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Biomedical subjects

F L Coe

Publications and source records attributed to F L Coe.

At least 91 records · Page 5Linked to original sources
PubMed1986

Evidence that serum calcium oxalate supersaturation is a consequence of oxalate retention in patients with chronic renal failure.

Serum oxalate rises in uremia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uremic patients. Crystal formation suggests that either uremic serum is supersaturated with calcium oxalate, or local oxalate production or accumulation causes regional supersaturation. To test the first alternative, we ultrafiltered uremic serum and measured supersaturation with two different methods previously used to study supersaturation in urine. First, the relative saturation ratio (RSR), the ratio of the dissolved calcium oxalate complex to the thermodynamic calcium oxalate solubility product, was estimated for 11 uremic (before and after dialysis) and 4 normal serum samples using a computer program. Mean ultrafiltrate oxalate predialysis was 89 +/- 8 microM/liter (+/- SEM), 31 +/- 4 postdialysis, and 10 +/- 3 in normals. Mean RSR was 1.7 +/- 0.1 (predialysis), 0.7 +/- 0.1 (postdialysis), and 0.2 +/- 0.1 (normal), where values greater than 1 denote supersaturation, less than 1, undersaturation. Second, the concentration product ratio (CPR), the ratio of the measured calcium oxalate concentration product before to that after incubation of the sample with calcium oxalate monohydrate crystal, was measured in seven uremic and seven normal serum ultrafiltrates. Mean oxalate was 91 +/- 11 (uremic) and 8 +/- 3 (normal). Mean CPR was 1.4 +/- 0.2 (uremic) and 0.2 +/- 0.1 (normal). Predialysis, 17 of 18 uremic ultrafiltrates were supersaturated with respect to calcium oxalate. The degree of supersaturation was correlated with ultrafiltrate oxalate (RSR, r = 0.99, r = 29, P less than 0.001; CPR, r = 0.75, n = 11, P less than 0.001). A value of ultrafiltrate oxalate of 50 microM/liter separated undersaturated from supersaturated samples and occurred at a creatinine of approximately 9.0 mg/dl.

Adult↗
PubMed1986

Preliminary report of a new treatment strategy for advanced pelvic malignancy: surgical resection and radiation therapy using afterloading catheters plus an inflatable displacement prosthesis in the treatment of advanced primary and recurrent rectal cancer.

An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the need for full high-dose pelvic irradiation.

Brachytherapy↗
PubMed1985

Cellular contribution to pH-mediated calcium flux in neonatal mouse calvariae.

Net calcium flux from cultured neonatal mouse calvariae into the culture medium is pH dependent, and acidified culture medium causes egress of calcium from bone. To determine whether calcium flux is mediated by pH effects on bone cell function, we cultured calvariae for 24 h with sodium azide, acetazolamide, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or after three successive freeze-thaw cycles, treatments that would be expected to alter bone cell function. We recultured bones for 3 h with the respective treatment and measured calcium flux. Sodium azide and freeze-thaw cycles produced a net influx of calcium (JCa = -22 +/- 7 and -23 +/- 6 nmol X bone-1 X 3 h-1, respectively) compared with net efflux of control bones (JCa = 35 +/- 6) at a similar initial medium pH. Acetazolamide reduced net flux to 0 (JCa = 7 +/- 6). PTH and 1,25(OH)2D3 increased net calcium efflux from bone (JCa = 78 +/- 7 and 74 +/- 10, respectively). Despite changing net flux, the slope dependence of net flux on medium pH was the same in the control group and all five treated groups of bones. The similarity of slopes indicates that the pH dependence of net flux is not a result of pH acting on bone cells but probably an effect of altered mineral equilibria. The difference in net flux at similar pH indicates that calcium efflux is partially inhibited by acetazolamide and stimulated by both PTH and 1,25(OH)2D3.

Acetazolamide↗
PubMed1985

Response of serum 1,25(OH)2D3 to variation of ionized calcium during chronic acidosis.

Chronic ammonium chloride (NH4Cl) administration causes metabolic acidosis and prevents the normal rise of serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] during a low-calcium diet (LCD, 0.002% calcium). The suppression of serum 1,25(OH)2D3 was not due to reduced parathyroid hormone concentration, elevated serum phosphorus, or total calcium concentration. Acidosis increased blood ionized Ca [Ca2+] and proton [H+] concentrations. Serum 1,25(OH)2D3 levels were inversely correlated with both [Ca2+] and [H+]. To determine the independent effects of [Ca2+] on serum 1,25(OH)2D3 we varied [Ca2+] at a constant [H+] by infusing either EGTA or saline for 24 h after 11 days of LCD and NH4Cl. EGTA, preequilibrated with three concentrations of Ca, lowered [Ca2+] and raised 1,25(OH)2D3 but did not alter [H+] or serum phosphorus concentration. The log of serum 1,25(OH)2D3 varied linearly and inversely with arterial blood [Ca2+] during saline (r = -0.884, n = 8, P less than 0.001) and EGTA infusions (r = -0.798, n = 22, P less than 0.001). At all levels of [Ca2+], rats infused with EGTA had a higher serum 1,25(OH)2D3 than those infused with saline. Log serum 1,25(OH)2D3 was correlated neither with [H+] nor pH. Elevated [Ca2+] and not [H+] appears to suppress the serum 1,25(OH)2D3 response to LCD during NH4Cl acidosis in the rat.

Acidosis↗
PubMed1985

Hyperkalemia during acute ammonium chloride acidosis in man.

The relationship between acid base parameters and serum potassium concentration was studied in controls and in patients during acute ammonium chloride-induced metabolic acidosis. Serum potassium was best correlated with serum bicarbonate during control (r = -0.323; p less than 0.01) and acidosis (r = -0.437; p less than 0.001). The slopes and intercepts were similar in both instances and the combined correlation was highly significant (r = -0.493; p less than 0.001). Examination of the 95% joint confidence region revealed that during acidosis serum potassium was rarely above 5.0 mEq/l when serum bicarbonate was greater than 16 mEq/l. It is probably not sound clinical practice to ascribe hyperkalemia to acute mild metabolic acidosis.

Acidosis↗
PubMed1985

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

One reason that some people are prone to calcium oxalate nephrolithiasis is that they produce urine that is subnormal in its ability to inhibit the growth of calcium oxalate crystals. We have identified in human urine a glycoprotein (GCI) that inhibits calcium oxalate crystal growth strongly, and at low concentrations (10(-7) M); in this study, we have isolated GCI molecules from the urine of normal people and patients with calcium oxalate stones. GCI from stone formers is abnormal in three ways: it contains no detectable gamma-carboxyglutamic acid (Gla), whereas normal GCI contains 2-3 residues of Gla per mole; about half of the GCI in urine of patients inhibits crystal growth 4-20 times less than normal GCI as judged by its performance in a kinetic growth assay, in vitro; at the air-water interface, patient GCI has a film collapse pressure approximately half of normal. GCI molecules from the urine of patients with calcium oxalate nephrolithiasis are intrinsically abnormal, and these abnormalities could play a role in the genesis of stones.

1-Carboxyglutamic Acid↗
PubMed1985

Evidence that blood ionized calcium can regulate serum 1,25(OH)2D3 independently of parathyroid hormone and phosphorus in the rat.

This study asks whether arterial blood ionized calcium concentration (Ca++) can regulate the serum level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] independently of serum phosphorus and parathyroid hormone (PTH). We infused either PTH (bovine 1-34, 10 U/kg body wt/h) or saline into awake and unrestrained rats for 24 h, through a chronic indwelling catheter. PTH raised total serum calcium and arterial blood ionized calcium, yet serum 1,25(OH)2D3 fell from 35 +/- 6 (mean +/- SEM, n = 10) with saline to 12 +/- 3 pg/ml (n = 11, P less than 0.005 vs. saline). To determine if the decrease in serum 1,25(OH)2D3 was due to the elevated Ca++, we infused PTH into other rats for 24 h, along with varying amounts of EGTA. Infusion of PTH + 0.67 micron/min EGTA reduced Ca++, and 1,25(OH)2D3 rose to 90 +/- 33 (P less than 0.02 vs. PTH alone). PTH + 1.00 micron/min EGTA lowered Ca++ more, and 1,25(OH)2D3 increased to 148 +/- 29 (P less than 0.01 vs. saline or PTH alone). PTH + 1.33 micron/min EGTA lowered Ca++ below values seen with saline or PTH alone, and 1,25(OH)2D3 rose to 267 +/- 46 (P less than 0.003 vs. all other groups). Thus, during PTH infusion lowering Ca++ with EGTA raised 1,25(OH)2D3 progressively. There were no differences in serum phosphorus concentration or in arterial blood pH in any group infused with PTH. The log of serum 1,25(OH)2D3 was correlated inversely with Ca++ in all four groups infused with PTH (r = -0.737, n = 31, P less than 0.001), and also when the saline group was included (r = -0.677, n = 41, P less than 0.001). The results of this study indicate that serum 1,25(OH)2D3 may be regulated by Ca++ independent of PTH and serum phosphorus levels in the rat. Since 1,25(OH)2D3 regulates gastrointestinal calcium absorption, there may be direct feedback control of 1,25(OH)2D3, by its regulated ion, Ca++.

Animals↗
PubMed1985

Role of fetal 1,25-dihydroxyvitamin D production in intrauterine phosphorus and calcium homeostasis.

During intrauterine life, fetal mineral accretion depends on active transfer from mother to fetus by the placenta. To evaluate the role of fetal production of 1,25-dihydroxyvitamin D in regulation of fetal phosphorus, calcium, and parathyroid homeostasis, studies were performed in ewes and their fetal lambs. Fetal nephrectomy caused a rise in fetal serum phosphorus and a fall in total calcium 5 days after nephrectomy. Fetal blood ionized calcium also fell and serum parathyroid hormone rose. In sham-nephrectomized fetuses, all four measurements were unchanged compared to control values. Simultaneous maternal values of ionized calcium were normal in control and nephrectomized fetuses. Fetal ureteral severance and drainage of urine into the fetal peritoneal cavity produced none of the effects of fetal nephrectomy. Daily intravenous injection of 1,25-dihydroxyvitamin D into fetuses after nephrectomy prevented the rise in serum phosphate, and serum calcium did not fall. The results suggest that fetal 1,25-dihydroxyvitamin D regulates fetal phosphate homeostasis, perhaps by the placenta, which in turn regulates blood-ionized calcium concentration.

Animals↗
PubMed1985

Effects of dietary calcium restriction on 1,25-dihydroxyvitamin D3 net synthesis by rat proximal tubules.

We measured in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) production by kidney proximal tubules prepared by Percoll density centrifugation from male and female rats. 1,25(OH)2D3 in tubule extracts was determined by a sensitive and specific radioreceptor assay. Ingestion of diets adequate in vitamin D3 and containing either normal calcium (1.2% Ca, NC), reduced calcium (0.6% Ca, RCD) or low calcium (0.002% Ca, LCD) increased 1,25(OH)2D3 net synthesis (for male rats, NC vs. RCD vs. LCD 1.8 +/- 0.1 SEM vs. 9 +/- 2 vs. 17 +/- 2 pmol/mg protein/20 min; P less than 0.05 for all comparisons). At either level of reduced calcium intake, tubules from male rats produced more 1,25(OH)2D3 than tubules from females. Serum 1,25(OH)2D3 and tubule cyclic adenosine monophosphate (cAMP) content rose in parallel with progressive dietary calcium restriction, and males had higher circulating 1,25(OH)2D3 and tubule cAMP content than females at each level of reduced calcium intake. L-Epinephrine (10(-4) mol/L), in vitro, increased tubule accumulation of 1,25(OH)2D3 and cAMP. Yohimbine, and alpha 2-receptor antagonist, blocked this response, whereas prazosin was without effect. Increased 1,25(OH)2D3 net synthesis by tubules from male vs. female rats partly explains the higher serum levels and enhanced mineral conservation demonstrated previously in male rats. Preparation of proximal tubules from vitamin D-replete rats permits studies in vitro of 1,25(OH)2D3 production and regulation under more physiologic conditions in which parathyroid hormone, inorganic phosphorus, and calcium may be varied independently.

Animals↗
PubMed1985

Recurrence after a single renal stone in a community practice.

The natural history of recurrence of kidney stones was studied in a community urology practice, in which treatment with agents such as thiazide, allopurinol or oral phosphate has not been consistent or widespread. Using life-table analysis, the mean interval to first recurrence was 8.8 +/- 1.2 years and was not influenced by gender, age at first occurrence, or family history of stones. The tempo of recurrence justifies an individual approach to evaluation and treatment.

Adult↗
PubMed1984

Elevated 1,25(OH)2D3, intestinal absorption, and renal mineral conservation in male rats.

We studied the physiological importance of elevated serum 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] in male rats. Male and female rats of equal weight consumed either a high calcium diet (1.20% calcium; HCD), a low calcium diet (0.02% calcium; LCD), or a normal calcium diet (0.60% calcium; NCD). With all three diets, serum 1,25(OH)2D3 was higher in males than females and rose in both sexes with decreasing diet calcium. There was a direct correlation between serum 1,25(OH)2D3 and proximal duodenal 45Ca uptake (r = 0.667; P less than 0.001). With NCD, we performed a balance study and found a direct correlation between serum 1,25(OH)2D3 and both 5-day fractional calcium absorption (r = 0.703; P less than 0.01) and fractional phosphorus absorption (r = 0.679; P less than 0.01). In addition, serum 1,25(OH)2D3 was directly correlated with 5-day calcium retention (r = 0.772; P less than 0.001) and phosphorus retention (r = 0.830; P less than 0.001). Males grew faster than females (F ratio = 1,194; P less than 0.001). Elevated 1,25(OH)2D3 in males appears to be of biological significance and may help satisfy a greater, growth-related, need for calcium.

Absorption↗
PubMed1984

Pathophysiology of hypercalciuria.

The mechanisms responsible for hypercalciuria may involve intestinal calcium transport, renal tubule calcium reabsorption, and the regulation of bone mineral content. Both parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may alter urine calcium. For these reasons, understanding the pathogenesis of hypercalciuria in patients has proven to be difficult. We present here an analysis of pathways that regulate systemic calcium homeostasis and of the various mechanisms that have been proposed to explain normocalcemic hypercalciuria in humans. Available evidence seems to implicate disordered regulation of 1,25(OH)2D3 as a basis for at least one common form of hypercalciuria.

Benzothiadiazines↗
PubMed1984

Mechanism of chronic hypocalciuria with chlorthalidone: reduced calcium absorption.

Chlorthalidone, like other benzothiadiazides, lowers urine calcium excretion chronically. If intestinal calcium absorption did not fall or bone accretion did not increase, serum calcium and the filtered load of calcium would increase and urine calcium would return to pretreatment levels. To determine whether overall intestinal calcium absorption fell, we fed chlorthalidone (5 mg X kg body wt-1 X 24 h-1) to 10 adult male rats eating 15 g/day of a 0.6% calcium diet. Compared with 10 control rats, chlorthalidone reduced urine calcium [2.1 +/- 0.1 (SE) vs. 5.8 +/- 0.5 mg/6 days; P less than 0.001]. Fecal calcium rose (307 +/- 9 vs. 257 +/- 12; P less than 0.005) because percent intestinal calcium absorption fell (41 +/- 2 vs. 52 +/- 2; P less than 0.002). Twenty other rats given the same diet were injected subcutaneously with 1,25(OH)2D3 (50 ng/day). In these rats, chlorthalidone reduced urine calcium (23 +/- 3 vs. 59 +/- 3; P less than 0.001) and percent intestinal calcium absorption (60 +/- 1 vs. 66 +/- 1; P less than 0.01). With or without 1,25(OH)2D3, chronic administration of chlorthalidone reduces intestinal calcium absorption, and this reduction seems to be the mechanism that permits urine calcium excretion to remain low.

Animals↗
PubMed1984

Isolation of calcium oxalate crystal growth inhibitor from rat kidney and urine.

Glycoproteins that slow the growth rate of calcium oxalate monohydrate crystals were purified from rat kidney homogenate and urine by selective heat denaturation (for rat kidney homogenate), DEAE-cellulose column chromatography, and gel permeation column chromatography. Both kidney and urine inhibitors were glycoproteins with an apparent mol wt of 1.4 X 10(4), as determined by high-performance liquid chromatography. They contained gamma-carboxyglutamic acid and a high percentage of aspartic acid and glutamic acid but had few aromatic amino acid residues. Both inhibitors contained fucose, mannose, glucose, galactose, glucosamine, galactosamine, and N-acetylneuraminic acid but no glucuronic acid. Kinetic studies suggest that purified inhibitors bind to calcium oxalate monohydrate seed crystals according to a Langmuir adsorption isotherm with similar dissociation constants of 14 X 10(-8)M for rat urine inhibitor and 8.7 X 10(-8) M for rat kidney inhibitor. The isolation of similar glycoproteins from kidney and urine suggests that urinary crystal growth inhibitor may be produced in the kidneys.

Amino Acids↗
PubMed1984

Evidence for size and charge permselectivity of rat ascending colon. Effects of ricinoleate and bile salts on oxalic acid and neutral sugar transport.

We have measured unidirectional transmural fluxes of oxalate and neutral sugars across rat ascending colon in vitro, under short-circuit conditions, to characterize permeability barriers selective for size and charge. Ionic oxalate appears to be transported preferentially to sodium oxalate. Mucosal addition of taurocholate (1 mM), deoxycholate (1 mM), or ricinoleate (1 mM) increased bidirectional oxalate fluxes, and the ricinoleate effects were independent of medium calcium. Bidirectional fluxes of uncharged sugar molecules fell sharply at molecular weights above 76 (molecular radius above 3 A), and oxalate transport was retarded relative to that of uncharged molecules of similar size, suggesting that there is both size and charge permselectivity. Ricinoleate increased fluxes of all neutral molecules tested but changed neither the exclusion limits nor the cation selectivity of the epithelium. Bile salts and ricinoleate increase oxalate transport, probably by making more channels available, but do not alter size and charge selectivity.

Animals↗
PubMed1983

Purification and characterization of the principal inhibitor of calcium oxalate monohydrate crystal growth in human urine.

Using an assay of the rate of crystal growth of calcium [14C]oxalate monohydrate, we ascertained that the factor responsible for more than 90% of the crystal growth inhibition in human urine is a nondialyzable macromolecule. We have purified this factor using DEAE-cellulose chromatography, followed by Bio-Gel P-10 column chromatography with 50% formamide as the eluent, and finally by gel permeation chromatography. About 5 mg of the inhibitor was obtained from normal 24-h adult urine, with 16% recovery of the original inhibitory activity. The inhibitor isolated was found to be a highly acidic glycoprotein with Mr = 1.4 X 10(4). It is rich in acidic amino acids, including gamma-carboxyglutamic acid, and contains few aromatic and basic amino acids. Two or three phosphate groups are covalently linked to the inhibitor. In the presence of the inhibitor, the kinetics of calcium oxalate monohydrate crystal growth inhibitor showed that the macromolecule binds to the crystal surface according to a Langmuir adsorption isotherm with a dissociation constant, Kd = 5.3 X 10(-7) M. The inhibitor readily formed an insoluble monolayer at the air-water interface and showed an unusually high surface stability with a collapse pressure of 41.5 dynes/cm. The urinary inhibitor closely resembled in all properties the calcium oxalate monohydrate crystal growth inhibitor that we had isolated from human embryonic kidney tissue culture medium (Nakagawa, Y., Margolis, H. C., Yokoyama, S., Kézdy, F. J., Kaiser, E. T., and Coe, F. L. (1981) J. Biol. Chem. 256, 3936-3944).

Amino Acids↗