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PubMed1998

The Brn-3c transcription factor contains a neuronal-specific activation domain.

Brn-3a, Brn-3b and Brn-3c are closely related POU family transcription factors which are expressed predominantly in neuronal cells. Previously Brn-3a has been shown to activate a number of gene promoters in co-transfections carried out in different cell types, while Brn-3b inhibits the basal activity of these promoters. We show here that Brn-3c activates the same promoters as Brn-3a but only in co-transfections into neuronal cells and not in other cell types. This effect is dependent upon an N-terminal region of Brn-3c which acts as a neuronal cell specific activation domain when linked to a heterologous DNA binding domain. To our knowledge this is the first report of an activation domain with apparently neuronal specific activity.

Animals↗
PubMed1978

Neuron specific protein (NSP) in neuroblastoma cells: relation to differentiation.

The spectrum of enolase enzyme forms has been examined in several lines of neuroblastoma cells and compared to those present in whole brain. The neuron specific enolase (NSP) is greatly decreased in the cultured cells as judged by activity profiles and radioimmunoassay. The synthesis of neuronal enolase appears to be extensively depressed in these cells while the total enolase activity is not affected. The non-neuron form of enolase (NNE) apparently compensates for the lack of the neuronal forms in the cultured cells. The preponderance of NNE in cultured neurons suggests that this enzyme is present in immature neurons, and that neuroblastoma cells are not fully differentiated with respect to the enolase function. Dibutyryl cyclic adenosine monophosphate treatment does increase NSP levels in mouse neuroblastoma cells, but not to the levels expected for fully differentiated neurons. The results indicate that NSP is a molecular correlate of fully differentiated neurons.

Animals↗
PubMed2002

Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study.

OBJECTIVE: The aim of this study was to investigate whether serial serum neuron-specific enolase (NSE) can be used to predict neurological prognosis in patients remaining comatose after cardiopulmonary resuscitation (CPR). DESIGN. Observational cohort study. Clinicians were blinded to NSE results. SETTING: Eighteen-bed general ICU. PATIENTS: Comatose patients admitted to the ICU after CPR. INTERVENTIONS: Serum NSE was measured at admission and daily for 5 days. MEASUREMENTS AND RESULTS: Patients received full intensive treatment until recovery or until absence of cortical response to somatosensory evoked potentials more than 48 h after CPR proved irreversible coma. Of the 110 patients included (mean GCS at ICU admission 3, range 3--9), 34 regained consciousness, five of whom died in hospital. Seventy-six patients did not regain consciousness, 72 of whom died in hospital. Serum NSE at 24 h and at 48 h after CPR was significantly higher in patients who did not regain consciousness than in patients who regained consciousness (at 24 h: median NSE 29.9 microg/l, range 1.8-250 vs 9.9 microg/l, range 4.5-21.5, P<0.001; at 48 h: median 37.8 microg/l, range 4.4-411 vs 9.5 microg/l, range 6.2-22.4, P= 0.001). No patient with a serum NSE level >25.0 microg/l at any time regained consciousness. Addition of NSE to GCS and somatosensory evoked potentials increased predictability of poor neurological outcome from 64% to 76%. CONCLUSIONS: High serum NSE levels in comatose patients at 24 h and 48 h after CPR predict a poor neurological outcome. Addition of NSE to GCS and somatosensory evoked potentials increases predictability of neurological outcome.

Aged↗
PubMed1991

Complete structure of the human gene encoding neuron-specific enolase.

At least three genes encode the different isoforms of the glycolytic enzyme enolase. We have isolated the gene for the human gamma- or neuron-specific enolase and determined the nucleotide sequence from upstream to the 5' end to beyond the polyadenylation site. The gene contains 12 exons distributed over 9213 nucleotides. Introns occur at positions identical to those reported for the homologous rat gene, as well as for the human alpha- or nonneuronal enolase gene, supporting the existence of a single ancestor for the members of this gene family. Primer extension analysis indicates that the gene has multiple start sites. The putative promoter region lacks canonical TATA and CAAT boxes, is very G + C-rich, and contains several potential regulatory sequences. Furthermore, an inverted Alu sequence is present approximately 572 nucleotides upstream of the major start site. A comparison of the 5'-flanking region of the human gamma-enolase gene with the same region of the rat gene revealed a high degree of sequence conservation.

Amino Acid Sequence↗
PubMed2004

Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy.

The aim of this study was to evaluate serum concentrations of neuron-specific enolase (NSE) as a marker of the severity of hypoxic ischemic encephalopathy (HIE) and to elucidate the relation among the concentrations of NSE, grade of HIE and short-term outcome. Forty-three asphyxiated full-term newborn infants who developed symptoms and signs of HIE (Group 1) and 29 full-term newborn infants with meconium-stained amniotic fluid but with normal physical examination (Group 2) were studied with serial neurological examination, Denver developmental screening test (DDST), electroencephalogram and computerized cerebral tomography (CT) for neurological follow-up. Thirty healthy infants were selected as the control group. In the patient groups, two blood samples were taken to measure NSE levels, one between 4 and 48 h and the other 5-7 days after birth. Serum NSE levels were significantly higher in infants with HIE compared to those infants in Group 2 and control group. The mean serum concentrations of the second samples decreased in all groups studied but they were significantly higher in Group 1 compared to those in Group 2. Serum NSE concentrations of initial samples were significantly higher in patients with stage III HIE than in those with stages II and I. The sensitivity and specificity values of serum NSE as a predictor of HIE of moderate or severe degree (cut-off value 40.0 microg/l) were 79 and 70%, respectively, and as a predictor of poor outcome (cut-off value 45.4 microg/l) were calculated as 84 and 70%, respectively. The predictive capacity of serum NSE concentrations for poor outcome seems to be better than predicting HIE of moderate or severe degree. However, earlier and/or CSF samples may be required to establish serum NSE as an early marker for the application of neuroprotective strategies.

Asphyxia Neonatorum↗
PubMedDate not supplied

Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo.

PURPOSE: In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA). METHODS: Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models. RESULTS: Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa in Western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions. CONCLUSION: These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Cyfra 21-1, neuron specific enolase and prognosis of non-small cell lung cancer: prospective study in 621 patients.

BACKGROUND: CYFRA 21-1, a serum cytokeratin 19 fragment, and neuron specific enolase (NSE), the gamma-subunit of enolase, are putative markers of lung cancer. Their clinical applicability as prognostic factors in non-small cell lung cancer (NSCLC) would need an appraisal by simultaneous evaluation of other known survival determinants in a large population followed over a long period. AIM: To determine the prognostic value of different clinical and routine biological variables at presentation with particular attention paid to the above-mentioned markers. METHODS: 621 histologically proven and previously untreated NSCLC patients have been prospectively studied (seven were lost to follow-up). Median follow-up was 4 years and 2 months. At presentation, 16 clinical and biological variables were recorded. Serum NSE and CYFRA 21-1 were assayed blind without any clinical information given. RESULTS: The serum CYFRA 21-1 distribution differed significantly according to histology, disease stage and performance status, with the highest levels observed in squamous cell carcinomas, metastatic stage, positive mediastinal nodal status and poor performance status. However, the respective "receiver operating characteristic" curves showed that the CYFRA 21-1 serum level did not accurately predict tumour stage. Serum NSE distribution correlated neither with tumour stage nor with performance index and its sensitivity in the whole NSCLC was low. In the Cox proportional hazard model, the following variables were independent determinants of a poor outcome: performance status 2 or 3, hazard ratio (HR): 2.25; Nodal status N(2-3), HR: 1.84; Metastatic disease, HR: 1.73; NSE>12.5 ng/ml, HR: 1.52; CYFRA 21-1>3.6 ng/ml, HR: 1.41 and Tumour status T(3-4), HR: 1.31. When the survival analysis was restricted to the 274 patients affected by a metastatic stage, we observed that performance status, nodal status, NSE and CYFRA 21-1 remained prognostic determinants with similar hazard ratios. CONCLUSION: The prognostic information given by a high serum CYFRA 21-1 level is independent from other well-known variables such as performance status and disease stage and is perennial throughout extended follow-up period. A high NSE level also prognosticates a poor outcome probably by reflecting tumour heterogeneity and underestimated neuroendocrine differentiation.

Aged↗
PubMed2005

Immunohistochemical localization of gastrin-releasing peptide, neuronal nitric oxide synthase and neurone-specific enolase in the uterus of the North American opossum, Didelphis virginiana.

The present study has demonstrated the immunohistochemical localization of gastrin-releasing peptide (GRP), neuronal nitric oxide synthase (nNOS) and neurone-specific enolase (NSE) in the uterus of the North American opossum. Although the presence of GRP, nNOS and NSE has been reported recently in the uterus of eutherian species this is the first description of these peptides in a metatherian species. Metatherian mammals are of interest because in these species it is the prolonged lactation phase of development that is the period of primary reproductive investment rather than intrauterine development as is true of eutherian mammals. The opossum, like other marsupial species, has a very abbreviated gestation period which in Didelphis lasts only 12.5 days. GRP was localized in the cytoplasm of cells forming the surface lining epithelium and the glandular epithelium of the opossum endometrium late in pregnancy, at 11.5 days of gestation. Likewise, immunoreactivities of nNOS and NSE were found primarily within the epithelial cells of the endometrium at 11.5 days of gestation. As these peptides and enzymes appear primarily at the time of establishment of the yolk sac placenta (between day 10 and day 12.5 gestation), the present results strongly suggest that these factors may play a fundamental role in the placentation of the opossum.

Animals↗
PubMed1997

Serum neuron-specific enolase as a tumor marker in the diagnosis and follow-up of small-cell lung cancer.

Serum samples for the determination of neuron-specific enolase (NSE) levels were collected at diagnosis, after induction of chemotherapy and at relapse in order to assess the value of NSE in the diagnosis and management of small-cell lung cancer (SCLC). At diagnosis, 47 of 64 patients with SCLC (73%) had abnormal NSE values (i.e. NSE > 12.5 micrograms/l). Mean NSE values were significantly higher in patients with extensive disease compared to limited disease. Patients with other malignancies or benign lung diseases presented with elevated NSE levels in approximately 15 and 4% of cases. Sensitivity, specificity and predictive value of positive results of NSE at diagnosis were 74, 83 and 71%, respectively, for a cutoff value of 12.5 micrograms/l. In responders mean NSE dropped significantly from 46.1 micrograms/l before chemotherapy to 17.0 micrograms/l after three cycles of chemotherapy. Nonresponders as a group showed a nonsignificant drop. At relapse mean NSE increased from 6.5 micrograms/l at the time of response to 51.9 micrograms/l at the time of progression, but in 5 of the 18 evaluable patients normal levels persisted. Thus, evolution of NSE in patients receiving chemotherapy correlated well with tumor volume in patients who responded, but often failed to predict a therapeutic outcome in patients with apparently chemoresistant tumor (i.e. some nonresponders showed a decrease in NSE levels). A similar lack of correlation between NSE levels and tumor volume was seen at the time of relapse. We conclude that the determination of NSE levels is of doubtful utility in the diagnosis and follow-up of SCLC patients.

Adult↗
PubMed2005

Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer.

STUDY OBJECTIVES: To assess the diagnostic values of carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments (CYFRA 21-1) as markers of pleurisy in primary lung cancer. DESIGN: Prospective case-control study. SETTING: A tertiary university hospital. PATIENTS: Thirty-four patients with lung cancer and 16 patients with tuberculous pleurisy. MEASUREMENTS AND RESULTS: Levels of CEA, NSE, and CYFRA 21-1 were measured by immunoassay in the serum and pleural fluid of patients with lung cancer and of patients with tuberculous pleurisy. Patients with lung cancer were found to have significantly higher serum and pleural fluid levels of CEA and CYFRA 21-1 than patients with tuberculous pleurisy. Using cutoff values of 5 ng/mL, 20 ng/mL, and 3.3 ng/mL for serum CEA, NSE, and CYFRA 21-1, respectively, the sensitivities and specificities of these tumor markers were as follows for differentiating malignant effusion from benign: CEA, 68% and 93%; NSE, 34% and 93%; and CYFRA 21-1, 45% and 100%. Using cutoff values of 5 ng/mL, 20 ng/mL, and 45 ng/mL for pleural fluid, the sensitivities and specificities were as follows: CEA, 82% and 94%; NSE, 36% and 94%; and CYFRA 21-1, 61% and 81%. A combination of pleural fluid CEA and NSE increased sensitivity and specificity. CONCLUSIONS: In the diagnosis of malignant effusion associated with lung cancer, the determinations of CEA and NSE in pleural fluid could enhance diagnostic yield better than those of all three tumor markers.

Antigens, Neoplasm↗
PubMed2003

Technical performance and diagnostic utility of the new Elecsys neuron-specific enolase enzyme immunoassay.

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra- and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (inter-laboratory median: 1.3%) and from 1.3 to 8.5 (inter-laboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and inter-assay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n = 723) and in patients with lung cancer (n = 333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n = 183), the cut-off value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n = 188) and was significantly higher (p < 0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n = 374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturer's declaration up to 370 ng/ml) and a short incubation time of 18 min.

Adenocarcinoma↗
PubMed1994

Pulmonary infiltration with eosinophilia and increased serum levels of squamous cell carcinoma-related antigen and neuron specific enolase.

We report a case of pulmonary infiltration with eosinophilia (PIE), associated with increased serum levels of squamous cell carcinoma-related antigen (SCC) and neuron specific enolase (NSE). The diagnosis of PIE was confirmed by examination of bronchoalveolar lavage fluid and specimens of transbronchial lung biopsy. It was suggested that PIE was probably induced by a course of amoxicillin for a sore throat. Corticosteroid therapy resulted in clinical improvement of symptoms, resolution of pulmonary infiltrates on chest roentgenogram and reduction in serum levels of SCC and NSE.

Adrenal Cortex Hormones↗
PubMed2000

[The use of neuron specific enolase in the prognosis and followup of neuroblastoma in children. Results of a retrospective series of 21 patients].

OBJECTIVE: To report the results of seric neuron specific enolase in pediatric neuroblastoma. PATIENTS AND METHODS: Our retrospective study concerns 21 children treated in our institution from 1992 to 1998 for neuroblastoma. Seric NSE was determined by immunoenzymology technique at different stages of the disease and the treatment. RESULTS: Mean value for the 39 dosages of the whole patients was 127.9 ng/ml with a sensitivity of 56%, five patients has presented normal values. Mean value for the 18 patients in stage IV was 132.38 ng/ml. We also observed in 3 patients, an evolution of the seric NSE parallel to this of the disease under chemotherapy. CONCLUSION: NSE represents a moderate sensitive and specific tumor marker for pediatric neuroblastoma. However, it represents a good value in prognosis and follow-up after chemotherapy.

Biomarkers, Tumor↗
PubMed1992

Serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy and survival in non-small cell lung cancer.

The prognostic value of serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) was prospectively assessed in 42 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated within two chemotherapy trials. Pretreatment NSE levels ranged from 4.6 to 34.6 ng/mL (median value, 7.5) and were above 10 ng/mL in ten patients (23.8%). LDH levels varied between 85 U/L and 2,484 U/L (median value, 220) and were above 250 U/L in 12 patients (29.3%). Elevated levels of both enzymes were significantly more common in patients with metastatic disease than in those with locoregional disease (40% v 9% for NSE and 40% v 18% for LDH, respectively). Strong positive correlation (correlation factor 0.693) was found between NSE and LDH serum levels. The levels of both markers did not correlate with age, sex, previous therapy, performance status, or histology. Responses to chemotherapy were seen more frequently in patients with elevated NSE levels (six of ten, 60%) than in those with normal values (seven of 32, 22%; P = .02). Similar correlation was found for LDH: Response was seen in seven of 12 patients with elevated levels (58%) and in six of 29 (21%) of those with normal values (P = .02). In a logistic regression analysis, both markers considered individually remained significant when adjusted by sex, age, performance status, prior therapy, histology, and extent of disease. Three pretreatment characteristics, high levels of NSE and LDH (both considered as continuous variables) and metastatic disease, were found to be associated with shorter survival; with adjustment for extent of disease, however, NSE and LDH were no longer correlated with shorter survival. These data suggest potential clinical value of NSE and LDH determination in treatment selection of NSCLC patients.

Adult↗
PubMed1992

[Cerebrospinal fluid neuron-specific enolase (NSE) and S-100b protein in Guillain-Barré syndrome--their relations to prognosis].

We measured the cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods in 12 patients with Guillain-Barré syndrome (GBS), and 46 control subjects, and evaluated their clinical values in relation to prognosis. The 4 patients with the remarkably elevated level of NSE or S-100b in the acute stage recovered slowly over 1 year after onset, while the 2 patients showed the normal NSE and S-100b levels and recovered within 4 months. In 6 patients, the NSE and/or S-100b were slightly or moderately increased in the acute stage. They recovered from 1.5 to 11 months after onset, and the two patients showing very early recovery have the remarkably increase of S-100b in the recovery stage. These results suggest that CSF NSE and S-100b may be useful biochemical markers for estimation of prognosis in GBS patients.

Adolescent↗
PubMed2006

[Role of the cut-off value of serum neuron-specific enolase in differentiating small cell lung cancer from non-small cell lung cancer].

OBJECTIVE: To determine the cut-off value of serum neuron-specific enolase (NSE) level for distinguishing small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). METHODS: Serum NSE levels were measured by enzyme-linked immunosorbent assay in 137 patients with NSCLC or SCLC, and the best cut-off value was analyzed using ROC curve. RESULTS: The positivity rate of serum NSE was significantly higher in patients with SCLC than in those with NSCLC (P<0.01). The best cut-off value was 15.45 microg/L using ROC curve, which gave a sensitivity of 66.7% and specificity of 65.7%. CONCLUSION: Serum NSE level may allow simple and cost-effective differentiation of SCLC and NSCLC.

Biomarkers, Tumor↗
PubMed1994

Neuron-specific enolase and myelin basic protein: relationship of cerebrospinal fluid concentrations to the neurologic condition of asphyxiated full-term infants.

OBJECTIVE: We questioned whether neuron-specific enolase (NSE) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) in the first 72 hours of life are correlated with the neurologic condition of asphyxiated full-term infants in the neonatal period and at 1 year of age. PATIENTS AND METHODS: Sixty-nine asphyxiated infants were studied with serial neurologic examination, cranial ultrasonography, and neurologic follow-up. CSF samples were obtained by lumbar puncture at 12 and 72 hours of life. NSE was measured by enzyme immunoassay, and MBP was measured by radioimmunoassay. RESULTS: Twenty infants had no neonatal encephalopathy and 49 exhibited different stages of encephalopathy. NSE and MBP concentrations in CSF at 12 and 72 hours of life were related to the degree of neonatal encephalopathy. Neither NSE nor MBP levels were correlated with any perinatal factors. Infants with documented brain injury had the highest concentrations of both NSE and MBP. The concentrations of these two biochemical markers at both 12 and 72 hours correlated with adverse outcome (death or cerebral palsy at 1 year). Based on a receiver operating characteristics curve analysis for any given specificity, NSE at 12 hours was a more accurate marker than MBP at either 12 or 72 hours for distinguishing infants with motor impairment at age 1 year from infants with normal outcome at the same age. CONCLUSIONS: Our findings suggest that NSE and MBP are reliable biochemical markers for early estimates of hypoxic-ischemic brain damage in asphyctic full-term newborns, NSE being superior to MBP.

Asphyxia Neonatorum↗
PubMed1990

Neuron-specific expression of high-molecular-weight clathrin light chain.

High-molecular-weight forms of clathrin light chains LCa and LCb contain inserted sequences and are expressed in brain tissue but have not been observed in peripheral tissues. Monoclonal antibodies specific for the high-molecular-weight form of LCb and all forms of LCa were used to analyze their expression in different species and different neuronal cell types. High-molecular-weight light chains were found in bovine, rat, mouse, chicken, and human brain, indicating a conserved pattern of expression. Neuron-specific expression of the high-molecular-weight light chains was suggested by analysis of human brain gray matter and white matter. The former contained a higher proportion of light chains with insertion sequences. Immunohistochemical analysis localized the high-molecular-weight form of LCb to synapses and neuronal perikarya, but not to glial cells. Immunofluorescent labeling of cultured chicken dorsal root ganglia confirmed expression in neurons but not Schwann cells. These results indicate that the high-molecular-weight forms of clathrin light chains are restricted in expression and found in neuronal cells.

Animals↗