study, we investigated differential gene expression patterns in EBV-immortalized lymphoblastoid B cell lines (LCL) from MS-affected individuals (MSLCL) and controls by using RNAseq and qRT-PCR. RNAseq data from LCL mapped to the human genome and a virtual virus metagenome were used to identify possible biomarkers for MS or disease-relevant risk factors, e.g., the relapse rate. We observed that lytic EBNA-1 transcripts seemed to be negatively correlated with age leading to an increased expression in LCL from younger PBMC donors. Further, HERV-K (HML-2) GAG was increased upon EBV-triggered immortalization. Besides the well-known transactivation of HERV-K18, our results suggest that another six HERV loci are up-regulated upon stimulation with EBV. We identified differentially expressed genes in MSLCL, e.g., several HERV-K loci, ERVMER61-1 and ERV3-1, as well as genes associated with relapses. In summary, EBV induces genes and HERV in LCL that might be suitable as biomarkers for MS or the relapse risk.
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Retrovirus Endógenos , Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Humanos , Retrovirus Endógenos/genética , Herpesvirus Humano 4 , Esclerosis Múltiple/genética , Leucocitos Mononucleares/metabolismo , RecurrenciaRESUMEN
Neuroblastoma (NB) is the commonest solid tumor outside the central nervous system in infancy and childhood with a unique biological heterogeneity. In patients with advanced, metastasizing neuroblastoma, treatment failure and poor prognosis is often marked by resistance to chemo- or immunotherapy. Thus, identification of robust biomarkers seems essential for understanding tumor progression and developing effective therapy. Here, we have studied the expression of human endogenous retroviruses (HERV) as potential targets in NB cell lines during stem-cell medium-induced microenvironmental change. Quantitative PCR revealed that relative expression of the HERV-K family and HERV-W1 ENV were increased in all three NB cell lines after incubation in stem-cell medium. Virus transcriptome analyses revealed the transcriptional activation of three endogenous retrovirus elements: HERV-R ENV (ERV3-1), HERV-E1 and HERV-Fc2 ENV (ERVFC1-1). Known malignancy markers in NB, e.g. proto-oncogenic MYC or MYCN were expressed highly heterogeneously in the three investigated NB cell lines with up-regulation of MYC and MYCN upon medium-induced microenvironmental change. In addition, SiMa cells exclusively showed a phenotype switching from loosely-adherent monolayers to low proliferating grape-like cellular aggregates, which was accompanied by an enhanced CD133 expression. Interestingly, the overexpression of HERV was associated with a significant elevation of immune checkpoint molecule CD200 in both quantitative PCR and RNA-seq analysis suggesting tumor escape mechanism in NB cell lines after incubation in serum-free stem cell medium.
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OBJECTIVES: Magnetic resonance imaging (MRI) is a cornerstone in diagnosis of myopathies. Recently, imaging techniques, such as histogram analysis are used to obtain novel imaging biomarkers. The present study sought to elucidate possible associations between histopathology derived from muscle biopsies and histogram parameters derived from clinical MRI in myositis and other myopathies. METHODS: 20 patients with myopathies were included in this retrospective study. MRI was performed using a 1.5T MRI scanner including T2- and T1- weighted images. The histogram parameters of the MRI sequences were obtained of the biopsied muscle. The histopathology analysis included the scoring systems proposed by Tateyama et al., Fanin et al., Allenbach et al. and immunohistochemical stainings for MHC-I, CD68, CD8 and CD4. RESULTS: Entropy derived from T2-weighted images showed strong positive associations with the inflammation scores (r=0.71, p=0.0005 with Allenbach et al score and r=0.68, p=0.001 with Tateyama score). Furthermore, there were strong associations between entropy derived from T2-weighted images with MHC-I staining (r=0.67, p=0.022), with the amount of CD20 cells (r=0.70, p=0.022), with the amount of CD4 positive cells (r=0.78, p=0.0075) and with the amount of CD8 positive cells (r=0.79, p=0.004). Other parameters showed no associations with the investigated histopathology features. CONCLUSIONS: Entropy derived from T2-weighted images showed strong associaitions with inflammation scores and with the sole amount of immune cells in myopathies. These results need to be confirmed by clinical studies, whether it is also related to clinical performance or can predict treatment response.
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Miositis , Biopsia , Recuento de Células , Humanos , Imagen por Resonancia Magnética , Miositis/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
BACKGROUND: The time interval between two potential components of the same motor unit potential (MUP) is measured for jitter analysis. Enhanced jitter is generally thought to result from impaired neuromuscular transmission as occurs in myasthenia gravis or during reinnervation. METHODS: Within a database of conventional video-electromyography (EMG) recordings 4 MUP with peculiar jitter patterns were identified. In 1 spontaneously discharging MUP, massive and chaotic jitter was seen with a mean consecutive difference (MCD) of 9.3 ms. In 2 spontaneously discharging MUP a certain potential subgroup jittered relative to the other part(s) of the MUP (MCD 2.0 and 3.3 ms). A jittering satellite was detected in a fourth voluntarily recruited MUP (MCD 0.6 ms). RESULTS: These different jitter patterns recorded with conventional EMG technique may mainly result from dysmyelination. CONCLUSIONS: A new look at the contribution of dysmyelination to abnormal jitter is also warranted in single fiber EMG recordings.
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Electromiografía/métodos , Neuronas Motoras/fisiología , Fibras Musculares Esqueléticas/fisiología , Anciano , Neuropatías del Plexo Braquial/fisiopatología , Femenino , Humanos , Masculino , Parálisis/fisiopatologíaRESUMEN
OBJECTIVES: Diffusion-weighted imaging (DWI) can reflect histopathologic changes in muscle disorders. The present study sought to elucidate possible associations between histopathology derived from muscle biopsies and DWI in myositis and other myopathies. METHODS: Nineteen patients (10 women, 52.6%) with a mean age 51.43 ± 19 years were included in this retrospective study. Apparent diffusion coefficients (ADC) were evaluated with a histogram approach of the biopsied muscle. The histopathology analysis included the scoring systems proposed by Tateyama et al., Fanin et al., Allenbach et al. and immunhistochemical stainings for MHC, CD68, CD8, and CD4. RESULTS: There was a tendency that skewness was lowered with increasing Tateyama score, but it did not reach statistical significance (p = .14). No statistical differences for the other scores were identified. There was a tendency that kurtosis was higher in MHC negative stained patient compared to positive patients, but statistically significance was not reached (p = .07). ADC histogram parameters did not correlate with CD68 and CD8 positive stained cells. There was a trend for skewness to correlate with the amount of CD4-positive cells (r = .57, p = .07). CONCLUSION: The present study could not identify statistical significant associations between DWI and histopathology in muscle diseases based upon a small patient sample. Presumably, the investigated histopathology scores are more specific for certain disease aspects, whereas ADC values reflect the whole cellularity of the investigated muscle, which might cause the negative results.
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Enfermedades Musculares , Miositis , Adulto , Anciano , Biopsia , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Musculares/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a relatively rare disease with progressive limb weakness and sensory loss. A few patients show a severely progressing course without major response to intravenous immunoglobulin or plasma exchange therapy. CIDP-MGUS (monoclonal gammopathy of undetermined significance) is a seldom CIDP variant that has been rarely addressed in therapeutic studies. In the presented CIDP-MGUS case, B cell depletion with rituximab had a favourable effect on the disease course, clinically and in nerve conduction studies.
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Complex repetitive discharges (CRDs) are poorly understood phenomena in needle electromyography (EMG) recordings. The data presented here suggest that CRDs may mainly be a sign of motor unit reinnervation. EMG "video" data of 108 CRDs from neurogenic (ND, n = 39) and myogenic (MD, n = 14) disorders were retrospectively analyzed for cycle duration, potential-free time intervals, spike components (SC), maximum amplitudes, blockade, and increased jitter. CRD-SC in ND disorders (9.3 ± 7.8) outnumbered those in MD disorders (6.3 ± 6.2). The CRD cycle duration was correlated with SC and silent periods (p each < 0.000001). Blockade was observed in 36% and increased jitter in 27% of the CRDs. A higher number of CRD-SC in ND vs. MD fits the known differences in motor unit dimensions. Blockade and increased jitter are known features of diseased neuromuscular junctions, such as during reinnervation. The SC patterns of single CRD cycles resemble reinnervation potentials. Thus, CRDs may result from myo-axonal re-excitation in sprouting motor units. The purpose of this investigation was to better understand the circumstances under which CRDs may occur and eventually to contribute to the understanding of their pathogenesis.
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OBJECTIVES: Magnetic resonance imaging (MRI) is a cornerstone in diagnosis of myopathies. The present study sought to elucidate possible associations between electromyography (EMG) findings and histogram parameters derived from clinical MRI in myositis and other myopathies. MATERIALS AND METHODS: Twenty six patients with myopathies were included in this retrospective study. Clinical MRI was performed with a 1.5T MRI scanner including T2- and T1-weighted images. EMG analysis was performed during clinical diagnostic workup. The histogram parameters of the MRI sequences were obtained of the same muscle, which was investigated with EMG. RESULTS: Several correlations were identified between mean duration of the motor unit potentials (MUP) and histogram parameters derived from T1- and T2-weighted images. The highest for T1-weighted images was mode (r = -.73, P < .0001) and for T2-weighted images was p25 (r = -.57, P = .022). There were significant differences for several histogram parameters between muscles with pathological spontaneous activity and without. So, for T1-weighted images, the best discrimination was achieved with mean (P = .096), and for T2-weighted images for p10 (P = .05). Mean SI values derived from T1-weighted images achieved an AUC of 0.84 with a sensitivity of 0.81 and a specificity of 0.86 to discriminate patients with and without pathological spontaneous activity (PSA). CONCLUSIONS: The present study identified strong associations between histogram analysis derived from morphological MRI sequences and the duration of the MUP derived from EMG in myopathies strengthening the fact that both diagnostic modalities can reflect disease state in a similar fashion. Histogram parameters can predict muscles with PSA.
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Electromiografía/métodos , Imagen por Resonancia Magnética/métodos , Miositis/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miositis/fisiopatología , Estudios RetrospectivosRESUMEN
An ischemic stroke during sexual intercourse is very rare. A basilar artery thrombosis during sexual intercourse has not been described previously. We report a young woman with a life-threatening basilar artery thrombosis during sexual intercourse, with a resulting locked-in syndrome. The positive high intensity transient signals (HITS) diagnosis showed a right-to-left shunt and is in line with paradoxic embolism. The molecular genetics revealed a homozygosity 4G/4G in the region PAI1, -675 (promoter polymorphism) as a risk factor for ischemic stroke. Sexual intercourse is a possible, albeit unusual stroke cause, especially in young people.
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Arteria Basilar/patología , Coito , Accidente Cerebrovascular/etiología , Trombosis/complicaciones , Adolescente , Adulto , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trombosis/patologíaRESUMEN
INTRODUCTION: Motor unit hyperexcitability (MUH) may become manifest in needle electromyography (EMG) recordings as fasciculation potentials, myokymic discharges, or neuromyotonic discharges. Here, we describe a further MUH phenomenon. METHODS: Needle EMG recordings of the Neurology Hospital of Halle (Saale) stored in a video mode as .wav data between 2000 and 2015 were screened for spontaneous continuous motor unit single discharges (SCMUSD). RESULTS: We identified 23 video needle EMG waveforms from 14 patients with SCMUSD. The corresponding motor units discharged at a rate of about 6 H Z (6.3 ± 4.0; range, 1.3-18.1). The coefficient of variation of the discharge rate was 3.5% ± 1.7%. Neurogenic disorders were diagnosed in 12 patients, limb girdle muscle dystrophy was diagnosed in one patient, and stiff-limb syndrome was diagnosed in one patient. DISCUSSION: Spontaneous continuous motor unit single discharge, as described here, widens the spectrum of MUH phenomena.
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Potenciales de Acción , Neuronas Motoras/fisiología , Enfermedades Neuromusculares/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Electrodos , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora , Músculo Esquelético/inervación , Enfermedades Neuromusculares/diagnósticoRESUMEN
Up to now relatively little is known about interlimb reflexes (ILR). Especially it is not well known whether ILR may habituate or not to subsequent stimuli. The main aim of the present investigation was to explore the short term habituation behavior of ILR. The electromyogram was recorded over the tonically active biceps brachii (BB) muscle in 11 healthy subjects contralateral and ipsilateral to supramaximum electrical stimuli (9-12 mA) that were delivered at 1.0 and 0.4 Hz over the left sural nerve. In addition, a selective averaging method was used to investigate the influence of preceding stimuli on the ILR. Thus, 30 blocks of 3 subsequent stimuli were used. All 1st ILR of each block were averaged together. Averages were also obtained for 2nd and 3rd ILR. While ILR amplitudes gained significantly both ipsilateral and contralateral to the stimulus (p < 0.05) after train stimuli as compared with single stimuli, ILR amplitudes showed a significant decrease at 1.0 Hz versus 0.4 Hz stimuli. ILR amplitudes decreased significantly after the 2nd and 3rd stimulus relative to the 1st (p < 0.05). ILR can be recorded bilaterally remote from the stimulus site. Furthermore, ILR show clear short term habituation behavior.
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The aetiology of inflammatory myopathies is not clearly known. A predominance of activated Cd8+ T lymphocytes in inflammatory infiltrates has already been detected. Superantigens activate lymphocytes in an oligoclonal manner. In the present investigation, we investigated local effects after injection of the superantigen (Sag) Staphylococcus enterotoxin A (SEA) in the quadriceps femoris muscle of Lewis rats. Histopathology and gene expression profiling was performed after injection of SEA or saline (control group) after one, three and 10 days. Histology revealed focal myositis predominated by Cd8+ T lymphocytes with a perimysial, endomysial and perivascular distribution, peaking 3 days after SEA injection. Using DNA microarray analysis (Affymetrix Rat Genome 230 2.0) genes that were differentially over-expressed at least 15 times at days one, three or ten after SEA injection were further analysed. One day after SEA injection over-expressed genes were related to the immune response (e.g. Fcnb, CD8a) but also to cell proliferation, differentiation and migration (e.g. Mpp2). Three days after SEA injection, differentially overexpressed genes were mainly related to the immune reaction with a clear signature for a Cd8+ T lymphocyte response (e.g. Cd3d, Cd8, Prf1, Gzmb). Ten days after SEA injection, the differentially overexpressed genes were again associated with the immune reaction (e.g. Cd3d, Il2) but also with regenerative processes and wound healing (e.g. Tgfa, Tpm1, Ripply1). The inflammatory response induced by SEA in Lewis rats shares histological and molecular similarities to polymyositis in humans. Therefore, SEA induced myositis can be taken as a new and apt model for polymyositis.
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Enterotoxinas/inmunología , Miositis/inmunología , Superantígenos/inmunología , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II , Péptidos y Proteínas de Señalización Intracelular , Activación de Linfocitos , Masculino , Proteínas de la Membrana , Modelos Animales , Ratas , Ratas Endogámicas Lew , Superantígenos/metabolismoRESUMEN
BACKGROUND: Cutaneous aesthesia is frequently impaired following thermal injury. The perception of pressure and touch is compromised. METHODS: We analysed 352 patient files retrospectively and tested the perception in deep burn-damaged skin of children. The skin regions examined were classified into groups according to treatment: group 1: necrosectomyâ +â split-thickness skin graft; group 2: epifascial necrosectomyâ +â split-thickness skin graft; group 3: epifascial necrosectomyâ +â Integra®â +â split- thickness skin graft. We used clinically adequate test procedures. RESULTS: 31 children (3 to 16 years old) were included with a total of 228 areas of skin examined, 22 boys and 9 girls, mean total body surface area affected 17.6â %, mean age at time of accident 4.9 years. Perceived sensation in group 3: touching with sharp point = 34 out of 47 areas (6 patients), touching with blunt point = 47 out of 57 areas (6 patients), touching with soft tip = 37 out of 56 areas (7 patients), repositioning hair shafts = 9 out of 12 areas (4 patients), pressure of Frey hair = 40 out of 43 areas (7 patients). In group 1, differentiation of touch stimuli was possible in 7 out of 13 children (70 out of 94 skin areas). The simultaneous threshold was 1.8â cm (SDâ 1.4), compared with 1.2â cm (SDâ 1.1) in the control group. The successive threshold was 1.6â cm (SDâ 0.9) and 1.8â cm (SDâ 1.5) in the control group. In group 2, differentiation of touch stimuli was possible in 3 out of 6 children (27 out of 52 skin areas). The simultaneous threshold was 3.4â cm (SDâ 1.3) and 3.4â cm (SDâ 1.1) in the control group. The successive threshold was 2.4 (SDâ 1.0) and 1.7 (0.7) in the control group. One patient was examined in group 3. Differentiation of touch stimuli was possible in 4 out of 15 skin areas. The simultaneous threshold was 3.9â cm (SDâ 0.8) and 2.9â cm (SDâ 1.1) in the control group. The successive threshold was 2.7 (SDâ 1.4) and 2.1 (1.0) in the control group. In 93â % to 100â % of tested areas, vibration aesthesia was detectable. Vibration aesthesia did not differ between tune fork and biothesiometer. Four children with 11 different skin areas (group 3) were tested with sensory-evoked potentials. There was no significant difference between case group and control group. CONCLUSION: The sensory perception (receptors and nerve cells) of touch and pressure in deep burns suffered during childhood has an unexpected and high potential for regeneration.
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Quemaduras , Regeneración , Trasplante de Piel , Tacto , Adolescente , Quemaduras/fisiopatología , Quemaduras/cirugía , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , PielRESUMEN
More than eight percent of the human genome consists of human endogenous retroviruses (HERVs). Typically, the expression of HERVs is repressed, but varying activities of HERVs have been observed in diseases ranging from cancer to neuro-degeneration. Such activities can include the transcription of HERV-derived open reading frames, which can be translated into proteins. However, as a consequence of mutations that disrupt open reading frames, most HERV-like sequences have lost their protein-coding capacity. Nevertheless, these loci can still influence the expression of adjacent genes and, hence, mediate biological effects. Here, we present WebHERV (http://calypso.informatik.uni-halle.de/WebHERV/), a web server that enables the computational prediction of active HERV-like sequences in the human genome based on a comparison of genome coordinates of expressed sequences uploaded by the user and genome coordinates of HERV-like sequences stored in the specialized key-value store DRUMS. Using WebHERV, we predicted putative candidates of active HERV-like sequences in Hodgkin lymphoma (HL) cell lines, validated one of them by a modified SMART (switching mechanism at 5' end of RNA template) technique, and identified a new alternative transcription start site for cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1).
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Objective: MRI is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an emergent imaging modality sensitive to microstructural alterations in tissue. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules. Electromyography (EMG) is a clinically used diagnostic tool in myositis. The aim of this study was to elucidate possible associations between ADC values and EMG findings in myositis patients. Method: Seven patients (eight investigated muscles) with myositis (mean age 51.43 ± 19 years) were included in this study. The diagnosis was confirmed by histopathology in every case. DWI was obtained with a 1.5-T scanner using two b-values 0 and 1000 s/mm². In all patients, a needle electromyography (EMG) was performed within 3 days to the MRI. The following EMG parameters were studied: motor unit action potential (MUAP) amplitudes and durations, as well as pathological spontaneous activity. Spearman's correlation coefficient was used to analyze associations between investigated parameters. Results: The estimated mean ADC mean value was 1.51 ± 0.29 × 10-3 mm²/s, mean ADC min was 1.28 ± 0.27 × 10-3 mm²/s, and mean ADC max was 1.73 ± 0.28 × 10-3 mm²/s. Correlation analysis identified significant associations between ADC mean and duration of the MUAP (p = .78 P = .0279) and between ADC min and duration of the MUAP (p = .85, P = .01). There were no significant differences according to pathological spontaneous activity. Conclusion: ADC mean and ADC min showed strong positive correlations with the duration of the MUAP in myositis patients. Both modalities might similarly reflect muscle fiber loss in myositis patients.
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Miositis/fisiopatología , Potenciales de Acción/fisiología , Adulto , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Electromiografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuronas Motoras/fisiología , Miositis/patología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Human endogenous retroviruses (ERVs) have been found to be associated with different diseases, e.g., multiple sclerosis (MS). Most human ERVs integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human ERVs can be reactivated, e.g., by hypoxia. Interestingly, MS has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and ERVs. As a model, we used human SH-SY5Y neuroblastoma cells after treatment with the hypoxia-mimetic cobalt chloride and analyzed differences in the gene expression profiles in comparison to untreated cells. The vicinity of up-regulated genes was scanned for endogenous retrovirus-derived sequences. Five genes were found to be strongly up-regulated in SH-SY5Y cells after treatment with cobalt chloride: clusterin, glutathione peroxidase 3, insulin-like growth factor 2, solute carrier family 7 member 11, and neural precursor cell expressed developmentally down-regulated protein 9. In the vicinity of these genes we identified large (>1,000 bp) open reading frames (ORFs). Most of these ORFs showed only low similarities to proteins from retro-transcribing viruses. However, we found very high similarity between retrovirus envelope sequences and a sequence in the vicinity of neural precursor cell expressed developmentally down-regulated protein 9. This sequence encodes the human endogenous retrovirus group FRD member 1, the encoded protein product is called syncytin 2. Transfection of syncytin 2 into the well-characterized Ewing sarcoma cell line A673 was not able to modulate the low immunostimulatory activity of this cell line. Future research is needed to determine whether the identified genes and the human endogenous retrovirus group FRD member 1 might play a role in the etiology of MS.
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The pathogenesis of multiple sclerosis (MS) has not been clarified. In addition to environmental factors; genetic determinants have been implicated in the pathogenesis of MS. Furthermore, endogenous retroviruses (ERV) might play a role in MS. The presence of oligoclonal immunoglobulin in cerebrospinal fluid (CSF) is a typical feature of MS. Recently, genetic polymorphisms in loci on human chromosomes 6, 14 and 18 have been identified as major determinants of CSF antibody levels in MS. The functional relevance of these single nucleotide polymorphisms (SNPs) remains unclear and none of them is located in an open reading frame. In previous studies, we identified ERV sequences in the vicinity of MS associated SNPs. Here, we describe the identification of ERV sequences in the neighborhood of SNPs associated with CSF antibody levels. All of the identified SNPs are located in the vicinity of ERV sequences. One of these sequences has very high homology to a sequence derived from the so-called MS-associated retrovirus (MSRV). Another cluster of three ERV sequences from the immunoglobulin heavy chain locus has retained the typical organization of retroviral genomes. These observations might shed new light on a possible association between ERVs and MS pathogenesis.
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Retrovirus Endógenos/genética , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/virología , Bandas Oligoclonales/líquido cefalorraquídeo , Bandas Oligoclonales/genética , Secuencia de Bases , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 6/genética , Bases de Datos de Ácidos Nucleicos , Genoma Viral , Humanos , Esclerosis Múltiple/líquido cefalorraquídeo , Sistemas de Lectura Abierta , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: Diffusion-weighted imaging (DWI) has the potential of being able to reflect histopathology architecture. A novel imaging approach, namely histogram analysis, is used to further characterize tissues on MRI. The aim of this study was to correlate histogram parameters derived from apparent diffusion coefficient (ADC) maps with serological parameters in myositis. METHODS: 16 patients with autoimmune myositis were included in this retrospective study. DWI was obtained on a 1.5 T scanner by using the b-values of 0 and 1000 s mm-2. Histogram analysis was performed as a whole muscle measurement by using a custom-made Matlab-based application. The following ADC histogram parameters were estimated: ADCmean, ADCmax, ADCmin, ADCmedian, ADCmode, and the following percentiles ADCp10, ADCp25, ADCp75, ADCp90, as well histogram parameters kurtosis, skewness, and entropy. In all patients, the blood sample was acquired within 3 days to the MRI. The following serological parameters were estimated: alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, C-reactive protein (CRP) and myoglobin. All patients were screened for Jo1-autobodies. RESULTS: Kurtosis correlated inversely with CRP (p = -0.55 and 0.03). Furthermore, ADCp10 and ADCp90 values tended to correlate with creatine kinase (p = -0.43, 0.11, and p = -0.42, = 0.12 respectively). In addition, ADCmean, p10, p25, median, mode, and entropy were different between Jo1-positive and Jo1-negative patients. CONCLUSION: ADC histogram parameters are sensitive for detection of muscle alterations in myositis patients. Advances in knowledge: This study identified that kurtosis derived from ADC maps is associated with CRP in myositis patients. Furthermore, several ADC histogram parameters are statistically different between Jo1-positive and Jo1-negative patients.