Recurrence of posterior polymorphous corneal dystrophy is caused by the overgrowth of the original diseased host endothelium |
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Authors: | Stanislava Merjava Eva Malinova Petra Liskova Martin Filipec Zuzana Zemanova Kyra Michalova Katerina Jirsova |
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Institution: | (1) Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, Ikeda 4-22-1, Kumamoto 860-0082, Japan;(2) Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark;(3) Department of Pharmacy, Taku City Hospital, 1771-4 Taku-cho, Taku-Shi, Saga 846-0031, Japan |
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Abstract: | Peplomycin (PEP), an anti-tumor antibiotic related structurally to bleomycin, is widely used, especially for squamous cell
carcinoma but shows renal toxicity. We prepared monoclonal antibodies (mAbs) against N-(γ-maleimidobutyryloxy)succinimide-conjugated PEP. The mAbs were monospecific for PEP, but did not react with bleomycin and
other anticancer antibiotics. The mAbs enabled us to develop an immunocytochemical (ICC) method for detecting the uptake of
PEP in the rat kidney. Two hours after a single i.v. administration of PEP, ICC revealed immunostaining for PEP in irregularly
shaped cytoplasmic granules of the proximal tubules in which the microvilli were also stained. Also, staining occurred in
the distal tubules and collecting ducts, in both of which we observed scattered swollen cells, reminiscent of necrotic cells,
in which both the nuclei and cytoplasm reacted strongly with the antibody. Twenty-four hours after injection, PEP in the proximal
tubules completely vanished, but yet significant amounts of PEP remained in both the distal tubules and collecting ducts.
Distribution patterns of PEP in cells of the kidneys resembled, in some ways, those of our recent ICC studies for an organic
cation aminoglycoside antibiotic gentamicin. This ICC suggests that PEP taken up in the proximal tubule cells is localized
in the lysosomes, and organic cation transporters and bleomycin hydrolase might be involved in entrance and/or disappearance
of PEP in this cell type. Furthermore, the distal tubules and collecting ducts may be the sites readily affected by some chemotherapeutic
agents. |
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