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  1. Article ; Online: Fast-track preparation of lung specimens for electron microscope observations of the pulmonary endothelial glycocalyx.

    Wakatsuki, Mone / Takaki, Takashi / Ushiyama, Akira / Honda, Kazuho / Iijima, Takehiko

    Medical molecular morphology

    2023  Volume 56, Issue 4, Page(s) 239–249

    Abstract: The glycocalyx (GCX) covers the luminal surface of blood vessels and regulates vascular permeability. As GCX degradation predicts various types of vasculopathy, confirming the presence of this structure is useful for diagnosis. Since the GCX layer is ... ...

    Abstract The glycocalyx (GCX) covers the luminal surface of blood vessels and regulates vascular permeability. As GCX degradation predicts various types of vasculopathy, confirming the presence of this structure is useful for diagnosis. Since the GCX layer is very fragile, careful fixation is necessary to preserve its structure. We explored appropriate and feasible methodologies for visualizing the GCX layer using lung tissue specimens excised from anesthetized mice. Each specimen was degassed and immersed in Alcian blue (ALB) fixative solution, and then observed using electron microscopy. Specimens from septic mice were prepared as negative GCX controls. Using these immersion-fixed specimens, the GCX layer was successfully observed using both transmission and scanning electron microscopy; these observations were similar to those obtained using the conventional method of lanthanum perfusion fixation. Spherical aggregates of GCX were observed in the septic mouse specimens, and the GCX density was lower in the septic specimens than in the non-septic specimens. Of note, the presently reported methodology reduced the specimen preparation time from 6 to 2 days. We, therefore, concluded that our novel method could be applied to human lung specimens and could potentially contribute to the further elucidation of vasculopathies.
    MeSH term(s) Mice ; Humans ; Animals ; Glycocalyx ; Electrons ; Endothelium, Vascular ; Microscopy, Electron, Scanning ; Lung
    Language English
    Publishing date 2023-07-05
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2190059-0
    ISSN 1860-1499 ; 1860-1480
    ISSN (online) 1860-1499
    ISSN 1860-1480
    DOI 10.1007/s00795-023-00360-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.

    Nakayama, Masaaki / Miyazaki, Masanobu / Hamada, Chieko / Ito, Yasuhiko / Honda, Kazuho

    Clinical and experimental nephrology

    2023  Volume 27, Issue 9, Page(s) 717–727

    Abstract: Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. ... ...

    Abstract Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.
    MeSH term(s) Humans ; Peritoneal Fibrosis/diagnosis ; Peritoneal Fibrosis/etiology ; Japan/epidemiology ; Peritoneal Dialysis/adverse effects ; Peritoneum/pathology ; Dialysis Solutions/adverse effects ; Sclerosis/complications ; Sclerosis/pathology
    Chemical Substances Dialysis Solutions
    Language English
    Publishing date 2023-06-06
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 1338768-6
    ISSN 1437-7799 ; 1342-1751
    ISSN (online) 1437-7799
    ISSN 1342-1751
    DOI 10.1007/s10157-023-02360-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Recent advances in electron microscopy for the diagnosis and research of glomerular diseases.

    Honda, Kazuho / Takaki, Takashi / Kang, Dedong

    Kidney research and clinical practice

    2022  Volume 42, Issue 2, Page(s) 155–165

    Abstract: Recent technical advances in the detection of backscattered electrons during scanning electron microscopy (SEM) have improved resolution and have provided several new technologies for research and clinical practice in kidney disease. The advances include ...

    Abstract Recent technical advances in the detection of backscattered electrons during scanning electron microscopy (SEM) have improved resolution and have provided several new technologies for research and clinical practice in kidney disease. The advances include three-dimensional (3D) electron microscopy (3D-EM), correlative light and electron microscopy (CLEM), low-vacuum SEM (LVSEM), and scanning transmission electron microscopy (STEM). 3D-EM analysis used to be laborious, but recently three different technologies, serial block-face SEM, focused ion beam SEM, and array tomography, have made 3D-EM easier by automating sectioning and the subsequent image acquisition in an SEM. CLEM is a method to correlate light microscopic images, especially immunofluorescent and electron microscopy images, providing detailed ultrastructure of the area of interest where the immunofluorescent marker is located. LVSEM enables the use of SEM on materials with poor electron conductivity. For example, LVSEM makes it possible for high resolution, 3D observation of paraffin sections. Finally, STEM is a method to observe ultrathin sections with improved resolution by using the focused electron beam scanning used in SEM and not the broad electron beam used in transmission electron microscopy. These technical advances in electron microscopy are promising to provide plenty of novel insights for understanding the pathogenesis and diagnosis of various glomerular diseases.
    Language English
    Publishing date 2022-05-04
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2656420-8
    ISSN 2211-9132
    ISSN 2211-9132
    DOI 10.23876/j.krcp.21.270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Introduction.

    Honda, Kazuho / Masutani, Kosuke

    Nephron

    2020  Volume 144 Suppl 1, Page(s) 1

    Language English
    Publishing date 2020-12-01
    Publishing country Switzerland
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000511269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Gemcitabine alters sialic acid binding of the glycocalyx and induces inflammatory cytokine production in cultured endothelial cells.

    Gunji, Mariko / Sawa, Chika / Akiyama, Minako / Mukai, Shumpei / Takaki, Takashi / Kang, Dedong / Honda, Kazuho

    Medical molecular morphology

    2023  Volume 56, Issue 2, Page(s) 128–137

    Abstract: Gemcitabine (GEM) is an anticancer drug inhibiting DNA synthesis. Glomerular thrombotic microangiopathy (TMA) has been reported as an adverse effect. However, the precise mechanism of GEM-induced endothelial injury remains unknown. Cultured human ... ...

    Abstract Gemcitabine (GEM) is an anticancer drug inhibiting DNA synthesis. Glomerular thrombotic microangiopathy (TMA) has been reported as an adverse effect. However, the precise mechanism of GEM-induced endothelial injury remains unknown. Cultured human umbilical vein endothelial cells (HUVECs) in the confluent phase were exposed to GEM (5-100 μM) for 48 h and evaluated cell viability and morphology, lectin binding concerning sialic acid of endothelial glycocalyx (GCX), and immunofluorescent staining of platelet-endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor receptor 2 (VEGFR2). The mRNA expression of α2,6-sialyltransferase (ST6Gal1), sialidase (neuraminidase-1: NEU-1), and interleukin (IL)-1β and IL-6 was also evaluated. GEM exposure at 5 μM induced cellular shrinkage and intercellular dissociation, accompanied by slight attenuation of PECAM and VEGFR2 immunostaining, although cell viability was still preserved. At this concentration, lectin binding showed a reduction of terminal sialic acids in endothelial GCX, probably associated with reduced ST6Gal1 mRNA expression. IL-1β and IL-6 mRNA expression was significantly increased after GEM exposure. GEM reduced terminal sialic acids in endothelial GCX through mRNA suppression of ST6Gal1 and induced inflammatory cytokine production in HUVECs. This phenomenon could be associated with the mechanism of GEM-induced TMA.
    MeSH term(s) Humans ; Glycocalyx ; Gemcitabine ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Cells, Cultured ; Platelet Endothelial Cell Adhesion Molecule-1/genetics ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Sialic Acids/metabolism ; Lectins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
    Chemical Substances Gemcitabine ; Interleukin-6 ; Vascular Endothelial Growth Factor A ; Platelet Endothelial Cell Adhesion Molecule-1 ; Sialic Acids ; Lectins ; RNA, Messenger
    Language English
    Publishing date 2023-01-09
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2190059-0
    ISSN 1860-1499 ; 1860-1480
    ISSN (online) 1860-1499
    ISSN 1860-1480
    DOI 10.1007/s00795-022-00347-4
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  6. Article ; Online: Clinicopathological differences in focal segmental glomerulosclerosis depending on the accompanying pathophysiological conditions in renal allografts.

    Taneda, Sekiko / Honda, Kazuho / Koike, Junki / Ito, Naoko / Ishida, Hideki / Takagi, Toshio / Nagashima, Yoji

    Virchows Archiv : an international journal of pathology

    2023  Volume 483, Issue 6, Page(s) 809–819

    Abstract: Primary focal segmental glomerulosclerosis (FSGS) is thought to be caused by circulating factors leading to podocytopathy, whereas segmental sclerotic lesions (FSGS lesions) have several causes. We studied the clinicopathological differences of FSGS- ... ...

    Abstract Primary focal segmental glomerulosclerosis (FSGS) is thought to be caused by circulating factors leading to podocytopathy, whereas segmental sclerotic lesions (FSGS lesions) have several causes. We studied the clinicopathological differences of FSGS-lesions in 258 cases of FSGS in renal allografts, depending on the following accompanying pathophysiology: recurrence of primary FSGS, calcineurin inhibitor (CNI)-induced arteriolopathy, antibody-mediated rejection (ABMR), and other conditions. All cases were categorized with the Columbia classification. Recurrent FSGS developed the earliest after transplantation and showed the highest percentage of the collapsing (COL) variant in which collapse of the glomerular capillaries with epithelial hypertrophy was apparent. FSGS accompanying CNI-induced arteriolopathy predominantly developed the not otherwise specified (NOS) variant, showing severe ultrastructural endothelial injury. On the contrary, approximately 7% of the cases showed the COL variant, presenting glomerular endothelial damage such as double contours of glomerular basement membrane and endothelial cell swelling as well as epithelial cell proliferation. FSGS with ABMR had the highest creatinine levels and cellular variant percentage, with marked inflammation and ultrastructural endothelial injury. Approximately two-thirds of the cases without ABMR, CNI-induced arteriopathy, or recurrent FSGS had other coexisting conditions such as glomerulonephritis, T cell-mediated rejection, and reflux nephropathy with progressive tubulointerstitial fibrosis. Most of these cases were of the NOS variant. The clinicopathologic features of post-transplant FSGS differed depending on the associated conditions, and endothelial injury was apparent especially in cases of CNI-induced arteriolopathy and ABMR. Precise observation of FSGS lesions may facilitate the diagnosis and clinical management of FSGS during renal transplantation.
    MeSH term(s) Humans ; Glomerulosclerosis, Focal Segmental/complications ; Glomerulosclerosis, Focal Segmental/pathology ; Kidney Transplantation/adverse effects ; Kidney/pathology ; Kidney Glomerulus/pathology ; Antibodies ; Allografts/pathology
    Chemical Substances Antibodies
    Language English
    Publishing date 2023-11-18
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-023-03703-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Juvenile Membranous Nephropathy Developed after Human Papillomavirus (HPV) Vaccination.

    Arakawa, Haruna / Yokoyama, Shohei / Ohira, Takehiro / Kang, Dedong / Honda, Kazuho / Ueda, Yoshihiko / Tojo, Akihiro

    Vaccines

    2022  Volume 10, Issue 9

    Abstract: A 16-year-old girl with no history of renal disease had a fever of 38 °C after her second HPV vaccination and was identified as positive for proteinuria. As she maintained urinary protein of 3.10 g/gCr and 5-9 urinary red blood cells/HPF, a renal biopsy ... ...

    Abstract A 16-year-old girl with no history of renal disease had a fever of 38 °C after her second HPV vaccination and was identified as positive for proteinuria. As she maintained urinary protein of 3.10 g/gCr and 5-9 urinary red blood cells/HPF, a renal biopsy was performed and small spikes on PAM staining with the granular deposition of IgG1++ and IgG3+ on the glomerular capillary wall were discovered by immunofluorescence, although PLA2R immunostaining was negative. Analysis by electron microscope showed electron density deposition in the form of fine particles under the epithelium. The diagnosis was secondary membranous nephropathy stage II. Immunostaining with the anti-p16 INK4a antibody was positive for glomerular cells, and Western blot analysis of urinary protein showed a positive band for p16 INK4a. However, laser-microdissection mass spectrometry analysis of a paraffin section of glomeruli failed to detect HPV proteins. It is possible that the patient was already infected with HPV and administration of the HPV vaccine may have caused secondary membranous nephropathy.
    Language English
    Publishing date 2022-09-01
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10091442
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  8. Article ; Online: A case of acute poststreptococcal glomerulonephritis complicated by interstitial nephritis related to streptococcal pyrogenic exotoxin B.

    Kanazawa, Nobuhiro / Iyoda, Masayuki / Hayashi, Junichi / Honda, Kazuho / Oda, Takashi / Honda, Hirokazu

    Pathology international

    2022  Volume 72, Issue 3, Page(s) 200–206

    Abstract: This paper presents the case of a patient who developed acute kidney injury and nephrotic syndrome following streptococcal cutaneous infection. He presented with microhematuria, severe proteinuria and systemic edema 5 days after infection. Blood ... ...

    Abstract This paper presents the case of a patient who developed acute kidney injury and nephrotic syndrome following streptococcal cutaneous infection. He presented with microhematuria, severe proteinuria and systemic edema 5 days after infection. Blood examination showed elevated creatinine level, hypocomplementemia, and elevated anti-streptolysin O level. Renal biopsy revealed endocapillary proliferative glomerulonephritis with tubulointerstitial nephritis (TIN). Immunofluorescence revealed C3-dominant glomerular staining, while electron microscopy showed hump-shaped subepithelial deposits. The patient was therefore diagnosed with poststreptococcal glomerulonephritis. The unique histological feature was C3 deposition in the tubular basement membrane (TBM), in which we detected streptococcal pyrogenic exotoxin B (SpeB), a nephritogenic antigen produced by streptococci. No nephritis-associated plasmin receptor or plasmin activity was evident in the TBM. These nephritogenic antigens and upregulation of plasmin activity were observed in glomeruli. This case suggests that TIN after poststreptococcal infection might be partially attributable to SpeB toxicity.
    MeSH term(s) Acute Kidney Injury/etiology ; Adult ; Bacterial Proteins/adverse effects ; Bacterial Proteins/metabolism ; Exotoxins/adverse effects ; Exotoxins/metabolism ; Glomerulonephritis/etiology ; Glomerulonephritis/physiopathology ; Humans ; Male ; Nephritis, Interstitial/etiology ; Nephritis, Interstitial/physiopathology ; Nephrotic Syndrome/etiology ; Streptococcal Infections/complications ; Streptococcal Infections/pathology
    Chemical Substances Bacterial Proteins ; Exotoxins ; erythrogenic toxin
    Language English
    Publishing date 2022-02-11
    Publishing country Australia
    Document type Case Reports
    ZDB-ID 1194850-4
    ISSN 1440-1827 ; 1320-5463
    ISSN (online) 1440-1827
    ISSN 1320-5463
    DOI 10.1111/pin.13203
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  9. Article ; Online: Significance of Multinucleated Polyploidization of Tubular Epithelial Cells in Kidney Allografts.

    Kounoue, Noriyuki / Oguchi, Hideyo / Tochigi, Naobumi / Mikami, Tetuo / Yamaguchi, Yutaka / Honda, Kazuho / Yonekura, Takashi / Muramatsu, Masaki / Itabashi, Yoshihiro / Sakai, Ken

    Nephron

    2023  Volume 147 Suppl 1, Page(s) 28–34

    Abstract: Introduction: Multinucleated polyploidization (MNP) of tubular epithelial cells is occasionally observed in kidney allografts. The present study aimed to clarify the clinical and pathological significance of MNP of tubular epithelial cells in kidney ... ...

    Abstract Introduction: Multinucleated polyploidization (MNP) of tubular epithelial cells is occasionally observed in kidney allografts. The present study aimed to clarify the clinical and pathological significance of MNP of tubular epithelial cells in kidney allografts.
    Methods: Fifty-eight 1-year biopsies from 58 patients who underwent kidney transplantation at our hospital from January 2016 to December 2017 were included. MNP was counted in each specimen, and the specimens were divided into two groups by the median value. The differences in clinical and pathological characteristics were compared. Ki67-positive cells were counted among tubular epithelial cells to explore the association between cell cycle and MNP. In an additional cohort, MNP was compared between biopsies after precedent T-cell-mediated rejection and precedent medullary ray injury.
    Results: The 58 cases were divided into two groups by the median total amount of MNP: group A (MNP > 3) and group B (MNP ≤ 3). Maximum t-score before the 1-year biopsy was significantly higher in group A compared with group B. Other clinical or histological characteristics did not differ significantly. Total amount of Ki67-positive tubular epithelial cells was significantly correlated with total amount of MNP. Significantly higher amount of MNP was observed in cases with precedent T-cell-mediated rejection compared with precedent medullary ray injury. On receiver operating characteristic curve analysis, the cut-off value of MNP to predict precedent T-cell-mediated rejection was 8.5.
    Conclusions: MNP in tubular epithelial cells reflects prior tubular inflammation in kidney allografts. High amount of MNP indicates precedent T-cell-mediated rejection rather than precedent medullary ray injury caused by nonimmune etiologies.
    MeSH term(s) Humans ; Ki-67 Antigen ; Kidney/pathology ; Transplantation, Homologous ; Epithelial Cells ; Biopsy ; Allografts ; Graft Rejection/etiology
    Chemical Substances Ki-67 Antigen
    Language English
    Publishing date 2023-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000530339
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  10. Article ; Online: PLA2R-positive membranous nephropathy in IgG4-related disease.

    Ushio, Yusuke / Akihisa, Taro / Karasawa, Kazunori / Seki, Momoko / Kobayashi, Shizuka / Miyabe, Yoei / Kataoka, Hiroshi / Ito, Naoko / Taneda, Sekiko / Akiyama, Shin'ichi / Hebisawa, Akira / Kawano, Mitsuhiro / Honda, Kazuho / Hoshino, Junichi

    BMC nephrology

    2024  Volume 25, Issue 1, Page(s) 66

    Abstract: Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder ... ...

    Abstract Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases.
    Case presentation: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy.
    Conclusions: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.
    MeSH term(s) Male ; Humans ; Aged ; Glomerulonephritis, Membranous/complications ; Glomerulonephritis, Membranous/diagnosis ; Receptors, Phospholipase A2 ; Immunoglobulin G4-Related Disease/complications ; Immunoglobulin G4-Related Disease/diagnosis ; Nephrotic Syndrome/complications ; Nephritis, Interstitial/complications ; Nephritis, Interstitial/diagnosis ; Immunoglobulin G ; Autoantibodies
    Chemical Substances Receptors, Phospholipase A2 ; Immunoglobulin G ; Autoantibodies
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2041348-8
    ISSN 1471-2369 ; 1471-2369
    ISSN (online) 1471-2369
    ISSN 1471-2369
    DOI 10.1186/s12882-024-03511-3
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