• Applied Microscopy
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• v.27 no.4
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• pp.391-402
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• 1997

Using the electron microscopical method, this study was attempted to investigate the ultrastructural characteristics of glomeruli in FGS/Kist mice showing high proteinuria. The mucus-like substances were observed in glomerular capillary lumen which were usually narrowed by the widening of mesangial area filled with electron-dense deposits. Some portions of basal lamina in capillary wall were projecting to urinary space. Moreover, many vacuoles were observed in the cytoplasm of visceral epithelial cells, and an irregular-shaped fusion or effacement of foot processes were often shown in areas adjacent to basal lamina of glomeruli.

• Childhood Kidney Diseases
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• v.16 no.1
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• pp.21-31
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• 2012

Focal segmental glomerulosclerosis (FSGS) is the name of the primary glomerular disease as well as the terminology to describe the secondary phenomena of any other glomerular diseases. It is characterized by sclerosis, hyalinosis, foam cell infiltration, vacuolar change of podocytes, and halo formation in the glomerulus. Throughout the interstitium, lymphocytes infiltration, tubular atrophy and vascular changes are accompanied. Occasionally, IgM and/or C3 depositions are noted in the sclerotic areas. Electron microscopically, diffuse effacement of foot processes are seen in non-sclerotic area like minimal change disease. Podocyte injury patterns including vacuolar changes are frequently examined. Recently, Columbia group has suggested morphologic classification of FSGS and they demonstrated very good prognosis of tip lesion and poor prognosis of both collapsing and cellular types. However, the pathogenetic classification has been suggested by others; hyperfilteration, podocyte injury, genetic lesions etc. Further studies are necessary to understand and treat this disease.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.2
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• pp.67-75
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• 2002

The human complement receptor type 1 (CR 1, C3 b/C4b receptor) is a polymorphic membrane glycoprotein expressed on human erythrocytes, peripheral leukocytes, plasma and renal glomerular podocytes, which consists of transmembrane and cytoplasmic domains with 30 repeating homologous protein domains known as short consensus repeats (SCR). CR1 has been used as an inhibitor for inflammatory and immune system for the past several years. Recently; it is reported that CRl was found to suppress the hyper-acute rejection in xeno-transplantation and can be used to cure autoimmune diseases. A soluble form of CRl, called sCRl, is a recombinant CRl by cleaving the transmembrane domain at C-terminus and has been expressed in Chinese Hamster Ovary (CHO) cells. Several purification methods for sCR1 from CHO cells have been reported, but most of them require complicated steps at high cost. Moreover, such methods are mostly performed under the pH condition apt to denaturing sCR1 and causes sCRl losing its activity. We here report a rapid and efficient method to purify sCR1 from CHO cell. The new method consists of a two-stage of cell culture by cultivating cells in serum medium followed by serum-free medium, and a two-stage of column purification by means of heparin and gel filtration column chromatography. By using this novel method, sCR1 can be purified in a simple and effective way with high yield and purity, furthermore, the purified sCR1 was confirmed to retain its activity to suppress the complement activation in vivo and ex vivo.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.41-57
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• 1997

This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.

• The Korean Journal of Zoology
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• v.11 no.4
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• pp.103-117
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• 1968

Insect hemocytes during metamorphosis were studies by histchemical and autoradiographic methods is Pieris rapae (Lepidoptera). The hemocytes were classified into six types, prohemocytes, plasmatocytes, podocytes, granular hemocytes, spherule cells and oenocytoids on the basis of the transitions in shapes and inclnsions of cytoplasms. Proteins, nucleic acids, polysaccharides and lipids in the hemocytes were detected histochemically from larval to pupal stages to learn the rise and fall of them during growth and metamorphosis. Most of the granules consisted of glycogen, neutral mucopolysaccharides and mucoprotein in addition to some granules of neutral fats and phospholipids were found in the granular hemocytes and spherule cells. Mitotic figures and DNA synthetic activities were observed in every type of hemocytes from 2nd to 5th instars, suggesting the all types of hemocytes originated from the prohemocytes. The cytoplasmic filaments of plasmatocytes and pdocytes extended very long in prepupa and pupa and the vermiform cells were the transformed plasmatocytes due to their further differentiation.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.130-138
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• 1998

In this study, the effect of verapamil (VER) on cyclosporin A (CsA)-induced nephrotoxicity was investigated in uninephrectomized rats. Male Wistar rats were administered CsA (50 mg/kg/day, p.o.) or VER (0.5 mg/kg/day, i.p.) with CsA (50 mg/kg/day, p.o.) for 20 days. The urinary N-acetyl-$\beta$-D-glucosaminidase (NAG) activity along with BUN, serum creatinine, creatinine clearance (CLcr), body weight, and 24 hr-urine output were measured and histopathologic changes of kidney were evaluated by light and electron microscopy. The results obtained from this study can be summarized as follows: While NAG activity, BUN and serum creatinine was progressively increased and CLcr significantly decreased in CsA group, VER almost signifi-cantly (p<0.05) suppressed and normalized CsA-induced changes in VER+CSA group. While urine output increased until 12th days and thereafter progressively decreased in CsA group, it gradually increased in control and VER+CSA group. While body weight progressively made a gain in control and VER+CSA groups, it significantly (p<0.05) lost in CsA group. On light microscopy, the glomerular hyperemia and proximal convoluted tubular (PCT) dilatation, focal tubular cell vacuolation and necrosis were clearly evident in CsA group, but, were not seen in other groups. Ultrastructural studies revealed thickened glomerular endothelium and basal lamina of capillary, irregular shaped pedicels of podocytes, indistinct slit pores and narrowed bowman's space. The large oval vacuoles with dense debris and phagosome were distributed in apical zone and deformed microvilli and mitochondria were seen in the PCT cell of CsA group. But, glomeruli and PCT cell were relatively preserved in normal apperance in other groups. In conclusion, it is suggested that verapamil has a protective effect on cyclosporine-induced nephrotoxicity in uninephrectomized rats.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.1-7
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• 2018

Objectives : Diabetic nephropathy is one of the most significant chronic complications of diabetes. Advanced glycation end products (AGEs) have been implicated in the development of diabetic nephropathy. GS-E3D is an enzymatic modified red ginseng extract by pectin lyase and has an increased concentration of the ginsenoside Rd compared to an unmodified red ginseng extract. In this study, we evaluated the preventive effects of GS-E3D on renal dysfunction in the type 2 diabetic db/db mice. Methods : GS-E3D (100 or 250 mg/kg body weight per day) was given to db/db mice through oral gavage for 6 weeks. Body weight and blood glucose levels were examined. At the end of the experiment, albuminuria was measured. The renal tissues were collected for histological examination, and immunohistochemical staining was used to detect renal accumulation of AGEs and podocyte loss Results : In the db/db mice, severe hyperglycemia developed, and albuminuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. No difference in blood glucose levels was noted between GS-E3D-treated and vehicletreated diabetic db/db mice. However, GS-E3D treatment significantly reduced albuminuria and AGE accumulations in diabetic mice. Moreover, the loss of podocytes was restored by GS-E3D treatment. Conclusions : GS-E3D might be beneficial for the treatment of diabetic nephropathy. The ability of GS-E3D on to attenuate albuminuria and podocyte dysfunction in the db/db mice may be mediated by the inhibition of AGE accumulation.

• Journal of Genetic Medicine
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• v.20 no.1
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• pp.6-14
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• 2023

Fabry disease (FD), a rare X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A gene gene encoding α-galactosidase A (α-Gal A). The functional deficiency of α-Gal A results in progressive accumulation of neutral glycosphingolipids, causing multi-organ damages including cardiac, renal, cerebrovascular systems. The current treatment is comprised of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy and adjunctive supportive therapy. ERT has been introduced 20 years ago, changing the outcome of FD patients with proven effectiveness. However, FD patients have many unmet needs. ERT needs a life-long intravenous therapy, inefficient bio-distribution, and generation of anti-drug antibodies. Migalastat, a pharmacological chaperone, augmenting α-Gal A enzyme activity only in patients with mutations amenable to the therapy, is now available for clinical practice. Furthermore, these therapies should be initiated before the organ damage becomes irreversible. Development of novel drugs aim at improving the clinical effectiveness and convenience of therapy. Clinical trial of next generation ERT is underway. Polyethylene glycolylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations with longer dosing interval. Moss-derived enzyme has a higher affinity for mannose receptors, and seems to have more efficient access to podocytes of kidney which is relatively resistant to reach by conventional ERT. Substrate reduction therapy is currently under clinical trial. Gene therapy has now been started in several clinical trials using in vivo and ex vivo technologies. Early results are emerging. Other strategic approaches at preclinical research level are stem cell-based therapy with genome editing and systemic mRNA therapy.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.138-148
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• 2004

Purpose: Regardless of the underlying diseases, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes. We examined the molecular basis for this alteration of the podocyte phenotypes, including quantitative and distributional changes of ZO-1 protein as a candidate contributing to the pathogenic changes in the barrier to protein filtration. Methods: To investigate whether high glucose and advanced glycosylation endproduct(AGE) induce podocyte cytoskeletal changes, we cultured rat GEpC under 1) normal glucose(5 mM=control) or 2) high glucose(30 mM) or 3) AGE-added or 4) high glucose plus AGE-added conditions. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results: By confocal microscopy, we observed that ZO-1 moves from peripheral cytoplasm to inner actin filaments complexes in both AGE-added and high glucose condition. In Western blotting, high glucose or AGE-added condition decreased the ZO-1 protein expression by 11.1%(P>0.05) and 2.3%(P>0.05), respectively compared to the normal glucose condition. High glucose plus AGE-added condition further decreased ZO-1 protein expression to statistically significant level(12%, P<0.05). No significant change was seen in the osmotic control. In RT-PCR, high glucose plus AGE-added condition significantly decreased the expression of ZO-1 mRNA by 12% compared to normal glucose condition. Conclusion: We suggest that both high glucose and AGE-added condition induce the cytoplasmic translocation and suppresses the production of ZO-1 at transcriptional level and these changes may explain the functional changes of podocytes in diabetic conditions.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.54-61
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• 2008

Purpose : This study was designed to clarify the mechanism of proteinuria in nephrotic syndrome patients by using puromycin aminonucleoside (PAN) nephrosis model. Methods : Following administration of various concentrations of PAN and antioxidants we observed the changes of podocyte cytoskeletons in cultured rat glomerular epithelial cells (GEpC) by method of scanning electron microscope, reactive oxyten species (ROS) analysis, permeability assay, confocal microscope, and Western blot assay. Results : PAN not only induced the ultrastructural changes of GEpC, such as shortening and fusion of microvilli, but also separated the intercellular gaps and linear ZO-1. PAN induced oxidative stresses in time and dose dependent manners and increases of intercellular permeability in anti-oxidants inhibitable manners. High concentration of PAN induced not only actin polymerization and disorganization, but also the conglomerulation and internal dislocation of ${\alpha}-actinin$ protein. The intensities of fluorescences of ZO-1 protein were diminished and internalized by PAN in a dose-dependent manner, which were inhibited by anti anti-oxidants. Conclusion : PAN induced the changes of podocytes cytoskeleton and junctional barriers by way of increasing ROS in GEpC that resulted in increasing their permeability in a antioxidatn-inhibitable manner. Glomerular hyperpermeability induced by PAN mediateing through oxidative stresses is thought to take part in the mechanism of proteinuria in nephrotic syndrome.