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Relationship between MRI and morphometric kidney measurements in diabetic and non-diabetic rats.

The aim of the present study was to determine the applicability of magnetic resonance imaging (MRI) as a non-invasive measure of kidney volume in vivo in diabetic and non-diabetic rats. Magnetic resonance, T1 weighted Spin Echo, images were obtained after injection of contrast in anesthetized control (N = 14) and hyperglycemic streptozotocin (STZ)-diabetic rats (N = 14). On MRI imaging the total kidney, cortex, medullary and pelvic volumes were calculated. Immediately after MRI measurements the left kidneys were removed before weighing either as a clamped kidney weight (that is, the kidney containing blood and urine) or as a wet kidney weight (the kidney drained of blood and urine), while the right kidneys were perfusion-fixed for morphometric measurements. On thin kidney slices obtained from perfusion-fixed kidneys the cortex, medullary and pelvic fractions were measured and subsequently the cortex, medulla and pelvic volumes were calculated. The cortical volume was measured according to three different approaches. The corticomedullary boundary was defined either to the arcuate arteries, to a curved line following the glomeruli, or to a line at the top of the medullary rays. Both in control and diabetic rats, MRI measured kidney volumes were similar to the volume of perfusion-fixed kidneys, while the clamped kidney weight, and in particular the wet kidney weights, were smaller than the MRI obtained volumes. Good agreement was found between the MRI measured cortex and medulla volumes when the cortex was defined to the top of the medullary rays in the morphometric analysis. In conclusion, the present study demonstrates that MRI allows a reliable non-invasive estimate of renal morphology at a macroscopic level in both diabetic and non-diabetic rats.

Animals↗

Age-associated changes in the kidney of the laboratory mouse.

This paper describes a qualitative and quantitative morphological investigation of the kidneys of male laboratory mice without macroscopic pathology at 6, 12, 24 and 34 months of age. In the 6- and 12-month old adults there were no signs of microscopic pathological changes in either the kidney cortex or medulla. However, at 24 and 34 months of age minor pathology, such as focal interstitial inflammation, was detected. In both these age groups there were a few glomeruli with sclerotic changes. There were no significant differences in the total volume of the kidneys, cortex, medulla or other structures with age. There was a significant increase in the diameter of the glomeruli with age but no change in the total numbers of glomeruli. The increase in volume of the glomerulus appears to be due to cellular components rather than changes in the blood vessels. It is concluded that in animals without macroscopic pathological changes there are only minor alterations in kidney structure with age, and that any alterations which do take place occur very late in the life span.

Age Factors↗

Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin.

BACKGROUND: Cold ischemic injury plays an important role in short- and long-term function of kidneys after transplant. Antimicrobial peptides have not previously been studied for their impact on cold ischemia in transplanted kidneys. METHODS: Bactenecin (L- and D-forms) was added to University of Wisconsin (UW) preservation solution for 3-day cold storage of dog kidneys. Effects on membrane permeability were studied in synthetic liposomes and in kidney cortex tissue slices. The role of bactenecin as a tissue mitogen and direct cytoskeletal stabilizer were studied with cultured cells and in vitro. RESULTS: Bactenecin (both L- and D- forms) resulted in significant decreases in postoperative serum creatinine and time required for return of creatinine to the normal range showing the effect was independent of chirality. Bactenecin permeabilized synthetic liposomes and altered kidney cortex tissue slice membrane permeability characteristics, irrespective of chirality. Neither did bactenecin act as a mitogen for either primary renal tubule or Madin-Darby canine kidney (MDCK) cells stored in UW solution, nor did it appear to directly affect cytoskeletal dynamics. CONCLUSIONS: These results show that the antimicrobial peptide bactenecin can improve the quality of static cold storage of kidneys. The mechanism of its action is independent of receptor binding and does not appear to involve either an effect on the cytoskeleton or via activity as a mitogen. Current evidence best supports the hypothesis that bactenecin protects against cold ischemic injury by a controlled permeabilization of the membranes of the kidney during cold storage.

Actins↗

Morphologic and biochemical abnormalities of kidney lysosomes in mice with an inherited albinism.

The light-ear mutation in the mouse may serve as a useful model for the human inherited oculocutaneous albinisms such as the Hermansky-Pudlak and Chédiak-Higashi syndromes. The authors have investigated the kidney lysosomes of le/le mutant mice by histochemical methods. A striking increase in the staining reaction for the lysosomal enzymes beta-galactosidase and acid-phosphatase was evident in kidney cortex of the mutant mice, in comparison with +/+ controls. The lysosomal protease, cathepsin C, is also found to be elevated in the mutant. By light microscopy, there appeared to be an increase in the number of lysosomes in mutant kidney. Electron microscopy revealed the presence of large, multilamellar granules in proximal tubule cells. Analysis of sedimentation through sucrose gradients demonstrated the presence of a low-density population of lysosomes in the mutant kidney. In addition, a striking accumulation of ceroidlike pigment was observed. The molecular lesions responsible for the melanolysosomal syndromes in mice and man are still unidentified.

Albinism↗

Immunoelectron microscopic localization of the electrogenic Na/HCO(3) cotransporter in rat and ambystoma kidney.

Immunofluorescence analysis has revealed that electrogenic Na(+)/HCO(3)(-) (NBC1) is expressed in the proximal tubule of rat kidney and in the proximal and distal tubules of the salamander AMBYSTOMA: tigrinum kidney. The present study was undertaken to define the detailed subcellular localization of the NBC1 in rat and AMBYSTOMA: kidney using high-resolution immunoelectron microscopy. For this purpose, two rabbit polyclonal antibodies raised against amino acids 928 to 1035 and amino acids 1021 to 1035 of the C-terminus of rat kidney (rkNBC1) were developed. The affinity-purified antibodies revealed a strong band of approximately 140 kD in immunoblots of membranes from rat kidney cortex but no signal in membranes isolated from outer and inner medulla. Deglycosylation reduced the apparent molecular weight to approximately 120 kD, corresponding to the predicted molecular weight. A similar but weaker band was also present in membranes isolated from the lateral part of Ambystoma: kidney. In rat kidney, immunohistochemistry confirmed the presence of rkNBC1 in convoluted segments of the proximal tubules. In ultrathin cryosections or Lowicryl HM20 sections from rat kidney cortex, distinct immunogold labeling was associated with the basolateral plasma membrane of segments S1 and S2 of proximal tubules, whereas in S3 no labeling was observed. The labeling density was similar at the basal and lateral plasma membrane and was specifically associated with the inner surface of the membrane consistent with the internal position of the C-terminus of the transporter. In contrast, rkNBC1 was absent from the apical plasma membrane and not observed in intracellular vesicles, including those closely associated with basolateral plasma membrane. In Ambystoma: kidney, a weak labeling was present in the basolateral membrane of the proximal tubule and stronger labeling was observed in the late distal segment. The results demonstrate that rkNBC1 is expressed only in segment S1 and segment S2 of rat proximal tubule as well as Ambystoma: proximal and late distal tubule and that rkNBC1 is present in both basal and lateral plasma membranes and absent in intracellular vesicles of the apical plasma membrane.

Ambystoma↗

Development of solute transport in rabbit proximal tubule. II. Morphologic segmentation.

We examined the segmental morphologic maturation of the proximal tubule in order to identify some of the factors influencing the development of solute transport. Proximal tubules from the outer, middle, and inner kidney cortex were obtained from rabbits during the entire period of development and studied using transmission and scanning electron microscopy, microdissection, and semiquantitative morphometric analysis. The location of the tubule in the cortex was established by identifying its own glomerulus. The 1-wk-old rabbit showed the most immature proximal tubules in the outer cortex and a gradation of more mature tubules toward the inner zone. Only the inner cortical tubules were segmented at this time. The outer cortical tubules showed limited development for the 1st 2-3 wk after birth, while the inner cortical tubules were morphologically mature by 3-4 postnatal wk. Morphometric analysis revealed that the areas of apical, basolateral, and mitochondrial membranes developed at similar rates. Clearly, morphologic maturation of proximal tubules was reached at different times depending on the cortical origin. We conclude that a serial developmental examination of transport in proximal tubules should require the careful identification of the origin of each tubule in the cortex; otherwise, time-dependent comparisons will be complicated by the inclusion of nephrons of diverse postnatal ages. In practice, at this time, the use of proximal tubules from the inner cortex throughout development, or from the outer cortex beyond 2-3 wk of age, permits such serial measurements and comparisons in the rabbit.

Absorption↗

Lipid composition of the rat kidney.

The lipid fractions free fatty acids, triglycerides, cholesterol, cholesterol esters and phospholipids of rat kidney cortex, outer and inner medulla were analyzed by thin-layer chromatography. The concentrations of 23 individual fatty acids in the lipid fractions of each zone were determined by gas chromatography; 14 of them were evaluated by an analysis of variance. For most of the lipid fractions a corticomedullary concentration gradient was found, the highest concentrations occurring in the cortex. The lipid classes primarily determined the pattern of individual fatty acid concentrations. A significant concentration difference between the three zones only existed for 4 of 14 fatty acids. Long chain fatty acids were found in a higher concentration in the phospholipids of cortex and outer medulla (about 95%) in comparison to the inner medulla (65%).

Animals↗

Glutamate metabolism in rat kidney mitochondria.

1. Kidney cortex mitochondria did not swell in ammonium or potassium salts of glutamate even in the presence of valinomycin or 2,4-dinitrophenol. Aminooxyacetate diminished the reduction of nicotinamide nucleotides in intact mitochondria in the presence of glutamate. 2. Transamination with oxaloacetate appeared to be the main pathway of glutamate metabolism in isolated rat kidney cortex mitochondria under various metabolic conditions. Ammonia formation was negligible. The gamma-aminobutyrate pathway was found to be of almost no importance.

Adenosine Diphosphate↗

The effects of natural exposure to high levels of zinc and cadmium in the immature pony as a function of age.

To study the effects of environmental exposure to zinc and cadmium in immature foals, five pregnant ponies were raised within 2.9 km of the New Jersey Zinc Smelter in Palmerton, Pennsylvania. The mares and their foals were kept outdoors on timothy hay and orchard grass. The foals were examined daily for signs of illness and blood samples were taken monthly for estimation of serum zinc, copper, and ceruloplasmin levels. The foals were sacrificed at 2.5, 4.5, 8.5, 13.5, and 18.5 months of age. Necropsy revealed generalized osteochondrosis in joints of the limbs and cervical vertebrae, lymphoid hyperplasia, and eosinophilia. Two of the foals had developed mild lameness. The concentrations of zinc, cadmium, copper, lead, magnesium, and calcium were determined in liver, kidney cortex, and pancreas. The concentration of cadmium and zinc were the only elements that were greatly elevated in all three tissues as compared to control animals. The concentration of cadmium was directly correlated with age in the three tissues (e.g., 23.9 to 212.7 micrograms/g wet wt in kidney cortex), whereas zinc was significantly increased (range 132 to 954 micrograms/g wet wt in liver) but there was no correlation with age. It was concluded that the development of osteochondrosis is associated with increased exposure to zinc and possibly cadmium. The classical signs of cadmium toxicosis, such as renal damage and osteomalacia, were not observed.

Aging↗

Potassium depletion stimulates mRNA expression of proximal tubule AT1 angiotensin II receptors.

Dietary potassium (K+) deficiency is associated with blood pressure elevation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effect of low [K+] on expression of kidney AT1 angiotensin receptors. In rabbits fed a K+-deficient diet for 14 days, plasma [K+] was significantly reduced compared to rabbits fed a standard diet (control: 4.06 +/- 0.12 vs. K+-deficient: 2.66 +/- 0.19 mmol/l; p < 0.001; n = 6-9). By Northern hybridization or RNase protection assays, dietary K+ deficiency caused an increase in mRNA expression for AT1 receptors in kidney cortex (43.5 +/- 12.9% increase vs. control; p < 0.04; n = 8), and in proximal tubule segments in suspension (76.4 +/- 28.8% increase vs. control; p < 0.005; n = 6). K+ deficiency had no effect on AT1 receptor mRNA expression in liver, or on mRNA expression of beta-actin in kidney cortex, proximal tubule suspensions, or liver. To determine if low extracellular [K+] might directly modulate AT1 receptor mRNA expression, primary cultures of rabbit proximal tubule cells were incubated for 1, 3, 6 or 24 h in media with or without 5 mmol/l K+. Incubation of cells in 0 mmol/l K+ caused a 99.2 +/- 32.9% increase in AT1 receptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h. Incubation of proximal tubule cells in 0 mmol/l K+ also caused a significant increase in basolateral membrane specific binding of [125I]-angiotensin II (p < 0.05; n = 4). These results indicate that dietary K+ deficiency and low extracellular [K+] stimulate expression of kidney AT1 angiotensin II receptors. Increased AT1 receptor mRNA and protein expression in proximal tubule may promote enhanced sodium reabsorption in K+ deficiency.

Angiotensin II↗

Decreased renal cytochrome P450 2C enzymes and impaired vasodilation are associated with angiotensin salt-sensitive hypertension.

Excess dietary salt intake differentially modulates the activity of cytochrome (CYP) P450 enzymes in kidney cortex. Exactly how increased angiotensin (Ang) II levels and hypertension change the regulatory effect of high salt on CYP450 enzymes remains unclear. The present study investigated the effects of combined administration of Ang II and a high-salt diet on P450 epoxygenase and hydroxylase protein levels in kidney, as well as afferent arteriolar responses to acetylcholine and sodium nitroprusside. High dietary salt administration for 14 days resulted in increased renal cortical CYP2C11 protein levels, and a significant increase of CYP2C11 and CYP2C23 protein levels in renal microvessels. Administration of Ang II in combination with a high-salt diet prevented the upregulation of renal cortical CYP2C11 protein expression observed with high dietary salt alone, and significantly downregulated expression of CYP2C11, CYP2C23, and CYP2J protein in renal microvessels. A high-salt diet alone decreased CYP4A protein in kidney cortex, and renal cortical CYP4A protein level remained at a low level in Ang II-infused rats treated with a high-salt diet. Increases in blood pressure during Ang II infusion were greater in rats fed a high-salt diet. In addition, afferent arteriolar responsiveness to acetylcholine and sodium nitroprusside was significantly attenuated in Ang II-treated rats versus controls. This decrease was significantly enhanced in Ang II-treated rats given a high-salt diet. These results support the hypothesis that an inability to upregulate CYP2C and maintain CYP2J in the rat kidney and impaired afferent arteriolar vasodilation with chronic Ang II infusion contribute to salt-induced elevation of arterial pressure.

Angiotensin II↗

Different vascular endothelial growth factor (VEGF), VEGF-receptor 1 and -2 mRNA expression profiles between clear cell and papillary renal cell carcinoma.

OBJECTIVES: To examine vascular endothelial growth factor (VEGF), VEGF-receptor-(R)1, and R2 mRNA levels in renal cell carcinoma (RCC), a tumour generally refractory to most medical therapy, but for which a potentially useful therapeutic alternative is inhibition of angiogenesis. PATIENTS AND METHODS: VEGF, VEGF-R1 and -R2 mRNA levels were analysed using the quantitative reverse transcription-polymerase chain reaction. RNA was extracted from 84 conventional (clear cell) RCCs (cRCC), 20 papillary (pRCC), six chromophobe (chRCC), and 27 corresponding kidney cortex tissues, obtained from 110 patients in whom high-quality RNA was available from the tumours (53 women and 57 men, mean age 64.7 years, range 25-85). RESULTS: The VEGF, VEGF-R1, and -R2 mRNA levels were higher in tumour than in kidney cortex tissues. Among the RCC types, cRCC had higher VEGF levels than pRCC. In cRCC, VEGF-R2 levels were higher in stage I-II than in more advanced stages. In pRCC, VEGF and VEGF-R2 levels were higher in stage III than in stage I-II tumours. In cRCC, patients with VEGF levels below the median had a significantly shorter survival time than those with higher levels. By contrast, in pRCC, VEGF, VEGF-R1 and -R2 RNA levels above the median were related to adverse survival. Using multivariate analysis in cRCCs, VEGF-R1 mRNA level was the last factor to be omitted after stepwise elimination analysis. CONCLUSION: VEGF and its receptors were associated with tumour stage and survival, but were not independent prognostic factors. Different RCC types had different expression patterns of VEGF and receptor mRNA levels. We conclude that different pathways might be involved in regulating angiogenesis in the specific RCC types. Detailed knowledge of angiogenesis in RCC is essential when designing new treatment trials where angiogenesis inhibition is used.

Adult↗

The production and characterization of a monoclonal antibody specific for the 94,000 dalton enkephalin-degrading peptidase from rabbit kidney brush border.

We have prepared a monoclonal antibody specific for a major 94,000 dalton protein from the brush border membrane of rabbit kidney cortex. The monoclonal antibody was used for the immunoaffinity purification of this protein after solubilization of brush border membranes with octylglucoside. The 94,000 dalton protein is a peptidase capable of cleaving the Gly3-Phe4 bond of methionine-enkephalin. Identification of this peptidase as a previously described 94,000 dalton enkephalinase of kidney cortex was confirmed by its sensitivity to EDTA and inhibitors such as thiorphan and phosphoramidon.

Aminopeptidases↗

Expression of a rabbit renal ascorbic acid transporter in Xenopus laevis oocytes.

We examined the expression of renal ascorbic acid transporter(s) in Xenopus laevis oocytes after microinjection of cells with poly(A)+ RNA extracted from rabbit kidney cortex. Concomitant expression of the Na+-glucose cotransporter served as a control in these studies. Injection of poly(A)+ RNA into oocytes produced over a fivefold increase in the uptake of [14C]ascorbic acid (570 microM) compared with water-injected cells. Size fractionation of the kidney cortex mRNA by sucrose gradient revealed that the mRNA species that induced ascorbic acid transporter expression in oocytes was present in a fraction centered around 2.0 kilobases (kb) and had a size range of 1.8-3.1 kb. Injection of the active fraction into oocytes produced a > 40-fold increase in ascorbic acid uptake compared with water-injected controls. Expression of ascorbic acid transporter(s) was noticeable as early as 2 days after injection and was maximal after 7 days; it was also dependent on the amount of mRNA injected into oocytes. The induced uptake of [14C]ascorbic acid after injection of mRNA into oocytes was 1) Na+ dependent, as indicated by the almost complete lack of transport on removal of Na+ from the incubation medium; 2) significantly inhibited by unlabeled ascorbic acid and its structural analogue isoascorbic acid but not by D-glucose; and 3) saturable as a function of increasing the substrate concentration in the incubation medium (100-1,000 microM), with an apparent Km of 258 +/- 72.5 microM and a maximum velocity of 29.6 +/- 2.8 pmol.oocyte-1.2 h-1. These data demonstrate that X. laevis oocytes are a suitable system to functionally express the mammalian renal ascorbic acid transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels.

Mice were exposed to cadmium (Cd) concentrations ranging from 0 to 100mg CdCl(2)/l in the drinking water for 1, 4, 8, 16 and 23 weeks. Urine samples were taken regularly, Cd content was determined in blood, liver, kidney and urine and histological analyses of the kidney were performed. Kidney cortex Cd content increased linearly with time and dose, while blood levels reached a plateau at 8 weeks and liver at 16 weeks in mice exposed to 100mg CdCl(2)/l after which both started to decrease. Urinary Cd levels were not correlated with the kidney Cd content. A multivariate regression model taking into account the actual Cd intake, calculated from the volume of water taken in by each animal and the exposure concentration, confirmed that blood is an indicator of acute exposure, while kidney Cd content is a reliable indicator of chronic exposure. The urinary protein content was significantly increased from 16 weeks on in mice exposed to 100mg CdCl(2)/l (p<0.05), while other signs of proximal tubular damage (glucosuria, enzymuria) were not detected. Histologically more vacuoles and lysosomes were present in the proximal tubule cells with increasing time and dose. The results indicate that chronic exposure to low doses of Cd induced functional and histological signs of early damage at concentrations in or below the ones generally accepted as safe. Our study does not corroborate the statement that urine Cd levels are a reliable indicator of total Cd body burden, at least when the body burden is low.

Administration, Oral↗

Human uridine diphosphate-glucuronosyltransferase UGT2B7 conjugates mineralocorticoid and glucocorticoid metabolites.

Mineralocorticoid and glucocorticoid hormones are metabolized as glucuronide conjugates. Using labeled [(14)C]uridine diphosphate glucuronic acid and microsomal preparations from human embryonic kidney 293 cells stably expressing the different human and monkey uridine diphosphate glucuronosyltransferase (UGT)2B enzymes, it is demonstrated that the two human allelic variants UGT2B7H((268)) and UGT2B7Y((268)) conjugate aldosterone, its A-ring reduced metabolites (5alpha-dihydroaldosterone and 3alpha,5beta-tetrahydroaldosterone), and both 5alpha- and 5beta-tetrahydrocortisone epimers. The two variants of UGT2B4 also glucuronidate tetrahydroaldosterone, whereas all enzymes tested were inefficient to produce cortisol glucuronide derivatives. Kinetic analyses reveal that UGT2B7 polymorphisms glucuronidate mineralocorticoids with a 5.5- to 20-fold higher affinity than glucocorticoids. For the first time, a significant difference between the two allelic variants of UGT2B7 is described, because UGT2B7H((268)) possesses an 11-fold higher aldosterone glucuronidation efficiency (ratio Vmax((app.))/Km((app.))) than UGT2B7Y((268)). RT-PCR experiments demonstrate the expression of UGT2B7 in human kidney and in renal proximal tubule epithelial cells, suggesting that mineralocorticoids and glucocorticoids are metabolized in their target tissue. Measurement of aldosterone glucuronidation and normalization with the UGT2B protein contents in monkey tissues demonstrate that liver and kidney glucuronidate this hormone with a similar velocity. Immunohistochemical studies performed in monkey kidney cortex reveal a restrictive expression of UGT2B proteins in the epithelial cells of the proximal tubules. Because expression of the mineralocorticoid receptor was detected in the distal tubule epithelial cells, the present data suggest a two-cell mechanism of aldosterone action and metabolism in the kidney.

Aldosterone↗

Chloride channels of intracellular organelles and their potential role in cystic fibrosis.

Chloride channels were previously purified from bovine kidney cortex membranes using a drug affinity column. Reconstitution of the purified proteins into artificial liposomes and planar bilayers yielded chloride channels. A 64 x 10(3) M(r) protein, p64, identified as a component of this chloride channel, was used to generate antibodies which depleted solubilized kidney membranes of all chloride channel activity. This antibody has now been used to identify a clone, H2B, from a kidney cDNA library. Antibodies, affinity-purified against the fusion protein of H2B, from a kidney cDNA library. Antibodies, affinity-purified against the fusion protein of H2B, also depleted solubilized kidney cortex from all chloride channel activity. The predicted amino acid sequence of p64 shows that it contains two and possibly four putative transmembrane domains and potential phosphorylation sites by protein kinases A and C. There was no significant homology to other protein (or DNA) sequences in the data base including other anion channels or the cystic fibrosis transmembrane conductance regulator. The protein is expressed in all cells tested and probably represents the chloride channel of intracellular organelles. Cystic fibrosis (CF) is associated with a defect in a cyclic-AMP-activated chloride channel in secretory epithelia which leads to decreased fluid secretion. In addition, many mucus glycoproteins show decreased sialylation but increased sulfation. We have recently shown that the pH of intracellular organelles is more alkaline in CF cells, an abnormality that is due to defective chloride conductance in the vesicle membranes. We postulate that the defect in the intracellular chloride channel, and hence the alkalization, could explain the glycosylation abnormalities since the pH optimum of Golgi sialyltransferase is acid while that of focusyl- and sulfotransferases is alkaline. Defects in sialyation of glycolipids might also generate receptors for Pseudomonas, which is known to colonize the respiratory tract of CF patients.

Adenosine Triphosphatases↗

Complete analysis of the trace elements of the kidney.

The distribution of trace elements in kidney cortex and medulla and in their subcellular fractions was studied by inductively coupled plasma mass spectrometry (ICP-MS). This technology allows the analysis of almost all the elements of the periodic table, along with their isotopes, in the same experiment. Acid digestion of the tissue (samples) was required before ICP-MS elemental analysis. Mineralization in 8 N nitric acid for 2 min in a Parr microwave acid digestion bomb, inside a regular microwave oven working at medium power, gave good sensitivity and reproducible results. Trace element determinations could be precisely performed, despite the presence of a considerable amount of organic matter. Cortex/plasma and medulla/plasma inorganic ratios were taken as indicators of the inorganic bioaccumulation. The highest enrichment factors of elements found in the cortex were Mn greater than Co greater than Tl greater than Zn greater than Rb greater than Mo greater than Cu and the highest element enrichments of the medulla were Tl greater than Mn greater than Co greater than Rb greater than Zn greater than Bi greater than Mo greater than Ni greater than Cu. Subcellular fragmentation of the kidney cortex and medulla indicated that the majority of the trace elements was located in the cytosolic fraction. The membrane fraction of the medulla contained significant amounts of Hg and Al: 120.7 and 32.0 mg/g protein, respectively. Cu and Zn were the most abundant trace elements found in the brush border membrane from the cortex: 120.7 and 68.2 mg/g protein, respectively. These quantities are largely in excess of what is bound, for example, to alkaline phosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗