We report idiopathic intranuclear inclusion bodies in the renal tubular epithelia of two cases of among the 960 Japanese quail (Coturnix coturnix japonica) in the course of the acute oral toxicity and dietary toxicity test. Basophilic inclusion bodies were seen only in the nuclei of renal tubular epithelia. We could not classify our case into any adenovirus infection by clinical signs and lesions. The inclusion bodies were only identified as adenovirus-like particles based upon the electronmicroscopical features.
Animals ; *Coturnix ; Epithelial Cells/*ultrastructure ; *Intranuclear Inclusion Bodies ; Kidney Tubules/*ultrastructure

The purpose of this study was to determine the expression and distribution of band 3 in the collecting duct and connecting tubules of the kidney of the marmoset monkey (Callithrix jacchus), and to establish whether band 3 is expressed in type A intercalated cells. The intracellular localization of band 3 in the different populations of intercalated cells was determined by double-labeling immunohistochemistry. Immunohistochemical microscopy demonstrated that band 3 is located in the basolateral plasma membranes of all type A intercalated cells in the connecting tubule (CNT), cortical collecting duct (CCD), and outer medullary collecting duct (OMCD) of the marmoset. However, type B intercalated cells and non-A/ non-B intercalated cells did not show band 3 labeling. Electron microscopy of the CNT, CCD and OMCD confirmed the light microscopic observation of the basolateral plasma membrane staining for band 3 in a subpopulation of interacted cells. Basolateral staining was seen on the plasma membrane and small coated vesicles in the perinuclear structure, some of which were located in the Golgi region. In addition, there was no labeling of band 3 in the mitochondria of the CNT, CCD and in OMCD cells. The intensity of the immunostaining of the basolateral membrane was less in the CNT than in the CCD and OMCD. In contrast, band 3 immunoreactivity was greater in the intracellular vesicles of the CNT. From these results, we suggest that the basolateral Cl-/HCO3- exchanger in the monkey kidney is in a more active state in the collecting duct than in the CNT.
Animals ; Anion Exchange Protein 1, Erythrocyte/*metabolism ; Callithrix/*metabolism ; Gene Expression Profiling/veterinary ; *Gene Expression Regulation ; Immunohistochemistry/veterinary ; Kidney Tubules/cytology/physiology/ultrastructure ; Kidney Tubules, Collecting/cytology/*metabolism/ultrastructure ; Male ; Microscopy, Electron, Transmission/veterinary

This study was aimed at investigating the mechanisms of clinically important overt hyperkalemia in diabetes mellitus with underlying hyporeninemic hypoaldosteronism known as a classic model of the syndrome of hyporeninemic hypoaldosteronism (SHH). Rats (Sprague-Dawley, male) were streptozotocin-treated (60 mg/kg, ip) and used after 60 days. Rats with plasma glucose levels higher than 300 mg/dL (mean +/- SEM, 423 +/- 20 mg/dL, n = 8) were selected as the diabetic group. Age-matched normal rats served as control (mean plasma glucose, 88 +/- 2, mg/dL, n = 8). Serum potassium concentrations and osmolalities as well as serum creatinine levels were significantly higher in the diabetic than in the control group (5.07 +/- 0.09 vs. 4.68 +/- 0.11 mEq/L; 330 +/- 14 vs 290 +/- 3 mOsm/L; 0.40 +/- 0.03 vs 0.31 +/- 0.02 mg/dL, p < 0.05). Plasma renin activity (PRA) in the diabetic group was significantly lower than that in the control group (6.0 +/- 1.0 vs 12.1 +/- 1.1 ng Al/ml/h, p < 0.001). Plasma aldosterone concentration (PAC) was also significantly lower in the former than in the latter (368 +/- 30 vs 761 +/- 57 pg/ml, p < 0.001). Renomegaly, abnormal distal tubular cells with few organelles, and increased lipid droplets with pyknotic nucleus in zona glomerulosa of the adrenal glands were noted in the diabetic group. In conclusion, multifactorial causes including insulinopenia, hyperosmolality, elevated serum creatinine level and hypoaldosteronism with possible contribution of altered distal tubular response to aldosterone may have interacted to develop hyperkalemia in these diabetic rats.
Animals ; Diabetes Mellitus, Experimental/blood/*complications/pathology ; Disease Models, Animal ; Hyperkalemia/*complications ; Hypoaldosteronism/*complications ; Kidney Tubules, Distal/ultrastructure ; Male ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Zona Glomerulosa/ultrastructure

OBJECTIVETo explore the toxic effects of lead acetate on the apoptosis and ultrastructure of human renal tubular epithelial cells (HK-2).

METHODSAfter HK-2 cells were exposed to 5, 10 and 20 µmol/L lead acetate for 24 h, the morphological changes of HK-2 cells were observed by Hochest 33342-PI staining, and the ultrastructure changes of HK-2 cells were examined under a electron microscope, LDH activity and MDA content in supernatant of HK-2 cellular culture were detected by spectrophotometer, DNA damage of HK-2 was determined by DNA ladder and the apoptotic rates of HK-2 cells were measured by flow cytometry.

RESULTSThe morphological changes of apoptotic HK-2 cells in exposure group were observed by Hochest 33342-PI staining. The cytoplasm vacuoles, karyopycnosis, nuclear membrane vague and apoptotic bodies in HK-2 cells of exposure group were found under electron microscopy. LDH activity and MDA contents in exposure group increased significantly, as compared to control group (P < 0.01). The results of DNA Ladder showed that DNA damage of HK-2 cells in exposure group appeared. The apoptotic rates of HK-2 cells exposed to 5, 10, 20 µmol/L lead acetate were 14.16% ± 2.94%, 19.45% ± 2.73%, 25.01% ± 3.97%, respectively, which were significantly higher than that (5.81% ± 2.18%) in control group (P < 0.05).

CONCLUSIONLead acetate could remarkably induce the apoptosis of HK-2 cells and affect the kidney.

Apoptosis ; drug effects ; Cell Line ; Epithelial Cells ; cytology ; drug effects ; ultrastructure ; Humans ; Kidney Tubules, Proximal ; cytology ; drug effects ; ultrastructure ; Organometallic Compounds ; toxicity

We report a case of IgA kappa light chain deposition disease and combined adult Fanconi syndrome with Auer rod-like intracytoplasmic inclusions in plasma cells and proximal renal tubular cells in a 54-yr-old female. Cytochemical stainings revealed a strong acid phosphatase activity of the inclusions and weak periodic acid-Schiff positivity, whereas the reactions for peroxidase and alpha-naphthyl acetate esterase were negative. An immunostaining verified IgA-kappa inside the plasma cells. Kidney biopsy revealed Bence Jones cast nephropathy with kappa light chain positivity, and Congo red staining was negative. Electron microscopy showed needle-shaped crystals located in tubular epithelial cells.
Fanconi Syndrome/diagnosis/etiology/*pathology ; Female ; Humans ; *Immunoglobulin A/analysis ; Immunoglobulin kappa-Chains/analysis ; Inclusion Bodies/*ultrastructure ; Kidney Tubules, Proximal/pathology/*ultrastructure ; Middle Aged ; Paraproteinemias/*pathology ; Plasma Cells/pathology/*ultrastructure

OBJECTIVETo observe the transdifferentiation of renal tubular epithelial cells in tubulointerstitial fibrosis.

METHODSThe renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were kept 25 days after renal vein ligature. The kidneys were dissected every 5 days by killing 5 rats. The morphological changes of the kidney were observed by light microscopy, electron microscopy, polarizing microscopy and immunohistochemistry method.

RESULTSThe histological changes showed tubular atrophy and disappearance, widening of intertubular spaces with increased lymphocytes and mononuclear cells infiltration and fibrosis. The CK marker in injured and atrophic epithelial cells gradually weakened, but the alpha-SMA, vimentin, TGF-beta(1), collagen I and III showed gradually stronger positivity for immunohistochemistry. Some interstitial cells became positive for CK. Electron microscopy revealed decreased mitochondria, increased endoplasmic reticulum and microfilament of the tubular epithelial cells which merged into the interstitium. During the early stage of tubulointerstitial fibrosis, there was proliferation of type III collagen and then followed by type I collagen at later stage when observing the Sirius Red stained sections under the polarizing microscope.

CONCLUSIONTubular epithelial cells can transdifferentiate to fibroblasts during the process of tubulointerstitial fibrosis.

Actins ; analysis ; Animals ; Cell Differentiation ; Collagen ; analysis ; Epithelial Cells ; cytology ; Fibrosis ; Immunohistochemistry ; Keratins ; analysis ; Kidney Tubules ; chemistry ; pathology ; ultrastructure ; Male ; Rats ; Rats, Wistar

In order to clarify morphologic changes associated with cyclosporine (CS) nephrotoxicity, CS in ethyl alcohol at 25 mg/kg/day i.p. was administered to male Sprague-Dawley rats for periods of 1 to 8 weeks. Mean systolic BP was slightly increased in the CS group at 4 weeks (p < 0.05), but there was no difference compared to a control group at 8 weeks. Blood urea nitrogen was significantly elevated at 4 weeks and continued to rise (p < 0.005), whereas serum creatinine was elevated at 8 weeks. Microscopic examination of the kidneys from CS-treated rats at one week revealed cytoplasmic vacuolization in all segments of the proximal tubules, tubular inclusion bodies, and peritubular capillary congestion. Ultrastructurally, some vacuoles were neutral fat droplets, while others appeared as single membrane-bound structures due to dilatation of the endoplasmic reticulum. The tubular inclusion bodies were enlarged autolysosomes filled with distorted mitochondrial fragments. At two weeks, tubular regeneration was prominent, in addition to the above mentioned toxic tubulopathy. At four weeks, focal areas of interstitial fibrosis and tubular atrophy associated with cystic dilatation were seen. At 8 weeks, interstitial and intratubular microcalcification were present, in addition to patchy foci of interstitial fibrosis, but vascular lesions were not demonstrated. Although renal tubular changes characterized by vacuolization, inclusion bodies, and microcalcification and interstitial fibrosis are not specific for CS toxicity, these changes are commonly found in both humans and rats at high doses of CS.
Acute Disease ; Animal ; Body Weight/drug effects ; Chronic Disease ; Cyclosporine/*toxicity ; Immunosuppressive Agents/*toxicity ; Kidney Diseases/*chemically induced/*pathology ; Kidney Tubules/drug effects/pathology/ultrastructure ; Male ; Microscopy, Electron ; Rats ; Rats, Sprague-Dawley

No abstract available.
Asymptomatic Diseases ; Biological Markers/analysis ; Biopsy ; Crystallization ; Fluorescent Antibody Technique ; Humans ; Immunoglobulin Light Chains/*analysis ; Kidney Diseases/*diagnosis/immunology/pathology ; Kidney Tubules, Proximal/*immunology/ultrastructure ; Male ; Microscopy, Electron ; Proteinuria/*diagnosis/immunology/pathology

BACKGROUNDIntrarenal activation of the renin angiotensin system (RAS) plays an important role in mediating renal fibrosis. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II (AngII) receptor antagonists have been shown to exert a protective role against diabetic and non-diabetic nephropathy. However, the exact mechanism of how blocking local RAS prevents renal fibrosis is unclear. The present study was to investigate the influence of a new AngII receptor antagonist, irbesartan (Irb), on AngII-induced hypertrophy in human proximal tubular cell line (HK-2).

METHODSThe cell line, HK-2, was grown in Dulbeccos's Modified Eagle's Medium containing 10% heat-inactivated fetal calf serum. After rested in serum-free medium for 24 hours, the effects of Irb on AngII (10(-7) mol/L)-induced [(3)H]-leucine incorporation, total protein content (measured by the Coomassie brilliant blue G250 method), and change in cell size (determined by scanning electron microscopy) were observed. The influence of Irb on the cell cycle was analyzed by fluorescence activated cell sorter (FACS) flow cytometry.

RESULTSAngII induced cell hypertrophy in a time and dose dependent manner. Stimulation of cells with AngII for 48 hours resulted in a increase in [(3)H]-leucine incorporation [0 hour: (5584 +/- 1016) cpm/10(5) cells vs 48 hours: (10741 +/- 802) cpm/10(5) cells, P < 0.05], which was significantly attenuated by treatment with Irb. AngII significantly increased the total protein content in HK-2 cells [control: (0.169 +/- 0.011) mg/10(5) cells vs AngII group: (0.202 +/- 0.010) mg/10(5) cells, P < 0.05], which was also markedly inhibited by cotreatment with Irb (P < 0.01). Scanning electron microscopy showed that AngII induced an increase in average physical cell size, which was significantly inhibited by Irb [control: (11.92 +/- 1.62) microm; AngII group: (20.63 +/- 3.83) micro m; AngII + Irb group: (13.59 +/- 3.15) micro m; P < 0.01 vs control, respectively]. Furthermore, flow cytometry revealed that AngII arrested cells in the G(0)-G(1) phase, which was significantly reversed by treatment with Irb [G(0)-G(1) cells in AngII group: (76.09 +/- 1.82)%, in AngII + Irb group: (67.00 +/- 2.52)%, P < 0.05].

CONCLUSIONIrb can inhibit AngII-induced hypertrophy in HK-2 cells.

Angiotensin II ; pharmacology ; Angiotensin II Type 1 Receptor Blockers ; Biphenyl Compounds ; pharmacology ; Cell Cycle ; drug effects ; Cells, Cultured ; Humans ; Hypertrophy ; Kidney Tubules, Proximal ; drug effects ; pathology ; ultrastructure ; Protein Biosynthesis ; Tetrazoles ; pharmacology

To investigate whether a series of water-soluble cross-linked chitosan derivates synthesized in the guide of imprinting technology could be used as a uranium chelating agent to protect cells exposed to depleted uranium (DU), the imprinted chitosan derivates with high UO2(2+) chelating ability were screened, and cell model of human renal proximal tubule epithelium cells (HK-2) exposed to DU (500 micromol.L-1) was built, chitosan derivates (400 mg.L-1 ) was added to test group and diethylenetriaminepentaacetic acid (DTPA, 50 mg.L-1) was added to positive control group. The results showed that three Cu2+ imprinted chitosan derivates had higher uranium chelating ability (>49 microg.mg-1) than chitosan and non-imprinted chitosan derivates. Compared to the cells exposed to DU only, survival of cells in group added chitosan derivates rose up significantly (increased from 57.3% to 88.7%, and DTPA to 72.6%), and DU intracellular accumulation decreased, membrane damage and DNA damage also eased. Among the imprinted chitosan derivates, Cu2+ imprinted penta dialdehyde cross-linked carboxymethyl chitosan (Cu-P-CMC) was the best, and better than DTPA. From ultrastructure observation, the DU precipitates of test group added Cu-P-CMC were most grouped in a big hairy clusters in a string together outside cells. It is possible that the DU-chitosan derivates precipitates are too big to enter into cells, and from this way, the DU uptake by cells decreased so as to detoxication.
Antioxidants ; metabolism ; Apoptosis ; drug effects ; Cell Line ; Cell Survival ; drug effects ; Chelating Agents ; administration & dosage ; chemistry ; pharmacology ; Chitosan ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacology ; Copper ; chemistry ; pharmacology ; Cross-Linking Reagents ; administration & dosage ; chemistry ; pharmacology ; DNA Damage ; drug effects ; Epithelial Cells ; cytology ; ultrastructure ; Humans ; Inactivation, Metabolic ; Kidney Tubules, Proximal ; cytology ; ultrastructure ; Microscopy, Electron, Transmission ; Uranium ; toxicity ; Water