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Biomedical subjects

D R Wilson

Publications and source records attributed to D R Wilson.

At least 127 records · Page 7Linked to original sources

Cloning and sequence analysis reveal structural variation among related zein genes in maize.

We have isolated a gene encoding one of the 19,000 dalton zein proteins from a maize genomic library constructed in Charon 4A. This gene occurs on a 7.7 kb Eco RI fragment, and based on Southern hybridization analysis, represents one of several homologous sequences present in the maize genome. The nucleotide sequence of the gene predicts a protein composed of 235 amino acids, including a signal peptide of 21 amino acids. There are no intervening sequences in the gene. By comparing the nucleotide sequence of this gene with that of a homologous cDNA clone, we have identified a basis for microheterogeneity within the gene family. The 5' nucleotide sequences of the genomic and cDNA clones are identical, but they differ in the center of the protein, where repeated amino acid sequences occur. A nucleotide sequence encoding a conserved peptide of 20 amino acids is repeated nine times in the center of both of these clones.

Base Sequence↗

Prostaglandin synthesis inhibition during volume expansion: collecting duct function.

The aim of this study was to examine the possible role of renal prostaglandins in the response of the inner medullary collecting duct (IMCD) to acute volume expansion. Collecting duct microcatheterization and clearance studies were carried out in anesthetized rats, volume-expanded with isotonic Ringer's solution. In volume-expanded control animals, there was no significant sodium or chloride reabsorption between the beginning and end (papillary tip) of the IMCD. Administration of indomethacin or meclofenamate prior to and during volume expansion in two other groups of rats resulted in significant water, sodium, and chloride reabsorption along the IMCD and markedly blunted the diuretic, natriuretic and chloriuretic response to volume expansion. Because delivery to the beginning of the duct was not significantly decreased, enhanced reabsorption in the IMCD largely accounted for the decrease in natriuresis and chloriuresis. Inner medullary tissue fluid chloride concentration increased after inhibition of prostaglandin synthesis. The results indicate that renal prostaglandins, perhaps by directly decreasing sodium chloride reabsorption, have an important role in the decrease in collecting duct reabsorption of sodium and chloride observed with acute volume expansion.

Animals↗

Urea handling by the distal tubule and collecting duct of the rat during urea--saline, isotonic saline, or urea diuresis.

The aims of the present study were to examine the effects of urea and isotonic saline loads separately and together on urea handling in the medullary collecting duct and surface distal tubules of the rat kidney. Microcatheterization of the medullary collecting duct during isotonic saline diuresis (saline at 5% of body weight per hour, plasma urea 4.3 mM/L), showed an increase in the remaining fraction of filtered urea from 56.2% at the beginning (corticomedullary junction) to 68.5% at the end (papillary tip) of the medullary collecting duct (n = 17 paired samples in six rats, p less than 0.05). There was no change in the fraction of filtered urea along the medullary collecting duct during urea diuresis (plasma urea 87 mM/L, n = 15 paired samples in six rats) or during urea--saline diuresis (plasma urea 103 mM/L, n =32 paired samples in nine rats). Micropuncture of surface distal tubules in the same animals showed an increase in the fraction of filtered urea between end-distal samples and the beginning of the medullary collecting duct from 28.9 to 56.2% during isotonic saline diuresis (p less than 0.001), and from 53.6 to 75.3% during urea--saline diuresis (p less than 0.01), but no change during urea diuresis (63.6 to 60.0%, p = NS). Our conclusions are as follows. (1) Urea entry into the medullary collecting duct during steady-state diuresis occurs at low intratubular urea contractions (isotonic saline diuresis) but not at high concentrations (urea--saline diuresis and urea diuresis). (2) Urea entry between the surface distal tubule and the beginning of the medullary collecting duct occurs during saline diuresis (isotonic saline diuresis and urea--saline diuresis) but not urea diuresis. The latter finding suggests that isotonic saline loads affect urea transport differently in juxtamedullary nephrons compared to superficial nephrons.

Animals↗

Percutaneous transluminal dilatation of the renal artery: follow-up studies on renovascular hypertension.

Percutaneous transluminal dilatation of 80 renal artery stenoses was attempted in 68 patients. The procedure was technically successful in 58 (85%) patients. Fifty (86%) of the 58 patients were initially cured or improved. Life-table analysis of this group gives a cumulative success rate of 81% for a 3 year period. Hypertension recurred in only seven patients. There were no deaths related to the procedure, but four major complications occurred, including two secondary nephrectomies.

Adolescent↗

Removable fluid-containing chamber for in vivo guinea pig skin studies.

A removable, fluid-tight chamber is discussed that may be used to measure ion flux through the skin. This chamber adheres to clipped guinea pig skin with the use of silicone rubber adhesive, where hair stubble facilitates attachment. The technique also should work well for other hairy species. Experiments may be performed on hairless skin provided the adhesive is incompletely cured and the chamber is held in place by a strap.

Animals↗

Hypercalcemia with ovarian carcinoma: evidence of a pathogenetic role for prostaglandins.

A 70-year-old white woman had a lower abdominal mass and hypercalcemia. Physical and radiologic evidence was found for the presence of nonmetastatic pelvic tumor. Biochemical tests confirmed the presence of hypercalcemia with evidence of active bone resorption. Plasma parathyroid hormone (PTH) and the nephrogenic urinary cyclic AMP excretion were low; levels of plasma prostaglandins were elevated. Bone biopsy revealed histologic evidence of extensive osteoclastic bone resorption. At operation, a papillary serous cystadenocarcinoma of the ovary was removed. Postoperatively, the serum calcium fell to normal, and plasma prostaglandins became undetectable. Short-term incubation of ovarian tumor fragments demonstrated the production by tumor tissue of a substance causing bone resorption in an in vitro bioassay. The production of this substance was blocked by indomethacin. Radioimmunoassay of the incubation medium revealed significant amounts of prostaglandins of the E + F series. Parathyroid hormone was not detected in the medium. These data implicate tumor-produced prostaglandins as mediators of the hypercalcemia in this patient.

Aged↗

Urea handling by the medullary collecting duct of the rat kidney during hydropenia and urea infusion.

Previous micropuncture studies of distal tubule fluid and ureteral urine have indicated a varying degree of urea reabsorption in the collecting duct. In the present experiments the microcatheterization technique was used to directly determine urea, Na, K, total solute and fluid reabsorption along the length of the medullary collecting duct in anesthetized hydropenic rats and in rats given low dose urea infusion (Purea 18.9 mM/l). In hydropenic rats, the remaining fraction of filtered urea did not change significantly along the collecting duct, as indicated both by regression analysis of all samples and by comparison of paired samples from the corticomedullary junction and papillary tip. During low dose urea infusion, urine osmolality increased in proportion to the increase in urea concentration and again there was no net urea reabsorption between the beginning and end of the duct. However, during urea infusion, analysis of samples from the beginning, mid-zone, and end of the collecting duct indicated that urea entry occurred in the proximal portion of the duct (beginning to mid-zone, P less than 0.01) and that urea reabsorption occurred in the distal portion (mid-zone to end, P less than 0.01). The lack of significant net urea reabsorption along the duct despite the excretion of moderately concentrated urine, has despite the excretion of moderately concentrated urine, has implications for the concept of medullary urea recycling and for models of the urinary concentrating mechanism. The finding of functional heterogeneity with respect to urea handling in the collecting duct in vivo, with both reabsorption are secretion being demonstrated, raises the possibility that internal recycling of urea in the medullary collecting duct itself may contribute to maintenance of a high papillary interstitial urea concentration.

Animals↗

Protective effect on vitamin D2 on bone apposition from the inhibitory action of hydrocortisone in rats.

Using the technique of short interval sequential tetracycline labeling, it was documented that the apposition of mineralized bone matrix in adult male Sprague-Dawley rats was inhibited by hydrocortisone. The inhibition occurred as early as six days after the onset of the treatment and was dose dependent over a dose range of 0.62 to 20 mg per kg body weight per day. Vitamin D2 supplements by injection protected bone from this hydrocortisone action. 64 I. U. of vitamin D2 injected daily was able to prevent the inhibition of bone apposition by 20 mg per kg body weight per day of hydrocortisone. The results imply that vitamin D or its metabolites may compete with hydrocortisone in some cellular mechanisms and support the usefulness of vitamin D supplements in the treatment and the prevention of steroid-induced osteoporosis.

Animals↗

Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis.

The purpose of this investigation was to determine in which nephron segments ammonia was added to or removed from the lumenal fluid of the rat. Ammonium was measured in proximal and distal tubular fluid samples obtained by micropuncture and in collecting duct fluid samples obtained by microcatheterization. Water abstraction was assessed by examining the tubular fluid-to-plasma inulin concentration, (TF/P)In. In normal or acidotic rats, the vast bulk of the final urine ammonium appeared in the proximal tubular fluid samples. Most of this ammonia was lost, however, in transit from the proximal to the distal tubule so that only 20 to 30% of the excreted ammonium was present at the distal site. Ammonia reentered the lumenal fluid primarily in the cortical collecting duct in acidotic rats and in the medullary collecting duct in normal rats. Although the pattern was qualitatively similar in both groups of rats, the absolute quantity of ammonium in each nephron segment of normal rats was about 10 to 20% of that in acidotic animals.

Acidosis, Renal Tubular↗

Ammonia addition into the medullary collecting duct of the rat.

The purpose of these studies was to determine if ammonia is added directly to the medullary collecting duct of the rat, and if so, to estimate its quantitative contribution to ammonium excretion. Samples of fluid were obtained along the length of the medullary collecting duct by retrograde microcatheterization. To document net addition of ammonium, we measured the ammonium concentration in tubular fluid by an enzymatic isotope technique, and we calculated the degree of fluid reabsorption from the ratio of the inulin concentration in tubular fluid and plasma. The ammonium concentration corrected for water reabsorption ([NH4+]/[TF/P]In) rose progressively from the beginning to the end of the medullary collecting duct, indicating net ammonia addition to this nephron segment. By calculation, it appears that about 40% of the excreted ammonium reached the urine by direct addition of ammonia to the duct fluid.

Ammonia↗

The importance of dietary protein in the zinc deficiency of uremia.

The pathogenesis of zinc deficiency and its relationship to hypogeusia were studied in three chronic dialysis units in Toronto. The difference between low plasma zinc levels at two of the hospitals compared to the normal levels in the third hospital was significantly related to levels of dietary zinc intake which in turn was due to the levels of dietary protein intake. Thus one cause of zinc deficiency in chronic uremia is dietary protein deprivation. In addition, in the hospital with normal plasma levels there was a small but significant rise in plasma zinc postdialysis in contrast to the other two hospitals where there was no change. Thus slight leaching of zinc from dialysis equipment could help prevent zinc deficiency in such patients. Hypogeusia was more common in zinc-deficient patients.

Ageusia↗

Effect of renal denervation, furosemide, and acute saline loading on postobstructive diuresis in the rat.

The effect of acute or chronic renal denervation, furosemide, or acute saline loading on the postobstructive diuresis (POD) which occurs after relief of 24-h bilateral ureteral obstruction (BUO) was studied in anaesthetized rats. Acute renal denervation during POD 1--2 h after relief of BUO had no effect on glomerular filtration rate of sodium, potassium, water, or solute excretion, in contrast with its natriuretic and diuretic effect in sham-operated rats. Intravenous furosemide or acute saline loading caused a further marked increase in sodium and water excretion during POD, demonstrating the ability of the kidney undergoing POD to respond to other types of natriuretic stimuli. Chronic renal denervation prior to BUO had no effect on subsequent POD. The lack of response of the BUO kidney undergoing POD to acute denervation contrasts with the changes in renal function following denervation of the unilateral postobstructive kidney. The results indicate that the kidney undergoing POD after relief of BUO may be functionally denervated and suggest that inhibition of renal nerve activity could contribute to the pathophysiology of POD.

Animals↗

Urea secretion in medullary collecting duct of the rat kidney during water and mannitol diuresis.

During steady-state water or mannitol diuresis, the microcatheterization technique was used to study the handling of urea, fluid, sodium, potassium, and total solute along the length of the medullary collecting duct in anesthetized rats. During water diuresis, the remaining fraction of filtered urea increased along the collecting duct as indicated both by regression analysis of all samples and by comparison of paired data from the beginning and end of the duct [(TF/P)urea/In = 43.3 and 50.7%, respectively]. During mannitol diuresis, similar urea entry into the medullary collecting duct was observed, (TF/P)urea/In increasing from 60.7 to 66.5%. Comparison of collecting duct urea handling in proximal and distal segments (beginning to midzone and midzone to papillary tip) suggested that urea entry occurred to a greater extent in the distal portion of the medullary collecting duct. The results demonstrate urea secretion into the medullary collecting duct in diuretic states when urine flow is high and intratubular urea concentration low. Whether urea entry into the collecting duct is an active or passive process cannot be determined from this study, but comparison between urea concentrations in the papillary interstitial fluid and in the urine or tubular fluid raises the possibility of an active urea secretory mechanism in the collecting duct.

Absorption↗

A possible role of vitamin D in the genesis of parenteral-nutrition-induced metabolic bone disease.

Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.

25-Hydroxyvitamin D 2↗