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PubMed1987

A monoclonal antibody against neuron-specific enolase. Immunohistochemical comparison with a polyclonal antiserum.

There is skepticism about the value of antisera to neuron-specific enolase (NSE) for immunohistochemical identification of neural and neuroendocrine differentiation in neoplasms, because of reports of detection of NSE, in a large percentage of nonneuroendocrine neoplasms. By immunohistochemical methods, the authors compared a monoclonal antibody to NSE (Mab NSE) with a heterologous antiserum to NSE (Het NSE) on 348 samples of tumors of diverse histogenesis. They studied 93 neural and neuroendocrine tumors and 255 nonneuroendocrine, nonneural tumors. The Mab NSE was slightly less sensitive but clearly more specific than the Het NSE in recognizing neural and neuroendocrine differentiation. Only 2% of the nonneuroendocrine, nonneural tumors reacted positively with Mab NSE; in contrast, 20% of the same tumors were positive with the Het NSE. Moreover, intense nonspecific staining was frequent with Het NSE, which often rendered interpretation difficult. Because of its superior specificity, the Mab NSE used in this study is more valuable than the heterologous antiserum as a diagnostic reagent in tumor diagnosis.

Antibodies, Monoclonal↗
PubMedDate not supplied

Neuron-specific enolase-like immunoreactivity in human Leydig cells.

Using the peroxidase anti-peroxidase immunocytochemical technique, neuron-specific enolase (NSE)-like immunoreactivity (NSE-LI) was revealed in Leydig cells of adult human testes at the light microscopic level. Differences in the NSE staining intensity were observed between the individual Leydig cells, separate cell groups within a testis and between the testes of individual patients. Together with the already established substance P-like immunoreactivity (SP-LI), the results obtained provided further evidence for the possible neuroectodermal origin of human Leydig cells and their presumable relation to the APUD- or the Diffuse Neuroendocrine System (DNES).

Adult↗
PubMed1996

Neurone-specific enolase levels in pleural effusions in patients with rheumatoid arthritis.

BACKGROUND: High pleural fluid levels of neurone-specific enolase (NSE) have been reported, not only in patients with small cell lung cancer but also in those with chronic inflammatory diseases. METHODS: NSE concentrations were determined in pleural fluid and serum from 342 patients with pleural effusions including 17 with rheumatoid arthritis. RESULTS: The median NSE concentration in pleural fluid was higher in rheumatoid effusions than in any other condition studied. The median pleural fluid:serum NSE ratio was highest in patients with rheumatoid arthritis (11.6) and about unity in all other diseases including small cell lung cancer (0.9). In patients with rheumatoid arthritis pleural fluid concentrations of NSE correlated inversely with pleural fluid glucose concentrations and the pH of the pleural fluid. CONCLUSIONS: A high pleural fluid:serum NSE ratio was found consistently in pleural effusions from patients with rheumatoid disease.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Cytosolic levels of neuron-specific enolase in squamous cell carcinomas of the lung.

To study the behavior and possible correlations of neuron-specific enolase (NSE) with other clinicobiological parameters, we measured the cytosolic levels of this marker by means of an immunoradiometric assay (IRMA) in 95 squamous cell lung carcinoma samples. We also analyzed the levels of pS2, tissue-type plasminogen activator (t-PA), hyaluronic acid (HA), free beta subunit of human chorionic gonadotropin (beta-HCG), CYFRA 21.1 and CA 125 in cytosol. On the cell surface we analyzed the concentrations of epidermal growth factor receptor (EGFR), HA, erbB-2 oncoprotein, CD44s, CD44v5 and CD44v6. Other parameters considered were clinical stage, lymph node involvement, histological grade (HG), ploidy and the cellular S-phase fraction measured by flow cytometry on nuclei obtained from fresh tissues. In the 95 squamous cell carcinomas the cytosolic levels of NSE varied from 4.5 to 2235 ng/mg protein (median: 267) and were significantly higher (p < 0.001) than those observed in 38 samples of normal pulmonary tissue obtained from the same patients (range: 56-657; median: 141.5). When classifying tumors according to the different parameters analyzed, we observed that the levels of NSE were higher in aneuploid than in diploid cases (p = 0.046) and in those that were HG3 than in those that were HG2 (p < 0.001). Tumors with high NSE levels (> 422 ng/mg protein; 75th percentile) were more likely to have high S-phase values (p = 0.012) and were more frequently aneuploid (p = 0.038) and HG3 (p < 0.001) than those with low levels of NSE (< 180 ng/mg protein; 25th percentile). These results lead us to the following conclusions: 1) the cytosolic concentrations of NSE are significantly higher in squamous cell carcinomas than in healthy pulmonary tissue, and 2) the cytosolic concentrations of NSE are not correlated with clinical stage or nodal involvement. However, in our study higher levels of the enzyme were statistically correlated with aneuploidy, histological grade 3 and S-phase. This may explain its association with poorer outcome and progression, but also the more favorable response of tumors with elevated NSE to chemotherapy, as suggested by other groups.

Adult↗
PubMed1985

Increased level of immunoreactive neuron-specific enolase in thyroid C cells from dogs and guinea pigs after chronic hypercalcemia.

Immunocytochemical localization of neuron-specific enolase (NSE) in thyroid C cells was investigated in various mammalian species. In bovine thyroid glands most of the C cells were weakly immunoreactive to anti-NSE antiserum. In other mammalian species, including dogs, guinea pigs, rabbits, cats, pigs, rats, hamsters, mice, and monkeys, some C cells or only a few C cells were weakly immunoreactive to the antiserum. It seems that normal C cells contain NSE in small amounts only or are devoid of NSE. After chronically induced hypercalcemia, C cells revealed hypertrophic and hyperplastic features. Whereas immunoreactive calcitonin was markedly decreased, marked increase of immunoreactive NSE was observed in C cells of both dogs and guinea pigs; almost all C cells were filled with reaction product for NSE. After administration of ethylenethiourea for a period of 3-8 months, C cells revealed a marked decrease of secretory granules and appearance of vesicular inclusions of various sizes, which were immunoreactive to the calcitonin antiserum, indicating a disturbance of calcitonin synthesis. No immunoreactivity for NSE was observed in C cells from dogs and guinea pigs so treated. In rabbits showing hypocalcemic tetany, calcitonin immunoreactivity was very intense and NSE immunoreactivity was faint to negative in the C cells. Thus, the level of NSE in C cells was clearly connected with the functional activity of the cells.

Animals↗
PubMed1987

Immunohistochemical identification of neuron-specific enolase and calbindin in the vestibular receptors of human fetuses.

Immunohistochemical techniques were used to identify neuron-specific enolase (NSE) and calbindin in the vestibular receptors and ganglia of human fetuses at 10 weeks of gestation. NSE was found in vestibular ganglion cells and in a few sensory cells. The pattern of immunoreactivity in the sensory epithelia was characteristic of the appearance of NSE in these structures. Calbindin was found in vestibular ganglion cells and sensory cells which displayed a strong immunoreactivity. These findings are discussed with regard to synaptogenesis and they indicate that the vestibular receptors show biochemical signs of maturation consistent with the possibility of synaptic activity.

Calbindins↗
PubMed2006

The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN) and neuropeptide study.

In this study we examined the superior colliculus of the midbrain of the one-humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti-neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal population as well as for the enkephalins, somatostatin (SOM) and substance P (SP). It was found that, unlike in most mammals, the superior colliculus is much larger than the inferior colliculus. The superior colliculus is concerned with visual reflexes and the co-ordination of head, neck and eye movements, which are certainly of importance to this animal with large eyes, head and neck, and apparently good vision. The basic neuronal architecture and lamination of the superior colliculus are similar to that in other mammals. However, we describe for the first time an unusually large content of neurons in the superior colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid. We classified the majority of these neurons as small (perimeters of 40-50 microm), and localized diffusely throughout the superficial grey and stratum opticum. In addition, large pyramidal-like neurons with perimeters of 100 microm and above were present in the intermediate grey layer. Large unipolar cells were located immediately dorsal to the deep grey layer. By contrast, small neurons (perimeters of 40-50 microm) immunopositive to SOM and SP were located exclusively in the superficial grey layer. We propose that this system may be associated with a pain-inhibiting pathway that has been described from the periaqueductal grey matter, juxtaposing the deep layers of the superior colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be important in relation to the camel's life in the harsh environment of its native deserts, often living in very high temperatures with no shade and a diet consisting largely of thorny branches.

Adaptation, Physiological↗
PubMed1994

Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives.

The major transcript of the FE65 gene is a neuron-specific mRNA that encodes a nuclear protein whose aminoterminal domain strongly activates the transcription of a reporter gene when fused to a heterologous DNA-binding domain. FE65 gene expression is regulated during neuronal differentiation of the NTERA-2 cell line, and it is temporally and spatially restricted during mouse embryo development. It is first detected around day 10 of gestation in the basal plate of the neural tube, and then, at the subsequent stages of development and in the newborn animals, it is found solely in neural structures. Its expression is most abundant in the neural crest derivatives (e.g. spinal and encephalic ganglia), ganglionic structures of sense organs (ganglionic layer of the retina and olfactory epithelium), as well as the ganglionic structures of the autonomic nervous system. Thus FE65 gene expression can be considered a marker of the development of embryo ganglionic derivatives.

Animals↗
PubMed2005

Soy isoflavones modulate the expression of BAD and neuron-specific beta III tubulin in male rat brain.

Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. There is evidence that soy isoflavones influence neuronal apoptosis or proliferation in vitro and in vivo. However, little research has been done to investigate the effects of soy isoflavones on markers of neuronal apoptosis and survival in vivo. We examined brain BAD (a proapoptotic member of Bcl-2 protein family) and neuron-specific beta III tubulin (an early marker of neuronal differentiation/survival) levels in male rats fed either a standard chow rich of soy isoflavones (Phyto-600) or one free of soy isoflavones (Phyto-free) life-long (from conception until time tissue collected). Among five brain regions, the expression of BAD was highest in medial basal hypothalamus (MBH); the next highest in hippocampus; moderate in amygdala and frontal cortex; and lowest in cerebellum in Phyto-free fed animals. In animals on Phyto-600 diet, the levels of BAD were significantly decreased in frontal cortex and MBH; but significantly increased in the amygdala. The expression of beta III tubulin was highest in frontal cortex; moderate in amygdala, hippocampus and MBH; and lowest in cerebellum in the Phyto-free group. In rats fed with the Phyto-600 diet, levels of beta III tubulin were significantly increased in amygdala, frontal cortex, hippocampus and MBH compared to Phyto-free values. In summary, these findings provide evidence for the neuroprotective potential of soy isoflavones in the amygdala, frontal cortex, hippocampus and MBH. This implies that consumption of soy isoflavones may be beneficial on learning and memory, anxiety-related behaviors, and recovery from trauma.

Animals↗
PubMedDate not supplied

Relationship of alpha MSH-specific neurons to the arcuate opiocortin neuronal system as determined by dual antigen immunocytochemical procedures.

The cross-immunoreactivity, topography, and fiber projections of the alpha MSH-immunoreactive specific neurons in the forebrain of the rat appear to be distinctly different from that of the neurons in the hypothalamic arcuate opiocortin system. The cell bodies, immunoreactive only to alpha-MSH, have a specific pattern of distribution in the dorsal and lateral hypothalamic regions from the level of the retrochiasmatic region to the premammillary area of the posterior hypothalamus. Immunoreactive fibers of these cells appear to extend into regions of the cerebral cortex and hippocampus. An antomical relationship between the immunostained fibers and/or terminals of the arcuate opiocortin pool of neurons and the alpha-MSH-immunoreactive perikarya is described utilizing the ABC (Avidin-Biotin-Peroxidase Complex) and ABC-GO (Glucose Oxidase) or glucose oxidase-antiglucose oxidase complex methods of immunocytochemistry in which two tissue antigens with contrasting colors are demonstrated in the same tissue section.

Adrenocorticotropic Hormone↗
PubMed2004

Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2.

GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein expression in CA1 pyramidal neurons, which leads to a reduced capacity for neuronal Cl- extrusion. This effect is mediated by endogenous BDNF acting on tyrosine receptor kinase B (TrkB), with down-stream cascades involving both Shc/FRS-2 (src homology 2 domain containing transforming protein/FGF receptor substrate 2) and PLCgamma (phospholipase Cgamma)-cAMP response element-binding protein signaling. The plasmalemmal KCC2 has a very high rate of turnover, with a time frame that suggests a novel role for changes in KCC2 expression in diverse manifestations of neuronal plasticity. A downregulation of KCC2 may be a general early response involved in various kinds of neuronal trauma.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation.

Neurofibrillary tangles, which are major pathological hallmarks of Alzheimer's disease (AD), are composed of paired helical filaments (PHFs) containing hyperphosphorylated tau. Specific kinases regulate tau phosphorylation and are closely linked to the pathogenesis of AD. We have characterized a human tau-tubulin kinase 1 (TTBK1) gene located on chromosome 6p21.1. TTBK1 is a serine/threonine/tyrosine kinase that is conserved among species and belongs to the casein kinase 1 superfamily. It is specifically expressed in the brain, especially in the cytoplasm of cortical and hippocampal neurons. TTBK1 phosphorylates tau proteins in both a Mg2+- and a Mn2+-dependent manner. Phosphopeptide mapping and immunoblotting analysis confirmed a direct tau phosphorylation by TTBK1 at Ser198, Ser199, Ser202 and Ser422, which are also phosphorylated in PHFs. TTBK1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that TTBK1 is a neuron-specific dual kinase involved in tau phosphorylation at AD-related sites and is also associated with tau aggregation.

Animals↗
PubMed1993

S100 protein and neuron-specific enolase on monocytic leukemic CD1+ cells, probable precursors of Langerhans cells.

Langerhans cells are characterized by specific markers, such as Birbeck granules and CD1a antigen. S100 protein and neuron-specific enolase are less specific but are expressed only on Langerhans cells among the cells of the phagocytic mononuclear system. In this study, the expression of these two antigens on many monocytic leukemic cells is shown. These cells could be precursors of Langerhans cells which have been transformed into malignant cells.

Antigens, CD↗
PubMed1996

Calretinin as a marker of specific neuronal subsets in primate substantia nigra and subthalamic nucleus.

Neurons immunoreactive for the calcium-binding protein calretinin (CR) were visualized in the substantia nigra (SN) pars compacta (SNc), reticulata (SNr) and lateralis (SNl), the ventral tegmental area (VTA) and the subthalamic nucleus (STN) of squirrel monkeys. The density of CR perikarya was high in VTA, moderate in SNc, low in SNr/SNl, and very low in STN. The SNc/VTA complex also displayed a CR-rich neuropil. Some CR perikarya and fibers occurred in specific sectors of STN. These data suggest that CR may play a role in specific neuronal subpopulations in all components of primate basal ganglia.

Animals↗
PubMed1997

An enzyme immunoassay for neuron-specific enolase in cerebrospinal fluid.

A direct (as opposed to competitive) enzyme immunoassay (EIA) was developed to detect neuron-specific enolase (NSE) in cerebrospinal fluid (CSF). Most common methods of evaluating NSE levels have utilized radioimmunoassay. These are highly sensitive, but cannot be employed in laboratories not equipped or licensed for the use of radioisotopes. The EIA developed here shows sensitivity within the physiological range of values for CSF-NSE (> I ng/ml) and can be used in laboratories with appropriate densitometric scanning capabilities. The assay was applied to CSF samples obtained from patients with a variety of diagnoses at the time of surgical intervention for their respective disorders. While there were no diagnostically significant differences between the level of NSE in CSF from patients with different neurological disorders utilized in the development of this procedure, we were able to differentiate between marginally different levels of NSE. We conclude that we have developed a safe, fast, reliable, and sensitive assay for NSE in the CSF that can be used to study NSE levels in a variety of neurological cases.

Analysis of Variance↗
PubMed1987

Neuron specific enolase demonstration in the diagnosis of a solid-cystic (papillary cystic) tumour of the pancreas.

Immunoreactivity to neuron specific enolase (NSE) was demonstrated in a solid-cystic (papillary cystic) tumour of the human pancreas, employing immunohistochemical methods. Positive staining for NSE was found with two different antisera. In addition, sodium-dodecyl-sulphate-polyacrylamide-gel-electro-phoresis (SDS-PAGE) of tumour homogenate revealed a distinct band reacting with a NSE antiserum. However, we failed to detect any hormonal products or neuroendocrine granules in the tumour. Therefore the authors advise caution in using the enzyme as a differential diagnostic tool, especially in surgical pathology of epithelial pancreatic neoplasms occurring in young females. In individual cases electron microscopy will be necessary since solid-cystic tumours of the pancreas consistently show large intracytoplasmic zymogen-like granules.

Electrophoresis, Polyacrylamide Gel↗
PubMedDate not supplied

Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients.

PURPOSE: In a recent study, we found the presence of serum autoantibody against neuron-specific enolase (NSE) in glaucoma patients. The purpose of the present paper is to investigate further the clinical significance of the presence of the serum antibody against NSE in glaucoma patients. METHODS: Serum autoantibody against NSE was examined by Western blot analysis in 143 patients with glaucoma (normal tension glaucoma [NTG], 45 cases; primary open angle glaucoma [POAG] 98 cases). Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and the serum autoantibody-negative patients. RESULTS: Maximum IOP in the serum anti-NSE antibody-positive patients was significantly lower than that in the negative patients (P <.05). However, no statistical differences were observed in visual field loss, disc cupping, or other clinical factors. During the clinical course, rates of the presence of anti-NSE antibody were significantly higher in the early stages of POAG (P <.0001) with visual field deterioration than without it. Although it was not statistically significant, the positive rates of serum anti-NSE antibody were relatively higher in the later stages of POAG and NTG with visual field deterioration than without it. CONCLUSION: The present observations suggest that the presence of serum autoantibody against NSE may be clinically useful for predicting the progression of visual field loss in POAG patients.

Aged↗
PubMed1982

Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer.

Serum neuron-specific enolase (NSE) levels in 94 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with those in 30 adult controls. 38 of the SCLC patients had limited disease and 56 had extensive disease. Serum NSE was raised (greater than 12.0 ng/ml) in 69% of all patients (mean 52.35 +/- 11.56, range 4.1-850 ng/ml); it was raised in 15/38 (39%) of patients with limited stage disease and in 49/56 (87%) of those with extensive stage disease. Extensive stage patients had significantly higher mean NSE level (59 ng/ml) than did limited stage patients (13.8 ng/ml). Serum NSE was raised in 34/41 (84%) of patients with metastases at 1 or 2 sites and in all patients with metastases at 3 or more sites. Serial measurements in 23 patients receiving combination chemotherapy showed an excellent correlation between serum NSE and clinical response. Continuous cell-lines of SCLC, established from 10 of the patients in this study, all expressed high levels of NSE. These studies indicate that serum NSE may be a useful marker for staging and for monitoring response to therapy in patients with SCLC.

Antineoplastic Agents↗