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PubMed1992

[Central nervous system disorders in myotonic dystrophy--with special reference to neuron-specific enolase, S-100b protein and creatine kinase BB isoenzyme levels in CSF].

In order to evaluate central nervous system disorders in myotonic dystrophy (MyD), neuron-specific enolase (NSE), S-100b protein and creatine kinase BB (CK-BB) isoenzyme were measured using enzyme immunoassay in MyD. Intelligence quotient (IQ) test (WAIS, 17 cases), electro-encephalography (17 cases) and brain computed tomography (18 cases) were examined. In patients with MyD, NSE level was significantly elevated in comparison with 25 age-sex matched control subjects. In some cases of MyD levels of S-100b protein and CK-BB in CSF were elevated. IQ test disclosed intellectual impairment in 70.6% of the patients examined and EEG study demonstrated slowing of basic rhythm in the majority of the cases. On brain CT both enlarged ventricles and dilated sulci were commonly found. The results of the present study suggest that in MyD the CNS is involved not only functionally but structurally as well. Since NSE, S-100b and CK-BB are localized in neuronal and glia cells, their elevated levels in CSF indicate existence of organic lesions in the central nervous tissue in patients with MyD.

Adult↗
PubMed2004

The receptor tyrosine kinase Off-track is required for layer-specific neuronal connectivity in Drosophila.

The nervous system in many species consists of multiple neuronal cell layers, each forming specific connections with neurons in other layers or other regions of the brain. How layer-specific connectivity is established during development remains largely unknown. In the Drosophila adult visual system, photoreceptor (R cell) axons innervate one of two optic ganglia layers; R1-R6 axons connect to the lamina layer, while R7 and R8 axons project through the lamina into the deeper medulla layer. Here, we show that the receptor tyrosine kinase Off-track (Otk) is specifically required for lamina-specific targeting of R1-R6 axons. Otk is highly expressed on R1-R6 growth cones. In the absence of otk, many R1-R6 axons connect abnormally to medulla instead of innervating lamina. We propose that Otk is a receptor or a component of a receptor complex that recognizes a target-derived signal for R1-R6 axons to innervate the lamina layer.

Aging↗
PubMed2002

Enhanced expression of neuron-specific enolase (NSE) in pyothorax-associated lymphoma (PAL).

Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma of mostly large cell type developing in the pleural cavity of patients with long-standing pyothorax. Neuron-specific enolase (NSE) is an enolase comprising gamma subunit and is located at high levels in neuronal and neuroendocrine cells, together with their neoplasias. Expression of NSE at protein and mRNA levels was examined in PAL and other types (non-PAL) of non-Hodgkin's lymphomas. In PAL, serum levels of NSE were elevated (5.32 to 168.0, mean 42.6 ng/ml) and tended to decrease after incisional biopsy followed by chemotherapy (2.38 to 195.5, mean 34.1 ng/ml). Two cell lines established from two cases of PAL produced and secreted NSE in the culture medium. Immunohistochemistry revealed that the positive rate for NSE staining in PAL (10 of 14 cases, 71.4%) was significantly higher than that in non-PAL cases (6 of 38 cases, 15.8%) (P < 0.01). RT-PCR analysis showed that the expression levels of NSE mRNA in two cell lines and a biopsy sample from PAL were rather similar to those of the control samples from non-neoplastic lymph nodes. These findings suggest the posttranscriptional regulation of NSE in PAL. Thus, an elevation of serum NSE level in patients with chronic pyothorax may be an indicator of PAL development.

Adolescent↗
PubMed1989

Neuron-specific splicing of C-SRC RNA in human brain.

The C-SRC, C-YES, and FYN genes encode three closely related tyrosine protein kinases that are expressed in human neural tissues. A unique form of the C-SRC gene has been demonstrated to be expressed in avian and murine brain tissues as the result of alternative splicing between the third and fourth exons. This neuronal-specific splicing event adds to the C-SRC mRNA an 18 base pair exon capable of encoding the same six amino acids in both avian and murine neural tissues. The C-YES and FYN genes share with C-SRC similar exon-intron boundaries and a high degree of amino acid sequence homology in the 3/4 exon coding region. However, potential alternative splicing of the C-YES and FYN genes in this region has not been previously investigated. In this study we have compared the expression of C-SRC, C-YES, and FYN RNAs in human lung, liver, brain, and placenta tissues and prepared cDNA clones spanning exons 3 and 4 for each of these genes from the different tissues. Sequence analysis of these cDNA clones revealed that the splicing patterns for the FYN and C-YES genes were the same among the various tissues, whereas C-SRC cDNAs isolated from brain contained 18 additional bases with the capacity to code for the same six amino acids present in the neural-specific forms of avian and murine pp60c-src.

Amino Acid Sequence↗
PubMed1998

Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.

BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.

Adult↗
PubMed1990

Neuron-specific enolase as a follow-up marker in small cell bronchial carcinoma. A prospective study in an unselected series.

The value of measurement of serum neuron-specific enolase (NSE) as a follow-up marker was investigated in 88 patients with small cell bronchial carcinoma. Of these, 42 had extensive disease and 46 had limited disease. The mean NSE levels before treatment, at response, and at recurrence in extensive disease were 107, 10, and 52 ng/ml, respectively, and the corresponding levels in limited disease were 35, 10, and 19 ng/ml, respectively. All differences were statistically clearly significant. However, the sensitivity of NSE in serum at response was 66% and at recurrence, 38%. The predictive value of an NSE decrease at response was 88%, and at recurrence, 72%. It is concluded that NSE changes during follow-up support the evaluation of the outcome but cannot be used as a monitoring agent in an individual patient.

Adult↗
PubMed2006

Neuron-specific Enolase and myelin basic protein in cerebrospinal fluid of patients with first episode schizophrenia.

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P<0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P< 0. 05). These findings suggested that patients with schizophrenia had cerebral injury.

Adolescent↗
PubMed1990

Ontogenic changes in expression of neuron-specific enolase (NSE) and its mRNA in the Purkinje cells of the rat cerebellum: immunohistochemical and in situ hybridization study.

In the postnatal development of rats, neuron-specific enolase (NSE)-immunoreactivity first appeared in the Purkinje cells at postnatal day 3 (P3) and elevated strikingly at P9 when almost all the Purkinje cell somata and dendrites exhibited the intense immunoreactivity. In situ hybridization signals for NSE-mRNA also increased markedly in the Purkinje cell somata from P3 to P9. These results indicate that the NSE synthesis is transiently enhanced in the Purkinje cells from P3 to P9 at the transcriptional level. At P11 and thereafter NSE-immunoreactive Purkinje cells decreased in number, and no significant immunoreaction was detected in their somata and dendrites in the adulthood, whereas distinct immunoreactivity for NSE was still detected in the Purkinje cell axons until the adult stage. However, the signals for NSE-mRNA were still localized in the Purkinje cell somata after P11 until the adult. The possible involvement of the negative translational control and/or the axoplasmic transport of NSE was briefly discussed to explain this discrepancy between NSE-immunoreactivity and its mRNA expression in the Purkinje cells in the late postnatal development.

Animals↗
PubMed2000

Comparative prognostic value of lactate dehydrogenase and neuron-specific enolase in small-cell lung cancer patients treated with platinum-based chemotherapy.

The influence of pretreatment serum levels of lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) on survival was investigated in a series of 263 consecutive patients with small-cell lung cancer. LDH was elevated in one-half of the patients, NSE in 79%. Both were significantly higher when the disease was considered extensive than when it was limited. The markers were significantly correlated (r= 0.54, P=1.03 x 10(-20)), and both had a significant impact on survival in the univariate analysis. The multivariate survival analysis of the entire population showed that LDH, along with performance status, extent of disease, and albumin, was a more important prognostic factor than NSE. Only when LDH was removed from the model did NSE become an independent prognostic factor. In the separate multivariate survival analyses of limited and extensive disease, LDH remained an independent prognostic factor. For extensive disease, NSE did not even appear in the model when LDH was excluded; for limited stage disease, NSE did become a weak independent prognostic factor when LDH was excluded. In conclusion, LDH, which is less expensive to assay than NSE, is also a stronger independent prognostic factor for small-cell lung cancer and should be part of the initial work-up. In clinical trials, stratification for LDH levels should be considered because of its prognostic weight.

Adult↗
PubMed2004

Serum neuron-specific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures.

PURPOSE: To evaluate the discriminative power of serial, simultaneous determinations of serum neuron-specific enolase (NSE), prolactin (PRL) and creatine kinase (CK) in differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES). METHODS: Prospective measurement of the three markers after 44 single seizures (32 ES and 12 PNES) during continuous video-EEG monitoring at seven different sampling points. RESULTS: Patients with ES had a significantly greater increase in PRL at 10, 20, 30 min, 1 and 6 h. The sensitivity for elevated NSE and CK was low. PRL showed a higher sensitivity. However, the corresponding positive predictive value was lower than in CK and NSE. Additionally, PRL had the lowest specificity of all parameters. CONCLUSIONS: The limited discriminative power of PRL, CK, and NSE calls into question if these markers are helpful in differentiating PNES and ES.

Adolescent↗
PubMed2002

Immediate S-100B and neuron-specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients.

The neuroproteins S-100B and neuron-specific enolase (NSE) released into the circulation are suggested to be reliable markers for primary brain damage. However, safe identification of relevant post-traumatic complications after minor head injury (MHI) is often hampered by acute intoxication of the patients. The objective of this study was to determine the diagnostic validity of immediate plasma measurements of S-100B and NSE in comparison with neurological examinations and cerebral computed tomography (CCT) findings in alcohol-intoxicated MHI patients. One hundered thrity-nine MHI individuals were enrolled in this prospective study during Munich's Oktoberfest 2000. Plasma levels of S-100B and NSE as well as serum alcohol and glucose values were determined by fully automated assays immediately after admission. The results were compared with Glasgow Coma Scale score, a brief neurological examination, and the CCT findings. Without being influenced by alcohol, median S-100B levels of the CCT+ group were significantly increased compared with those of the CCT- group (P < 0.001). NSE, alcohol, and glucose levels showed no significant group differences. As calculated by the ROC analysis, a cutoff value of 0.21 ng/mL with an area under the curve of 0.864 clearly differentiates between CCT+ and CCT- patients at a sensitivity of 100%, a specificity of 50.0%, and a positive likelihood ratio of 2.0. Although acute alcohol intoxication did not confound plasma measurements of S-100B and NSE, only S-100B levels below the cutoff level of 0.21 ng/mL seem to indicate absence of primary brain damage. Thus, in addition to routine neurological examinations, S-100B measurements immediately after admission might help to reduce CCT scans in alcohol-intoxicated patients early after MHI.

Adult↗
PubMed1997

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part II--Must samples be spun within 30 min?

Sangtec 100 (S-100) (Sangtec Medical, Sweden) and neurone-specific enolase (NSE) assays are showing promise in the assessment of cerebral damage following cardiopulmonary bypass (CBP). The manufacturer's instructions state, however, that samples must be spun and frozen within 30 min, which is inconvenient for serial studies. We, therefore, investigated whether strong blood samples at room temperature (RT) or 4 degrees C for up to 48 h affected the measured levels. Blood samples were taken before and after CBP in six patients and stored for 15 min, 4, 8, 24 or 48 h at RT or 4 degrees C. S-100 and NSE levels did not alter in either 'before surgery' or CPB samples when stored for up to 48 h at 4 degrees C. There was a small, nonsignificant rise when stored at RT. Samples may, therefore, be collected throughout long operations or stored overnight without affecting NSE or S-100 plasma levels.

Blood Preservation↗
PubMed1988

An immunohistochemical demonstration of neuron-specific enolase in the Merkel cells of the frog taste organ.

The Merkel cells in the taste organ of the frog were investigated by immunohistochemistry using neuron-specific enolase (NSE) antiserum. NSE-immunoreactivity was found exclusively in the Merkel cells lying at the base of the taste organ. The distribution and the profiles of the NSE-immunoreactive Merkel cells coincided with serotonin-containing cells previously reported at the same place.

Animals↗
PubMed1990

[Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with cervical spondylosis and ossification of posterior longitudinal ligaments].

We examined the levels of neuron-specific enolase (NSE) and S-100 protein in the cerebrospinal fluid (CSF) in 39 cases of cervical spondylosis (CS), in 16 cases of ossification of posterior longitudinal ligaments (OPLL), and in 29 control subjects by means of highly sensitive enzyme immunoassay methods. The levels (mean +/- SD) of NSE and S-100 protein in the control subjects, CS cases, and OPLL cases were shown as follows: NSE = 4.7 +/- 2.1, 8.0 +/- 3.4, 6.0 +/- 3.1 ng/ml, S-100b = 0.42 +/- 0.22, 0.72 +/- 0.40, 0.67 +/- 0.27 ng/ml, respectively. CS patients with a muscle atrophy of upper limbs showed a rise in NSE levels and this was especially seen in cases of cervical spondylotic amyotrophy (CSA). There were positive correlations between the distance of the A-P diameters of the spinal canal and the amount of NSE in OPLL cases (r = -0.6915, p less than 0.01). CS patients with severe spinal cord compressions demonstrated by myelo CT showed higher levels of NSE and S-100b. These results suggest that NSE, S-100 protein can be used as reliable markers to evaluate the damage of the spinal cord in CS and OPLL.

Adult↗
PubMed1989

Computer-aided mapping of specific neuronal populations in the human brain.

Antibody-staining methods and computer-aided microscopic systems have been used to generate high-resolution panoramic maps of specific neuronal populations in the human brain (4,6,11). This report focuses on the problems inherent in attempting high-resolution mapping of large brain sections, and describes how they are solved by computer-aided mapping. Further applications of computers to the study of brain structure are considered.

Brain↗
PubMed1993

Differential expression of neuron-specific enolase mRNA in mouse neuroblastoma cells in response to differentiation inducing agents.

1. The mouse neuroblastoma cell line N-115 was used as a model system to study neuronal differentiation induced by treatment of cells with different agents. 2. The extent of morphological differentiation obtained with dibutyryl cyclic AMP (dbc-AMP), dimethyl sulfoxide (DMSO), retinoic acid (RA), and serum-free medium was correlated to the expression of the mRNA for the gamma isoform of the glycolytic enzyme enolase, a recognized neuron-specific marker. 3. A 4-day treatment of the cells with any of the differentiation inducing agents used in this study resulted in the extension of long neurites, though differences in cell body shape were observed depending on the agent used. 4. Northern blot analysis revealed that changes in the level of gamma enolase-specific mRNA correlate with the extent of morphological differentiation, with a 5- to 20-fold increase depending on the differentiation inducing agent used. 5. Finally, we found that a high cell density causes a significative increase in the level of the gamma enolase-specific message in cells maintained in growing conditions.

Animals↗
PubMed2003

Neuron-specific gene manipulations to transparent zebrafish embryos.

To investigate the molecular basis of neural network formation, we introduced a novel double-cassette vector approach for visualizing and manipulating neuronal development in living zebrafish embryos. Two genes are physically linked in the double-cassette vector system, which ensures co-expression of an effector-protein and an EGFP-reporter in the same neuron. By generating transgenic enhanced green fluorescent protein (EGFP) expressing zebrafish lines, we first established that EGFP under control of either the olfactory marker protein (OMP) gene promoter or the nicotinic acetylcholine receptor beta3 (nAChRbeta3) gene promoter, directed strong EGFP expression to the olfactory sensory neurons and the retinal ganglion cells (RGCs), respectively. These transgenic lines allowed the visualization of the development of the entire olfactory sensory neurons and RGCs in vivo. By injection of vectors with EGFP under control of either the OMP or the nAChRbeta3 gene promoter, we followed the development of individual olfactory sensory neurons and RGCs. The double-cassette expression vector strategy enabled us to clarify the roles of protein kinase A (PKA) and glycogen synthase kinase-3beta (GSK-3beta) in the development of olfactory sensory neurons and RGCs. The combination of visualization and neuron-specific gene manipulation provides a powerful reverse genetic in vivo approach for the study of genes of interest in neural differentiation, axonal pathfinding, and synaptogenesis.

Animals↗
PubMed2006

Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats.

Human fetal brain is a potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative diseases. We explored whether NSCs isolated from cortex and striatum of human fetuses, aged 6-9 weeks post-conception, maintain their regional identity and differentiate into specific neuron types in culture and after intrastriatal transplantation in neonatal rats. We observed no differences between cortex- and striatum-derived NSCs expanded as neurospheres in proliferative capacity, growth rate, secondary sphere formation, and expression of neural markers. After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2- and parvalbumin-containing neurons. However, whereas cortical NSCs produced higher number of glutamatergic and tyrosine hydroxylase- and calretinin-positive neurons, several-fold more neurons expressing the striatal projection neuron marker, DARPP-32, were observed in cultures of striatal NSCs. Human cortical and striatal NSCs survived and migrated equally well after transplantation. The two NSC types also generated similar numbers of mature NeuN-positive neurons, which were several-fold higher at 4 months as compared to at 1 month after grafting. At 4 months, the grafts contained cells with morphologic characteristics of neurons, astrocytes, and oligodendrocytes. Many of neurons were expressing parvalbumin. Our data show that NSCs derived from human fetal cortex and striatum exhibit region-specific differentiation in vitro, and survive, migrate, and form mature neurons to the same extent after intrastriatal transplantation in newborn rats.

Animals↗