The Effect of Differential Modulation of the N-methyl-D-aspartate Receptor on Growth and intracellular Calcium Ion Concentration in Normal Human Oral Keratinocytes

The purpose of this study was to examine the interaction between the agents [N-methyl-D-aspartate (NMDA), arachidonic acid (AA), and Nitric Oxide Synthase Inhibitor (NOS-I)] and cultured normal human oral keratinocytes (NHOK) in order to elucidate the mechanisms by which epithelial growth and regeneration are regulated. We also examined whether AA and NOS-I could protect NHOK from glutamate cytotoxicity and the change of intracellular calcium ion concentration. NHOK were obtained from gingival tissue of 20 individuals aged 20 to 29, and third passage (P3) cells were used for this study. Cell viability was measured by the MTT assay and DNA synthesis by the BrdU assay. The microscopic features of NHOK were observed and changes in intracellular calcium ion concentration were measured. NMDA and NNA induced an initial increase in cell number. Low concentration of AA induced an increase in cell number while high concentrations of AA induced a decrease in cell number. The decrease in cell number induced by NMDA at the seventh day was abolished by the addition of low concentrations of AA or NOS inhibitors. Low concentrations of AA or NMDA with high concentrations of AA significantly increased the DNA synthesis rate at four hours. NMDA and AA both induced an increase in intracellular calcium ion concentration, and AA enhanced NMDA-induced intracellular calcium ion in a concentration-dependent manner. NMDA-induced NHOK death was associated with intracellular calcium ion change and the promotion of cell differentiation. Low concentrations of AA protected NHOK cells from NMDA-induced death.

Interaction between the p75 neurotrophin receptor and a novel adaptor protein

The neurotrophin plays an important role in the development, differentiation and survival of the nervous system in vertebrates. It exerts its cellular effects through two different receptors, the Trk receptor tyrosine kinase neurotrophin receptor and the p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. Trk and p75 neurotrophin receptors utilize specific target proteins to transmit signals into the cell. An ankyrin-rich membrane spanning protein (ARMS) was identified as a new p75 interacting protein and serves as a novel downstream target of p75 neurotrophin receptor. We sought to delineate the interaction between p75 and ARMS by deletion constructs of p75 and green fluorescent protein (GFP)-tagged ARMS. We examined the interaction between these two proteins after overexpressing them in HEK-293 cells. Using both Western blot analysis and immunocytochemistry followed by confocal laser scanning microscopy, we found out that the intracellular domain of the p75 neurotrophin receptor was important for the interaction with ARMS. The results from this study suggest that ARMS may play an important role for mediating the signals from p75 neurotrophin receptor into the cell

Identification and Characterization of a Dual-Acting Antinematodal Agent against the Pinewood Nematode, Bursaphelenchus xylophilus

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca2+ channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound

A Validation Study of the Korean Version of SPAN

Purpose: The SPAN, which is acronym standing for its four components: Startle, Physiological arousal, Anger, and Numbness, is a short post-traumatic stress disorder (PTSD) screening scale. This study sought to develop and validate a Korean version of the SPAN (SPAN-K). Materials and Methods: Ninety-three PTSD patients (PTSD group), 73 patients with non-psychotic psychiatric disorders (psychiatric control group), and 88 healthy participants (normal control group) were recruited for this study. Participants completed a variety of psychiatric assessments including the SPAN-K, the Davidson Trauma Scale (DTS), the Clinician-Administered PTSD Scale (CAPS), and the State-Trait Anxiety Inventory (STAI). Results: Cronbach's alpha and test-retest reliability values for the SPAN-K were both 0.80. Mean SPAN-K scores were 10.06 for the PTSD group, 4.94 for the psychiatric control group, and 1.42 for the normal control group. With respect to concurrent validity, correlation coefficients were 0.87 for SPAN-K vs. CAPS total scores (p<0.001) and 0.86 for SPAN-K vs. DTS scores (p<0.001). Additionally, correlation coefficients were 0.31 and 0.42 for SPAN-K vs. STAI-S and STAI-T, respectively. Receiver operating characteristic analysis of SPAN-K showed good diagnostic accuracy with an area under the curve (AUC) of 0.87. The SPAN-K showed the highest efficiency at a cutoff score of 7, with a sensitivity of 0.83, a specificity of 0.81, positive predictive value (PPV) of 0.88, and negative predictive value (NPV) of 0.73. Conclusion: These results suggest that the SPAN-K had good psychometric properties and may be a useful instrument for rapid screening of PTSD patients.This study was supported by a grant of the Korean Academy of Anxiety Disorders, Korean Neuropsychiatric Association, and Korean Research Foundation (2006-2005152), Republic of Korea

Quantitative Evaluation of the Accuracy of Micro-Computed Tomography in Tooth Measurement

Micro-computed tomography (MCT) is a noninvasive technique for visualizing morphological characteristics of teeth in a detailed and accurate manner, without causing any tooth destruction. A large amount of information can be obtained from such scans. The slices can be recreated in any plane, and the data can be represented as either two-dimensional (2D) or three-dimensional (3D) images. In addition, the internal and external anatomy can be demonstrated simultaneously or separately, and the images can be assessed qualitatively and quantitatively. However, only the qualitative accuracy of MCT had been evaluated previously. The aim of the present study was to evaluate the accuracy of MCT quantitatively by comparing the values obtained by MCT with those of other imaging methods. Twelve teeth were scanned using a desktop X-ray micro-CT scanner, and the images were reconstructed and measured. Values obtained by direct measurement served as the primary reference for linear measurements. Measurements made by a 3D scanner and by photography were additional references. MCT was found to be a reliable method of making linear measurements and may be a useful device for measuring distance and for observing both internal and external tooth structure using the reconstructed 3D form

The three-dimensional relationship on a virtual model between the maxillary anterior teeth and incisive papilla

Statement of problem. The incisive papilla as an anatomical landmark has historically been used to determine anterior incisal tooth position for complete denture prostheses. There are numerous data regarding its position, but 3-dimensional orthographic measurements are scarce. Purpose. The purpose of this study was to evaluate the orthographic anteroposterior distance between the posterior border of the incisive papilla and a reference point or vector. Material and methods. Using a 3-dimensional laser scanner and reconstruction computer software, 9 measurements were made orthographically on an individually established reference plane. The following 3 measurements were made to determine the spatial relationship between the anterior tooth and the incisive papilla: IP, incisor to papilla, IIC, incisor to intercanine line, and ICP, intercanine line to papilla. In addition, the following 6 measurements were made to evaluate the correlation of the factors determining arch shape with the previously described 3 measurements: ICW, intercanine width, AL, arch length, AW, arch width, ICR, incisor to canine radius, ICA, incisor to canine angle, and IMA, incisor to molar angle. The correlation among all values was investigated. Descriptive statistics and an independent sample t test between genders was performed (α=.05). Results. The average IP distance (SD) was 11.96 (1.37) mm with no significant gender difference (P=.052). There were gender differences in IIC (P=.001), AL (P=.017), and ICA (P=.013). ICA had the largest negative or positive correlation coefficients with parameters related to the incisive papilla such as IP, IIC, and ICP. Conclusions. The mean IP value obtained by 3-dimensional orthographic measurements was significantly larger than the classical data, however, it is impossible to make direct comparisons. The central incisor position of dentate subjects has a significant relationship with the ICA value which represents the premaxillary divergence. (J Prosthet Dent 2007;98:312-318)This study was supported by a grant of the Korea Health 21 Research and Development Project, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG1-CH09-0001).

Signet-ring cell carcinoma of the appendix: a case report with an emphasis on sonographic findings

In this report, we present a rare case of primary signet-ring cell carcinoma of the appendix in a 51-year-old woman with right lower quadrant pain. Since non-specific concentric appendiceal wall thickening was found in a radiologic evaluation, it was misdiagnosed as non-tumorous appendicitis. An in-depth examination of the correlation between sonographic and histopathologic findings demonstrated that a single markedly thickened hypoechoic layer was well correlated with the diffuse infiltration of tumor cells in both the submucosal and muscle layers. If this sonographic finding is observed in certain clinical settings, such as potential ovarian and peritoneal metastasis, submucosal infiltrative tumors, including signet-ring cell carcinoma, should be considered in the differential diagnosis

Human Mesenchymal Stem Cell-Derived Schwann Cell-Like Cells Exhibit Neurotrophic Effects, Via Distinct Growth Factor Production, in a Model of Spinal Cord Injury

Human bone marrow-derived mesenchymal stem cells (hMSCs) are considered a desirable cell source for autologous cell transplantation therapy to treat nervous system injury due to their ability to differentiate into specific cell types and render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. To potentiate their possible trophic effect, hMSCs were induced without genetic modification to adopt characteristics of Schwann cells (SCs), which provide trophic support for regenerating axons. The induced hMSCs (shMSCs) adopted a SC-like morphology and expressed SC-specific proteins including the p75 neurotrophin receptor, which correlated with cell-cycle exit. In addition, shMSCs secreted higher amounts of several growth factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) when compared with uninduced hMSCs. Coculture of shMSCs with Neuro2A cells significantly increased neurite outgrowth and cell proliferation but decreased cell death. Transplantation of shMSCs in an ex vivo model of spinal cord injury dramatically enhanced axonal outgrowth, which was mediated by HGF and VEGF secretion and also decreased cell death. These results demonstrate that shMSCs could serve as an endogenous source of neurotrophic growth factors to facilitate axonal regeneration while at the same time protecting the resident cells at the site of tissue injury. We propose that these induced hMSCs without genetic modification are useful for autologous cell therapy to treat nervous system injury. (C) 2010 Wiley-Liss, Inc.1

Induction of a Neuronal Phenotype from Human Bone Marrow-Derived Mesenchymal Stem Cells

Human mesenchymal stem cell (hMSCs) isolated from human adult bone marrow have self-renewal capacity and can differentiate into multiple cell types in vitro and in vivo. A number of studies have now demonstrated that MSCs can differentiate into various neuronal populations. Due to their autologous characteristics, replacement therapy using MSCs is considered to be safe and does not involve immunological complications. The basic helix-loop-helix (bHLH) transcription factor Olig2 is necessary for the specification of both oligodendrocytes and motor neurons during vertebrate embryogenesis. To develop an efficient method for inducing neuronal differentiation from MSCs, we attempted to optimize the culture conditions and combination with Olig2 gene overexpression. We observed neuron-like morphological changes in the hMSCs under these induction conditions and examined neuronal marker expression in these cells by RTPCR and immunocytochemistry. Our data demonstrate that the combination of Olig2 overexpression and neuron-specific conditioned medium facilitates the neuronal differentiation of hMSCs in vitro. These results will advance the development of an efficient stem cell-mediated cell therapy for human neurodegenerative diseases.This research was supported by a grant from the NationalResearch Foundation of Korea (M-SC, 2006-KRF-531-C00043)

Sonographic findings of malignant appendix tumors in seven cases

We report the sonographic features of confirmed malignant appendiceal tumors in seven cases. The histologic diagnoses of these tumors were mucinous cystadenocarcinoma (n = 2), colonic type adenocarcinoma (n = 4), and signet-ring cell carcinoma (n = 1). The 2 mucinous cystadenocarcinomas showed mucocele type, which had markedly enlarged inner luminal diameters (mean, 23 mm; range, 15–31 mm) and thick, irregular walls (mean wall thickness, 5.5 mm; range, 5–6 mm). In contrast, the 5 nonmucinous carcinomas (4 adenocarcinomas and 1 signet-ring cell carcinoma) showed nonmucocele type, which had relatively small inner luminal diameters (mean ± standard deviation [SD], 6.6 ± 4.5 mm; range, 2–15 mm) and prominent wall thickening (mean wall thickness ± SD, 6.2 ± 2.3 mm; range, 3–10 mm). Of the 5 nonmucinous tumors, only one had a discernible mass, three had thick irregular walls, two had loss of the wall layer pattern, and four had submucosal hypoechogenicity. Regardless of the histologic type, five of the seven malignant appendiceal tumors showed a severe periappendiceal fat infiltration or periappendiceal abscess, suggestive of perforation.Although the sonographic findings of the malignant appendiceal tumors were nonspecific, some of the sonographic features seen in these seven cases may help radiologists consider the possibility of underlying malignant appendiceal tumors