Investigation of Cell Migration and Invasion Using Real-time Cell Analysis, as well as the Association with Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinomas

The recently developed technology of real-time cell analysis (RTCA) was designed to analyze cell migration and invasion in vitro. In this study, we investigated these cellular factors in oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth with RTCA. We also examined the associated matrix metalloproteinases (MMPs) and integrins. We used the cell lines SCC-4 and SAS, which are human poorly differentiated OSCCs from the tongue, and HO-1-u-1, which are human poorly differentiated OSCCs from the floor of the mouth. Using RTCA, cell migration was assessed on fibronectin–coated CIM-Plates, and invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells demonstrated a high ability for cell migration and invasion compared with SAS and HO-1-u-1 cells. The SCC-4 cells also expressed high levels of MMP-9 and integrin α1 mRNA compared with SAS and HO-1-u-1 cells. The MMP inhibitor Marimastat blocked migration and invasion of all OSCCs. The findings suggest that MMP-9 is associated with cell migration and invasion in OSCCs, and indicate that RTCA will be useful for analyzing the metastatic capability of OSCCs and developing more effective new drugs for this disease

Quantification of Cell Migration and Invasion, and Their Association with Periostin in Anaplastic Thyroid Cancer, Using a Real-time Cell Analyzer

Anaplastic thyroid cancer (ATC) is known to be a highly malignant cancer of the thyroid with a high mortality rate. In a previous study, we used real-time cell analysis (RTCA) to analyze cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth. In the present study, we investigated cell migration and invasion of ATC using RTCA, as well as their association with periostin, matrix metalloproteinases (MMPs), and integrins. Experiments were performed on TCO-1 and HTC/C3 cells, which are human ATC cell lines. OSCC cell lines were used for comparison. Using the cell analysis system, cell migration was assessed on fibronectin-coated CIM-Plates, whereas invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells exhibited high cell migration and invasion activity compared with other OSCC cell lines. TCO-1 cells exhibited equivalent cell invasion but stronger migration than SCC-4 cells. Although TCO-1 cells had strong invasive activity, they did not express MMP-9, unlike SCC-4 cells. Conversely, periostin expression was high in TCO-1 cells. Therefore, periostin expression appears to be associated with the cell migration and invasion activity of ATC. The RTCA system will be useful for the analysis of the metastatic characteristics of ATC in head and neck cancer

Predicting the outcome of chronic kidney disease by the estimated nephron number: The rationale and design of PRONEP, a prospective, multicenter, observational cohort study

<p>Abstract</p> <p>Background</p> <p>The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number.</p> <p>Methods/Design</p> <p>The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice.</p> <p>Discussion</p> <p>This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.</p> <p>Trial registration</p> <p>UMIN-Clinical Trial Registration, UMIN000004784.</p

Schwann-Spheres Derived from Injured Peripheral Nerves in Adult Mice - Their In Vitro Characterization and Therapeutic Potential

Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call “Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature-Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these “Schwann-spheres" would provide a more potential autologous cell source for such transplantation

シキュウタイ ケツニョウ ケイド タンパクニョウ オ トモナウ IgA ジンショウ カンジャ ニ オケル ヘントウ テキシュツ ステロイド パルス ヘイヨウ リョウホウ

京都大学0048新制・課程博士博士(社会健康医学)甲第14908号社医博第25号新制||社医||6(附属図書館)27346UT51-2009-M822京都大学大学院医学研究科社会健康医学系専攻(主査)教授 中山 健夫, 教授 小川 修, 教授 三森 経世学位規則第4条第1項該当Doctor of Public HealthKyoto UniversityDA

Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: A meta-analysis

Objectives: Cerebrospinal fluid (CSF) lactate is produced by bacterial anaerobic metabolism and is not affected by blood lactate concentration, an advantage over CSF glucose in differentiating bacterial meningitis from aseptic meningitis. However, the previous investi- gations have shown mixed results of the sensitivity and specificity. Our study’s purpose was to assess the utility of CSF lactate in differentiating bacterial meningitis from aseptic meningitis. Methods: We searched MEDLINE and EMBASE for clinical studies that included CSF lactate mea- surement in bacterial meningitis and aseptic meningitis. Test characteristics were pooled using hierarchical summary ROC curve and random effects model. Results: Thirty three studies were included. The pooled test characteristics of CSF lactate were sensitivity 0.93 (95% CI: 0.89 e 0.96), specificity 0.96 (95% CI: 0.93 e 0.98), likelihood ratio positive 22.9 (95% CI: 12.6 e 41.9), likelihood ratio negative 0.07 (95% CI: 0.05 e 0.12), and diag- nostic odds ratio 313 (95% CI: 141 e 698). Pretreatment with antibiotics lowered the sensitivity 0.49 (95% CI: 0.23 e 0.75). CSF lactate of around 35 mg/dl (34 e 36 mg/dl) had higher sensitivity and specificity than those of around 27 mg/dl (26 e 28 mg/dl). Conclusions: CSFlactate’s highnegative likelihoodratio may make it useful for rulingoutbacterial meningitis though pretreatment with antibiotics reduces clinical accuracy. CSF lactate of 35 mg/dl could be optimal cut-off value for distinguishing bacterial meningitis from aseptic meningitis

Pulmonary Lymphangiomyomatosis in Childhood? : Marked Smooth Muscle Cell Proliferation of the Lung in a Preadolescent Girl with Repeated Pneumothorax and Progressive Dyspnea

A 13-year-old girl with repeated spontaneous pneumothorax and progressive dyspnea is described. The biopsy specimen of the lung showed marked proliferation of smooth muscle cells in the thickened bullous wall and alveolar septa, which was similar to the findings of the pulmonary lymphangiomyomatosis. Pulmonary lymphangiomyomatosis is one of the diseases which should be considered when children have progressive dyspnea, chylous effusions and repeated spontaneous pneumothorax

Characteristic features of statistical models and machine learning methods derived from pest and disease monitoring datasets

While many studies have used traditional statistical methods when analysing monitoring data to predict future population dynamics of crop pests and diseases, increasing studies have used machine learning methods. The characteristic features of these methods have not been fully elucidated and arranged. We compared the prediction performance between two statistical and seven machine learning methods using 203 monitoring datasets recorded over several decades on four major crops in Japan and meteorological and geographical information as the explanatory variables. The decision tree and random forest of machine learning were found to be most efficient, while regression models of statistical and machine learning methods were relatively inferior. The best two methods were better for biased and scarce data, while the statistical Bayesian model was better for larger dataset sizes. Therefore, researchers should consider data characteristics when selecting the most appropriate method