{"created":"2023-10-18T06:42:40.626009+00:00","id":2000052,"links":{},"metadata":{"_buckets":{"deposit":"1632fa35-1200-4be6-b6c2-62c52dc3ca75"},"_deposit":{"created_by":12,"id":"2000052","owner":"12","owners":[12],"pid":{"revision_id":0,"type":"depid","value":"2000052"},"status":"published"},"_oai":{"id":"oai:obihiro.repo.nii.ac.jp:02000052","sets":["6:8"]},"author_link":[],"control_number":"2000052","item_3_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Pathological studies on progressive glomerulonephropathy in common marmosets","subitem_alternative_title_language":"en"}]},"item_3_date_granted_12":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2023-09-29"}]},"item_3_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"帯広畜産大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10105","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_3_degree_name_9":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（獣医学）","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Veterinary Medicine","subitem_degreename_language":"en"}]},"item_3_description_11":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"2023","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"コモンマーモセットの背景病変のなかでも，腎症は自然発生性に生じる病変としていくつか報告されているが，いまだに不明な点も多い．また，体系的な評価方法もないため，種々の実験において腎臓病変を評価する際の妨げとなる．そこで，本研究ではコモンマーモセットの進行性糸球体腎症について，光学顕微鏡学的検査で病理組織学的な病変スコアを評価し，そのスコアから腎症をグレーディングすることで，本腎症の体系的な評価を試みた．\n第１章では，コモンマーモセットの進行性糸球体腎症を光学顕微鏡学的検査で糸球体病変，再生尿細管，硝子円柱，間質への炎症性細胞浸潤と線維化についてスコア化した．そしてこれらのスコアの合計値に基づき，腎症を5つのグレードに分類した．さらに，透過型電子顕微鏡学的検査により各腎症グレードにおける超微形態学的な特徴，糸球体病変と年齢の関係性および糸球体病変の初期変化とその病態の進行について調べた．その結果，腎症グレード1では，光学顕微鏡的に顕著な糸球体病変が認知できないにもかかわらず，電子顕微鏡学的検査では足細胞の足突起の消失が認められた．腎症グレード2では，光学顕微鏡的に糸球体門部から糸球体末梢側に向かって軸性のメサンギウム基質やメサンギウム細胞の増殖が明らかとなり，電子顕微鏡的にも腎症グレード1よりも糸球体足細胞の足突起の消失は進行していた．腎症グレード3では，糸球体メサンギウムの病変は門部から末梢側に向かってメサンギウム基質の増加やメサンギウム細胞の増殖が明らかとなり，糸球体基底膜とパラメサンギウム領域の血管内皮直下にマッソン・トリクローム染色で赤色に染色される沈着物がみられた．透過型電子顕微鏡観察では，同領域に高電子密度の沈着物が認められた．腎症グレード4 では，糸球体基底膜の走行や配列の不整が顕著となり，同部位には高電子密度の沈着物および細胞質成分が透過型電子顕微鏡検索で観察された．以上の結果より，本分類類方法を使用することで，コモンマーモセットの進行性糸球体腎症について病変の進行に合わせたグレーディングを可能とした．\n第２章では，若齢のコモンマーモセット5例の腎臓について，光学顕微鏡学的，電子顕微鏡学的検査に合わせて免疫組織学的検査を実施し， 若齢で本腎症がまだ初期と考えられる段階での免疫グロブリンの関与について形態学的に調べた．その結果，若齢の動物で，光学顕微鏡的な病変が認められないにもかかわらず，電子顕微鏡的には足細胞の足突起の消失が認められ，さらにIgM の沈着がメサンギウム領域に認められた．腎症グレードが進行するとメサンギウム領域へのIgA の沈着が認められ，さらにメサンギウム領域や糸球体係蹄壁へのIgG の沈着も認められた．以上の結果により，若齢動物においても，すでにメサンギウム基質の増加やIgM，IgA の沈着が認められることが分かった．また，進行性糸球体腎症の病態進行において，病変初期ではIgM が沈着し， IgA やIgG の沈着が病変の進行に関与している可能性が示された．\nコモンマーモセットの進行性糸球体腎症では， 病変初期の足細胞の足突起の消失が特徴的であることから， 第３章として足細胞の足突起のスリット膜を構成する重要な分子であるネフリンの発現状況について調べた．その結果，ネフリンの発現は腎症グレード0～2で連続的な線状パターンを示したが，腎症グレード3の例では，非連続性の線状パターンあるいは粗顆粒状パターンを示し，光学顕微鏡的な検査でもパターンの違いが明らかであった．さらに，形態学的解析により，コモンマーモセットの進行性糸球体腎症の足細胞におけるネフリン発現量は，腎症グレードが増加するに伴い低下することが明らかになった．また，硝子円柱の組織学的スコアが増加するに伴い，ネフリン発現量が低下する傾向も認められた．ネフリン発現パターンの変化はスリット膜構造の変化を反映していると考えられ，これらの結果は，病変の進行に伴ってスリット膜構造が変化し，この変化とネフリン発現の減少や硝子円柱の増加が密接に関連していることを示唆している．\n本研究では，コモンマーモセットの進行性糸球体腎症の病理組織学的なグレーディングを可能にした．そして，超微形態学的特徴や免疫グロブリンの沈着，ネフリンの発現について，各腎症グレードの詳細を明らかにした．本研究の成果は，毒性試験を含む多くの研究で腎病変を判断する一助となるものと考える．","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Among the background lesions of common marmosets, some nephropathies have been reported as spontaneous lesions, but there are still many unclear points. In addition, the absence of a systematic evaluation method hinders evaluation of the renal lesions in various experiments. Therefore, in this study, I attempted to systematically evaluate spontaneous progressive glomerulonephropathy in common marmosets by evaluating the histopathological score by light microscopy and grading the nephropathy based on the score.\nIn Chapter 1, spontaneous progressive glomerulonephropathy in common marmosets was scored for glomerular lesions, regenerating tubules, hyaline casts, interstitial inflammatory cell infiltration, and fibrosis by light-microscopy. Based on the sum of these scores, nephropathy was classified into 5 grades. In addition, transmission electron microscopy (TEM) was used to examine the ultrastructural characteristics of each grade of nephropathy, the relationship between glomerular lesions and age, and the initial changes and progression of glomerular lesions. As a result, in nephropathy grade 1, effacement of podocyte foot processes was observed electron-microscopically, although there was no significant glomerular lesion light-microscopically. In grade 2 nephropathy, mesangial cell proliferation and mesangial matrix increasing from the glomerular hilum to the peripheral side of the tuft is revealed by light-microscopy, and glomerular basement membrane lesions are more advanced than in grade 1 nephropathy by electron-microscopy. In grade 3 nephropathy, glomerular mesangial lesions revealed mesangial cell proliferation and mesangial matrix increasing from the hilus to the peripheral side of the tuft. In Masson's trichrome-stained sections, red deposits were observed under the endothelium of the glomerular basement membrane and the paramesangial region. TEM examination revealed electron-dense deposits in the same regions. In nephropathy grade 4, irregular arrangement of the glomerular basement membrane was remarkable. At the same sites, electron-dense deposits or cytoplasmic components were observed by TEM. Based on these results, the use of this classification enabled grading according to the progression of lesions for progressive glomerulonephropathy in common marmosets.\nIn Chapter 2, immunohistochemical examination was performed to investigate about the involvement of immunoglobulin along with light-microscopy and electron-microscopy on the kidneys of 5 young common marmosets whose nephropathy is still considered to be in the early stages. As a result, in young animals, although no lesions were observed on light-microscopy, electron-microscopy showed effacement of podocyte foot processes. In addition, IgM deposition was observed in the mesangial region by immunohistochemical examination. As the grade of nephropathy progressed, IgA deposition was observed in the mesangial region, and IgG deposition was also observed in the mesangial region and the glomerular loop. From these results, it was found that an increase in the mesangial matrix and the deposition of IgM and IgA were already observed in young animals. In addition, in the progression of progressive glomerulonephropathy, the deposition of IgM occurred in the early stage of the lesion, and the deposition of IgA and IgG may be involved in the progression of the lesion.\nIn the progressive glomerulonephritis of the common marmoset, the effacement of the foot process of the podocyte in the early stage of the lesion is characteristic, and the expression of nephrin which is an important molecule constituting the slit membrane of the foot process of the podocyte was examined in Chapter 3. As a result, nephrin expression showed a continuous linear pattern in nephropathy grades 0-2, but showed a discontinuous linear pattern or a coarse granular pattern in patients with nephropathy grade 3. In this way, the difference in staining pattern of nephrin was clearly demonsterated by light microscopic examination. Furthermore, morphometrical analysis revealed that the expression of nephrin in the podocytes of common marmosets with progressive glomerulonephropathy decreased as the nephropathy progressed. In addition, nephrin expression tended to decrease as the histological score of hyaline casts increased. Because changes in nephrin expession pattern reflect changes in the slit membrane structure, these results suggest that the slit-membrane structure changes with the progression of the lesion and that this change is closely related to a decrease in nephrin expression and an increase in hyaline casts.\nThis study enabled histological grading of progressive glomerulonephropathy in common marmosets. And details of each nephropathy grade were clarified in terms of ultrastructural morphology, immunoglobulin deposition, and nephrin expression. I believe that the results will help determination of renal lesions in many studies including toxicologic studies.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_3_description_8":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"博士学位論文","subitem_description_language":"ja","subitem_description_type":"Other"},{"subitem_description":"大学院畜産学研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"乙第17号"}]},"item_3_publisher_5":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"帯広畜産大学","subitem_publisher_language":"ja"}]},"item_3_rights_14":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"山田, 直明","subitem_rights_language":"ja"}]},"item_3_subject_20":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"649","subitem_subject_language":"ja","subitem_subject_scheme":"NDC"}]},"item_3_version_type_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山田, 直明","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-10-18"}],"filename":"Yamada.pdf","filesize":[{"value":"4 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"全文　Full text","objectType":"fulltext","url":"https://obihiro.repo.nii.ac.jp/record/2000052/files/Yamada.pdf"},"version_id":"4cd9494e-03e9-4aec-a758-a9ca2c00f148"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-10-18"}],"filename":"Abstract(Yamada).pdf","filesize":[{"value":"140 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"全文の要旨　Abstract","objectType":"abstract","url":"https://obihiro.repo.nii.ac.jp/record/2000052/files/Abstract(Yamada).pdf"},"version_id":"155e5c6d-7023-4661-8c67-d26a7cdb99ab"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-10-18"}],"filename":"Evaluation(Yamada).pdf","filesize":[{"value":"338 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"審査の要旨　Evaluation","objectType":"other","url":"https://obihiro.repo.nii.ac.jp/record/2000052/files/Evaluation(Yamada).pdf"},"version_id":"0263da38-dba4-41cc-8bad-a47112cd77e7"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"コモンマーモセットの進行性糸球体腎症に関する病理学的研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"コモンマーモセットの進行性糸球体腎症に関する病理学的研究","subitem_title_language":"ja"}]},"item_type_id":"3","owner":"12","path":["8"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2023-10-18"},"publish_date":"2023-10-18","publish_status":"0","recid":"2000052","relation_version_is_last":true,"title":["コモンマーモセットの進行性糸球体腎症に関する病理学的研究"],"weko_creator_id":"12","weko_shared_id":-1},"updated":"2024-01-18T07:50:10.622380+00:00"}