• Advances in pediatric surgery
• /
• v.7 no.1
• /
• pp.15-20
• /
• 2001

The pathophysiology of Hirschsprung's disease (HD) is not fully understood, but recent studies have disclosed that neural cell adhesion molecule (NCAM) and glial cell line-derived neurotrophic factor (GDNF) play important roles in the formation of aganglionic bowel of Hirschsprung's disease. To evaluate the roles of NCAM and GDNF in HD, immunohistochemical analysis was performed using formalin-fixed and paraffin-embedded tissue sections. On the basis of the results, we tried to evaluate them as diagnostic markers. The specimens were obtained from 7 patients with HD who underwent modified Duhamel operation. The diagnosis was based on the clinical findings and the absence of ganglion cells in the nerve plexuses by routine microscopy. NCAM immunoreactivity was found in the nerve plexuses and scattered nerve fibers in the smooth muscle layers of ganglionic segments. In aganglionic segments, the number of NCAM positive nerve fibers in the smooth muscle layers was significantly reduced compared with ganglionic segments. In two cases the nerve plexuses in aganglionic segments, NCAM was negligible. The smooth muscle cells showed diffuse immunoreactivity for GDNF and the staining intensity was not different in the aganglionic and ganglionic segments. However, higher expression of GDNF in the nerve plexus of the ganglionic segments was noted comparing to aganglionic segments. These data suggest that both NCAM and GDNF may play important roles in pathogenesis of Hirschsprung's disease and immunohistochemical staining for NCAM can be used as an ancillary diagnostic tool for HD.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3131-3135
• /
• 2015

Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.

• Advances in pediatric surgery
• /
• v.8 no.1
• /
• pp.23-27
• /
• 2002

Infantile hypertrophic pyloric stenosis (IHPS) a common childhood disorders characterized by nonbilious projectile vomiting, an olive shaped mass in the right upper quadrant of the abdomen and visible gastric peristaltic wave in the upper abdomen. Its etiology and pathogenesis are not clear but abnormal nerve distribution of the pylorus has been $postulated^{2-6}$. We performed immunocytochemical staning to the pyloric muscle from 10 IHPS and 3 controls patients, utilizing specific monoclonal antibody to NCAM(neural cell adhesion molecule). In IHPS patients, the number of NCAM protein immunoreactive nerve fibers were less than that in normal subjects. Auerbach myenteric plexuse was well developed and interbundle nerve plexuse was present but nerve fibers supplying individual muscle cells in smooth muscle bundles were poorly developed. These results indicate reduction of innervation in smooth muscles in IHPS patients that possibly contributes to the pathogenesis of IHPS.

• Molecules and Cells
• /
• v.39 no.10
• /
• pp.762-767
• /
• 2016

Fasciclin II (FasII), the Drosophila ortholog of neural cell adhesion molecule (NCAM), plays a critical role in synaptic stabilization and plasticity. Although this molecule undergoes constitutive cycling at the synaptic membrane, how its membrane trafficking is regulated to ensure proper synaptic development remains poorly understood. In a genetic screen, we recovered a mutation in Drosophila mical-like that displays an increase in bouton numbers and a decrease in FasII levels at the neuromuscular junction (NMJ). Similar phenotypes were induced by presynaptic, but not postsynaptic, knockdown of mical-like expression. FasII trafficking assays revealed that the recycling of internalized FasII molecules to the cell surface was significantly impaired in mical-like-knockdown cells. Importantly, this defect correlated with an enhancement of endosomal sorting of FasII to the lysosomal degradation pathway. Similarly, synaptic vesicle exocytosis was also impaired in mical-like mutants. Together, our results identify Mical-like as a novel regulator of synaptic growth and FasII endocytic recycling.

• Journal of Korean Neurosurgical Society
• /
• v.60 no.4
• /
• pp.417-423
• /
• 2017

Objective : Repair of sensorial nerve defect is an important issue on peripheric nerve surgery. The aim of the present study was to determine the effects of sensory-motor nerve bridging on the denervated dermatomal area, in rats with sensory nerve defects, using a neural cell adhesion molecule (NCAM). Methods : We compared the efficacy of end-to-side (ETS) coaptation of the tibial nerve for sural nerve defect repair, in 32 Sprague-Dawley rats. Rats were assigned to 1 of 4 groups : group A was the sham operated group, group B rats had sural nerves sectioned and buried in neighboring muscles, group C experienced nerve sectioning and end-to-end (ETE) anastomosis, and group D had sural nerves sectioned and ETS anastomosis was performed using atibial nerve bridge. Neurological evaluation included the skin pinch test and histological evaluation was performed by assessing NCAM expression in nerve terminals. Results : Rats in the denervated group yielded negative results for the skin pinch tests, while animals in the surgical intervention groups (group C and D) demonstrated positive results. As predicted, there were no positively stained skin specimens in the denervated group (group B); however, the surgery groups demonstrated significant staining. NCAM expression was also significantly higher in the surgery groups. However, the mean NCAM values were not significantly different between group C and group D. Conclusion : Previous research indicates that ETE nerve repair is the gold standard for peripheral nerve defect repair. However, ETS repair is an effective alternative method in cases of sensorial nerve defect when ETE repair is not possible.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.1
• /
• pp.55-59
• /
• 2014

Dehydroevodiamine HCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impairment and depression induced by stress.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.5
• /
• pp.518-524
• /
• 2008

Chromosome 18q alteration plays a key role in colorectal tumorigenesis, and loss of heterozygosity at 18q is associated with a poor prognosis in colon cancer. DCC(Deleted in Colorectal Cancer) is a putative tumor- suppressor gene at 18q21 that encodes a transmembrane protein with structural similarity to neural cell adhesion molecule that is involved in both epithelial and neuronal cell differentiation. DCC is implicated in regulation of cell growth, survival and proliferation. Thus, tumor progression in squamous cell carcinoma, stomach cancer, colorectal cancer correlates with downregulation of DCC expression. The mechanism for DCC suppression is associated with hypermethylation of the DCC gene promoter region. Hence, the goal of this study is to identify the promoter methylation responsible for the down-regulation of DCC expression in oral squamous cell carcinoma. 12 of tissue specimens for the study are excised and gathered from 12 patients who are diagnosed as SCC in department of OMS, dental hospital, dankook university. To find expression of DCC in each tissue samples, immunohistochemical staining, RT-PCR gene analysis and methylation specific PCR are processed. The results are as follows. 1. In the DCC gene RT-PCR analysis, 5(41.6%) of 12 specimens of oral squamous cell carcinoma did not expressed DCC gene. 2. In the promoter methylation specific PCR analysis, 5(41.6%) of 12 specimens showed promoter methylation of DCC gene. 3. In the immunohistochemical staining of poor differentiated and invasive oral squamous cell carcinoma, loss of DCC expression was observed. These findings suggest that methylation of the DCC gene may play a role in loss of gene expression in invasive oral squamous cell carcinoma.

• BMB Reports
• /
• v.54 no.3
• /
• pp.164-169
• /
• 2021

Neuronal growth regulator 1 (NEGR1) is a GPI-anchored membrane protein that is involved in neural cell adhesion and communication. Multiple genome wide association studies have found that NEGR1 is a generic risk factor for multiple human diseases, including obesity, autism, and depression. Recently, we reported that Negr1-/- mice showed a highly increased fat mass and affective behavior. In the present study, we identified Na/K-ATPase, beta1-subunit (ATP1B1) as an NEGR1 binding partner by yeast two-hybrid screening. NEGR1 and ATP1B1 were found to form a relatively stable complex in cells, at least partially co-localizing in membrane lipid rafts. We found that NEGR1 binds with ATP1B1 at its C-terminus, away from the binding site for the alpha subunit, and may contribute to intercellular interactions. Collectively, we report ATP1B1 as a novel NEGR1-interacting protein, which may help deciphering molecular networks underlying NEGR1-associated human diseases.

• Korean Journal of Biological Psychiatry
• /
• v.16 no.1
• /
• pp.5-14
• /
• 2009

Objectives : Most of the mechanisms reported for antidepressant drugs are the enhancement of neurite outgrowth and neuronal survival in the rat hippocampus. Neural cell adhesion molecule 140(NCAM140) has been implicated as having a role in cell-cell adhesion, neurite outgrowth, and synaptic plasticity. In this report, we have performed to elucidate a correlation among chronic antidepressant treatments, NCAM140 expression, and activation of phosphorylated cyclicAMP responsive element binding protein(pCREB) which is a downstream molecule of NCAM140-mediated intracellular signaling pathway in the rat hippocampus. Methods : Fluoxetine(10mg/kg) was injected acutely(daily injection for 5days) or chronically(daily injection for 14days) in adult rats. RNA and protein were extracted from the rat hippocampus, respectively. Real-time RT-PCR was performed to analyze the expression pattern of NCAM140 gene and western blot analyses for the activation of the phosphorylation ratio of CREB. Results : Chronic fluoxetine treatments increased NCAM140 expression 1.3 times higher than control in rat hippocampus. pCREB immunoreactivity in the rat hippocampus with chronic fluoxetine treatment was increased 4.0 times higher than that of control. Conclusion : Chronic fluoxetine treatment increased NCAM140 expression and pCREB activity in the rat hippocampus. Our data suggest that NCAM140 and pCREB may play a role in the clinical efficacy of antidepressants promoting the neurite outgrowth and neuronal survival.

• The Journal of Korean Physical Therapy
• /
• v.19 no.2
• /
• pp.41-55
• /
• 2007

Purpose: This study aimed to compare the effect on nerve regeneration of ultrasound irradiation in rats with peripheral nerve injury. Methods: To investigate alterations of the NCAM immunoreactivity in non-crushed part and crushed part of the spinal cord, the unilateral sciatic nerve of the rats were crushed. The expression of NCAM was used as the marked of peripheral nerve regeneration, and also plays an important role in developing nerve system. Experimental animals were sacrificed by perfusion fixation at post-injury 1, 3, 7, 14 days after ultrasound irradiation. The pulsed US was applied at a frequency of 1MHz and a spatial average-temporal average Intensity of 0.5W/of (20% pulse ratio) for 1 mins. The Luxol fast blue-cresyl violet stain were also done to observe the morphological changes. Results: Alteration of NCAM immunoreactivity in the crushed part and the non-crushed part of lower lumbar spinal cord were observed. NCAM-immunoreactivity cells were some increased in the dorsal horn lamina I, III and cell ventral horn at 1 day after unilateral sciatic nerve injury. However, there was not significant difference in the relationship between crushed part and non-crushed part. NCAM-inmmunoreactivity was remarkably increased at 3 days after unilateral sciatic nerve injuryin the gray matter and white matter. NCAM-immunoreactivity was increased in the ventral horn and post horn of experimental crushed part. Also, NCAM-immunoreactivity in large motor neurons in ventral horns lamina VIII, IX were increased at 7 days after unilateral sciatic nerve injury. At 14 days after sciatic nerve crushed injury, there was no significant difference. All group were decreased for 14 days. In the time course of NCAM expression, all groups showed a significant difference at 3day groups(p<0.05). Whereas, CC group was noted a significant difference between 3day and 7 day group respectively. In NCAM expression, there were significantly increased in all group. In the relationship between CNC group and ENC group, significant difference was detected among 3, 7, 14 day group(p<0.05). The difference between CC group and ENC group were noted in all groups(p<0.05). Conclusion: It is consequently suggested that the effects of the ultrasound irradiation may increase the NCAM immunoreactive neurons and glial cell in the spinal cord after unilateral sciatic nerve crushed injury. Therefore, the increased NCAM immunoreactivity in the spinal cord may reflect the neuronal damage and healing process induced by a ultrasound irradiation after peripheral nerve injury in rat.