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IL-6 Plays Crucial Roles in Sporadic Colorectal Cancer through the Cytokine Networks including CXCL7  [PDF]
Takashi Uchiyama, Hirokazu Takahashi, Hiroki Endo, Eiji Sakai, Kunihiro Hosono, Yoji Nagashima, Atsushi Nakajima
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.326112
Abstract: IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 signaling and the cytokine network in sporadic colorectal cancer. We investigated the serum IL-6 levels in patients with sporadic colorectal adenoma, cancer patients, and normal controls. In addition, the expressions of IL-6, gp130, and the IL-6 receptor subunit were investigated in biopsy specimens collected from these subjects. Furthermore, the expressions of CXCL7 and CXCR2, a chemokine and its receptor involved in IL-6 production, were also investigated. We observed an elevated level of serum IL-6 in colorectal cancer patients and an increased expression of IL-6 in colorectal cancer tissues, compared with the levels in a control group and in patients with adenoma. The phosphorylation of gp130 was also increased in the colorectal cancer tissues, compared with that in control and adenoma tissues. The expressions of CXCL7 and CXCR2 in the colorectal cancer tissues were also higher than those in control and adenoma tissues. IL-6 signaling is involved in sporadic colorectal cancer. In addition, the increased expressions of CXCL7 and CXCR2 might, in turn, increase the expression of IL-6 in colorectal cancer. Further studies are required to elucidate the function of the IL-6 signaling and the cytokine network in sporadic colorectal cancer.
Decreased Semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis
Takagawa Shu,Nakamura Fumio,Kumagai Ken,Nagashima Yoji
BMC Musculoskeletal Disorders , 2013, DOI: 10.1186/1471-2474-14-40
Abstract: Background Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF165). It has been shown that Sema3A competitively antagonizes VEGF165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients. Methods Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney’s inflammation scoring system. The localization of Sema3A, VEGF165 and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels of Sema3A, VEGF-A and NRP1 mRNA were determined using quantitative real-time polymerase chain reaction (qPCR). Results In OA specimens, Sema3A, VEGF165 and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction of Sema3A mRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio of Sema3A/VEGF-A mRNA expression levels with DAS28-CRP (R = 0.449, p = 0.013). Sema3A mRNA levels also correlated with Rooney’s inflammation score, especially in perivascular infiltrates of lymphocytes (R = 0.506, p = 0.004), focal aggregates of lymphocytes (R = 0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = 0.536, p = 0.002). Conclusions Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.
Thymic Alterations in GM2 Gangliosidoses Model Mice
Seiichi Kanzaki,Akira Yamaguchi,Kayoko Yamaguchi,Yoshitsugu Kojima,Kyoko Suzuki,Noriko Koumitsu,Yoji Nagashima,Kiyotaka Nagahama,Michiko Ehara,Yoshio Hirayasu,Akihide Ryo,Ichiro Aoki,Shoji Yamanaka
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012105
Abstract: Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb?/? mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies.
Review of juxtaglomerular cell tumor with focus on pathobiological aspect
Naoto Kuroda, Hiroko Gotoda, Chisato Ohe, Shuji Mikami, Keiji Inoue, Yoji Nagashima, Fredrik Petersson, Isabel Alvarado-Cabrero, Chin-Chen Pan, Ondrej Hes, Michal Michal, Zoran Gatalica
Diagnostic Pathology , 2011, DOI: 10.1186/1746-1596-6-80
Abstract: Juxtaglomerular cell tumor (JGCT) is a very rare cause of hypertension that was first described by Robertson et al. in 1967 and the name was coined by Kihara in 1968 [1,2]. To date, approximately 100 cases with JGCT have been reported. Clinically, this tumor is characterized by hypertension, hyperaldosteronism and hypokalemia secondary to excessive renin secretion by tumor cells [3-8]. In this article, we introduce the general overview of JGCT with focus on pathobiological aspects.This tumor affects adolescents and young adults, with peak prevalence in the second and third decades of life with a female predominance [8-10]. Haab et al. (1995) detected eight JGCTs among 30,000 patients at a hypertensive clinic [11].Patients with JGCT present with various symptoms including headaches, retinopathy, double vision, dizziness, nausea, vomiting, polyuria and proteinuria [8,12]. Most of these symptoms may be attributed to hypertension or hypokalemia. Clinically, JGCT is subdivided into three categories [13]. The typical variant, which accounts for the majority of JGCT, has characteristically high renin concentration, hyperaldosteronism, hypokalemia and hypertension [4,5]. Second most common presentation is the atypical variant showing hypertension with normal potassium level [8]. The third, non-functioning variant is very rare and is characterized by a normal blood pressure and normal potassium level [14-16]. Clinicians should strongly suspect JGCT if they encounter adolescent or young adult patients with severe or even moderate hypertension associated with an unexplained secondary hyperaldosteronism [6]. JGCT may cause malignant hypertension [17]. A case of JGCT associated with membranous glomerulonephritis was also reported [18].Ultrasonography of the kidneys usually shows a hypoechoic mass [19,20]. Computed tomography (CT) scan is very useful for the detection of renal tumor, even when other imaging analyses is negative [8,21]. CT scan shows finding of low, low-to iso- or
Adult Nephroblastoma with Predominant Epithelial Component: A Differential Diagnostic Candidate of Papillary Renal Cell Carcinoma and Metanephric Adenoma—Report of Three Cases
Shiho Watanabe,Hiroshi Naganuma,Michio Shimizu,Satoshi Ota,Shin-ichi Murata,Naoki Nihei,Jun Matsushima,Shuji Mikami,Naoto Kuroda,Yoji Nagashima,Yukio Nakatani
Case Reports in Pathology , 2013, DOI: 10.1155/2013/675875
Abstract: Although nephroblastoma is the commonest renal tumor of childhood, it is rare in adults. In cases of predominantly epithelial type occurring in adulthood, it might be difficult to distinguish it from papillary renal cell carcinoma and metanephric adenoma. Here, we report three cases of adult epithelial nephroblastoma in 24-, 76-, and 21-year-old females. Histologically, the tumors were composed of papillotubular architectures of small and uniform tumor cells with high nucleocytoplasmic ratio without blastemal element. Immunohistochemically, the tumor cells were positive for WT-1 and CD57 but negative for AMACR, which was helpful to exclude the possibility of papillary renal cell carcinoma. Metanephric adenoma is a benign tumor, which can be distinguished by the observation of the cellular atypism and growth pattern. However, nephroblastoma with predominant epithelial element mimics the malignant counterpart of metanephric adenoma, that is, “metanephric adenocarcinoma.” 1. Introduction Nephroblastoma (Wilms tumor) is the most frequent renal tumor in childhood and accounts for 6%-7% of pediatric tumors. Nephroblastoma is most frequent in the first decade, and generally the initial presentation is abdominal distention. Histologically, nephroblastoma is composed of blastemal, epithelial, and stromal elements in various proportions. The blastemal element is densely packed and oval to spindle undifferentiated cells. The epithelial element forms abortive tubular and glomerulus-like structures. The stromal element is more or less differentiated nonepithelial cells, occasionally showing differentiation to the striated muscle, bone, and cartilage [1]. In cases that nephroblastoma is composed of a dominant epithelial element, differential diagnosis from papillary RCC, metanephric adenoma, and other renal tumors is challenging, especially in adult cases. Here, we report three cases of adult nephroblastoma with overwhelming epithelial element. We made comparison of immunohistochemical characteristics with metanephric adenomas, nephroblastoma, and conventional papillary RCCs and revealed that these are nephroblastoma with extremely epithelial element. In cases of scarce blastemal element, they are considered as the malignant counterpart of metanephric adenoma, “metanephric adenocarcinoma.” Such a tumor should be distinguished from papillary RCC and metanephric adenoma. 2. Case Reports Case 1. The patient was a 24-year-old Japanese female, who had developed gross hematuria. Her family or past history was not contributory. The general status or laboratory data was not
Nonfunctioning Juxtaglomerular Cell Tumor
Ryoko Sakata,Hiroaki Shimoyamada,Masahiro Yanagisawa,Takayuki Murakami,Kazuhide Makiyama,Noboru Nakaigawa,Yoshiaki Inayama,Kenichi Ohashi,Yoji Nagashima,Masahiro Yao,Yoshinobu Kubota
Case Reports in Pathology , 2013, DOI: 10.1155/2013/973865
Abstract: The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2?cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery. 1. Introduction Juxtaglomerular cell tumor (JGCT), a neoplasm derived from the juxtaglomerular cell of the kidney, was first described by Robertoson et al. and Kihara et al. [1, 2]. Since then, approximately 100 cases have been reported in the literature. Clinically, this tumor is characterized by hypertension due to excessive renin secretion by tumor cells causing secondary hyperaldosteronism [1–3]. Generally, its preoperative diagnosis is relatively easy, because of typical presence of hypertension concomitant with hypokalemia. However, it is quite difficult in cases of asymptomatic nonfunctioning JGCT [3]. Here, we present a case of nonfunctioning JGCT, which is the fourth case reported so far to the best of our knowledge [4–6]. 2. Case Report A 31-year-old woman was referred to our hospital with a left renal tumor incidentally detected during examination for left-side abdominal pain. She had no history of hypertension, and her blood pressure at presentation was 116/62?mmHg. All the laboratory data, including electrolyte levels, were within normal ranges. Unfortunately, preoperative plasma renin activity was not assayed. Unenhanced computed tomography (CT) revealed solitary well-circumscribed mass lesion measuring 2?cm with fine calcifications in the middle portion adjacent to the renal pelvis of the left kidney. Dynamic-enhanced CT demonstrated that the tumor was not enhanced in the corticomedullary (early) phase but enhanced in the excretory (late) phase (Figure 1). Magnetic resonance image (MRI) showed
Suppression of Methane Gas Emissions and Analysis of the Electrode Microbial Community in a Sediment-Based Bio-Electrochemical System  [PDF]
Yoshiyuki Ueno, Yoji Kitajima
Advances in Microbiology (AiM) , 2014, DOI: 10.4236/aim.2014.45032

The effects of bioelectrochemical systems (BESs) for the suppression of methane gas emissions from sediment were examined using a laboratory-scale reactor system. Methane gas emissions from acetate were suppressed by approximately 36% from control based on the installation of a BES in which carbon-graphite electrodes were buried in sediment and arbitrarily set at certain oxidative potentials (+300 mV vs Ag/AgCl) using a potentiostat. Meanwhile, methane gas emissions increased in the BES reactor where the electrode potential was set at -200 mV. Results obtained from pyrotag sequencing analysis of the microbial community on the surface of the buried electrodes targeting 16S rRNA genes demonstrated that the genusGeobacterhad drastically propagated in a sample from the reactor where the electrodes were buried. Quantitative analysis of 16S rRNA genes of archaea also revealed that the archaeal population had decreased to approximately 1/6 of its original level on the electrode of the BES set at +300 mV. This implied that the oxidation-reduction potential (ORP) in the sediment was raised to the inhibition level for methanogenesis in the vicinity of the buried electrode. Analysis of electron flux in the experiment revealed that electrons intrinsically used for methanogenesis were recovered via current generation in the sediment where a potential of +300 mV was set for the electrode, although most electrons donated from acetate were captured by oxygen respiration and other electron-accepting reactions. These results imply that BES technology is suitable for use as a tool for controlling re-dox-dependent reactions in natural environments, and that it also brought about changes in the microbial population structure and methanogenic activity in sediment.

Impacts to the Micronesian islands by environmental change of globalization and climate change
Shunsuke Nagashima
Journal of Ecology and Field Biology , 2010,
Abstract: This article focused on the environmental changes on atolls in Micronesia. First, we considered the problem. Second,we designed research that focused on the impacts of environmental changes especially in relation to globalization andglobal warming in the Federated States of Micronesia (FSM). The results were in accordance to the hypotheses that globalizationhad impacted prominently in communities on main islands and impact was lessened with increased distancefrom the centre. The fact that the islands are remotely situated and thus, in theory, do not have much outside influence,has not alleviated them from having societal concerns. The earth’s environmental change is causing an impact on themain islands as well. This has been governed by distinctive characteristics in their geographical, regional, and contents.Moreover, they showed stronger concerns about impacts on the environment than globalization. A set of questionnaireswas used as the principal assessment method to quantify the concerns relating to the environmental changes.
A Solution to the Missing Link in the Press-Schechter Formalism
Masahiro Nagashima
Physics , 2001, DOI: 10.1086/323490
Abstract: The Press-Schechter (PS) formalism for mass functions of the gravitationally collapsed objects is reanalyzed. It has been suggested by many authors that the PS mass function agrees well with the mass function given by $N$-body simulations, while many too simple assumptions are contained in the formalism. In order to understand why the PS formalism works well we consider the following three effects on the mass function: the filtering effect of the density fluctuation field, the peak ansatz in which objects collapse around density maxima, and the spatial correlation of density contrasts within a region of a collapsing halo because objects have non-zero finite volume. According to the method given by Yano, Nagashima & Gouda (YNG) who used an integral formula proposed by Jedamzik, we resolve the missing link in the PS formalism, taking into account the three effects. While YNG showed that the effect of the spatial correlation alters the original PS mass function, in this paper, we show that the filtering effect almost cancels out the effect of the spatial correlation and that the original PS is almost recovered by combining these two effects, particularly in the case of the top-hat filter. On the other hand, as for the peak ansatz, the resultant mass functions are changed dramatically and not in agreement especially at low-mass tails in the cases of the Gaussian and the sharp $k$-space filters. We show that these properties of the mass function can be interpreted in terms of the kernel probability $P(M_{1}| M_{2})$ in the integral formula qualitatively.
Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a Modified Foamy Virus Vector
Satoshi Horino, Toru Uchiyama, Takanori So, Hiroyuki Nagashima, Shu-lan Sun, Miki Sato, Atsuko Asao, Yoichi Haji, Yoji Sasahara, Fabio Candotti, Shigeru Tsuchiya, Shigeo Kure, Kazuo Sugamura, Naoto Ishii
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071594
Abstract: X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.
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