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Biomedical subjects

H E Williams

Publications and source records attributed to H E Williams.

At least 19 recordsLinked to original sources

Oxalate transport in cultured porcine renal epithelial cells.

Oxalate-containing kidney stones are the most common type (75%) of renal stones. In order to control oxalate excretion in the urine, a basic understanding of the cellular transport of oxalate is imperative. We have utilized the technique of continuous cell culture to establish and characterize a model system to study renal epithelial cell (LLCPK1) oxalate transport. Our data demonstrate that oxalate uptake in these cells is dependent on time, concentration and energy. The Km for oxalate uptake was 200 microM. Oxalate uptake was decreased at lower temperatures and elevated in an acidic extracellular environment. Both anion exchange inhibitors DIDS and SITS inhibited oxalate uptake. Sulfate, chloride, and bicarbonate decreased oxalate uptake, as did the diuretics bumetanide and furosemide. There was no evidence for the co-transport of oxalate with sodium. Our data show that monolayers of cultured kidney epithelial cells are a valuable model system for study of the basic cellular mechanisms of oxalate transport.

Animals

Correction of erythrocyte abnormalities in idiopathic calcium-oxalate nephrolithiasis and reduction of urinary oxalate by oral glycosaminoglycans.

Calcium-oxalate nephrolithiasis is associated with a defect in erythrocyte oxalate self-exchange and an abnormal rate of erythrocyte membrane protein phosphorylation. There is evidence that glycosaminoglycans (GAGs) have a regulatory effect on both of these processes. This study tested the hypothesis that modifications of erythrocyte oxalate self-exchange induced by oral GAGs are paralleled by similar changes in overall oxalate metabolism. 40 patients with idiopathic calcium-oxalate nephrolithiasis were treated for 15 days with 60 mg/day of a mixture of GAGs. By day 15 of treatment there were significant reductions from baseline in erythrocyte oxalate self-exchange (mean [SD] 1.67 [1.18] vs 2.59 [1.63] x 10(2) per min; p less than 0.005) and erythrocyte membrane protein phosphorylation (55.8 [7.3] vs 72.9 [6.8] x 10(-3) cpm/mg protein; p less than 0.005), but also in urinary oxalate excretion (0.24 [0.09] vs 0.31 [0.15] mmol/24 h; p less than 0.005). This finding suggests similar changes in both erythrocytes and other cells more important in oxalate handling. The changes had reversed by 15 days after withdrawal of treatment. Acute intravenous administration of GAGs (60 mg) induced a fall in carbon-14-labelled oxalate renal clearance (143 [13] vs 169 [28] ml/min; p less than 0.005), which strongly suggests the participation of the kidney. However, reduced oxalate absorption from the intestine, and even decreased synthesis of oxalate, cannot be ruled out.

Administration, Oral

Effect of nifedipine on urinary excretion of calcium and calcium-controlling hormones in essential hypercalciuria.

Nifedipine has been shown to lower urinary calcium in "essential" hypercalciuria. However, the mechanism(s) by which this action takes place is completely unknown. This study describes the effect of nifedipine on some calcium-controlling hormones in essential hypercalciuria. Nifedipine (20 mg/day) was administered to ten essential hypercalciuric patients, and urinary PgE2, plasma bicyclic PgE2, 1,25 vitamin D3, and PTH were assayed before and after drug administration. Nifedipine promoted a significant fall in urinary calcium (352.1 +/- 87.67 SD vs. 231.2 +/- 74.62 mg/hr; t = 7.35, p less than .0001) and PgE2 (343.92 +/- 42.71 vs. 245.03 +/- 35.41 SD ng/24 hr; t = 6.18, p less than .0002), as well as in plasma bicyclic PgE2 (310.00 +/- 30.91 vs. 200.00 +/- 31.62 SD pg/ml; t = 9.86, p less than .0001) and 1,25 (OH)2 vitamin D3 (32.77 +/- 3.23 vs. 26.94 +/- 2.94 SD pg/ml; t = 6.53, p less than .0001), while PTH remained unaltered (18.50 +/- 3.63 vs. 19.50 +/- 4.09 SD ng/ml; t = 0.85, p, ns). Urinary calcium and PgE2 correlated positively before (r = 0.81, p less than .005) but not after treatment. The fall in urinary PgE2 brought about by nifedipine seems to be due to an inhibition of PgE2 synthesis, since the absolute decrements in both urinary PgE2 and plasma PgE2 metabolites were positively correlated (r = 0.79, p less than .007). No correlation was found between the absolute decrements of plasma bicyclic PgE2 and 1,25 (OH)2 vitamin D3. These data seem to suggest that the fall in urinary calcium brought about by nifedipine is in some way related to PgE2 synthesis inhibition and to uncoupling of 1,25 (OH)2 vitamin D3 and PTH action.

Adult

Glycosaminoglycan content, oxalate self-exchange and protein phosphorylation in erythrocytes of patients with 'idiopathic' calcium oxalate nephrolithiasis.

1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro, heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.

Adult

Growth patterns, health and illness in preschool children from a multi-ethnic, poor socio-economic status municipality of Melbourne.

There are little longitudinal data available for sample populations of Australian children. Previous findings from the Brunswick Family Study, unlike earlier overseas studies, have shown that adverse family and social factors were not associated with growth abnormalities. Follow-up of 224 children from the cohort at 4 years of age has confirmed absence of significant growth disturbances, no mortality between 1 and 4 years, and serious morbidity due to organic illness in only 4% of the sample. However, 22% of the 4 year olds were found to have behaviour disturbances. These findings from a multi-ethnic, poorer socio-economic status population sample illustrate the importance of behaviour disturbances as one aspect of the new morbidity in Australian paediatrics and indicate that the once prevalent growth failure and organic morbidity consequent to family and social disadvantage have all but disappeared.

Child Behavior Disorders

The hyperoxaluric syndromes.

Oxalate is a major component of renal stones and an important determinant of calcium oxalate solubility in urine. Although the well-defined hyperoxaluric states are relatively uncommon, a significant number of patients with calcium oxalate stones have some degree of hyperoxaluria. For these reasons an understanding of both the causes of hyperoxaluria and methods of controlling oxalate synthesis and excretion is important. This review focuses on methods for the measurement of oxalate, the metabolic pathways of oxalate synthesis, the transport and excretion of oxalate, and the hyperoxaluric syndromes.

Erythrocytes

The quantitation of oxalate in amniotic fluid by ion-chromatography.

Calcium oxalate is the predominant constituent of most kidney stones. The rare genetic disorder, primary hyperoxaluria, is characterized by the continuous excessive synthesis and urinary excretion of oxalic acid, leading to stone formation and renal insufficiency. The earliest measurement of oxalate in suspected cases of primary hyperoxaluria is advantageous and would lend support for continued analysis and eventual confirmation of the disease. Therefore, we quantitated oxalate levels in amniotic fluid (AF) using medium pressure ion-exchange chromatography. The mean concentration of oxalate in amniotic fluid was 1.67 mg/l +/- 0.8 (SD); (range 0.64 to 5.11 mg/l). The mean oxalate/creatinine ratio (O/C) was 0.23 +/- 0.11 (SD); (range 0.07 to 0.53). This ratio is similar to that found in the urine of infants less than 1 year (0.19 +/- 0.10; n = 17). There was no significant difference between males and females in oxalate concentration or O/C ratio. Regression analysis showed no significant correlation of fetal age with oxalate, O/C or creatinine. Studies in 13 sets of di-amnionic twins showed no statistical difference in oxalate or O/C between twin A and B. This study demonstrates the ability to accurately quantitate oxalate in amniotic fluid by ion-chromatography, and suggests that this may have a potential application in the initial screening process for the prenatal detection of primary hyperoxaluria.

Amniotic Fluid

Oxalate synthesis, transport and the hyperoxaluric syndromes.

This article reviews the mechanisms involved in the synthesis, absorption, excretion and transport of oxalic acid, and the factors controlling these processes in man. The clinical syndromes associated with hyperoxaluria and recurrent calcium oxalate stone disease are reviewed, including new studies that raise the possibility of a generalized oxalate transport abnormality in some patients with renal stone disease. The important role of oxalate in the determination of calcium oxalate solubility in patients with calcium oxalate stone disease is emphasized and future directions for research in the prevention of recurrent calcium oxalate stone disease are discussed.

Animals

My four teachers.

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Australia

Reginald Webster.

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Australia

Chlorinated hydrocarbon insecticide residues in Tennessee honey and beeswax.

Several samples of commercial grade honey collected from different parts of tennessee during the summer of 1973 were analyzed for chlorinated hydrocarbon insecticide (CHI) residues. A "Modified Mill's Procedure" was used to cleanup the samples prior to gas chromatographic analysis using electron capture (EC) detection. The presence of CHI residues was confirmed by analysis on three different columns of widely varying polarity. Most of the samples contained CHI residues at 0.01-0.30 parts per billion (ppb) level. Beeswax produced during the same season contained several times higher levels of the residue than the honey samples. Recoveries of CHI residues varied from 81-95 percent by the procedure employed.

Bees