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Biomedical subjects

F L Coe

Publications and source records attributed to F L Coe.

At least 19 recordsLinked to original sources
PubMed1994

Role of nephrocalcin in inhibition of calcium oxalate crystallization and nephrolithiasis.

Kidney cells produce at least three proteins that slow the rate of calcium oxalate crystallization. Nephrocalcin (NC), one of the three, is an acidic glycoprotein that contains gamma-carboxyglutamic acid (GLA), and inhibits nucleation, aggregation and growth of calcium oxalate crystals. Nephrocalcin is abnormal in urine of stone-forming patients, in lacking GLA. It acts by absorbing to crystal surfaces. NC is produced by cultured renal proximal tubule cells, and by some lines of renal carcinoma cells, but its regulation is not yet characterized. Its sequence is not known, nor do we known the molecular basis for the abnormal character of NC is stone-forming patients. Compared to Tamm-Horsefall protein and uropontin, the two other inhibitors, NC is very potent, and is probably of major importance in protecting kidneys against supersaturations caused by normal water conservation.

Animals↗
PubMed1992

Nephrocalcin: biosynthesis by human renal carcinoma cells in vitro and in vivo.

Renal carcinoma cells removed surgically from two patients (one primary tumor and one bone metastasis) were maintained in short-term culture. Media conditioned by these cells contained calcium oxalate monohydrate crystal growth inhibitor, a glycoprotein named nephrocalcin (NC). NC was also detected in both cell lines by an enzyme-linked immunosorbent assay using anti-NC antibody raised in rabbits. The glycoprotein was purified from the culture medium and found to have an amino acid composition similar to that of normal human urinary NC. However, NC from the renal carcinoma cells, isolated in multiple forms by DEAE-cellulose column chromatography, contained larger amounts of carbohydrate residues than normal NC. Purified NCs showed a dissociation constant of 10(-6) to 10(-8) M toward calcium oxalate monohydrate crystal. Three renal carcinoma cell lines maintained in long-term culture failed to produce NC. Our study demonstrates that NC is produced by renal cell carcinoma cells (in vitro) from primary and metastatic tumors. Preliminary data suggest that urinary levels of NC corresponded with disease progression in patients with metastatic disease, suggesting that NC may be useful clinically as a tumor marker.

Aged↗
PubMed1992

Stone-forming potential of milk or calcium-fortified orange juice in idiopathic hypercalciuric adults.

Milk and orange juice (OJ) fortified with calcium-citrate-malate (CCM; calcium-citrate-malate salt is a coined term to describe a trademarked calcium delivery system found only in Citrus Hill Plus Calcium) were evaluated for their potential to alter urine chemistries and crystallization during the course of an eleven week, crossover study. Six male and six female, non-stone-forming, idiopathic hypercalciuric adults consumed 600 mg per day as beverage calcium for four consecutive weeks. The results show that both milk and CCM-fortified OJ (CCM-OJ) were well tolerated by male and female hypercalciurics since few significant changes occurred in overall urinary chemistry profiles. CCM-OJ did, however, significantly (P less than or equal to 0.05) increase urinary pH relative to milk in both sexes and urinary citrate concentration in women only. Both of these urinary parameters were significantly increased by CCM-OJ in both sexes relative to the basal period. The combined pH and citrate effects are recognized to protect against calcium oxalate stone formation through formation of the soluble calcium citrate salt. These data indicate that either milk or CCM-fortified orange juice can be consumed, at least within the limits tested, as a dietary source of calcium without increasing the risk of stone formation in a calcium-sensitive subpopulation. That the urine chemistries and crystallization of such calcium-sensitive individuals does not significantly change with the consumption of either beverage implies that the urine of normal individuals would be exceedingly unlikely to change as well.

Adolescent↗
PubMed1991

Inhibitors within the nephron.

Kidney-derived inhibitors of crystal growth and aggregation prevent supersaturations created by water conservation from expressing themselves in pathological soft tissue calcifications and intranephronal crystallizations. These inhibitors include nephrocalcin (NC), an acidic glycoprotein produced in proximal tubules and thick ascending limbs of Henle's loop, and the Tamm-Horsfall glycoprotein (THP), produced only in the thick ascending limb. NC inhibits growth and aggregation of calcium oxalate monohydrate (COM), the major crystalline component of human renal stones, THP inhibits only COM aggregation. Patients who form COM stones produce abnormal NC molecules that lack gamma-carboxyglutamic acid and fail to inhibit COM crystallizations normally.

Animals↗
PubMed1991

Isolation of nephrocalcin from kidney tissue of nine vertebrate species.

Nephrocalcin (NC), a urinary calcium oxalate monohydrate (COM) crystal growth inhibitor, was purified from kidneys of nine vertebrate species including humans. All isolates were glycoproteins with high contents of aspartic and glutamic acids and small amounts of basic and aromatic amino acids. Carbohydrate contents ranged from 4 to 16 wt% among the different species, but all contained fucose, mannose, galactose, glucose, galactosamine, glucosamine, and N-acetylneuraminic acid. Although amino acid and carbohydrate compositions were similar, dissociation constants derived from calcium oxalate monohydrate inhibition varied between 10(-7) and 10(-8) M, and highest affinity could be related to highest ability of the kidney of origin to concentrate urine. Using an antibody raised against NC from human kidney tissue culture medium, we found strong immunoreactivity with two species, pigs and sheep. Thus far all vertebrate kidneys possess COM growth-inhibiting material that seems to be of glycoprotein character, and all the glycoproteins isolated so far share similar features, suggesting NC-like proteins are a well-conserved trait.

Amino Acids↗
PubMed1991

Molecular abnormality of Tamm-Horsfall glycoprotein in calcium oxalate nephrolithiasis.

Tamm-Horsfall glycoprotein (THP) inhibits self-aggregation of calcium oxalate monohydrate (COM) crystals and may therefore be part of the natural defenses against deposition of COM in the kidney in the form of stones or nephrocalcinosis. We have studied THP from six patients with severe nephrolithiasis and have found that their THP inhibits COM self-aggregation less than normal THP under conditions of NaCl and THP concentration and pH similar to those of human urine. The reason for the reduced inhibition of COM crystal aggregation seems to be an enhanced self-aggregation of patient THP, which removes it from effective interactions with the COM crystals. In one family, the father and the oldest son both excreted THP that behaved abnormally and in similar ways, whereas THP from the other son and from the wife behaved normally.

Adult↗
PubMed1991

Evidence that nephrocalcin and urine inhibit nucleation of calcium oxalate monohydrate crystals.

Human urine, and nephrocalcin (NC), a glycoprotein of probable kidney cell origin, greatly reduce consumption of calcium and oxalate from metastably supersaturated solutions seeded with calcium oxalate crystals, a phenomenon usually referred to as inhibition of crystal growth. We seeded metastably supersaturated calcium oxalate solutions with calcium oxalate monohydrate crystals under conditions of ion clamping to maintain constant composition and measured ion consumption from pump delivery rates. Consumption rates increased continuously with time as if the solutions were autocatalytic. After incubation, the seeds were covered with innumerable crystallites, which were also free and numerous in the solution, reflecting self-nucleation. The addition of 20% whole, dialyzed urine, or purified NC reduced ion consumption rates markedly, and the only crystals observed at the end of incubation were the large original seeds. Crystals precoated with concentrated dialyzed urine or NC also showed reduced ion consumption. Urine and NC from patients with nephrolithiasis inhibited nucleation less than normal controls. Self-nucleation seems to be the preferred response in sparsely seeded, ion-clamped, supersaturated solutions, such as exist in the nephron. Urine and NC suppress self-nucleation in vitro by adsorbing to the surface of calcium oxalate crystals.

Calcium Oxalate↗
PubMed1989

Elucidation of multiple forms of nephrocalcin by 31P-NMR spectrometer.

Four forms of nephrocalcin have been routinely isolated from mammalian kidney tissues and urine using DEAE-cellulose column chromatography with a linear NaCl gradient. We have demonstrated that these four forms of nephrocalcin, isolated from bovine kidneys, contain different amounts of phosphate residues, and that alkaline phosphatase digestion converts these to only one form of nephrocalcin. The changes in the nephrocalcin before and after removal of phosphate residues were measured by 31P-NMR spectrometer. Loss of phosphate residues decreased the dissociation constant of nephrocalcin 10-fold toward calcium oxalate monohydrate crystals, suggesting the phosphate residues appear to be important in the inhibitory effects of calcium oxalate monohydrate crystal growth.

Animals↗
PubMed1989

Gestational hypercalciuria causes pathological urine calcium oxalate supersaturations.

Although normal pregnant women are more hypercalciuric than women with calcium oxalate nephrolithiasis (243 +/- 23 mg/day vs. 194 +/- 5 mg/day), pregnancy is not an established stone-forming state and pregnant women do not exhibit pathological crystalluria. One hypothesis to explain their lack of overt stone formation and pathological crystalluria is that pregnancy does not raise urine supersaturation with respect to stone forming salts such as calcium oxalate or calcium monohydrogen phosphate (brushite) to levels as high as in stone forming women. To test this hypothesis, we studied eleven normal women during each trimester of pregnancy, and between six and eight weeks post-partum. During pregnancy, hypercalciuria occurs with unchanged urine volume, citrate and magnesium excretions do not increase proportionally with calcium excretion, and urine pH increases. Supersaturations with respect to calcium oxalate (CaOx) and brushite (Br) are as high as those of women with calcium nephrolithiasis. The lack of pathological crystalluria and stones during pregnancy is not due to a failure of supersaturations to increase; urinary potential for crystallization is as high as in patients with established stone disease.

Adult↗
PubMed1989

Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins.

Normal urine inhibits both the growth and the aggregation of calcium oxalate monohydrate (COM) crystals but the molecules that inhibit aggregation are not well defined. We have developed a spectrophotometric assay method to measure the aggregation of COM crystals in vitro under conditions that avoid simultaneous crystal growth. At pH 7.2 and 90 mM NaCl, Tamm-Horsfall glycoprotein (THP) and nephrocalcin (NC), a major urinary inhibitor of COM crystal growth, inhibit COM crystal aggregation at concentrations as low as 2 X 10(-9) and 1 X 10(-8) M, respectively. When increasing NaCl to 270 mM or lowering pH to 5.7, inhibition by both glycoproteins, but more markedly by THP, is decreased. Urinary NC from calcium oxalate renal stone formers (SF NC) and NC isolated from calcium oxalate renal stones (stone NC) both inhibit COM crystal aggregation 10-fold less than NC from normal urine. Citrate is ineffective even at millimolar concentrations. Thus THP and NC are two major inhibitors of COM crystal aggregation in normal urine; SF NC and stone NC are defective aggregation inhibitors.

Adult↗
PubMed1989

Evidence that mouse renal proximal tubule cells produce nephrocalcin.

Nephrocalcin (NC) is a glycoprotein inhibitor of calcium oxalate monohydrate crystal growth present in urine and kidney tissue. To determine if kidney cells can produce NC, we have isolated proximal tubules from mouse kidney and cultured them in a serum-free medium containing supplements. The tubules accumulate p-aminohippurate and respond with increase in adenosine 3',5'-cyclic monophosphate to parathyroid hormone but not to arginine vasopressin. They produce 1,25 dihydroxyvitamin D3 when 25 hydroxyvitamin D3 is added as substrate. Medium conditioned for 3 days reacted by direct enzyme-linked immunosorbent assay (ELISA) with a rabbit antiserum to human urinary NC; the same antiserum was localized to the cells using immunoperoxidase staining. Using ion exchange and molecular sieve chromatography, we purified a glycoprotein calcium oxalate crystal-growth inhibitor the chromatographic behavior and amino acid and carbohydrate compositions of which closely resembled that of purified human urinary NC. Its dissociation constant toward the calcium oxalate crystal was 0.4-10 X 10(-7) M. Purified fractions of the protein cross-reacted with the antiserum tested by ELISA. Cultured proximal tubule cells produce a molecule that resembles NC from human urine, rat urine, and rat kidneys; proximal tubule is a probable site of NC production in vivo.

Animals↗
PubMed1988

Chlorthalidone promotes mineral retention in patients with idiopathic hypercalciuria.

In seven patients with severe idiopathic hypercalciuria and recurrent calcium oxalate nephrolithiasis, we have determined the effects on mineral balance of chronic treatment with chlorthalidone or trichlormethiazide, drugs that are widely used to lower urine calcium losses and reduce stone recurrence. Each person excreted above 350 mg of calcium daily while untreated, and was studied twice, before and after three to six months of treatment. Compared to pretreatment, the drugs reduced intestinal calcium absorption; but they reduced urine calcium loss even more, so calcium retention increased. Phosphate retention also increased. Serum levels of calcitriol, parathyroid hormone, calcium, phosphate, and magnesium were unchanged. At least in patients of this type, chlorthalidone and trichlormethiazide seem ideal treatments, that lower urine calcium yet increase calcium and phosphate retention. Whether patients with less severe hypercalciuria respond this way is unknown.

Adult↗
PubMed1988

Crystal adsorption and growth slowing by nephrocalcin, albumin, and Tamm-Horsfall protein.

Urine inhibition of calcium oxalate monohydrate (COM) crystal growth (CG) seems due to a glycoprotein that contains gamma-carboxyglutamic acid and has been named nephrocalcin (NC); however, Tamm-Horsfall protein (THP) and albumin resemble NC and make its measurement and role uncertain. NC in urine is aggregated to molecular mass 64 kDa and higher, similar to albumin (64 kDa) and THP (87 kDa). Albumin and THP are calcium binding, albumin adsorbs to COM crystals, and THP has been described as an inhibitor of COM growth. Antisera to NC have cross-reacted with THP even though the NC was isolated from cultured renal cells. Here we have compared highly purified NC, THP, and albumin adsorption with COM crystals and CG inhibition; also we compared their patterns of cross-reactivities with a new antiserum against NC and a monoclonal antibody to THP. NC adsorbs to COM crystals, THP does not. Albumin and THP do not inhibit CG. Cross-reactivity of albumin and THP to the antiserum is slight by direct enzyme-linked immunosorbent assay and nonexistent by competitive ELISA; reaction of NC to the anti-THP monoclonal antibody is absent.

Adsorption↗