研究者データベース

研究者情報

マスター

アカウント(マスター)

  • 氏名

    ELEWA YASER HOSNY ALI(エレワ ヤセル ホスニー アリ), エレワ ヤセル ホスニー アリ

所属(マスター)

  • 獣医学研究院 獣医学部門 基礎獣医科学分野

所属(マスター)

  • 獣医学研究院 獣医学部門 基礎獣医科学分野

独自項目

syllabus

  • 2020, 先端生命科学特論Ⅰ:発生生物学, Advanced Lecture on Life Science I:Developmental Biology, 博士後期課程, 獣医学院
  • 2020, 生命科学特論, Advanced Lecture on Life Sciences, 博士後期課程, 獣医学院

researchmap

プロフィール情報

所属

  • Zagazig大学, 准教授

学位

  • 博士(獣医学)(Zagazig大学)

プロフィール情報

  • エレワ, エレワ
  • ヤセル, ヤセル
  • ID各種

    201701020463950360

対象リソース

所属

  • Zagazig大学, 准教授

業績リスト

研究キーワード

  • Mucosa associated lymphoid tissue   Bone disorder   Reproductive disorders and infertility   Kidney diseases   Lymphocytes   Mediatinal fat-associated Lymphoid clusters   Innate immunity   autoimmunity   Respiratory diseases   

研究分野

  • ライフサイエンス / 細胞生物学

経歴

  • 2017年02月 - 現在 Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University Assistant professor
  • 2016年04月 - 現在 Department of Histology, Faculty of Veterinary Medicine Zagazig University, Zagazig, Egypt Associate professor
  • 2014年10月 - 2016年09月 Laboratory of Anatomy, Graduate school of Veterinary Medicine Hokkaido University, Japan JSPS post doc.
  • 2011年04月 - 2016年03月 Department of Histology, Faculty of Veterinary Medicine Zagazig University, Zagazig, Egypt Lecturer
  • 2011年07月 - 2012年01月 Laboratory of Anatomy, Graduate school of Veterinary Medicine Hokkaido University, Japan post Doctoral researcher
  • 2008年10月 - 2010年09月 Laboratory of Anatomy, Graduate school of Veterinary Medicine Hokkaido University, Japan Teaching volunteer
  • 2006年07月 - 2007年01月 Department of Structural Pathology, Institute of Nephrology, Graduate School of Medical and Dental Sciences Niigata University, Nigata, Japan Visiting researcher
  • 2002年05月 - 2006年02月 Department of Histology, Faculty of Veterinary Medicine Zagazig University, Zagazig, Egypt Demonstrator

学歴

  • - 現在   Faculty of Veterinary Medicine, Zagazig University

論文

  • Shiori Hiramatsu, Osamu Ichii, Takashi Namba, Yuki Otani, Teppei Nakamura, Md Abdul Masum, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 27 4 897 - 909 2021年08月 
    Diabetes mellitus (DM) is a predisposing factor for renal disorder progression and is referred to as diabetic kidney disease (DKD). However, there are no reports of DKD with an underlying autoimmune disorder. In this study, we compared the pathophysiological changes caused by DM induction after streptozotocin (STZ) injection in comparison with that in a control group receiving citrate buffer (CB) in the autoimmune disease model mice “BXSB/MpJ-Yaa” (Yaa) and the wild-type strain BXSB/MpJ. Both strains showed hyperglycemia after 12 weeks of STZ injection. Interestingly, the Yaa group developed membranous and proliferative glomerulonephritis, which tended to be milder glomerular lesions in the STZ group than in the CB group, as indicated by a decreased mesangial area and ameliorated albuminuria. Statistically, the indices for hyperglycemia and autoimmune abnormalities were negatively and positively correlated with the histopathological parameters for mesangial matrix production and glomerular proliferative lesions, respectively. STZ treatment induced renal tubular anisonucleosis and dilations in both strains, and they were more severe in Yaa. Significantly decreased cellular infiltration was observed in the Yaa group compared to the CB group. Thus, in DKD related to autoimmune nephritis, hyperglycemia modifies its pathology by decreasing the mesangial area and interstitial inflammation and aggravating renal tubular injury.
  • Takashi Namba, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Marina Hosotani, Yaser Hosny Ali Elewa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 2021年07月 
    The interleukin (IL) 36 subfamily belongs to the IL-1 family and is comprised of agonists (IL-36 alpha, IL-36 beta, IL-36 gamma) and antagonists (IL-36Ra, IL-38). We previously reported IL-36 alpha overexpression in renal tubules of chronic nephritis mice. To understand the localization status and biological relationships among each member of the IL-36 subfamily in the kidneys, MRL/MpJ-Fas(lpr/lpr) mice were investigated as autoimmune nephritis models using pathology-based techniques. MRL/MpJ-Fas(lpr/lpr) mice exhibited disease onset from 3 months and severe nephritis at 6-7 months (early and late stages, respectively). Briefly, IL-36 gamma and IL-36Ra were constitutively expressed in murine kidneys, while the expression of IL-36 alpha, IL-36 beta, IL-36Ra, and IL-38 was induced in MRL/MpJ-Fas(lpr/lpr) mice. IL-36 alpha expression was significantly increased and localized to injured tubular epithelial cells (TECs). CD44(+)-activated parietal epithelial cells (PECs) also exhibited higher IL-36 alpha-positive rates, particularly in males. IL-36 beta and IL-38 are expressed in interstitial plasma cells. Quantitative indices for IL-36 alpha and IL-38 positively correlated with nephritis severity. Similar to IL-36 alpha, IL-36Ra localized to TECs and PECs at the late stage; however, MRL/MpJ-Fas(lpr/lpr) and healthy MRL/MpJ mice possessed IL-36Ra(+) smooth muscle cells in kidney arterial tunica media at both stages. IL-36 gamma was constitutively expressed in renal sympathetic axons regardless of strain and stage. IL-36 receptor gene was ubiquitously expressed in the kidneys and was induced proportional to disease severity. MRL/MpJ-Fas(lpr/lpr) mice kidneys possessed significantly upregulated IL-36 downstream candidates, including NF-kappa B- or MAPK-pathway organizing molecules. Thus, the IL-36 subfamily contributes to homeostasis and inflammation in the kidneys, and especially, an IL-36 alpha-dominant imbalance could strongly impact nephritis deterioration.
  • Sao Oe, Md. Abdul Masum, Osamu Ichii, Takanori Nishimura, Teppei Nakamura, Takashi Namba, Yuki Otani, Yasuhide Nakayama, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 109 7 1220 - 1231 2021年07月 
    We investigated spatiotemporal changes in host tissues during foreign body reactions. Silicone tube was subcutaneously embedded into ICR mice, and tissue surrounding silicone (TSS) was observed at 2, 7, 14, 21, 28, 43, and 70 days (D) postsurgery. The thin layer (TL) and loose connective tissues (LCTs) (inside and outside the TSS) developed until D21 and densified afterward. Neutrophils infiltrated the TSS until D14 and formed neutrophil extracellular traps (NETs) in the TL during D7-21. In the LCTs, mast cell counts increased until D21, and macrophage numbers peaked at D14. Several macrophages showed LYVE-1 expression, supporting a tissue-remodeling role. Developmental indices of collagen fibers (CFs) and reticular fibers (RFs) increased during D2-21. NETs, but not neutrophils, were detected after D28. Mast cell numbers peaked at D43 and were maintained until D70. Myofibroblasts consistently localized to the TL from D14. During D21-28, the area of connective tissue (CNT), and CFs and RFs decreased and increased, respectively, and both remained constant during D28-70. The CF density remained constant from D21 and increased at D70. Thus, TSS showed two phases: inflammation and CNT development (D2-21), and inflammation convergence and CNT stabilization (D28-70). These results provide insights into foreign body reactions in clinical cases.
  • Yaser Hosny Ali Elewa, Mahmoud Mansour Abd Elwakil, Osamu Ichii, Teppei Nakamura, Sherif Kh A Mohamed, Yasuhiro Kon
    International journal of molecular sciences 22 13 2021年06月26日 
    Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group "PG") or phosphate buffer saline (PBS) (vehicle group "VG"). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.
  • Md Rashedul Islam, Osamu Ichii, Teppei Nakamura, Takao Irie, Akio Shinohara, Md Abdul Masum, Yuki Otani, Takashi Namba, Tsolmon Chuluunbaatar, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Animals : an open access journal from MDPI 11 6 2021年06月12日 
    Most mammalian ovarian follicles contain only a single oocyte having a single nucleus. However, two or more oocytes and nuclei are observed within one follicle and one oocyte, respectively, in several species, including cotton rat (CR, Sigmodon hispidus). The present study compared ovarian histology, focusing on folliculogenesis, between two inbred CR strains, HIS/Hiph and HIS/Mz. At 4 weeks of age, ovarian sections from both the strains were analyzed histologically. Multi-oocyte follicles (MOFs) and double-nucleated oocytes (DNOs) were observed in all stages of developing follicles in HIS/Hiph, whereas HIS/Mz had MOFs up to secondary stages and lacked DNOs. The estimated total follicles in HIS/Mz were almost half that of HIS/Hiph, but interstitial cells were well developed in HIS/Mz. Furthermore, immunostaining revealed no clear strain differences in the appearance of oocytes positive for Ki67, PCNA, and p63 in MOF or DNOs; no cell death was observed in these oocytes. Ultrastructural analysis revealed more abundant mitochondrial clouds in oocytes of HIS/Hiph than HIS/Mz. Thus, we clarified the strain differences in the CR ovary. These findings indicate that early events during folliculogenesis affect the unique ovarian phenotypes found in CRs, including MOFs or DNOs, and their strain differences.
  • Mahmoud A. Younis, Ikramy A. Khalil, Yaser H. A. Elewa, Yasuhiro Kon, Hideyoshi Harashima
    JOURNAL OF CONTROLLED RELEASE 331 335 - 349 2021年03月 
    Hepatocellular carcinoma (HCC) is a fatal disease with limited therapeutic choices. The stroma-rich tumor microenvironment hinders the in vivo delivery of most nanomedicines. Ultra-small lipid nanoparticles (usLNPs) were designed for the selective co-delivery of the cytotoxic drug, sorafenib (SOR), and siRNA against the Midkine gene (MK-siRNA) to HCC in mice. The usLNPs composed of a novel pH-sensitive lipid, a diversity of phospholipids and a highly-selective targeting peptide. A microfluidic device, iLiNP, was used and a variety of factors were controlled to tune particle size aiming at maximizing tumor penetration efficiency. Optimizing the composition and physico-chemical properties of the usLNPs resulted in an enhanced tumor accumulation, selectivity and in vivo gene silencing. The optimized usLNPs exerted potent gene silencing in the tumor (median effective dose, ED50 similar to 0.1 mg/Kg) with limited effect on the healthy liver. The novel combination synergistically-eradicated HCC in mice (similar to 85%) at a surprisingly-low dose of SOR (2.5 mg/Kg) which could not be achieved via individual monotherapy. Toxicity studies revealed the biosafety of the usLNPs upon either acute or chronic treatment. Furthermore, the SOR-resistant HCC established in mice was eradicated by 70% using this approach. We conclude that our strategy is promising for potential clinical applications in HCC treatment.
  • Marina Hosotani, Teppei Nakamura, Osamu Ichii, Takao Irie, Yuji Sunden, Yaser Hosny Ali Elewa, Takafumi Watanabe, Hiromi Ueda, Takashi Mishima, Yasuhiro Kon
    Biology open 10 2 2021年02月19日 
    Caudal autotomy in rodents is an evolutionarily acquired phenomenon enabling escape from predators, by discarding the tail skin after traumatic injuries. The histological mechanisms underlying caudal autotomy seem to differ among species. Cotton rats (Sigmodon hispidus), which are important laboratory rodents for human infectious diseases, possess a fragile tail. In this study, we compared the tail histology of cotton rats with that of laboratory rats (Rattus norvegicus), which have no fragility on their tail, to elucidate the process of rodent caudal autotomy. First, the cotton rats developed a false autotomy characterized by loss of the tail sheath with the caudal vertebrae remaining without tail regeneration. Second, we found the fracture plane was continuous from the interscale of the tail epidermis to the dermis, which was lined with an alignment of E-cadherin+ cells. Third, we found an obvious cleavage plane between the dermis and subjacent tissues of the cotton-rat tail, where the subcutis was composed of looser, finer, and fragmented collagen fibers compared with those of the rat. Additionally, the cotton-rat tail was easily torn, with minimum bleeding. The median coccygeal artery of the cotton rat had a thick smooth muscle layer, and its lumen was filled with the peeled intima with fibrin coagulation, which might be associated with reduced bleeding following caudal autotomy. Taken together, we reveal the unique histological features of the tail relating to the caudal autotomy process in the cotton rat, and provide novel insights to help clarify the rodent caudal autotomy mechanism.
  • Marina Hosotani, Osamu Ichii, Teppei Nakamura, Takashi Namba, Md Rashedul Islam, Yaser Hosny Ali Elewa, Takafumi Watanabe, Hiromi Ueda, Yasuhiro Kon
    Journal of anatomy 238 1 73 - 85 2021年01月 
    The ovarian bursa is a small peritoneal cavity enclosed by the mesovarium and mesosalpinx, which surrounds the ovaries and oviductal infundibulum in mammals. The ovarian bursa is considered as the structure facilitating the transport of ovulated oocytes into the oviduct. Our previous study revealed reduced oocyte pick-up function in the oviduct of lupus-prone MRL/MpJ-Faslpr / lpr mouse, suggesting the possibility of an escape of ovulated oocytes into the peritoneal cavity, despite the presence of an almost complete ovarian bursa in the mouse. In this study, we revealed anatomical and histological characteristics of the ovarian bursa in C57BL/6 N, MRL/MpJ, and MRL/MpJ-Faslpr / lpr mice. All strains had the foramen of ovarian bursa (FOB), with a size of approximately 0.04 to 0.12 cm2 , surrounded by the ligament of ovarian bursa (LOB), which is part of the mesosalpinx. The LOB was partially lined with the cuboidal mesothelial cells and consisted of a thick smooth muscle layer in all strains. In 6-month-old MRL/MpJ-Faslpr / lpr mice, in which the systemic autoimmune abnormality deteriorated and oocyte pick-up function was impaired, the size of the FOB tended to be larger than that of other strains. Additionally, in MRL/MpJ-Faslpr / lpr mice at 6 months of age, there was infiltration by numerous immune cells in the mesosalpinx suspending the isthmus; however, the LOB prevented severe inflammation and showed deposition of collagen fibers. These results not only indicate that the FOB is a common structure within mice, but also imply the physiological function of the LOB and its role in maintaining the microenvironment around the ovary, as well as regulating healthy reproduction.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Teppei Nakamura, Yasuhiro Kon
    Frontiers in immunology 12 665100 - 665100 2021年 
    Mediastinal fat-associated lymphoid clusters (MFALCs) are novel immune clusters that function in the pathogenesis of bleomycin (BLM)-induced pneumonitis in a C57BL/6 mouse model. However, we lack literature on the effects of BLM in an autoimmune disease mouse model (AIDM). In the present study, BLM sulfate (BLM group) or phosphate-buffered saline (PBS group) were intranasally administered in BXSB/MpJ-Yaa (Yaa) AIDM and its wild-type strains (BXSB/MpJ "BXSB") and the histopathology of MFALCs and lungs were examined on days 7 and 21 days. Immunohistochemical analysis was performed to detect lymphatic vessels (LVs), high endothelial venules (HEVs), proliferating, and immune cells. Furthermore, the mRNA expression of Yaa locus genes (TLR7, TLR8, Arhgap6, Msl3, and Tceanc) was detected in the lung tissues. Here, we show a dual effect of BLM on intra-thoracic immune hemostasis among Yaa AIDM and its corresponding wild-type strain (BXSB mice). The BLM group of BXSB mice displayed significantly higher values of lung injury scores (LIS) and size of MFALCs as compared with the corresponding PBS group. However, an opposite effect was detected in Yaa mice. Furthermore, Yaa mice displayed decreased serum autoantibody titers and downregulated expression of TLR7, TLR8, Msl3, and Tceanc in the lungs following BLM administration, especially on day 21. Interestingly, significant positive correlations were detected in both strains between the LIS and the size of MFALCs, LVs, HEVs, and proliferating cells. Conclusively, our findings revealed a crucial function of HEVs on the extent of lung injury and the development of MFALCs in BLM-administered Yaa AIDM and control BXSB mice with dual effects. Moreover, our data suggest that down regulation of Yaa locus genes could contribute as an important attributing factor leading to decrease in the degree of autoimmunity and lung injury in AIDM. Therefore, we suggest that genetic background contributes to BLM diversity among AIDM and the wild-type strain. Targeting some genes or venules could provide novel therapeutic approaches for some autoimmune-associated respiratory diseases via controlling the MFALCs development.
  • Lamiaa Wasef, Atef M. K. Nassar, Yasser S. El-Sayed, Dalia Samak, Ahmed Noreldin, Norhan Elshony, Hamida Saleh, Yaser H. A. Elewa, Shaimaa M. A. Hassan, Abdullah A. Saati, Helal F. Hetta, Gaber El-Saber Batiha, Masakazu Umezawa, Hazem M. Shaheen
    SCIENTIFIC REPORTS 11 1 2021年01月 
    Fipronil (FIP) is a phenylpyrazole insecticide that is commonly used in agricultural and veterinary fields for controlling a wide range of insects, but it is a strong environmentally toxic substance. Exposure to FIP has been reported to increase the hepatic fat accumulation through altered lipid metabolism, which ultimately can contribute to nonalcoholic fatty liver disease (NAFLD) development. The present study aimed to examine the function of cerium oxide nanoparticles (CeNPs) in protecting against hepatotoxicity and lipogenesis induced by FIP. Twenty-eight male albino rats were classified into four groups: FIP (5 mg/kg/day per os), CTR, CeNPs (35 mg/kg/day p.o.), and FIP+CeNPs (5 (FIP)+35 (CeNPs) mg/kg/day p.o.) for 28 consecutive days. Serum lipid profiles, hepatic antioxidant parameters and pathology, and mRNA expression of adipocytokines were assessed. The results revealed that FIP increased cholesterol, height-density lipoprotein, triacylglyceride, low-density lipoprotein (LDL-c), and very-low-density lipoprotein (VLDL-c) concentrations. It also increased nitric oxide (NO) and malondialdehyde (MDA) hepatic levels and reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzyme activities. Additionally, FIP up-regulated the fatty acid-binding protein (FABP), acetyl Co-A carboxylase (ACC1), and peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Immunohistochemically, a strong proliferation of cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba-1), cyclooxygenase-2 (COX-2) reactions in the endothelial cells of the hepatic sinusoids, and increased expression of caspase3 were observed following FIP intoxication. FIP also caused histological changes in hepatic tissue. The CeNPs counteracted the hepatotoxic effect of FIP exposure. So, this study recorded an ameliorative effect of CeNPs against FIP-induced hepatotoxicity.
  • Md Rashedul Islam, Osamu Ichii, Teppei Nakamura, Takao Irie, Md Abdul Masum, Marina Hosotani, Yuki Otani, Yaser Hosny Ali Elewa, Yasuhiro Kon
    The Journal of reproduction and development 66 6 529 - 538 2020年12月22日 
    Cotton rats (Sigmodon hispidus, CRs) are commonly used as animal models in biomedical research. However, the reproductive characteristics and ovarian development in the CRs has not been widely investigated. We have previously shown that female CRs, in particular, show several unique phenotypes associated with the urogenital system, such as chronic kidney disease and pyometra. Our investigation revealed unique morphologies in CR ovaries, particularly in oocytes. Cotton rat ovaries at 6-8 weeks of age were obtained from the Hokkaido Institute of Public Health, and their sections analyzed by light microscopy and transmission electron microscopy. Although the general histology and folliculogenesis of CR ovaries were similar to those of other experimental rodents, multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) were also observed. Although MOFs were found at all stages of follicular development, a greater frequency of MOFs was observed in the primary and secondary stages. However, DNOs tended to be frequently observed in primordial follicles. Almost all MOF oocytes and a few DNOs possessed a clear zona pellucida, expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and Forkhead box protein 2, a representative marker of oocytes and follicular epithelial cells. Thus, our investigations revealed the unique phenotypes of the CR ovary. As MOFs and DNOs are occasionally observed in human patients with infertility, the CR would be a useful animal model to study for gaining a better understanding of folliculogenesis and oocytogenesis, as well as their abnormalities in humans and other animals.
  • Hamida Saleh, Atef M. K. Nassar, Ahmed E. Noreldin, Dalia Samak, Norhan Elshony, Lamiaa Wasef, Yaser H. A. Elewa, Shaimaa M. A. Hassan, Abdullah A. Saati, Helal F. Hetta, Gaber El-Saber Batiha, Masakazu Umezawa, Hazem M. Shaheen, Yasser S. El-Sayed
    MOLECULES 25 15 2020年08月 
    Fipronil (FIP) is an insecticide commonly used in many fields, such as agriculture, veterinary medicine, and public health, and recently it has been proposed as a potential endocrine disrupter. The purpose of this study was to inspect the reproductive impacts of FIP and the possible protective effects of cerium nanoparticles (CeNPs) on male albino rats. Rats received FIP (5 mg/kg bwt; 1/20 LD50), CeNPs (35 mg/kg bwt) and FIP+CeNPs per os daily for 28 days. Serum testosterone levels, testicular oxidative damage, histopathological and immunohistochemical changes were evaluated. FIP provoked testicular oxidative damage as indicated by decreased serum testosterone (approximate to 60%) and superoxide dismutase (approximate to 50%), glutathione peroxidase activity (approximate to 46.67%) and increased malondialdehyde (approximate to 116.67%) and nitric oxide (approximate to 87.5%) levels in testicular tissues. Furthermore, FIP induced edematous changes and degeneration within the seminiferous tubules, hyperplasia, vacuolations, and apoptosis in the epididymides. In addition, FIP exposure upregulated interleukin-1 beta (IL-1 beta), nitric oxide synthase 2 (NOS), caspase-3 (Casp3) and downregulated the Burkitt-cell lymphomas (BCL-2), inhibin B proteins (IBP), and androgen receptor (Ar) mRNA expressions Casp3, nitric oxide synthase (iNOS), ionized calcium-binding adapter molecule 1(IBA1), and IL-1 beta immunoreactions were increased. Also, reduction of proliferating cell nuclear antigen (PCNA), mouse vasa homologue (MVH), and SOX9 protein reactions were reported. Interestingly, CeNPs diminished the harmful impacts of FIP on testicular tissue by decreasing lipid peroxidation, apoptosis and inflammation and increasing the antioxidant activities. The findings reported herein showed that the CeNPs might serve as a supposedly new and efficient protective agent toward reproductive toxicity caused by the FIP insecticide in white male rats.
  • Yuki Otani, Osamu Ichii, Md. Abdul Masum, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Cell and Tissue Research 381 1 203 - 216 2020年04月04日 [査読有り][通常論文]
     
    In mammals, the reproductive system and autoimmunity regulate mutual functions. Importantly, systemic autoimmune diseases are thought to cause male infertility but the underlying pathological mechanism remains unclear. In this study, the morpho-function of the testes in BXSB/MpJ-Yaa mice was analyzed as a representative mouse model for systemic autoimmune diseases to investigate the effect of excessive autoimmunity on spermatogenesis. At 12 and 24 weeks of age, BXSB/MpJ-Yaa mice showed splenomegaly and increased levels of serum autoantibodies, whereas no controls showed a similar autoimmune condition. In histological analysis, the enlarged lumen of the seminiferous tubules accompanied with scarce spermatozoa in the epididymal ducts were observed in some of the BXSB/MpJ-Yaa and BXSB/MpJ mice but not in C57BL/6N mice. Histoplanimetrical analysis revealed significantly increased residual bodies and apoptotic germ cells in the seminiferous tubules in BXSB/MpJ-Yaa testes without apparent inflammation. Notably, in stage XII of the seminiferous epithelial cycles, the apoptotic germ cell number was remarkably increased, showing a significant correlation with the indices of systemic autoimmune disease in BXSB/MpJ-Yaa mice. Furthermore, the Sertoli cell number was reduced at the early disease stage, which likely caused subsequent morphological changes in BXSB/MpJ-Yaa testes. Thus, our histological study revealed the altered morphologies of BXSB/MpJ-Yaa testes, which were not observed in controls and statistical analysis suggested the effects of an autoimmune condition on this phenotype, particularly the apoptosis of meiotic germ cells. BXSB/MpJ-Yaa mice were shown to be an efficient model to study the relationship between systemic autoimmune disease and the local reproductive system.
  • Gaber El-Saber Batiha, Amany Magdy Beshbishy, Muhammad Ikram, Zohair S Mulla, Mohamed E Abd El-Hack, Ayman E Taha, Abdelazeem M Algammal, Yaser Hosny Ali Elewa
    Foods (Basel, Switzerland) 9 3 2020年03月23日 
    Flavonoids are a class of natural substances present in plants, fruits, vegetables, wine, bulbs, bark, stems, roots, and tea. Several attempts are being made to isolate such natural products, which are popular for their health benefits. Flavonoids are now seen as an essential component in a number of cosmetic, pharmaceutical, and medicinal formulations. Quercetin is the major polyphenolic flavonoid found in food products, including berries, apples, cauliflower, tea, cabbage, nuts, and onions that have traditionally been treated as anticancer and antiviral, and used for the treatment of allergic, metabolic, and inflammatory disorders, eye and cardiovascular diseases, and arthritis. Pharmacologically, quercetin has been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia, and Theileria parasites. Additionally, it has shown beneficial effects against Alzheimer's disease (AD), and this activity is due to its inhibitory effect against acetylcholinesterase. It has also been documented to possess antioxidant, antifungal, anti-carcinogenic, hepatoprotective, and cytotoxic activity. Quercetin has been documented to accumulate in the lungs, liver, kidneys, and small intestines, with lower levels seen in the brain, heart, and spleen, and it is extracted through the renal, fecal, and respiratory systems. The current review examines the pharmacokinetics, as well as the toxic and biological activities of quercetin.
  • Hosotani M, Ichii O, Nakamura T, Masum MA, Otani Y, Elewa YHA, Kon Y
    Cell and Tissue Research 380 3 627 - 641 2020年02月 [査読有り][通常論文]
     
    According to our previous reports, impaired oocyte pickup was observed in the oviductal infundibulum of an autoimmune disease (AD) mouse model, suggesting a relationship between female infertility and AD. This study examines the relationship between AD and infundibulum morphofunction by focusing on the epithelial cilia. Healthy MRL/MpJ and AD-prone MRL/MpJ-Faslpr/lpr mice were examined at 3 and 6 months of age, representing early and late disease stages, respectively. Oocyte pickup indices decreased with AD progression indicated by splenomegaly, autoantibody production and increased T cell counts of infundibulum mucosa in MRL/MpJ-Faslpr/lpr mice. Ciliary beating frequency (CBF) and height in the infundibulum were faster and higher in MRL/MpJ-Faslpr/lpr mice than in MRL/MpJ mice at the early AD stages, although the absolute CBF values were lower at the late AD stage. At the late stage, ciliary height did not differ between mouse lines but the morphological index of cilia beating direction indicated randomized patterns in MRL/MpJ-Faslpr/lpr mice. The tracheal mucosa was also examined as a representative example of cilia morphology; its CBF decreased at the late AD stage in MRL/MpJ-Faslpr/lpr; however, there were no AD-related morphological changes. Our results demonstrate altered cilia motility in systemic and reproductive organs, with such morphological changes of the infundibulum likely impairing function, including oocyte pickup.
  • Tsolmon Chuluunbaatar, Osamu Ichii, Teppei Nakamura, Takao Irie, Takashi Namba, Md Rashedul Islam, Yuki Otani, Md Abdul Masum, Yuko Okamatsu-Ogura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in physiology 11 587214 - 587214 2020年 
    Cotton rats are one of the experimental rodents used for testing different infectious and non-infectious diseases, including gastrointestinal tract pathology. However, their intestinal morphological characteristics are still poorly understood. Here, we clarified the anatomical and histological characteristics of the cecum and ascending colon (AC) of young (1-3-month old), adult (4-6-month old), and old (10-12-month old) cotton rats. The large intestine (LI) in cotton rats is composed of the cecum, AC, transverse and descending colons, and rectum, and is similar to that of other mammals. The AC begins with a double or triple spiral loop-like flexure (SLLF) and ends with a coupled horseshoe-like flexure (HSLF). A single longitudinal mucosal fold (SLMF) was found at the beginning of the AC along the mesentery line and developed with age. Furthermore, the SLMF contained several lymphatic nodules (LNs), indicating their role in digestive and immunological functions. Small and large protuberant LNs were found in the cecum and SLLF, respectively, whereas thin and flat LNs were observed in the HSLF and transverse colon, respectively. Regarding sex-related differences, adult females had a significantly longer AC with a higher number of SLLFs compared to males. The SLMF length and LN number were also longer and higher, respectively, in adult females compared to adult males. These are crucial findings, indicating the presence of sex-related differences in the morphology of the LI in cotton rats, and ours is the first study to discover a sex difference in the mammalian LI lining. Our study clarified the unique morphology of the LI in cotton rats, which could serve as the principal model for elucidating species-specific digestive tract functions and gastrointestinal disorders.
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Yuki Otani, Takashi Namba, Yasuhiro Kon
    Frontiers in immunology 11 595672 - 595672 2020年 
    Lupus nephritis (LN) is a common complication in young patients and the most predominant cause of glomerulonephritis. Infiltrating immune cells and presence of immunocomplexes in the kidney are hallmarks of LN, which is closely associated with renal lesions (RLs). However, their regulatory mechanism in the kidney remains unclear, which is valuable for prevention of RL development. Here, we show the development of vasculature-associated lymphoid tissue (VALT) in LN, which is related to renal inflammatory cytokines, indicating that VALT is a unique tertiary lymphoid tissue. Transcriptomic analysis revealed different chemokines and costimulatory molecules for VALT induction and organization. Vascular and perivascular structures showed lymphoid tissue organization through lymphorganogenic chemokine production. Transcriptional profile and intracellular interaction also demonstrated antigen presentation, lymphocyte activity, clonal expansion, follicular, and germinal center activity in VALT. Importantly, VALT size was correlated with infiltrating immune cells in kidney and RLs, indicating its direct correlation with the development of RLs. In addition, dexamethasone administration reduced VALT size. Therefore, inhibition of VALT formation would be a novel therapeutic strategy against LN.
  • Md Rashedul Islam, Osamu Ichii, Teppei Nakamura, Takao Irie, Md Abdul Masum, Yuki Otani, Takashi Namba, Tsolmon Chuluunbaatar, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in physiology 11 601927 - 601927 2020年 
    The reproductive characteristics and ovarian development in cotton rats (Sigmodon hispidus, CRs) are unclear, although CRs are commonly used as animal models in biomedical research. We previously reported that young (6-8 weeks) CRs showed multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) in different stages of follicles. The developmental changes in neonatal CR ovaries were investigated in the present study and were compared with our findings in previous studies of unique phenotypes, particularly in oocytes. CR ovaries at postnatal days (PND) 0, 4, and 7 were obtained from the Hokkaido Institute of Public Health. Samples were analyzed by light and transmission electron microscopy. The general histology and folliculogenesis in CR ovaries were similar to those in other experimental rodents. However, DNOs were observed in all age categories and were frequently observed in primordial follicles, whereas MOFs started to develop from PND4 with greater frequency in primary follicles. Almost all developing follicles expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and forkhead box L2, which are representative markers of oocytes and follicular epithelial cells, respectively. Ki-67 staining demonstrated the proliferative activity of granulosa cells, but not of oocytes, in follicles. Moreover, rapid folliculogenesis of CR due to a small number of apoptotic oocytes was suggested, based on results of the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, confirming the formation of DNOs or MOFs. These findings clarify the development of unique phenotypes of neonatal CR ovaries and support it as a useful model to better understand folliculogenesis and oocytogenesis as well as their abnormalities in humans and other animals.
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in immunology 11 606488 - 606488 2020年 
    While chronic kidney disease is prevalent in adults, obstructive nephropathy (ON) has been reported in both young and old patients. In ON, tubulointerstitial lesions (TILs) have been widely investigated, but glomerular lesions (GLs) have been largely neglected. Here, we show a novel mechanism underlying GL development in ON in young and old mice. TILs develop earlier than GLs owing to infiltration of inflammatory cells in the tubulointerstitium, but GLs develop following the activation of Toll-like receptor 8 (Tlr8) even though the absence of inflammatory cells infiltrating the glomerulus. TLR8 and interleukin 1 beta (IL1β) proteins colocalize with reducing podocyte function markers (PFMs), indicating the activation of TLR8 signaling in injured podocytes. Furthermore, glomerular and serum levels of miR-21, an endogenous ligand for Tlr8, were higher in the ON mouse model than in the sham control. The glomerular expression of Tlr8 positively correlates with miR-21 and the downstream cytokines Il1b and Il6 and negatively correlated with PFMs (Nphs1 and Synpo). We also show the colocalization of TLR8 and IL1β proteins with reducing PFMs in both obstructed and collateral kidney of young and old mice. Furthermore, in vitro study results revealed higher expression of Tlr8 and its downstream cytokines in glomeruli from obstructed kidneys following treatment with miR-21 mimic than in the control. In conclusion, the overexpression of Tlr8 may serve as a plausible mechanism underlying GL development in ON through podocyte injury.
  • Takashi Namba, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 67 4 313 - 317 2019年11月 
    Bones play crucial roles in controlling motility, regulating electrolyte metabolism, and hematopoiesis. We examined age-related changes in bone morphofunction using 3-, 6-, and 13-month-old male C57BL/6N mice. Tibia weight and length generally increased with age. Phosphorus, hemoglobin, and hematocrit measurements in blood, indices of electrolyte metabolism and hematopoiesis, significantly decreased with age. Bone histology showed that osteocyte and osteoblast numbers in the tibia were significantly correlated with decreases in hemoglobin levels and hematocrit values. Furthermore, platelet levels in blood increased with age, negatively correlating with osteoblast and osteoclast number. Thus, we have demonstrated age-related changes in bone morphofunction in healthy mice, particularly quantitative alternations of bone-composing cells and hematopoietic activities.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Yuki Otani, Marina Hosotani, Md Abdul Masum, Rashedul Md Islam, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Histochemistry and cell biology 153 1 27 - 36 2019年10月 [査読有り][通常論文]
     
    The increased prevalence of aging-related chronic kidney disease (CKD) among humans is a problem worldwide. Aged cotton rats (Sigmodon hispidus) are considered novel model animals for studying CKD, especially as the females develop severe tubulointerstitial lesions with anemia. To investigate the renal pathologic features in aged male cotton rats and their characteristic glomerular injuries, the animals were divided into young, adult, old-aged, and advanced-aged groups (1-4, 5-8, 9-12, and 13-17 months, respectively) and pathologically analyzed. Anemia and renal dysfunction, as indicated by hematologic and serologic parameters, were significantly milder in the advanced-aged males than in the old-aged females. The males had increased urinary albumin-to-creatinine ratios from the old-age period, with the advanced-aged males having significantly higher levels than those in the old-aged females and young males. The old-aged females did not show clear glomerular injuries, whereas the advanced-aged males showed membranous lesions characterized by irregular and thickened glomerular basement membranes (GBMs). Characteristically, several large-sized projections from the GBM toward the podocytes were observed by microscopy, and podocytes covering these projections effaced their foot processes. The advanced-aged males showed aging-related IgG immune-complex depositions in the paramesangial regions and along the GBM. Furthermore, the positive reaction for podocin (a podocyte molecule) was granulated along the GBM. Thus, we clarified the albuminuria associated with altered glomerular structures in advanced-aged cotton rats, and that these phenotypes were closely associated with aging. These data help to clarify the aging-related pathogenesis of glomerular injury.
  • Boonyarattanasoonthorn Tussapon, Elewa Yaser, Hosny Ali, Tag-El-Din-Hassan, Hassan T, Morimatsu Masami, Agui Takashi
    INFECTION GENETICS AND EVOLUTION 73 55 - 65 2019年09月 [査読有り][通常論文]
  • Teppei Nakamura, Michael Schubert, Osamu Ichii, Yuji Sunden, Yaser Hosny Ali Elewa, Tomoji Yoshiyasu, Hideki Hattori, Osamu Tatsumi, Yasuhiro Kon, Ken-ichi Nagasaki
    PLOS ONE 14 8 e0221939  2019年08月29日 [査読有り][通常論文]
     
    Developmental anomalies of the thyroid gland lead to congenital malformations such as thyroglossal duct cysts and thyroid dysgenesis. However, the pathogenesis of thyroid dysgenesis remains unclear due to the lack of suitable animal models. This study demonstrated that Slc:Wistar/ST rats frequently developed unilateral thyroid dysgenesis, including hemiagenesis, characterized by the absence of one lobe. In Wistar/ST rats, each thyroid lobe was frequently different in size, and approximately 27% and 20% of the rats presented with hemihypoplasia and hemiagenesis of the thyroid gland, respectively. Dysgenesis was predominant on the left side in both sexes, without sex differences. At a young age, thyroid hemiagenesis did not alter body weight. In rats of both sexes with thyroid hemiagenesis, plasma total triiodothyronine and total triiodothyronine levels remained unchanged while plasma thyroid-stimulating hormone levels were significantly elevated in young rats. The remaining thyroid lobes increased in weight, but the follicular epithelial cells appeared normal in terms of their height and proliferating activities. On the side of thyroid dysgenesis, the parathyroid glands were normally localized and were situated at the same location as the contralateral glands. The ultimobranchial body remnants were localized at the level of the thyroid gland along with the cranial thyroid artery and vein, forming cell clusters or cystic structures and containing calcitonin-positive C-cells. In conclusion, Wistar/ST rats developed unilateral thyroid dysgenesis and may be novel and useful animal models for thyroid hemiagenesis in humans and for morphogenesis of pharyngeal pouch-derived organs.
  • Takashi Suzuki, Osamu Ichii, Teppei Nakamura, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Cell and Tissue Research 379 2 323 - 335 2019年08月 [査読有り][通常論文]
     
    Caspase (CASP) 3 is known as a representative effector CASP of apoptosis and recently as a mediator in inflammatory cell death called pyroptosis. Interestingly, homozygotes of Casp3 knockout (KO) mice with 129-background show complete embryonic lethality; however, some of those with C57BL/6 (B6)-background (B6.129S1-Casp3(tm1Flv)/J) survived at a lower rate (KO, 11%; WT, 22%), developing immune abnormality-associated renal phenotypes. Homozygotes of Casp3 KO mice with B6-background that survived for 8-12 months showed abnormality in the kidney and spleen but not in other organs. Briefly, these Casp3 KO kidneys showed proliferative glomerular lesions characterized by increased cells, matrices, immune complex depositions containing IgA and complement 3 in the mesangial area, podocyte injuries and inflammatory cell infiltrations in the tubulointerstitium. However, severe membranous lesion or renal dysfunction was not observed. Increased expression of inflammation-associated gene sets and inflammatory Casps, including Casp12, was observed in these Casp3 KO kidneys. Moreover, these Casp3 KO mice showed mild splenomegaly compared with WT mice. Thus, the long-surviving Casp3 KO mice with B6-background developed renal lesions with altered immune conditions. CASP3 deficiency and aging factors could affect this phenotype by altering the function and/or development of each cell in the kidney and immune organs.
  • Ai Dantsuka, Osamu Ichii, Annika Hanberg, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Teppei Nakamura, Yasuhiro Kon
    BMC Gastroenterology 19 1 102 - 102 2019年06月 [査読有り][通常論文]
     
    BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail. METHODS: Male and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33 weeks of age. RESULTS: Among the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions. CONCLUSIONS: Disease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors.
  • Takashi Namba, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Experimental Biology and Medicine 244 5 153537021983281 - 153537021983281 2019年04月28日 [査読有り][通常論文]
     
    Bones play crucial roles in motility, electrolyte metabolism, and immunity. Clinical cases have suggested bone dysfunction in several systemic autoimmune diseases. This study exhibited altered bone morpho-functions in BXSB/MpJ-Yaa as a murine autoimmune disease model. During clinical examinations, the serum Ca level was significantly higher in BXSB/MpJ-Yaa than the healthy control BXSB/MpJ at the early stage (two to four months), but that in BXSB/MpJ-Yaa decreased with advancing age. Further, the increase of urinary Ca with nephritis and white blood cells with mild anemia proceeded in BXSB/MpJ-Yaa with advancing age. The thyroid and parathyroid gland morphologies and serum parathormone level did not differ among strains, but the tibia was smaller in BXSB/MpJ-Yaa than in BXSB/MpJ especially during the late stage (six months). Histologically, osteoclasts and osteoblasts showed increased and decreased tendencies, respectively, in BXSB/MpJ-Yaa during the early stage, and osteoclasts and bone area significantly increased and decreased, respectively, compared with BXSB/MpJ at later stages. The bone morphological indices were affected by the expression of BXSB/MpJ-Yaa mutation genes and inflammatory genes in BXSB/MpJ-Yaa. In conclusion, systemic autoimmune diseases in BXSB/MpJ-Yaa are associated with the morpho-functional abnormalities of bones, calcium dynamics, and hematopoiesis, and each factor contributes to forming the phenotypes in this disease. Impact statement Bone disease, such as osteoporosis and rheumatoid arthritis, increases because of the progression of an aging society. Autoimmune disease are important and predisposing factors for the pathogenesis of the bone disease; however, the pathological mechanism is unclear. We have demonstrated that systemic autoimmune disease in BXSB/MpJ-Yaa is closely associated with the morpho-functional abnormalities of bones including bone marrow and has complicated pathology. The abnormalities are characterized by altered regulations of serum calcium, anemia tendency, and hematopoiesis with increased WBCs and decreased PLs, short length and low mass of long bones, imbalance in the populations of osteoclasts and osteoblasts, and increased expression of candidate genes for causing and/or exacerbating their phenotypes. Therefore, BXSB/MpJ-Yaa serves as a model to elucidate bone phenotypes in systemic autoimmune disease that would be affected by the factors in the bone as well as the other immune and/or mineral metabolism organs both in human and experimental medicine.
  • Hosotani M, Ichii O, Nakamura T, Masum MA, Otani Y, Otsuka-Kanazawa S, Elewa YHA, Kon Y
    Reproduction, fertility, and development 31 4 760 - 773 2019年04月 [査読有り][通常論文]
  • Yaser H A Elewa, Amany Abdel-Rahman Mohamed, Azza A A Galal, Nesma I El-Naseery, Osamu Ichii, Yasuhiro Kon
    Ecotoxicology and environmental safety 169 696 - 706 2019年03月 [査読有り][通常論文]
     
    Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
  • M A Masum, O Ichii, Y H A ELewa, Y Kon
    Lupus 28 3 324 - 333 2019年03月 [査読有り][通常論文]
     
    BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.
  • Teppei NAKAMURA, Miyuki NORIMURA, Kanako SUMI, Osamu ICHII, Yaser Hosny Ali ELEWA, Yasuhiro KON, Osamu TATSUMI, Hideki HATTORI, Tomoji YOSHIYASU, Ken-ichi NAGASAKI
    Experimental Animals 68 4 465 - 470 2019年 [査読有り][通常論文]
     
    The formation of the caudal vena cava is a complex process involving development, regression, and anastomosis. In mammals, the normal caudal vena cava runs to the right side of the abdominal aorta, while duplication of the caudal vena cava has been identified as a congenital abnormality in both companion animals and humans. The present study demonstrates that Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava. The prevalence was 30% and 24% for males and females, respectively, with no sex-related differences. In accordance with Saad et al. (2012)'s criteria, duplicated caudal vena cava were classified into two distinct variations. The dominant variation was a complete duplication without iliac anastomosis where the left caudal vena cava continued from the left common iliac vein and joined the left renal vein; the left renal vein ran to the right to join the right caudal vena cava. The alternative variation was an incomplete duplication where the left caudal vena cava joined the right infrarenal caudal vena cava at a more cranial point than in normal cases; the renal segment was unchanged. Iliac anastomosis was not found in any cases. Duplicated caudal vena cava neither affected the body weight nor the kidney weight. In conclusion, Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava in the absence of iliac anastomosis and appear to be a novel and useful animal model for duplicated caudal vena cava in animals and humans.
  • Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y
    Frontiers in veterinary science 6 2  2019年 [査読有り][通常論文]
  • Md. Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon
    Autoimmunity 1 - 13 2018年12月 [査読有り][通常論文]
  • Yaser Hosny Ali Elewa, Tatsuya Mizoguchi, Osamu Ichii, Teppei Nakamura, Yasuhiro Kon
    PLOS ONE 13 12 e0201330  2018年12月 [査読有り][通常論文]
  • Nesma Ibraheim El-Naseery, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 220 9 - 20 2018年11月 [査読無し][通常論文]
     
    The current study was conducted on a menopause rat model induced by ovariectomy to assess the histological and immunohistochemical alterations in the parotid glands and to verify the efficiency of human umbilical cord derived-mesenchymal stromal cell (hUCB-MSCs) in treating this condition. Eighteen adult female rats were equally divided into three groups: sham-operated (SHAM), ovariectomized (OVX) and OVX injected with hUCB-MSCs (OVX+hUCB-MSCs). At 3months post-ovariectomy, the salivary flow rate and size of the parotid glands were measured. The parotid glands were histologically investigated via H&E stained sections. Furthermore, immunohistochemical analysis for human CD105, human CD34, proliferating cell nuclear antigen (PCNA), single strand DNA (ssDNA), caspase 3, aquaporin (AQP)1, α-smooth muscle actin (α-SMA) and mouse CD34 were performed. The OVX group showed interstitial hemorrhage, dispersed acini and intracytoplasmic vacuoles in the acinar cells. Furthermore, immunohistochemical staining revealed a significant decrement in the number of ssDNA positive apoptotic cells, but a significant increment of PCNA positive proliferating cells, AQP1 positive blood capillaries, α-SMA positive myoepithelial cells and endogenous CD34 positive hematopoietic progenitor cells in the OVX+hUCB-MSCs group as compared with the OVX group. These findings suggest a potential regenerative therapy of MSCs to injured parotid gland structures. However, further investigations are required to illustrate the mechanism of hUCB-MSCs mediated parotid gland regeneration.
  • Teppei Nakamura, Yaser Hosny Ali Elewa, Osamu Ichii, Marina Hosotani, Wael A M Ghonimi, Osamu Tatsumi, Ken-Ichi Nagasaki, Yasuhiro Kon
    The Journal of veterinary medical science 80 9 1368 - 1372 2018年09月13日 [査読無し][通常論文]
     
    Parafollicular cells (C-cells) exist within the thyroid glands and display different distributions within the glands among mammalian species. In the one-humped camel (Camelus dromedarius), localization of the C-cells remains under debate. We herein investigated appearance of C-cells and the remnants of the ultimobranchial body, origin of C-cells, in the thyroid glands of one-humped camels. Macroscopically, a white mass was present at one-third the length from the cranial end of the thyroid glands where the cranial thyroid artery entered. In addition, large fossae were frequently found adjacent to the white mass. Histologically, the mass was mainly composed of connective tissues, thyroid follicles, and two types of cell clusters: one was composed of cells with clear cytoplasm and the other was composed of non-keratinized epidermoid cells. The mass and the fossae contained p63-positive cells, indicating that they consisted of ultimobranchial body remnants. Calcitonin was expressed in cells with clear cytoplasm, which were localized just beneath the fossae and in the cell clusters of the white mass. C-cells also resided in both subfollicular and interfollicular spaces adjacent to the white mass, but gradually decreased toward the periphery. C-cells tended to display round shapes in the ultimobranchial body remnants and subfollicular spaces, and spindle shapes in interfollicular spaces. In conclusion, we demonstrated that the ultimobranchial body remnants were limited to the region around the entrance of cranial thyroid artery and vein, and C-cells were mainly concentrated within and around the ultimobranchial body remnants.
  • Osamu Ichii, Teppei Nakamura, Taro Horino, Akira Yabuki, Yaser H A Elewa, Yasuhiro Kon
    The American journal of pathology 188 9 2120 - 2138 2018年09月 [査読無し][通常論文]
     
    The distal tubule (DT) helps regulate blood pressure and electrolytes. We describe a novel, autosomal recessive, morphofunctional DT abnormality in inbred mice evident as columnar alternations and age-related cystic changes. This abnormality developed in both sexes of DBA/2Cr. Similar phenotypes were observed in A/J, C3H/He, DBA/1J, and FVB/N strains, but not in AKR/N, BALB/c, or C57BL/6N strains. In DBA/2Cr, abnormal DT localized to straight and convoluted segments and showed IL-36α DT injury marker expression. However, DT epithelial proliferation, examined by bromodeoxyuridine incorporation, was not remarkably altered with the progression of abnormality. Abnormal DT epithelial cells in DBA/2Cr displayed elongated primary cilia, loose intercellular adhesions, and numerous vesicles with altered localization of CD9, Na+/K+ATPase, and E-cadherin, indicating altered cell function, adhesion, and polarity. DBA/2Cr-type D12Mit182-D12Mit83 was identified as a candidate locus designated DBA/2 renal cyst (drecy). Within drecy, the gene regulated by estrogen in breast cancer protein (Greb1) transcript variant 2 was significantly up-regulated in DBA/2Cr kidney versus C57BL/6N. Greb1 localized to DT cytoplasm in C57BL/6 and to cytoplasm and nucleus in DBA/2Cr. Greb1-overexpressing M-1 kidney cells showed an altered epithelial-mesenchyme phenotype. B6.D2-(D12Mit182-D12Mit83) congenic mice carrying drecy did not show DT abnormalities, whereas DBA/2Cr × B6.D2-(D12Mit182-D12Mit83) mice did. Identification of this novel DT abnormality regulated by a DBA/2Cr mouse chromosome 12-derived locus and additional genetic factors improve the understanding of DT pathogenesis.
  • Samah R. Khalil, Hesham A. Khalifa, Sabry M. Abdel-Motal, Hesham H. Mohammed, Yaser H.A. Elewa, Hend Atta Mahmoud
    Ecotoxicology and Environmental Safety 157 255 - 265 2018年08月15日 [査読無し][通常論文]
     
    Heavy metals are well known as environmental pollutants with hazardous impacts on human and animal health because of their wide industrial usage. In the present study, the role of Spirulina platensis in reversing the oxidative stress-mediated brain injury elicited by lead acetate exposure was evaluated. In order to accomplish this aim, rats were orally administered with 300 mg/kg bw Spirulina for 15 d, before and simultaneously with an intraperitoneal injection of 50 mg/kg bw lead acetate [6 injections through the two weeks]. As a result, the co-administration of Spirulina with lead acetate reversed the most impaired open field behavioral indices however, this did not happen for swimming performance, inclined plane, and grip strength tests. In addition, it was observed that Spirulina diminished the lead content that accumulated in both the blood and the brain tissue of the exposed rats, and reduced the elevated levels of oxidative damage indices, and brain proinflammatory markers. Also, because of the Spirulina administration, the levels of the depleted biomarkers of antioxidant status and interleukin–10 in the lead-exposed rats were improved. Moreover, Spirulina protected the brain tissue (cerebrum and cerebellum) against the changes elicited by lead exposure, and also decreased the reactivity of HSP70 and Caspase–3 in both cerebrum and cerebellum tissues. Collectively, our findings demonstrate that Spirulina has a potential use as a food supplement in the regions highly polluted with heavy metals.
  • Nakamura T, Ichii O, Irie T, Kouguchi H, Sotozaki K, Chihara M, Sunden Y, Nagasaki KI, Tatsumi O, Elewa YHA, Kon Y
    Cell Tissue Res 375 2 483 - 492 2018年08月 [査読有り][通常論文]
     
    Obesity induces metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases and has become a global health concern. Recent studies imply that fat accumulation in nonadipose tissue correlates with metabolic disorders. However, there are no suitable animal models to evaluate this phenomenon. This study investigated the characteristics of metabolic disorders found in cotton rat (Sigmodon hispidus). Blood biochemical examinations revealed that cotton rats, predominantly males, developed hyperinsulinemia, hyperglycemia, and dyslipidemia when fed a normal diet. The islets increased in size through -cell hyperplasia, which was associated with serum insulin level in both sexes, strongly indicating insulin resistance. In male cotton rats, oxidative stress was observed in cells, and macrophage infiltration into the visceral white adipose tissue was reported, both of which were associated with serum insulin level without visceral obesity. In contrast, female cotton rats developed hyperinsulinemia without histopathological changes that were reported in males. Adipocytes were found to be accumulated in the pancreas but not in the liver of both sexes during aging. Pancreatic fat accumulation was associated with the serum insulin level only in females. Taken together, cotton rats developed metabolic disorders associated with visceral fat inflammation in the absence of obesity. In addition, pancreatic ectopic fat may also be related to the early stages of these conditions. Thus, the cotton rat may serve as a novel and useful model for metabolic disorders characterized by visceral adipose inflammation and ectopic fat accumulation in the pancreas without obesity.
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon
    Scientific reports 8 1 10276 - 10276 2018年07月06日 [査読無し][通常論文]
     
    This study evaluated endothelial cells and podocytes, both being primary components of the glomerular filtration barrier, in the progression of membranoproliferative glomerulonephritis (MPGN) using modified scanning electron microscopy (mSEM) analysis. BXSB/MpJ-Yaa model mice exhibited autoimmune-mediated MPGN characterised by elevated serum autoantibody levels, albuminuria, renal dysfunctional parameters, and decreased glomerular endothelial fenestrations (EF) and podocyte foot process (PFP) effacement with immune cell infiltration. Similar to transmission electron microscopy, mSEM revealed a series of pathological changes in basement membrane and densities of EF and PFP in BXSB/MpJ-Yaa compared with control BXSB/MpJ at different stages. Further, immunopositive area of endothelial marker (CD34), podocyte functional molecules (Nephrin, Podocin, Synaptopodin, and Wilms' tumour 1 (WT1)), and vascular endothelial growth factor A (VEGF A) significantly decreased in the glomerulus of BXSB/MpJ-Yaa compared with BXSB at final stage. The indices of glomerular endothelial injuries (EF density and immunopositive area of CD34 and VEGF A) and podocyte injuries (PEP density and immunopositive area of podocyte functional molecules) were also significantly correlated with each other and with indices of autoimmune disease and renal dysfunction. Thus, our results elucidated the pathological crosstalk between endothelial cells and podocytes in MPGN progression and the usefulness of mSEM for glomerular pathological analysis.
  • Teppei Nakamura, Osamu Ichii, Takao Irie, Tatsuya Mizoguchi, Akio Shinohara, Hirokazu Kouguchi, Yuji Sunden, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Chihiro Koshimoto, Ken-Ichi Nagasaki, Yasuhiro Kon
    Histology and Histopathology 33 6 555 - 565 2018年06月01日 [査読無し][通常論文]
     
    Pharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands they were lined with columnar ciliated epithelium and a few goblet cells, but had no C-cells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.
  • Ahmed E. Noreldin, Yaser Hosny Ali Elewa, Yasuhiro Kon, Katsuhiko Warita, Yoshinao Z. Hosaka
    Acta Histochemica 120 4 323 - 328 2018年05月01日 [査読無し][通常論文]
     
    Osteoblast activating peptide (OBAP) is a newly discovered peptide detected in the rat stomach, which has a major role in osteogenesis. Recently, we revealed its localization in the parietal cells of the rat stomach. There have been no data regarding OBAP expression in the kidney, despite its role in calcium reabsorption in renal tubules. The current study aimed to inspect the expression of OBAP in the kidney of twelve 10-week-old male C3H/HeNJc1 mice using immunohistochemistry, and immunoelectron microscopic localization. The immunohistochemical investigation revealed an OBAP positive reaction mainly in the medulla, which was stronger than the cortex of the kidney and was concentrated in the distal convoluted tubules (DCT), connecting tubules (CT), and the thick limbs of the loop of Henle (HL). Moreover, we clarified that the OBAP was co-distributed with ghrelin and calbindin (markers of the DCT). Interestingly, immunoelectron microscopy demonstrated that OBAP was concentrated in the mitochondrial inner membrane of the DCT and CT. Based on these results, it was concluded that the mitochondria of the DCT, CT, and HL of the mice kidney generate OBAP. Furthermore, our results suggest that OBAP might have a role in the regulation of calcium reabsorption by the renal tubule however, further investigations are required to clarify this potential role.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Kozue Sotozaki, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Experimental biology and medicine (Maywood, N.J.) 243 5 418 - 427 2018年03月 [査読無し][通常論文]
     
    Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats ( Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Kensuke Takada, Teppei Nakamura, Md. Abdul Masum, Yasuhiro Kon
    Frontiers in Immunology 9 271 2018年02月15日 [査読無し][通常論文]
     
    Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson's trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.
  • Teppei Nakamura, Masataka Chihara, Osamu Ichii, Saori Otsuka-Kanazawa, Ken-Ichi Nagasaki, Yaser Hosny Ali Elewa, Osamu Tatsumi, Yasuhiro Kon
    PloS one 13 4 e0196364  2018年 [査読無し][通常論文]
     
    MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems.
  • Protective Effects of Miswak (Salvadora persica) against Experimentally Induced Gastric Ulcers in Rats. Oxidative Medicine and Cellular Longevity
    エレワ ヤセル
    Oxidative Medicine and Cellular Longevity. 2018 6703296 2018年 [査読無し][通常論文]
  • Samah R. Khalil, Walaa M. Elhady, Yaser H.A. Elewa, Noura E. Abd El-Hameed, Sozan A. Ali
    Biomedicine and Pharmacotherapy 97 1259 - 1268 2018年01月01日 [査読無し][通常論文]
     
    Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days). As a result, co-administration of SP with LA reduced the amount of lead that accumulated in both blood and liver tissue of the exposed rats and minimized the increased levels of lipid peroxidation, protein oxidation, DNA oxidative damage, and liver enzyme endpoints. In addition, because of SP administration, the levels of depleted biomarkers of antioxidant status and total antioxidant capacity in LA-exposed rats improved. Moreover, SP protected the liver tissue against the changes caused by LA exposure and also decreased the reactivity of HSP70 in the cytoplasm of hepatocytes. Collectively, our data suggest that SP has a potential use as a food supplement in the regions highly polluted with heavy metals such as lead.
  • Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y
    Frontiers in veterinary science 5 289  2018年 [査読有り][通常論文]
  • M. Hosotani, O. Ichii, T. Nakamura, S. O. Kanazawa, Y. Hosny Ali Elewa, Y. Kon
    LUPUS 27 1 82 - 94 2018年01月 [査読有り][通常論文]
     
    Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas(lpr/lpr) mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of oocyte cumulus complexes found in the ampulla was macroscopically counted, and that of ovulated oocytes was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas(lpr/lpr) mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas(lpr/lpr) mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas(lpr/lpr) mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.
  • Ichii O, Kimura J, Okamura T, Horino T, Nakamura T, Sasaki H, Elewa YHA, Kon Y
    Frontiers in Immunology 8 1346 2017年10月 [査読無し][通常論文]
     
    IL-36 alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36 alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36 alpha in kidney injury. IL-36 alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36 alpha localized to dilated DTs. IL-36 alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36 alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36 alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36 alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36 alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36 alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36 alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36 alpha may be a novel kidney injury marker useful for evaluating DT damages.
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yasuhiro Kon
    BMC NEPHROLOGY 18 280 2017年09月 [査読無し][通常論文]
     
    Background: The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Methods: Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Results: Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34(+) glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34(+) tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34(+) glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. Conclusions: From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.
  • Teppei Nakamura, Naoya Karakida, Ai Dantsuka, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Ken-ichi Nagasaki, Hideki Hattori, Tomoji Yoshiyasu
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 7 1230 - 1235 2017年07月 [査読有り][通常論文]
     
    Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.
  • Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    AUTOIMMUNITY 50 2 114 - 124 2017年03月 [査読有り][通常論文]
     
    Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively. Histopathologically, papillary malformations of the transitional epithelium in the pelvic-ureteric junction seemed to constrict the ureter luminal entrance. Characteristically, eosinophilic crystals were observed in the lumen of diseased ureters. These ureters were surrounded by infiltrating cells mainly composed of numerous CD3(+)T-cells and B220(+)B-cells. Furthermore, several Iba-1(+)macrophages, Gr-1(+)granulocytes, mast cells and chitinase 3-like 3/Ym1 (an important inflammatory lectin)-positive cells were detected. Eosinophils also accumulated to these lesions in diseased ureters. Some B6.MRL-(D11Mit21-D11Mit212) mice had duplicated ureters. We determined>100 single nucleotide variants between C57BL/6N- and MRL/MpJ-type chromosome 11 congenic regions, which were associated with nonsynonymous substitution, frameshift or stopgain of coding proteins. In conclusion, B6.MRL-(D11Mit21-D11Mit212) mice spontaneously developed hydronephrosis due to obstructive uropathy with inflammation. Thus, this mouse line would be useful for molecular pathological analysis of obstructive uropathy in experimental medicine.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    AUTOIMMUNITY 50 5 306 - 316 2017年 [査読有り][通常論文]
     
    MRL/MpJ-Fas(lpr) (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.
  • Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY 37 4-5 153 - 164 2016年10月 [査読有り][通常論文]
     
    Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd (mdx) (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.
  • Truc Quynh Thai, Huy Bang Nguyen, Sei Saitoh, Bao Wu, Yurika Saitoh, Satoshi Shimo, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon, Takashi Takaki, Kensuke Joh, Nobuhiko Ohno
    MEDICAL MOLECULAR MORPHOLOGY 49 3 154 - 162 2016年09月 [査読有り][通常論文]
     
    Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three-dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three-dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Daisuke Nakamura, Saori Nakamura, Shinobu Sato, Keisuke Yokoyama, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    HISTOCHEMISTRY AND CELL BIOLOGY 146 3 351 - 362 2016年09月 [査読有り][通常論文]
     
    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.
  • Sawa Onouchi, Osamu Ichii, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 365 2 367 - 379 2016年08月 [査読有り][通常論文]
     
    Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.
  • Daichi Shiozuru, Osamu Ichii, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 31 2 189 - 204 2016年02月 [査読有り][通常論文]
     
    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    IMMUNOLOGY 147 1 30 - 40 2016年01月 [査読有り][通常論文]
     
    We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.
  • M. Chihara, T. Nakamura, S. Otsuka-Kanazawa, O. Ichii, Y. H. A. Elewa, Y. Kon
    ANDROLOGY 3 5 991 - 999 2015年09月 [査読有り][通常論文]
     
    MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To evaluate the functions of these loci in detail, we examined the histopathological changes resulting from experimental cryptorchidism or transient scrotal heat stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1, B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice showed the highest heat resistance, indicating that the genetic interactions between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for maintaining spermatogenesis under continuous testicular hyperthermia. In contrast, immediately after SHS induction, germ cell loss via apoptosis was inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice. However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after SHS induction. Furthermore, testicular calcification owing to long-term damage by SHS induction was inhibited in all congenic strains in comparison with that in C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted independently to facilitate the recovery of heat-induced testicular damage by inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from heat stress damage. On the basis of these results, we concluded that MRL/MpJ-derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular heat sensitivity depending on the various heat stresses.
  • Amany Abdel-Rahman Mohamed, Azza A. A. Galal, Yaser H. A. Elewa
    ACTA HISTOCHEMICA 117 7 649 - 658 2015年 [査読有り][通常論文]
     
    This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure. (C) 2015 Elsevier GmbH. All rights reserved.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 357 3 731 - 741 2014年09月 [査読有り][通常論文]
     
    The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
  • Y. H. A. Elewa, O. Ichii, S. Otsuka, Y. Hashimoto, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 43 4 265 - 272 2014年08月 [査読有り][通常論文]
     
    Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.
  • Lee SH, Ichii O, Otsuka S, Elewa YH, Namiki Y, Hashimoto Y, Kon Y
    Journal of anatomy 219 6 743 - 755 2011年12月 [査読有り][通常論文]
     
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    Veterinary Research Communications 34 8 727  2010年12月 [査読有り][通常論文]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abu Al Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    VETERINARY RESEARCH COMMUNICATIONS 34 6 557 - 567 2010年08月 [査読有り][通常論文]
     
    Previously, the distribution of myoepithelial cells (mecs) in the salivary glands was studied by both immunohistochemistry, and transmission electron microscopy; however, little was elucidated concerning their morphological features, especially in goats. This study was performed to investigate the correlation between the cytoarchitecture of the mecs in goat major salivary glands (parotid, mandibular, and sublingual glands) and the nature of the saliva secretion. The cytoarchitectural features of the mecs were examined by scanning and transmission electron microscopy as well as immunohistochemically. The secretory endpieces in the parotid gland are of the pure serous type, but in both the mandibular and sublingual glands they are of the mixed type. In all studied glands, the intercalated ducts were covered by mecs which, unlike the large stellate cells that surrounded the secretory endpieces, were spindle-shaped with few cytoplasmic processes. Interestingly, the mecs were found to bulge on the basal surfaces of the serous acini and intercalated ducts in all glands and to be in close contact to the seromucous tubules surface in the mandibular and sublingual glands forming a continuous network around it. In conclusion, the differences in the degree of development of the mecs as well as the number of their cytoplasmic processes may be correlated with the nature of the secretion and the number of the secretory granules. Thus these observations may have some relevance in the diagnosis of atrophy and pathogenic conditions of these glands.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shinhyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 58 2 121 - 135 2010年08月 [査読有り][通常論文]
     
    The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.
  • Sameh Magdeldin, Yaser Elewa, Takako Ikeda, Junko Ikei, Ying Zhang, Bo Xu, Masaaki Nameta, Hidehiko Fujinaka, Yutaka Yoshida, Eishin Yaoita, Tadashi Yamamoto
    GENERAL PHYSIOLOGY AND BIOPHYSICS 28 3 266 - 275 2009年09月 [査読無し][通常論文]
     
    In order to investigate the effects of dietary supplementation rich in omega 3 and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted for I month, food consumption of ND and n-3 PUFA were similar while it decreased in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA while increased in n-6 PUFA fed mice comparing to control group. On the other hand, there was no difference between treatments in HDL and glucose levels. Expression of leptin (ob) gene transcripts in epididymal fat were significantly elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic ob receptor A (obRa) mRNA did not changed in response to diet regimes. Transmission and scanning electron microscopy showed different degrees in fatty changes in the liver of both PUFA groups including lipid droplet infiltration and Ito cells with over accumulated lipids. In conclusion, under PUFA dietary supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups and/or different endocrine involvement. Moreover, the coincidently structural changes observed in liver of this group direct us to call for further studies to investigate the anti-obesity effect and safety of these PUFA under high supplementation condition.

MISC

  • “Lymphoid tissues appearing in the urinary tract of animals (Urinary tract-associated lymphoid tissue, UTALT)”.
    O. Ichii, T. Nakamura, R. Ono, T. Horino, Y. H. A. Elewa, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “Morphological characteristics of the dromedary thyroid gland - and distribution of C cells”.
    T. Nakamura, O. Ichii, Y. H. A. Elewa, W. A. M. Ghonimi, K. Nagasaki, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “New findings of kidney disease - Kidney lesions found in Casp3 deficient mice”.
    T. Suzuki, O. Ichii, T. Nakamura, Y. H. A. Elewa, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “Morphological and functional changes observed in bone of autoimmune disease model”.
    T. Namba, O. Ichii, Y. H. A. Elewa, T. Nakamura, J. Kimura, Y. Otani, Md. A. Masum, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • Investigation for meiotic apoptosis of spermatocyte in autoimmune disease model mouse.
    エレワ ヤセル The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • Effect of systemic autoimmune abnormality in MRL/MpJ-Faslpr/lpr mice on the ciliary function.
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan 161th 2018年09月 [査読無し][通常論文]
  • “Mediastinal fat-associated lymphoid cluster and lung asthma development in papain induced lung asthma mice model
    Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon The 64th annual meeting of the Japanese the Anatomical Society (Oral Presentation). Aomori, Japan. 64th 2018年09月 [査読無し][通常論文]
  • “Overexpression of Toll-like receptor 9 correlates with podocyte injury found in murine autoimmune glomerulonephritis.
    エレワ ヤセル The 6th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2018. Sapporo, Japan. 161回 294 -294 2018年08月 [査読無し][通常論文]
  • “Glomerular lesions seen in male cotton rats (Sigmodon hispidus)”
    T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Sunden, Masum, M. A., Y, Y. H. A. Elewa, Y. Kon The 11th Annual Meeting of the Japanese Society of Veterinary Renal Urology. 11th 2018年08月 [査読無し][通常論文]
  • Local CD34-positive capillary decreased with the progression of lesion in respective area of kidney in mice.
    Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 17th International Conference on Nephrology and Urology. London, UK. 13th March 2018. 17th 2018年03月 [査読無し][通常論文]
  • “Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice.”
    Y. H. A. Elewa, O. Ichii, S, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Kuching, Sarawak, Malaysia. 6th P-18 2017年12月 [査読無し][通常論文]
  • BXSB/MpJ-Yaa MICE SHOW THE INCREASE OF APOPTOTIC SPERMATOCYTES IN STAGE Ⅻ SEMINIFEROUS TUBULES.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Kuching, Sarawak, Malaysia. October 12-13, 2017. 6th 2017年10月 [査読無し][通常論文]
  • ABNOLMALITY OF OVULATION AND OOCYTE-PICK-UP IN MRL/MpJ-Faslpr/lpr MICE.
    Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, S. Otsuka-Kanazawa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 6th 2017年10月 [査読無し][通常論文]
  • IL-1F6/IL-36α SIGNALING REGULATES RENAL INFLAMMATION.
    O. Ichii, J. Kimura, T. Okamura, T. Horino, T. Nakamura, H. Sasaki, H. A. Elewa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 6th 2017年10月 [査読無し][通常論文]
  • FAT ACCUMULATION CORRELATES WITH DIABETES MELLITUS IN MALE COTTON RATS (SIGMODON HISPIDUS).
    T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Y. Sunden, K.-I. Nagasaki, Y. H. A. Elewa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 2017年10月 [査読無し][通常論文]
  • “Mechanism and abnormality of ovulation and picking up of mammalian oocytes-Immune factors affecting the molecular morphology of the oviduct.”
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan. 5th 2017年09月 [査読無し][通常論文]
  • “Loss of endothelial fenestration correlates with podocyte injury in the mouse model of membranoproliferative glomerulonephritis.”
    Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan. 5th 2017年09月 [査読無し][通常論文]
  • “The unique phenotype in ovulation and corpus luteum formation in MRL/MpJ mouse.”
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 160th Meeting of the Japanese Society of Veterinary Sciences, September 13-16, 2017. Kagoshima, Japan. 160th 2017年09月 [査読無し][通常論文]
  • Histopathological features observed in the testis of autoimmune-prone BXSB/MpJ-Yaa mice.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health. 5th 2017年09月 [査読無し][通常論文]
  • Apoptosis of spermatocytes seen in BXSB / MpJ-Yaa mice - association with autoimmune abnormality.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 160th Meeting of the Japanese Society of Veterinary Sciences. 160th 2017年09月 [査読無し][通常論文]
  • “Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice”.
    Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon The 63th annual meeting of the Japanese the Anatomical Society. 63th 2017年09月 [査読無し][通常論文]
  • 市居修, 堀野太郎, 大田寛, 鈴木崇史, 中村鉄平, 中村鉄平, ELEWA Yaser, Hosny Ali, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 310 -310 2017年08月30日 [査読無し][通常論文]
  • 大谷祐紀, 市居修, ELEWA Yaser, Hosny Ali, 木村純平, MASUM Md. Abdul, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 312 -312 2017年08月30日 [査読無し][通常論文]
  • 中村鉄平, 中村鉄平, 市居修, 入江隆夫, 篠原明雄, 孝口裕一, 越本知大, 長崎健一, 寸田祐嗣, ELEWA Yaser Hosny, 辰巳治, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 309 -309 2017年08月30日 [査読無し][通常論文]
  • 細谷実里奈, 市居修, ELEWA Yaser, Hosny Ali, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 313 -313 2017年08月30日 [査読無し][通常論文]
  • “Pathological correlations between endothelial cells and podocytes in autoimmune-related injury of the mouse glomerulus.”
    Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 160th Meeting of the Japanese Society of Veterinary Sciences, September 13-16, 2017. Kagoshima, Japan. 160回 310 -310 2017年08月 [査読無し][通常論文]
  • Elucidation of mammalian reproductive - autoimmune coupling mechanism and analysis of pathological conditions caused by its failure.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura The 35th Scientific annual joint meeting of Hokkaido Veterinary Anatomy 35th 2017年08月 [査読無し][通常論文]
  • “CD34-positive capillary decreased with the progression of kidney disease in mouse models.”
    Md. A. Masum, Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon The 159th Meeting of the Japanese Society of Veterinary Sciences, September 6-8, 2016. Kanagawa, Japan. 159th 2016年09月 [査読無し][通常論文]
  • “Histopathological correlations between the mediastinal fat associated lymphoid clusters and bleomycin-induced pneumonitis in mice.”
    Y. H. A. Elewa, Md. A. Masum, T. Nakamura, O. Ichii, Y. Kon The 159th Meeting of the Japanese Society of Veterinary Sciences. September 6-8, 2016. Kanagawa, Japan. 159回 302 -302 2016年08月 [査読無し][通常論文]
  • “Histopathological evaluation of the possible protective role of royal jelly and cod liver oil against reproductive toxicity of tartrazine in adult male albino rats.”
    Y. H. A. Elewa, A. Moustafa, A.A. Mohamed, A. A.A. Galal, O. Ichii, Y. Kon The 8th international Toxicology symposium in Africa. Cairo, Egypt. 8th 2016年08月 [査読無し][通常論文]
  • Ali Elewa Yaser Hosny, Masum Md.Abdul, 中村 鉄平, 市居 修, 昆 泰寛 日本獣医学会学術集会講演要旨集 159回 302 -302 2016年08月 [査読無し][通常論文]
  • Masum Md.Abdul, Yaser Hosny Ali Elewa, 中村 鉄平, 市居 修, 昆 泰寛 日本獣医学会学術集会講演要旨集 159回 308 -308 2016年08月 [査読無し][通常論文]
  • 細谷 実里奈, 中村 鉄平, Hosny Ali Elewa Yaser, 市居 修, 昆 泰寛 日本獣医学会学術集会講演要旨集 159回 314 -314 2016年08月 [査読無し][通常論文]
  • “Sex-related difference of the mediastinal fat associated lymphoid clusters in MRL/MpJ-Faslpr autoimmune disease model mice.”
    Y. H. A. Elewa, O. Ichii, Y. Kon The 11th Scientific Vet. Med. (second international) conference. El-Ain-El Sokhna, Egypt. 11th 2016年03月 [査読無し][通常論文]
  • THAI Truc Quynh, NGUYEN Huy Bang, SAITOH Sei, SAITOH Yurika, SHIMO Satoshi, ELEWA Yaser, Hosny Ali, ICHII Osamu, KON Yasuhiro, TAKAKI Takashi, JOH Kensuke, OHNO Nobuhiko 日本顕微鏡学会関東支部講演会予稿集 40th 26 2016年 [査読無し][通常論文]
  • A Novel Mouse Mediastinal Fat-associated Lymphoid Tissue and Its Relationship with Autoimmune Disease
    Y. H. A. Elewa, O. Ichii, S. Otsuka-Kanazaw, Y. Kon The 5th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Bali, Indonesia 5th 2015年02月 [査読無し][通常論文]
  • マウス縦隔の脂肪関連リンパ球集積の性状解析(Characterization of mouse mediastinal fat-associated lymphoid clusters)
    Elewa Yaser, Hosny Ali, 市居 修, 大塚 沙織, 昆 泰寛 日本獣医学会学術集会講演要旨集 157回 330 -330 2014年08月 [査読無し][通常論文]
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yaser Hosny Ali Elewa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon JOURNAL OF ANATOMY 222 (3) 396 -396 2013年03月 [査読無し][通常論文]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon VETERINARY RESEARCH COMMUNICATIONS 34 (8) 727 -727 2010年12月 [査読無し][通常論文]
  • Yaser Elewa, 市居 修, 大塚 沙織, 金澤 智則, 李 愼曉, 並木 由佳, 昆 泰寛, 橋本 善春 日本獣医学会学術集会講演要旨集 150回 160 -160 2010年09月 [査読無し][通常論文]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shinhyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon JAPANESE JOURNAL OF VETERINARY RESEARCH 58 (2) 121 -135 2010年08月 [査読無し][通常論文]
     
    The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.
  • ヤギ耳下腺の年齢関連の構造変化(Age-related structural changes of parotid salivary glands in goat)
    Elewa Yaser, 橋本 善春, 市居 修, 大塚 沙織, 金澤 智則, 昆 泰寛 日本獣医学会学術集会講演要旨集 149回 211 -211 2010年03月 [査読無し][通常論文]

担当経験のある科目(授業)

  • 先端機器演習北海道大学獣医学研究院
  • 組織学実習北海道大学獣医学部
  • 解剖学実習北海道大学獣医学部

所属学協会

  • Japanese Society for promotion and Sciences (JSPS)- Alumni, Egypt   Egyptian Society of Veterinary medical sciences   Egyptian Society of Histology and Cytology   日本解剖学会   日本獣医学会   

共同研究・競争的資金等の研究課題

  • 縦隔関連リンパ組織に着目したヒト呼吸器・心血管疾患の革新的な治療戦略研究
    基盤研究(C):
    研究期間 : 2020年04月 -2023年04月
  • 若手研究(B)
    若手研究(B):
    研究期間 : 2017年04月 -2020年04月 
    代表者 : エレワ ヤセル


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