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Biomedical subjects

D C Harris

Publications and source records attributed to D C Harris.

At least 73 records · Page 4Linked to original sources
PubMed1990

Lead intoxication in an anuric patient: management by intraperitoneal EDTA.

Treatment of lead intoxication with intravenous ethylene-diamine-tetra-acetic acid (EDTA) depends on the urinary excretion of chelated lead. This route of excretion was absent in a 48-year-old patient with childhood lead exposure and end stage renal failure who developed encephalopathy and a rapidly progressive neuropathy thought to be due to acute lead intoxication. Diagnosis was confirmed by lead chelation with EDTA and neurophysiological studies. EDTA was added by the patient to her chronic ambulatory peritoneal dialysis (CAPD) fluid each week and chelated lead excreted in the dialysate. Intraperitoneal administration of EDTA was 70% as efficient in removing lead as intravenous administration. Four months of home chelation therapy was associated with resolution of the encephalopathy but no improvement in the peripheral neuropathy.

Anuria↗
PubMed1990

Attenuation of hypermetabolism in the remnant kidney by dietary phosphate restriction in the rat.

In vivo energy metabolism in remnant and normal kidney nephrons and the effect of dietary phosphate restriction on energy metabolism were studied. Tissue concentrations of ATP did not differ between remnant and normal kidneys; however, the tissue concentration of inorganic phosphate (Pi) was higher in remnant kidneys (1.17 +/- 0.10 vs. 0.82 +/- 0.09 mumol/g, P less than 0.05) as assessed by 31P-nuclear magnetic resonance (NMR). Intracellular pH was also higher in remnant kidneys (7.48 +/- 0.04 vs. 7.20 +/- 0.05, P less than 0.01), as was oxygen consumption (QO2) when normalized for rate of net tubular sodium reabsorption (Tna; 0.032 +/- 0.005 vs. 0.018 +/- 0.002 mumol.min-1.g-1, P less than 0.01). Compared with glycine supplemented controls, dietary phosphate restriction induced by the phosphate binder diaminodihydroacetoacetate, a maneuver which independently of protein restriction has been shown to ameliorate the progression of chronic renal failure, resulted in no major change in tissue levels of ATP, intracellular pH, or TNa+ but decreased Pi (0.62 +/- 0.07 vs. 1.40 +/- 0.11 mumol/g, P less than 0.01) and QO2 (4.0 +/- 0.4 vs. 7.7 +/- 1.0 mumol.min-1.g-1, P less than 0.01) in remnant kidneys. For the amount of sodium reabsorption performed, remnant kidneys are hypermetabolic, and this hypermetabolism is attenuated by dietary phosphate restriction. These data suggest that hypermetabolism may be involved in the tubulointerstitial mechanisms operant in the progression of chronic renal failure that occurs in the rat remnant kidney, and that attenuation of this abnormality may be the mechanism by which dietary phosphate restriction ameliorates this process.

Animals↗
PubMed1989

Hydroxyl radical production during oxidative deposition of iron in ferritin.

The chemistry of oxidative deposition of iron(III) in ferritin and apoferritin is poorly understood. This study was undertaken to look for radicals formed as the hydrous ferric oxide core is developed from Fe(II) and O2. Radicals were observed indirectly by using the spin-trapping reagent N-tert-butyl-alpha-phenylnitrone (PBN) at room temperature and directly by measuring ESR spectra of frozen solutions at 77 K. In both instances, radical production was inhibited by the hydroxyl radical scavenging agents dimethyl sulfoxide, thiourea, and mannitol and enhanced by the addition of hydrogen peroxide. These findings strongly suggest that hydroxyl radical, produced from the iron-catalyzed Haber-Weiss reaction, is a by-product of core formation in ferritin and is a precursor to the observed radicals. The yield of ESR-observable and spin-trapped radicals is quite low, being at the micromolar level when millimolar concentrations of ferrous ion are employed. Furthermore, radical production appears to be confined to the interior of the ferritin molecule, where cellular components would be protected from the oxygen-derived toxic effects of iron. It is postulated that hydroxyl radical-medicated oxidative damage to the protein, a process that may contribute to the formation of hemosiderin from ferritin, leads to the observed radicals. By serving as a sink for hydroxyl radical, the protein shell may therefore efficiently minimize damage to other biomolecules in the cell.

Apoferritins↗
PubMed1989

Preliminary X-ray diffraction analysis of human chorionic gonadotropin.

Hexagonal bipyramidal crystals of deglycosylated human chorionic gonadotropin have been grown using the method of vapor diffusion against ammonium sulfate. These crystals grow to nearly 0.4 mm along each axis, diffract to better than 3.5-A resolution and are relatively stable to irradiation. The crystals belong to the hexagonal space group P6(1)22 or enantiomer, and have unit cell parameters a = b = 88.7 A and c = 177.3 A.

Chorionic Gonadotropin↗
PubMed1989

Carcinoid tumour in the lacrimal gland.

A case of carcinoid tumour in the lacrimal gland is described, thought to be a metastasis from a known primary lesion in the mediastinum. The results of light and transmission electron microscopic examination are presented, and the possibility of the lesion representing a second primary tumour discussed.

Aged↗
PubMed1988

Radicals from "Good's" buffers.

Oxidative deposition of iron in ferritin or the autoxidation of iron in the absence of protein produces radicals from Good's buffers. Radical species are formed from the piperazine ring-based buffers Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Epps 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid, and Pipes 1,4-piperazinediethanesulfonic acid, but not from Mes (4-morpholineethanesulfonic acid) which contains a morpholine ring. The radicals all have half-lives around 10 min and display very similar electron paramagnetic resonance spectra consisting of at least 30 lines. The Hepes radical can be formed by the addition of potassium superoxide directly to the buffer and its production during iron(II) autoxidation is inhibited by superoxide dismutase (EC 1.15.1.1). Catalase (EC 1.11.1.6) accelerates the decay of the EPR spectrum. Thus the buffer radicals are secondary radical species produced from oxygen radicals formed during the iron catalyzed Haber-Weiss process. The deoxyribose/thiobarbituric acid assay for hydroxyl radical production shows that Hepes is an effective hydroxyl radical scavenging agent. The Hepes radical can also be formed electrolytically at a potential of +0.8 V (vs standard hydrogen electrode). Oxidation of Hepes at pH 10 during the autoxidation of iron(II) or by the addition of hydrogen peroxide produces a nitroxide radical. These results indicate that piperazine ring Good buffers should be avoided in studies of redox processes in biochemistry.

Buffers↗
PubMed1988

Hemangiopericytoma of the median nerve.

This is a case report of a hemangiopericytoma located within the median nerve at the wrist in a 79-year-old man. The tumor was removed without loss of function.

Aged↗
PubMed1988

Phosphate restriction reduces proteinuria of the uninephrectomized, diabetic rat.

Proteinuria is the clinical hallmark of diabetic nephropathy and the harbinger of progressive renal disease. Therefore, the present study was designed to examine the effect of phosphate restriction on the proteinuria of streptozotocin-induced diabetes mellitus in the rat. Uninephrectomy was performed in experimental and control groups to worsen the degree of diabetic nephropathy. Proteinuria was prevented in Sprague-Dawley rats treated with the intestinal phosphate binder, dihydroxyaluminum aminoacetate (DHAAA) (24.75 +/- 20.35 mg/d at 3 months v control, 77.45 +/- 44.72 mg/d, P less than 0.001); an effect that was independent of protein and caloric intake, plasma albumin and lipids, severity of diabetes, mean arterial pressures, cardiac output, and renal calcium accumulation. The effect of DHAAA on protein excretion and glomerular hemodynamics was examined in similarly prepared Munich-Wistar rats; these rats did not tolerate long-term studies. Three weeks of DHAAA again caused a consistent fall in proteinuria (5.98 +/- 7.28 v 34.94 +/- 24.28 mg/d) and in transmembrane hydraulic pressure difference (41.1 +/- 1.2 v 46.4 +/- 2.8 mm Hg, P less than 0.005). In conclusion, phosphate restriction significantly decreases the proteinuria of Sprague-Dawley and Munich-Wistar uninephrectomized rats with streptozotocin-induced diabetes mellitus. Micropuncture of Munich-Wistar rats suggests that a reduction of intraglomerular pressure may be at least partially responsible for such an effect.

Aluminum Hydroxide↗
PubMed1988

Tubular hypermetabolism as a factor in the progression of chronic renal failure.

Thus, in summary, we hypothesize that nephron loss by a time-limited insult (eg, an acute immunological insult, surgical removal of five sixths of normal nephrons) may cause events in the tubules of the remaining nephrons that contribute substantially, though not exclusively, to the inexorable progression to ESRD. Specifically, hypermetabolism in the remaining tubules as assessed by oxygen consumption and ATP synthesis rates has been found to occur. This hypermetabolism in residual nephrons appears to be due to the known increased sodium transport per nephron, but nonsodium transport events also appear to be involved. With respect to the latter phenomenon, we propose that an increase in growth factor response per tubule, as a mechanism of renal hypertrophy, activates the DAG----protein kinase C----Na/H antiporter system. We have evidence in support of this sequence of events by the demonstration of a two-fold increase in membrane (particulate) protein kinase C within 24 hours after removal of the contralateral kidney and an increase in intracellular pH as assessed by NMR spectroscopy. Activation of the Na/H antiporter not only leads to proton extrusion and cellular alkalinization, which may activate cellular alkalinization, which may activate cellular enzymes such as phospholipases, but also increases intracellular Na concentration, thereby further increasing Na/K-ATPase, ATP use, and enhancing ATP synthesis. The increase in mitochondrial oxygen consumption, which accompanies the enhanced ATP synthesis, would be expected to be associated with increased oxygen radicle generation. If the tissue scavengers of oxygen radicles are not sufficient to scavenge the increase in oxygen radicles, then lipid peroxidation and tissue damage will occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Remnant kidney hypermetabolism and progression of chronic renal failure.

To investigate the mechanisms whereby verapamil and dietary phosphate restriction slow progression of nephron loss after renal ablation, the effects of these maneuvers on inulin clearance (CIn), net sodium reabsorption (TNa+), oxygen consumption (QO2), and net glucose production (GP) were examined in isolated perfused normal and remnant kidneys. Preliminary studies characterized the isolated perfused remnant kidney perfusion. Adaptation to renal ablation was greater for QO2 (102% of normal), GP (138%), and kidney weight (79%) than CIn (51%) or TNa+ (40%). Verapamil (50 microM) lowered QO2 in remnant kidneys (1.64 +/- 0.24 vs. control 2.86 +/- 0.16 mumol.min-1.g-1, P less than 0.005), as did phosphate restriction (1.81 +/- 0.22 vs. control 3.05 +/- 0.40 mumol.min-1.g-1, P less than 0.05). These effects could not be accounted for by changes in CIn, TNa+, or GP and were not observed in normal kidneys. In summary 1) remnant kidneys are hypermetabolic compared with normal kidneys when assessed by QO2 and GP; 2) verapamil and phosphate restriction diminish the enhanced metabolic activity of remnant kidneys, an effect that is independent of TNa+; and thus 3) verapamil and phosphate restriction may slow progression of renal disease, at least in part by reducing renal metabolic demands.

Animals↗
PubMed1988

Glomerular hemodynamic adaptations in remnant nephrons: effects of verapamil.

Chronic verapamil administration has been shown to reduce the renal dysfunction, glomerular sclerosis, and mortality in partially nephrectomized rats; the mechanism is unknown. Therefore, the present micropuncture study examines the effect of verapamil on glomerular hemodynamics of Munich-Wistar rats 4 wk after five-sixths nephrectomy. Whole-kidney function was similar in nephrectomized rats treated with verapamil (Nx-VER) and saline (Nx-SAL), and glomerular filtration rate (GFR) was one-third of control. Both Nx-VER and Nx-SAL rats exhibited a similar degree of glomerular hyperperfusion and hyperfiltration. However, mean glomerular capillary hydrostatic pressure difference (delta P) was lower in Nx-VER than Nx-SAL rats (42.4 +/- 1.2 vs. 47.2 +/- 1.0 mmHg, P less than 0.005) because of an increase in Bowman's space hydrostatic pressure (PBS) in Nx-VER rats (15.5 +/- 0.8 vs. Nx-SAL 11.9 +/- 0.7 mmHg, P less than 0.005). Glomerular ultrafiltration coefficient (LpA) was significantly lower in Nx-SAL (P less than 0.005) than in Nx-VER or control rats. Urinary protein excretion and the magnitude of glomerular sclerosis in Nx-SAL and Nx-VER rats were not different. In conclusion, chronic VER administration normalizes LpA and reduces delta P, by increasing PBS, in Nx rats, alterations that neutralize each other, leading to the constancy of single-nephron GFR.

Adaptation, Physiological↗
PubMed1987

Verapamil protects against progression of experimental chronic renal failure.

Chronic administration of verapamil (Ver) decreases nephrocalcinosis and tubular ultrastructural abnormalities in the remnant model of chronic renal disease. In the present study, the effect of chronic Ver administration on renal function, renal histology and mortality after subtotal nephrectomy was examined. Fourteen days after staged subtotal nephrectomy rats were paired according to renal functional impairment, mean arterial pressure (MAP), and body weight. Rats were pair fed and received either Ver (0.1 micrograms/g sc bid, N = 10) or saline (0.1 ml sc bid, N = 10) for up to 23 weeks. Both members of each pair were sacrificed shortly before the uremic death of controls. At sacrifice, rats treated with Ver had a lower serum creatinine (2.29 vs. 2.99 mg/dl, P less than 0.05) and a higher creatinine clearance (318 vs. 164 microliters/min, P less than 0.05) than controls. In a second experiment, survival was superior in rats treated with Ver than in controls from week seven (P less than 0.0025 by week 14). Serum creatinine was higher at week 10 in control rats (1.68 vs. 1.10 mg/dl, P less than 0.05). MAP was no different between the two groups, irrespective of the time between Ver administration and the measurement of MAP. Histological damage and nephrocalcinosis were worse, and renal and myocardial calcium content was higher in controls. In conclusion, independent of any effect on systematic MAP, chronic administration of Ver protects against renal dysfunction, histological damage, nephrocalcinosis and myocardial calcification, and improves survival in the remnant model of chronic renal disease.

Animals↗
PubMed1986

Phosphate depletion arrests progression of chronic renal failure independent of protein intake.

Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 +/- 0.1 vs. 1.62 +/- 0.6 mg/deciliter, 17.0 +/- 10.3 vs. 257.6 +/- 13.4 mg/24 hr, and 16.6 +/- 4.4 vs. 39.2 +/- 11.7 ml/24 hr, respectively, all P less than 0.001). At this time, when serum phosphorus (SPi) and serum calcium (SCa2+) were normal, the rats were separated into two groups, matched and paired by body weight and SCr, and housed separately in metabolic cages. Animals of one group ingested a normal diet supplemented with dihydroxyaluminum aminoacetate (DHAAA), 15 g%, to induce phosphate depletion (PD). The second group ingested the same diet supplemented with 7.5% glycine and was the phosphate replete (PR) group. All rats were pair fed throughout the study to maintain similar caloric, protein, carbohydrate, vitamin, and mineral intakes. At six weeks after separation, SPi was decreased in PD vs. PR group (2.85 +/- 0.8 vs. 6.71 +/- 1.2 mg/deciliter, P less than 0.001) and SCa2+ was increased in the PD group (11.98 +/- 0.7 vs. 10.03 +/- 0.7 mg/deciliter, P less than 0.001). Urine urea nitrogen, body weight, and sodium, potassium and solute excretion were similar between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Hydroxide↗
PubMed1986

Prevention of hypercalcemia-induced renal concentrating defect and tissue calcium accumulation.

The mechanism of the concentrating defect of hypercalcemia is explored by examining the effect of concomitant phosphate restriction. Rats were pair fed a normal phosphorus diet, without (group 1) or with dihydrotachysterol (group 2), or a low-phosphorus diet (group 3). Hypercalcemia was comparable in groups 2 (12.1 +/- 0.6 mg/dl) and 3 (11.8 +/- 0.4 mg/dl), but serum phosphate was lower in group 3 than group 2 (3.8 +/- 0.7 vs. 7.1 +/- 1.1 mg/dl, P less than 0.005). Group 2 rats had impaired maximum urinary concentration after 24 h of fluid deprivation (2,441 +/- 450 mosmol/kg H2O, P less than 0.001) compared with group 1 (3,263 +/- 466 mosmol/kg H2O) or group 3 (3,332 +/- 515 mosmol/kg H2O) animals. Polydipsia and polyuria were found in group 2 rats only. Tubular calcium reabsorption was higher in group 2 (83.1 +/- 33.5 mg/24 h, P less than 0.001) than group 1 (47.0 +/- 26.1 mg/24 h) or group 3 (52.8 +/- 19.3 mg/24 h) animals, and medullary calcium concentration was higher in group 2 (7.57 +/- 3.08 nmol/mg dry wt, P less than 0.05) as compared to group 1 (5.04 +/- 1.37 nmol/mg dry wt) or group 3 (5.32 +/- 0.98 nmol/mg dry wt) rats. Total medullary solute concentration was significantly higher in group 3 than group 2 animals. Thus phosphate restriction prevents the defect of urinary concentrating ability of chronic hypercalcemia, probably by decreasing tubular uptake and tissue accumulation of calcium.

Animals↗
PubMed1986

Detrimental effect of hypophosphatemia on the severity and progression of ischemic acute renal failure.

Phosphate depletion may prevent progression of experimental chronic renal failure. The present study was designed to examine the effect of phosphate depletion on the severity and progression of ischemic acute renal failure. Two groups of rats, phosphate-depleted (PD) and phosphate-repleted (PR), were pair-fed a regular diet for 10 days; the diet of the PD rats also contained 15 g% dihydroxyaluminum aminoacetate. After 10 days, serum phosphate in PD rats averaged 3.9 +/- 0.7 mg%, compared to 6.1 +/- 0.6 mg% in the PR rats (p less than 0.001). The weight gain during the equilibration period was comparable in both groups (24.2 +/- 9.3 vs. 25.7 +/- 10.4 g; NS). Creatinine clearance, hematocrit, renal cortical adenine nucleotides, tissue calcium, mitochondrial calcium and mitochondrial respiration were similar in both groups after 10 days of the diet. A 50-min bilateral clamping of both renal arteries and veins was then undertaken in both groups. The PD rats demonstrated more severe acute renal failure at 24 h after the ischemic insult. Serum creatinine and creatinine clearance for the PD and PR rats were 4.0 +/- 0.6 versus 3.1 +/- 0.9 mg% (p less than 0.005) and 7.8 +/- 8.1 versus 85.3 +/- 70.7 microliter/min (p less than 0.001), respectively. Tissue calcium (131.3 +/- 103.0 vs. 63.5 +/- 36.0 mmol/kg dry weight; p less than 0.02) and mitochondrial calcium (49.4 +/- 24.0 vs. 29.5 +/- 14.6 nmol/mg prot.; p less than 0.02) were significantly higher in the PD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗