Cell Proliferation in the Developing Human Kidney

1998 ◽  
Vol 1 (1) ◽  
pp. 49-55 ◽  
Author(s):  
T. Nadasdy ◽  
G. Lajoie ◽  
Z. Laszik ◽  
K.E. Blick ◽  
G. Molnar-Nadasdy ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Renal Cell ◽  
Human Kidney ◽  
Proximal Tubules ◽  
Nuclear Antigen ◽  
Proliferation Index ◽  
Cell Populations ◽  
Collecting Ducts ◽  
Microscopic Features ◽  
Distal Tubules

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33–43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.

scholarly journals Proliferative activity of intrinsic cell populations in the normal human kidney.

1994 ◽  
Vol 4 (12) ◽  
pp. 2032-2039 ◽  
Author(s):  
T Nadasdy ◽  
Z Laszik ◽  
K E Blick ◽  
L D Johnson ◽  
F G Silva
Keyword(s):  
Renal Cell ◽  
Proliferative Activity ◽  
Human Kidney ◽  
Capillary Endothelium ◽  
Cell Populations ◽  
Tubular Epithelium ◽  
Paraffin Sections ◽  
Ki 67 ◽  
Collecting Ducts ◽  
Normal Human

The proliferative activity of various normal human renal cell populations is unknown. Recently, antibodies to cell proliferation-associated nuclear proteins, such as proliferating cell nuclear antigen (PCNA) and KI-67, which are applicable to archival paraffin sections, became available. With antibodies to PCNA and Ki-67 after microwave pretreatment of the paraffin sections, the proliferation indexes (ratio of positive nuclei with PCNA and Ki-67 antibodies/all nuclei counted x 100, i.e. percentage of positive cells) of 12 different intrinsic renal cell populations in 20 normal human kidneys have been determined. The following proliferation indexes (percentages of positive cells) were found with the PCNA and the Ki-67 antibodies, respectively: proximal tubular epithelium, 0.22, 0.24; thin limb of Henle, 0.29, 0.30; thick ascending limb of Henle, 0.32, 0.29; distal tubular epithelium (distal convoluted tubules and cortical collecting ducts, 0.33, 0.44; medullary collecting ducts, 0.32, 0.3; glomerular mesangial cells, 0.07, 0.12; glomerular visceral epithelial cells, 0.04, 0.08; glomerular parietal epithelial cells, 0.07, 0.1; glomerular capillary endothelium, 0.42, 0.47; peritubular capillary endothelial cells, 0.38, 0.43; endothelium of large intrarenal vessels (arteries and veins), 0.09, 0.12. Thus, normally capillary endothelium (glomerular and peritubular) appears to have the highest proliferation index in the human kidney by these techniques. These results indicate major variation in the proliferative activity of normal human renal cell populations, along with a significant correlation between PCNA and Ki-67 staining. Furthermore, this study provides normal values for the proliferative activity of different human renal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Ochratoxin A and Citrinin Induced Nephrosis in Beagle Dogs II. Pathology

1977 ◽  
Vol 14 (3) ◽  
pp. 261-272 ◽  
Author(s):  
D. N. Kitchen ◽  
W. W. Carlton ◽  
J. Tuite
Keyword(s):  
Ochratoxin A ◽  
Proximal Tubules ◽  
Lymphoid Tissues ◽  
Tubular Epithelial Cells ◽  
Beagle Dogs ◽  
Peripheral Lymph ◽  
Collecting Ducts ◽  
Gross Lesions ◽  
Colon And Rectum ◽  
Distal Tubules

Beagle dogs were given ochratoxin A (0.1 and 0.2 mg/kg) and citrinin (5 and 10 mg/kg) alone and in two dose combinations for 14 days. The gross lesions included focal peritonitis and intestinal intussusceptions in dogs given citrinin. Changes in the kidneys of dogs given ochratoxin A were degeneration and necrosis with desquamation of tubular epithelial cells, primarily in the straight segment of the proximal tubules. Dogs given 10 mg/kg citrinin had similar changes in the distal tubules and collecting ducts. Dogs given combined doses of citrinin and ochratoxin A had degeneration and necrosis in proximal and distal tubules, and in thin segments and the collecting ducts; there were desquamated cells and granular casts in the lumina. Dogs given ochratoxin A had necrosis of lymphoid tissues in the spleen, tonsil, thymus, peripheral lymph nodes and lymph nodules of the ileum, colon and rectum. There was ulceration of the mucosa of the intestine in dogs given large combined doses of ochratoxin A and citrinin.

R403 – Epidermal Proliferating Cell Nuclear Antigen in Aging Rats

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P178-P178 ◽  
Author(s):  
Tapan K Bhattacharyya ◽  
Paula Jackson ◽  
J Regan Thomas
Keyword(s):  
Cell Proliferation ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Proliferation Index ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Age Related ◽  
Two Parameters ◽  
Proliferating Cell ◽  
Effect Of Age

Problem To determine if epidermal cell proliferation in colony-raised Fischer 344 rats changes with age and diet. Methods Fischer 344 rats fed ad libitum and calorie-restricted (CR) diets were obtained from the NIA colonies, and young, young adult, and old animals from both groups were used for this study (six in each group). Tissue sections from the dorsal skin (DS) and foot plate (FP) were used for immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The proliferation index (PCNA-I) was computed from counts of stained and total number of keratinocytes. Simultaneous measurements of epidermal thickness were obtained from same sections. Data were analyzed with Excel and SPSS 14.0 software for statistics. Results Two-way analysis of variance (ANOVA) was applied to the data to probe the effect of age, diet, and age-diet interaction. A significant effect of age was noticed in the two parameters i.e., DS PCNA (F 3.96, P .011), FP epidermal width (F 3.37, P .021) and FP PCNA-I (F 9.0, P .000). A significant correlation between DS width and PCNA values was also noted (r 0.5, P .01). Conclusion There is a trend of reduction of PCNA positive cells with increasing age irrespective of thickness of epidermis, and this trend is more apparent in CR rats. Significance This cell proliferation study has implications in relation to CR effect on age-related disease conditions, and biogerontology. Support The study was partially funded by the 2007 Leslie Bernstein grant from AAFPRS foundation.

scholarly journals Evaluation of the Role of Na+/ K+ ATPase Ion Transporters and Na+/K+/ 2Cl and Na+/H+ Exchanger Cotransporters in Nephrons of Periophthalmus Waltoni Using Immunohistochemistry and Histology

2021 ◽  
Author(s):  
Kave Esfandiari ◽  
Mohammad Babaei ◽  
Mina Amiri-Farahani ◽  
Ali Kalantari-Hesari ◽  
Hassan Morovvati
Keyword(s):  
Epithelial Cells ◽  
Kidney Tissue ◽  
Proximal Tubules ◽  
Renal Tubules ◽  
Ion Regulation ◽  
Renal Histology ◽  
Collecting Ducts ◽  
Distal Tubules ◽  
Periophthalmus Waltoni

Abstract Kidneys play an important role in regulating the balance of water and ions in freshwater and seawater fish. However, complex kidney structures impair a comprehensive understanding of kidney function. In this study, in addition to renal histology, Na+/K+/ATPase ion transporter proteins and Na+/K+/2Cl− and NHE3 cotransporters were located in Priophthalmus waltoni kidney tissue to evaluate the ion regulation abilities of epithelial cells in various parts of nephrons. The renal tubules are composed of proximal tubules and distal tubules, followed by collecting tubes and finally collecting ducts. Light microscope immunohistochemistry was utilized to locate Na+/ K+-ATPase along renal tubules and collecting ducts. However, the distribution of the Na+/K+-ATPase immune response varies in different sections. Na+/K+/CL− cotransporter positioning was reported only in collecting tubes and collecting ducts, and proximal tubes and distal tubes did not respond to Na+/K+/Cl− cotransporter immunolocalization. Immunohistochemical response for NHE3 localization was detected only at the apex of epithelial cells of proximal tubules and collecting tubes. The distal tubes showed negative reaction and the collecting ducts showed a weak response to NHE3 safety immunolocalization.

Renal excretion of uric acid in the rat: a micropuncture and microperfusion study

1976 ◽  
Vol 230 (3) ◽  
pp. 768-776 ◽  
Author(s):  
F Roch-Ramel ◽  
F Diezi-Chomety ◽  
D De Rougemont ◽  
M Tellier ◽  
J Widmer ◽  
...  
Keyword(s):  
Uric Acid ◽  
Renal Excretion ◽  
Proximal Tubules ◽  
Free Flow ◽  
Collecting Ducts ◽  
Order Of Magnitude ◽  
Plasma Urate ◽  
Distal Tubules

Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption.

scholarly journals Light-Microscopic Immunocytochemistry for Gentamicin and Its Use for Studying Uptake of the Drug in Kidney

2009 ◽  
Vol 53 (8) ◽  
pp. 3302-3307 ◽  
Author(s):  
Kunio Fujiwara ◽  
Masashi Shin ◽  
Hayato Matsunaga ◽  
Tetsuya Saita ◽  
Lars-Inge Larsson
Keyword(s):  
Renal Toxicity ◽  
Rat Kidney ◽  
Proximal Tubules ◽  
Proximal Tubule Cells ◽  
Collecting Ducts ◽  
Immunocytochemical Method ◽  
Tubule Cells ◽  
Distal Tubules ◽  
Pretreatment Conditions ◽  
Single Intravenous Administration

ABSTRACT Gentamicin (GM) is a widely used antibiotic but shows renal toxicity. We produced a serum against GM (anti-GM) conjugated to bovine serum albumin with N-(gamma-maleimidobutyryloxy)succinimide. The antiserum was monospecific for GM and did not cross-react with the analog streptomycin, tobramycin, kanamycin, or amikacin. The antiserum also detected glutaraldehyde-fixed GM, and this enabled us to develop an immunocytochemical method for detecting the uptake of GM in rat kidney. Twelve hours after a single intravenous administration of GM, immunocytochemistry revealed that GM accumulated in the S1, S2, and S3 segments of the proximal tubules, as well as in the distal tubules and collecting ducts. By 12 h after injection, the drug was detected in cytoplasmic granules of the proximal tubule cells. However, early (1 h) after injection, drug accumulation was detected in the microvilli of these cells. The distal tubules and collecting ducts contained scattered swollen cells, reminiscent of necrotic cells, in which both the nuclei and the cytoplasm reacted strongly with GM. No staining occurred in the kidneys of saline-injected control rats. These results agree with previous studies showing that GM is endocytosed in the proximal tubules and accumulates in lysosomes. Additionally, our results show that GM also accumulates in the distal tubules and collecting ducts. This was achieved by systematically varying the pretreatment conditions—an approach necessary for detecting GM in different subcellular compartments. This approach should be useful for accurately detecting the uptake and toxicity of the antibiotic in different tissues.

scholarly journals Outbreaks of Renal Failure Associated with Melamine and Cyanuric Acid in Dogs and Cats in 2004 and 2007

2007 ◽  
Vol 19 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Cathy A. Brown ◽  
Kyu-Shik Jeong ◽  
Robert H. Poppenga ◽  
Birgit Puschner ◽  
Doris M. Miller ◽  
...  
Keyword(s):  
Renal Failure ◽  
Cyanuric Acid ◽  
Interstitial Fibrosis ◽  
Renal Tissue ◽  
Proximal Tubules ◽  
Hepatic Enzyme ◽  
Pet Food ◽  
Histologic Change ◽  
Collecting Ducts ◽  
Distal Tubules

Sixteen animals affected in 2 outbreaks of pet food-associated renal failure (2 dogs in 2004; 10 cats and 4 dogs in 2007) were evaluated for histopathologic, toxicologic, and clinicopathologic changes. All 16 animals had clinical and laboratory evidence of uremia, including anorexia, vomiting, lethargy, polyuria, azotemia, and hyperphosphatemia. Where measured, serum hepatic enzyme concentrations were normal in animals from both outbreaks. All animals died or were euthanized because of severe uremia. Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. Crystals and histologic appearance were identical in both outbreaks. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. These results indicate that the pet food-associated renal failure outbreaks in 2004 and 2007 share identical clinical, histologic, and toxicologic findings, providing compelling evidence that they share the same causation.

scholarly journals Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats

2019 ◽  
Vol 41 (11) ◽  
pp. 668-672
Author(s):  
Luana Grupioni Lourenço Antônio ◽  
Julio Cesar Rosa-e-Silva ◽  
Deborah Juliani Machado ◽  
Andrezza Telles Westin ◽  
Sergio Britto Garcia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Uterine Horn ◽  
Nuclear Antigen ◽  
Proliferation Index ◽  
Lesion Area ◽  
Group Iii ◽  
Group I ◽  
Significant Difference ◽  
Female Wistar Rats ◽  
Experimentally Induced

Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2, p = 0.023) and Group III (48.6 mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.

The effect of chronic hydrochlorothiazide administration on renal function in the rat

1986 ◽  
Vol 70 (4) ◽  
pp. 379-387 ◽  
Author(s):  
S. J. Walter ◽  
D. G. Shirley
Keyword(s):  
Filtration Rate ◽  
Distal Tubule ◽  
Inhibitory Effect ◽  
Proximal Convoluted Tubule ◽  
Proximal Tubules ◽  
Fluid Delivery ◽  
Collecting Ducts ◽  
Single Nephron ◽  
Distal Tubules ◽  
The Difference

1. Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7–10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. 2. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. 3. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. 4. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. 5. It is concluded that the return of sodium excretion to control levels during chronic hyrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. 6. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.

Preneoplastic and Neoplastic Lesions of Rat Hereditary Renal Cell Tumors Express Markers of Proximal and Distal Nephron

1995 ◽  
Vol 32 (4) ◽  
pp. 379-386 ◽  
Author(s):  
D. C. Wolf ◽  
H. E. Whiteley ◽  
J. I. Everitt
Keyword(s):  
Renal Cell ◽  
Collecting Duct ◽  
Lectin Binding ◽  
Proximal Tubules ◽  
Surface Glycoprotein ◽  
Distal Nephron ◽  
Con A ◽  
Cell Surface Glycoprotein ◽  
Renal Cell Tumors ◽  
Distal Tubules

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

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