RESUMEN
BACKGROUND AND PURPOSE: Elevated plasma concentrations of neural cell adhesion molecule 1 (NCAM1) and p75 neurotrophin receptor (p75) in patients with peripheral neuropathy have been reported. This study aimed to determine the specificity of plasma concentration elevation of either NCAM1 or p75 in a subtype of Charcot-Marie-Tooth disease (CMT) and its correlation with pathologic nerve status and disease severity. METHODS: Blood samples were collected from 138 patients with inherited peripheral neuropathy and 51 healthy controls. Disease severity was measured using Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), and plasma concentrations of NCAM1 and p75 were analyzed by enzyme-linked immunosorbent assay. Eight sural nerves from CMT patients were examined to determine the relation of histopathology and plasma NCAM1 levels. RESULTS: Plasma concentration of NCAM1, but not p75, was specifically increased in demyelinating subtypes of CMT (median = 7100 pg/mL, p < 0.001), including CMT1A, but not in axonal subtype (5964 pg/mL, p > 0.05), compared to the control (3859 pg/mL). CMT1A patients with mild or moderate severity (CMTNSv2 < 20) showed higher levels of plasma NCAM1 than healthy controls. Immunofluorescent NCAM1 staining for the sural nerves of CMT patients showed that NCAM1-positive onion bulb cells and possible demyelinating Schwann cells might be associated with the specific increase of plasma NCAM1 in demyelinating CMT. CONCLUSIONS: The plasma NCAM1 levels in demyelinating CMT might be a surrogate biomarker reflecting pathological Schwann cell status and disease progression.
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Enfermedad de Charcot-Marie-Tooth , Moléculas de Adhesión de Célula Nerviosa , Humanos , Axones/patología , Biomarcadores/sangre , Enfermedad de Charcot-Marie-Tooth/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Nervio Sural/patologíaRESUMEN
Background: Spinal tuberculosis (TB) may have a variable, non-specific presentation including back pain with- or without- constitutional symptoms. Further tools are needed to aid early diagnosis of this potentially severe form of TB and immunological biomarkers may show potential in this regard. The aim of this study was to investigate the utility of host serum biomarkers to distinguish spinal TB from mechanical back pain. Methods: Patients with suspected spinal TB or suspected mechanical back pain were recruited from a tertiary hospital in the Western Cape, South Africa, and provided a blood sample for biomarker analysis. Diagnosis was subsequently confirmed using bacteriological testing, advanced imaging and/or clinical evaluation, as appropriate. The concentrations of 19 host biomarkers were evaluated in serum samples using the Luminex platform. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to identify biomarkers with the potential to distinguish spinal TB from mechanical back pain. Results: Twenty-six patients with spinal TB and 17 with mechanical back pain were recruited. Seven out of 19 biomarkers were significantly different between groups, of which Fibrinogen, CRP, IFN-γ and NCAM were the individual markers with the highest discrimination utility (Area Under Curve ROC plot 0.88-0.99). A five-marker biosignature (CRP, NCAM, Ferritin, CXCL8 and GDF-15) correctly classified all study participants after leave-one-out cross-validation. Conclusion: This study identified host serum biomarkers with the potential to diagnose spinal TB, including a five-marker biosignature. These preliminary findings require validation in larger studies.
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Dolor de Espalda/diagnóstico , Biomarcadores/sangre , Tuberculosis de la Columna Vertebral/diagnóstico , Adulto , Dolor de Espalda/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Quimiocina CXCL10/sangre , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moléculas de Adhesión de Célula Nerviosa/sangre , Análisis de Componente Principal , Tuberculosis de la Columna Vertebral/sangreRESUMEN
Natural killer (NK) cells preferentially accumulate at maternal-foetal interface and are believed to play vital immune-modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal-foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4+ CD56bright dNK and investigated its origin and phenotypic and functional characteristics. CXCR4+ CD56bright dNK displayed a less activated and cytotoxic phenotype but an enhanced immunomodulatory potential relative to the CXCR4 negative subset. CXCR4+ CD56bright dNK promote Th2 shift in an IL-4-dependent manner and can be recruited from peripheral blood and reprogramed by trophoblasts, as an active participant in the establishment of immune-tolerance during early pregnancy. Diminished CXCR4+ dNK cells and their impaired ability to induce Th2 differentiation were found in RM patients and mouse models of spontaneous abortion. Moreover, adoptive transfer of CXCR4+ dNK cells to NK-deficient (Nfil3-/-) mice showed great therapeutic potential of CXCR4+ dNK via recovering the Th2/Th1 bias and reducing embryo resorption rates. The identification of this new dNK cell subset may lay the foundation for understanding NK cell mechanisms in early pregnancy and provide potential prognostic factors for the diagnosis and therapy of RM.
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Aborto Habitual/prevención & control , Tolerancia Inmunológica/inmunología , Células Asesinas Naturales/inmunología , Receptores CXCR4/genética , Receptores CXCR4/inmunología , Aborto Habitual/sangre , Aborto Habitual/inmunología , Animales , Decidua/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Moléculas de Adhesión de Célula Nerviosa/sangre , Moléculas de Adhesión de Célula Nerviosa/genética , Moléculas de Adhesión de Célula Nerviosa/inmunología , Embarazo , Primer Trimestre del Embarazo , Receptores CXCR4/sangreRESUMEN
OBJECTIVE: Neural cell adhesion molecule (NCAM), a glycoprotein widely distributed in the brain, has recently been shown to regulate neuroplasticity. However, the role of NCAM in vascular dementia (VaD) is still unclear. The purpose of this study is to determine whether NCAM is involved in the course of VaD. METHODS: Continuous recruitment of VaD patients and control population to join this study. Doctors or nurses are responsible for collecting their clinical characteristics including age, gender, formal education, heart rate, supine systolic blood pressure, supine diastolic blood pressure, fasting glucose, high-density lipoprotein, and low-density lipoprotein. Each participant received the Montreal Cognitive Assessment (MoCA) scale after being enrolled in the group. At the same time, their peripheral blood was collected, and their serum NCAM levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: 98 VaD patients and 83 age- and sex-matched controls were enrolled. There was no significant statistical difference between the VaD group and the control group in terms of the comparison of clinical characteristics (p > 0.05). The MoCA score of VaD patients was significantly lower than that of the controls (27.9 ± 1.4 vs. 23.0 ± 2.1 points, p < 0.001). In addition, the circulating NCAM level of VaD patients was also significantly lower than that of controls (21.7 ± 3.8 vs. 17.6 ± 4.2 ng/mL, p < 0.001). The circulating NCAM level of VaD patients was significantly positively correlated with MoCA score (r = 0.285, p = 0.026). After adjusting for clinical characteristics, circulating NCAM levels are still an independent pathogenic factor of VaD (regression coefficient = 0.223, p = 0.034). CONCLUSIONS: VaD patients have low circulating NCAM levels, which can be used as a potential predictor of VaD.
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Biomarcadores/sangre , Disfunción Cognitiva/diagnóstico , Demencia Vascular/complicaciones , Moléculas de Adhesión de Célula Nerviosa/sangre , Anciano , Presión Sanguínea , Estudios de Casos y Controles , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Factores de RiesgoRESUMEN
A novel electrochemical sensor for a neural cell adhesion molecule (CD56) was constructed by glycosyl imprinting. A sandwich-like multi-signal generation strategy was first proposed in glycosyl imprinting sensors via boric acid affinity. Glycosyl-imprinted polymers were formed by electro-polymerization with poly-sialic acid (PolySia) as a template molecule and p-aminobenzeneboronic (p-ABA) acid as a functional monomer. Methods such as scanning electron microscope (SEM), Fourier transform infrared spectrum (FT-IR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to characterize the successful formation of imprinted membranes. Confirmed by both simulation calculation and experimental results, a signal-amplified effect based on macromolecules was introduced for the first time. After re-absorption, aminobenzene borate was linked to the surface of the sensor by boric acid affinity due to the rich hexadoxyl structure of the CD56-terminal chain as a signal probe. Under optimal conditions, the detection limit of the sensor is as low as 0.47 ng/L, and it can be successfully applied to the detection of CD56 in human serum.
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Técnicas Biosensibles/métodos , Impresión Molecular/métodos , Moléculas de Adhesión de Célula Nerviosa/sangre , Ácidos Siálicos/química , Antígeno CD56/análisis , Antígeno CD56/sangre , Glicosilación , Humanos , Límite de Detección , Moléculas de Adhesión de Célula Nerviosa/análisis , PolimerizacionRESUMEN
Glutaric acidemia type I (GA1) is caused by severe deficiency of glutaryl-CoA dehydrogenase activity, resulting in an accumulation of glutaric acid and glutarylcarnitine (C5DC) in the organism. Patients affected by GA1 are asymptomatic in the neonate period but usually manifest chronically progressive neurodegeneration apart from severe encephalopathic crises associated with acute striatum necrosis. Neurological manifestations like dyskinesia, dystonia, hypotonia, muscle stiffness, and spasticity are present. Treatment is based on protein/lysine restriction and l-carnitine supplementation. In this work, we evaluated markers of neurodegeneration and inflammation, namely BDNF (brain-derived neurotrophic factor), NCAM (neuronal adhesion molecule), PDGF-AA (platelet-derived growth factor), and cathepsin-d in plasma of six treated GA1 patients. We first found marked increases of plasma C5DC concentrations in GA1 patients, as well as increased levels of the markers BDNF and cathepsin-d as compared to those of age-matched healthy children. Furthermore, C5DC concentrations were highly correlated with the levels of cathepsin-d. These results may demonstrate that brain tissue degeneration is present in GA1 patients and that there is a relationship between increased metabolites concentrations with this process. To the best of our knowledge, this is so far the first study showing altered peripheral parameters of neurodegeneration and inflammation in GA1 patients.
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Errores Innatos del Metabolismo de los Aminoácidos/sangre , Encefalopatías Metabólicas/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Catepsina D/sangre , Glutaril-CoA Deshidrogenasa/deficiencia , Degeneración Nerviosa/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Biomarcadores/sangre , Encefalopatías Metabólicas/complicaciones , Niño , Preescolar , Femenino , Glutaril-CoA Deshidrogenasa/sangre , Humanos , Lactante , Recién Nacido , Masculino , Degeneración Nerviosa/sangre , Degeneración Nerviosa/etiología , Moléculas de Adhesión de Célula Nerviosa/sangre , Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
BACKGROUND: Cell-cell adhesion is essential in maintaining the structure and function of an organ. Several adhesion molecules have recently been identified as associated with heroin dependence in both genetic and peripheral plasma studies. METHODS AND RESULTS: We reviewed literature concerning studies on adhesion molecules in opioid addictions in rodents and human, including human genetic associations in different ethnic groups, and treatment responses to methadone maintenance treatment in heroin-dependent patients. CONCLUSION: Some important and novel findings were summarized and discussed. Adhesion molecules in the peripheral plasma, e.g., cadherin-2 (CDH2), may be biomarkers for both methadone treatment outcome and nectin 4 may be an indicator for continued opioid use. Neural cell adhesion molecule (NCAM) in the central nervous system may regulate opioid withdrawal and analgesic responses. Future studies to uncover the mechanisms underlying the involvement of adhesion molecules in the pathological process of addictions will be an important research direction in the field.
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Moléculas de Adhesión de Célula Nerviosa/sangre , Trastornos Relacionados con Opioides/diagnóstico , Biomarcadores/sangre , Cadherinas/sangre , Humanos , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
BACKGROUND: Transcranial direct current stimulation (tDCS) is used for therapeutic purpose in severely brain-injured patients. The relationship between the recovery after tDCS and potential biomarkers in plasma has been limitedly investigated in patients with minimal conscious state (MCS). OBJECTIVE: To investigate soluble neuronal adhesion molecule (sNCAM) plasma levels in relation to tDCS and recovery processes in MCS. METHODS: sNCAM was measured in plasma before (T-1,T0), during (T1) and after (T2, T3) tDCS sessions in eight patients with a post traumatic etiology and at least one year of chronic state. RESULTS: While sNCAM levels were highly correlated overtime, no significant difference was observed in relation to tDCS. An inverse relation was observed between sNCAM levels at baseline and the tDCS long-lasting effects (T-1, râ¯=â¯-0.852, pâ¯= 0.007; T0, râ¯=â¯-0.787, pâ¯= 0.020). CONCLUSIONS: This exploratory research suggests the sNCAM levels, potentially associated with tDCS outcomes, as a candidate biomarker of neurobiological after-effects in MCS patients.
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Lesiones Encefálicas/terapia , Moléculas de Adhesión de Célula Nerviosa/sangre , Estado Vegetativo Persistente/terapia , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Anciano , Biomarcadores/sangre , Lesiones Encefálicas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Vegetativo Persistente/diagnóstico , Solubilidad , Resultado del Tratamiento , Adulto JovenRESUMEN
In multiple sclerosis (MS), several adhesion molecules are involved within the central nervous system in inflammatory and neurodegenerative processes that are associated to progressive disability and increasing brain atrophy. The neural cell adhesion molecule (NCAM) has been suggested to participate in the reparative mechanisms and in the remyelination processes, key issues in MS pathology. We aimed at investigating plasma levels of the seldom investigated soluble (s)NCAM, and as comparison those of intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1), and their association with clinical and MRI measures of lesion volumes and of global and regional atrophy. The cross-sectional study was conducted in 85 relapsing-remitting (RR)-MS, 53 progressive (P)-MS patients, and 42 healthy individuals (HI). Correlation of MRI measures with plasma levels of these adhesion molecules were not observed. In the MS and HI groups, sNCAM levels were significantly and positively associated with sVCAM-1 levels. Differently, the correlation between sICAM-1 and sVCAM-1 was observed only in MS patients. sNCAM and sVCAM-1 levels were higher in P-MS compared to HI (Pâ¯=â¯0.05 and Pâ¯=â¯0.028 respectively). The sVCAM-1 levels differed (Pâ¯<â¯0.001) among DMTs groups and HI. The association of sNCAM plasma levels with MS disease, as well as differences in sVCAM-1 levels in patients receiving different DMTs, deserve further investigation.
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Esclerosis Múltiple/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Anciano , Atrofia/diagnóstico por imagen , Atrofia/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Moléculas de Adhesión de Célula Nerviosa/genética , Estadísticas no Paramétricas , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disease and the early diagnosis and intervention are important for valid treatment of AD. However, there are few biomarkers for the diagnosis and monitoring of AD. In the present study, circulating APP, NCAM, Aß40, and Aß42 were measured in order to identify which marker or combination of markers could be useful, cost-effective and noninvasive biomarkers for diagnosing and continuously monitoring AD. The results showed that circulating APP, NCAM, Aß40, and Aß42 were different between the AD group and the control group. Importantly, the combination of the four biomarkers had the highest AUC (0.997) with the highest sensitivity (98.5). Therefore, circulating APP, NCAM, Aß40, and Aß42 can be used as desirable biomarkers for AD diagnosis and monitoring.
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Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/sangre , Precursor de Proteína beta-Amiloide/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Fragmentos de Péptidos/sangre , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Neural cell adhesion molecule (NCAM) is a glycoprotein and plays an important role in cell-cell adhesion, neural migration, neurite outgrowth, synaptic plasticity and brain development. We investigated the relationship between the serum NCAM concentration and cognitive deficit in first episode drug naïve schizophrenia (FES) patients. METHODS: Thirty FES patients and thirty healthy controls were recruited for this study. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Cognitive functions were assessed by measurement and treatment research to improve cognition in schizophrenia (MATRICS) and consensus cognitive battery (MCCB). Serum levels of NCAM were determined by ELISA. RESULTS: Schizophrenia patients had decreased serum NCAM concentrations than controls (-30%, p<0.001). Cognitive scores were significantly lower in FES patients than healthy controls (-34%, p<0.001). The NCAM concentrations were positively correlated with the total scores of MCCB (r=0.438, p=0.003). Multiple regression analysis confirmed that serum NCAM concentration was an independent contributor to MCCB total Scores. CONCLUSIONS: There were a close relationship between the serum NCAM concentrations and cognitive deficits in FES patients. Since NCAM has an important role in neurodevelopmental processes, these results support the neurodevelopmental dysfunction hypothesis of schizophrenia and suggest that an altered NCAM may be one of the risk factors for schizophrenia including cognitive deficits.
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Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/etiología , Moléculas de Adhesión de Célula Nerviosa/sangre , Esquizofrenia/sangre , Esquizofrenia/complicaciones , Psicología del Esquizofrénico , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Escalas de Valoración Psiquiátrica , Análisis de RegresiónRESUMEN
BACKGROUND AND PURPOSE: Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase. METHODS: The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves. RESULTS: From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P<0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P=0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%. CONCLUSIONS: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.
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Isquemia Encefálica/sangre , Hemorragia Cerebral/sangre , Accidente Cerebrovascular/sangre , Anciano , Anciano de 80 o más Años , Amina Oxidasa (conteniendo Cobre)/sangre , Apolipoproteína C-III/sangre , Biomarcadores/sangre , Isquemia Encefálica/diagnóstico , Estudios de Casos y Controles , Caspasa 3/sangre , Moléculas de Adhesión Celular/sangre , Hemorragia Cerebral/diagnóstico , Quimiocina CXCL1/sangre , Endostatinas/sangre , Proteína Ligando Fas/sangre , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibronectinas/sangre , Proteínas del Choque Térmico HSC70/sangre , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Subunidad gamma Común de Receptores de Interleucina/sangre , Interleucina-17/sangre , Interleucina-6/sangre , Modelos Logísticos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Factor de Crecimiento Nervioso/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Oportunidad Relativa , Fragmentos de Péptidos/sangre , Fosfopiruvato Hidratasa/sangre , Estudios Prospectivos , Curva ROC , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Accidente Cerebrovascular/diagnóstico , Factor de von Willebrand/metabolismoRESUMEN
Adhesion molecules are involved in nerve growth, synaptic plasticity and myelin formation and maintenance process. Neural cell adhesion molecule (CD56 or NCAM) seems to play a crucial role in all the above-mentioned events. Having found poly-sialylated NCAM increased re-expression on demyelinated axons within multiple sclerosis plaques we assessed soluble NCAM (sNCAM) in sera of patients with various types of peripheral nerve affections - demyelinating, axonal "inflammatory", axonal metabolic polyneuropathies and healthy controls. These data were compared with the clinical state using Overall Neuropathy Limitations Scale (ONLS) and nerve conduction studies. We found significantly increased sNCAM concentration in demyelinating polyneuropathies in comparison to axonal group and healthy controls as well as significantly increased sNCAM level in axonal group in comparison to healthy subjects. We also found high positive correlation between sNCAM and ONLS and strong negative correlation between sNCAM level and the lowest conduction velocity (Vmin) found in a patient. We conclude that sNCAM might be thought as a specific marker of peripheral nerve demyelination and as a sensitive marker of peripheral nerve injuries.
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Axones/metabolismo , Biomarcadores/sangre , Enfermedades Desmielinizantes/diagnóstico , Moléculas de Adhesión de Célula Nerviosa/sangre , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Adulto , Anciano , Axones/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell-cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.
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Encéfalo/patología , Trastornos del Conocimiento/complicaciones , Moléculas de Adhesión de Célula Nerviosa/sangre , Esquizofrenia/complicaciones , Ácidos Siálicos/sangre , Adulto , Mapeo Encefálico , Movimiento Celular/genética , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/genética , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Moléculas de Adhesión de Célula Nerviosa/genética , Plasticidad Neuronal/genética , Tamaño de los Órganos , Esquizofrenia/sangre , Esquizofrenia/genética , Ácidos Siálicos/genéticaRESUMEN
AIM: The exact pathomechanism of GNE myopathy remains elusive, but likely involves aberrant sialylation. We explored sialylation status of blood-based glycans as potential disease markers. METHODS: We employed immunoblotting, lectin histochemistry and mass spectrometry. RESULTS: GNE myopathy muscle showed hyposialylation of predominantly O-linked glycans. The O-linked glycome of patients' plasma compared with controls showed increased amounts of desialylated Thomsen-Friedenreich (T)-antigen, and/or decreased amounts of its sialylated form, ST-antigen. Importantly, all patients had increased T/ST ratios compared with controls. These ratios were normalized in a patient treated with intravenous immunoglobulins as a source of sialic acid. DISCUSSION: GNE myopathy clinical trial data will reveal whether T/ST ratios correlate to muscle function. CONCLUSION: Plasma T/ST ratios are a robust blood-based biomarker for GNE myopathy, and may also help explain the pathology and course of the disease.
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Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Complejos Multienzimáticos/metabolismo , Enfermedades Musculares/sangre , Enfermedades Musculares/enzimología , Ácido N-Acetilneuramínico/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Humanos , Lectinas/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Polisacáridos/sangreRESUMEN
Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. The enzyme is UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, and is encoded by the GNE gene. HIBM causes slowly progressive muscle weakness and atrophy. Patients are typically diagnosed at 20-30 years of age, and most patients are incapacitated and wheelchair-confined by 30-50 years of age. Some sialic acid containing glycoproteins, including neural cell adhesion molecule (NCAM), are hyposialylated in HIBM muscle biopsy samples. We developed a method to allow detection of serum NCAM sialylation using Western blot, and tested serum samples from several patients and a HIBM mouse model. Preliminary results showed a clear difference in polysialylated and hyposialylated forms of NCAM extracted from serum, and showed NCAM is hyposialylated in HIBM serum samples. This initial finding may prove useful in reducing the need for serial muscle biopsies in HIBM treatment trials. Additional studies are underway to further validate this finding and to evaluate the specificity, reliability, and robustness of this potential serum biomarker for HIBM.
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Miositis por Cuerpos de Inclusión/congénito , Ácido N-Acetilneuramínico/metabolismo , Moléculas de Adhesión de Célula Nerviosa/sangre , Adulto , Animales , Western Blotting , Carbohidrato Epimerasas/genética , Modelos Animales de Enfermedad , Humanos , Ratones , Persona de Mediana Edad , Mutación , Miositis por Cuerpos de Inclusión/genética , Miositis por Cuerpos de Inclusión/metabolismo , Adulto JovenRESUMEN
We analyzed hepatocellular carcinoma (HCC) with progenitor cell features using hepatic stem/progenitor cell marker neural cell adhesion molecule (NCAM). Approximately 8.3% of the operated HCC cases expressed NCAM, and 22.3% of the HCC patients had soluble NCAM levels >1000ng/ml (the "highly soluble" NCAM group). Soluble NCAM status was a significant independent factor predictive of long-term survival in patients with HCC, and high levels of soluble NCAM were significantly related to intrahepatic metastasis. The 140-kDa NCAM isoform was specifically detected in the "highly soluble" NCAM group of HCC patients andits related signals are potential drug targets for NCAM+ HCC.
Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Moléculas de Adhesión de Célula Nerviosa/biosíntesis , Anciano , Biomarcadores de Tumor/biosíntesis , Carcinoma Hepatocelular/metabolismo , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Moléculas de Adhesión de Célula Nerviosa/sangre , Valor Predictivo de las Pruebas , Pronóstico , Isoformas de Proteínas/metabolismo , Células Madre/metabolismo , Células Madre/patologíaRESUMEN
BACKGROUND: Bone marrow stem cells (BMSC) can participate to liver regeneration. However, conflicting results have been reported on this topic in patients undergoing liver resection. AIMS: To assess the impact of liver resection extent and presence of underlying liver disease in modulating BMSC mobilization. METHODS: We enrolled 29 patients undergoing liver resection of different extents, 5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by flow cytometry at different time-points after surgery. The hepatic commitment of mobilized BMSC was investigated by polymerase chain reaction. Liver specimens were collected during surgery for histopathological analysis. Hepatocyte growth factor and granulocyte-colony stimulating factor serum levels were measured by enzyme-linked immunosorbent assay. RESULTS: BMSC mobilization was found in patients undergoing major liver resection, especially in the presence of underlying disease. Ductular reactions were noted in patients with chronic hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM, cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte-colony stimulating factor levels increased following liver resection and the contemporaneous presence of liver disease was associated with their highest raise. CONCLUSIONS: Liver repair is mainly an endogenous process. BMSC become important in case of extensive resection, especially in the presence of underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte growth factor and granulocyte-colony stimulating factor seem to be involved in the dynamics underlying hepatic regeneration and BMSC recruitment.
Asunto(s)
Antígenos CD/sangre , Glicoproteínas/sangre , Movilización de Célula Madre Hematopoyética , Hepatectomía/métodos , Regeneración Hepática , Péptidos/sangre , Antígeno AC133 , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Factor de Crecimiento de Hepatocito/sangre , Humanos , Queratina-19/sangre , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Moléculas de Adhesión de Célula Nerviosa/sangre , alfa-Fetoproteínas/metabolismoRESUMEN
The neural cell adhesion molecule (NCAM) is a glycoprotein localised in the plasma membrane of neural and glial cells, which plays a role in myelination and remyelination. It increases in the cerebrospinal fluid (CSF) of acute multiple sclerosis (MS) patients treated with corticosteroids who are improving after an attack, but it has not been shown if it appears in its sialylated (PSA) or unsialylated form. We studied the NCAM and the PSA-NCAM in serum and CSF samples of 16 acute and non-acute MS patients and in the sera of 10 non-neurological controls. The NCAM and the PSA-NCAM were dosed by two different ELISA previously set-up. The NCAM in the serum and in the CSF of the control group presented mean levels similar to those shown in previous papers: 1620 +/- 216 and 970 +/- 210 ng/ml. In the MS patient group the means were 1700 +/- 546 in the sera and 926 +/- 285 in the CSFs. All the sera were PSA-NCAM-positive: the mean PSA-NCAM concentration in the control group was 3150 +/- 950 ng/ml, while in the MS patient group it was 3570 +/- 905 ng/ml. The correlation between serum levels of NCAM and PSA-NCAM was highly significant (p < 0.001). Student's "t" test did not show any significant difference between serum levels of the two groups, both for the NCAM and for the PSA-NCAM. CSF samples did not show any positive results for the PSA-NCAM, in either controls or in MS patients. These results demonstrate that the high levels of NCAM we previously found in the CSF of improving MS patients treated with steroids did not contain a quota of PSA-NCAM, but only the unsialylated soluble form of the molecule.
Asunto(s)
Esclerosis Múltiple/líquido cefalorraquídeo , Moléculas de Adhesión de Célula Nerviosa/líquido cefalorraquídeo , Ácidos Siálicos/química , Enfermedad Aguda , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/fisiopatología , Moléculas de Adhesión de Célula Nerviosa/sangre , Moléculas de Adhesión de Célula Nerviosa/químicaRESUMEN
INTRODUCTION: The neural cell adhesion molecule (N-CAM) plays important roles in neural migration, synaptogenesis and CNS development. Change of N-CAM fragments in CSF of schizophrenic patients was reported previously, and we aimed to detect difference in circulating N-CAM in the serum of schizophrenic patients and healthy controls. METHODS: Samples were from 14 chronic schizophrenic patients including 3 drug naïve patients and 11 healthy controls. After removal of albumin and globulin, N-CAM fragments were measured by Western blot technique with monoclonal antibody. RESULTS: N-CAM immunoreactive bands were detected primarily at 180, 140, 120, 75, 68 and 52 kDa. Samples from patients and controls showed similar patterns of bands, but schizophrenic patients showed increases or decreases at some bands intensity compared to healthy controls. The 68 kDa/73-75 kDa bands intensity ratio was substantially elevated in schizophrenic patients (0.262+/-0.14 in patients, 0.065+/-0.04 in controls) especially, the three drug naïve patients had a higher value of this ratio compared to the medicated patients. One drug naïve patient showed a decrease in this ratio after one month of antipsychotic medication. CONCLUSIONS: The results suggest elevated membrane turnover and/or abnormalities in the regulation of proteolysis of N-CAM in schizophrenia.