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Biomedical subjects

A L Yergey

Publications and source records attributed to A L Yergey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Simultaneous assessment of conformation and aggregation of beta-amyloid peptide using electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry was used to study conformation and aggregation of the synthetic beta-amyloid peptide, residues 1-40 (betaA4), as a function of concentration and sample aging. All mass spectra showed a major envelope of peaks corresponding to charge states of 7-3 of the monomeric form of betaA4. In addition, weaker envelopes of peaks corresponding to charge states of dimeric, trimeric, and tetrameric betaA4 species were seen under gentle ionization conditions. The average charge state of the envelope associated with the monomeric form decreased by ca. 0.5 z as samples were aged, indicating that the relatively open form (likely random coil) of the peptide was modified into the more compact form (likely beta-sheet) as a function of sample aging. The aggregate forms became weaker and ultimately were absent both in the more dilute solutions and in aged aliquots of the concentrated sample. These aggregates were interpreted as assemblies of the random coil form. We interpret our inability to see an ion envelope that can be associated with aggregates of the beta-sheet form to be a consequence of the presumed very compact nature of this form. A model for the formation of betaA4 fibrils is proposed and discussed.

Amyloid beta-Peptides↗
PubMed1996

Calcium kinetics in glycogen storage disease type 1a.

Glycogen storage disease type 1a (Von Gierke's disease) is one of the more common glycogen storage diseases (GSD). GSD 1a patients can have severe idiopathic osteopenia, often beginning at a young age. Since calcium tracer studies offer a sensitive probe of the bone microenvironment and of calcium deposition, kinetics might be disturbed in patients with GSD 1a. Plasma dilution kinetics obtained using the stable isotope 42Ca are shown in this paper to be quite different between GSD 1a patients and age-matched controls. Comparison of kinetic parameters in these two populations is made using a new binding site model for describing calcium dynamics at the plasma-bone interface. This model describes reversible binding of calcium ions to postulated short-term and long-term sites by a retention probability density function psi (t). Using this analysis, adult GSD subjects exhibited a significant decrease (P = 0.023) in the apparent half-life of a calcium ion on the longer-term site compared with controls. The general theory of calcium tracer dilution kinetics is then discussed in terms of a new model of short-term calcium homeostasis recently proposed by Bronner and Stein [5].

Adolescent↗
PubMed1996

Intestinal calcium absorption of women during lactation and after weaning.

We investigated whether intestinal calcium absorption and serum 1,25-dihydroxycholecalciferol (calcitriol) concentrations are higher in women during lactation and after weaning to compensate for calcium lost in breast milk. Measurements were obtained at 4.6 mo postpartum in 24 lactating women and 24 nonlactating women, at 9.6 mo postpartum in 24 lactating women (2.6 mo after complete weaning) and 24 nonlactating women. One-half of the women in each group were randomly assigned to receive 1 g supplemental Ca/d as calcium carbonate. Fractional calcium absorption was measured by using stable isotopic tracers 42Ca and 44Ca. Fractional absorption was 0.32+/-0.02 (+/-SEM) in both lactating and nonlactating women, but was higher in lactating women after weaning (0.37+/-0.02) compared with nonlactating postpartum control subjects (0.31+/-0.02). These effects were independent of calcium intake. Changes in serum calcitriol paralleled changes in fractional absorption. There were no differences in calcitriol concentrations between lactating and nonlactating women, but calcitriol was greater in women after weaning compared with postpartum control subjects. Lactating women who had resumed menses had higher fractional absorption and serum calcitriol than did lactating women who had not. Serum calcium and phosphorus concentrations were greater in lactating compared with nonlactating women; there were no differences between groups after weaning. We conclude that lactation stimulates increases in fractional calcium absorption and serum calcitriol, but the responses are only apparent after weaning or the resumption of menses.

Adult↗
PubMed1996

Analytical instruments for stable isotopic tracers in mineral metabolism.

Thermal ionization mass spectrometry (TIMS) is the best of four currently used techniques for obtaining results of high accuracy and precision in studies of metal metabolism. TIMS is also the most general technique because it allows measurements of all the metallic elements of interest. The highest absolute sensitivity as well as the ability to determine multiple elements are simultaneously obtained with inductively coupled plasma mass spectrometry (ICP-MS). Current results with this technique show that, although element quantification may be done with acceptable accuracy and precision, use of ICP-MS in metabolic studies at low levels of isotopic labels may be limited. The most favorable elements for study using ICP-MS in metabolic studies appear to be Mg, Zn and possibly Fe. Use of this technique is limited further by isobaric interferences from plasma jet ion molecule reactions, and metabolic studies of Ca are particularly limited. Acceptable levels of accuracy and precision have been obtained from fast atom bombardment-secondary ion mass spectrometry (FAB-SIMS), which has allowed these approaches to be used in metabolic studies of ZN, Fe and Ca, but the approaches are ultimately limited by hydride isobaric interferences. Both FAB-SIMS and gas chromatography-mass spectrometry of metal chelates have the advantage of using widely available instrumentation. GC-MS of metal chelates has been shown to be useful in studies of Cr and Se metabolism and for the determination of a number of other metals. Values of accuracy and precision from use of this approach have been satisfactory.

Calcium↗
PubMed1995

Quantitation of metal isotope ratios by laser desorption time-of-flight mass spectrometry.

Laser desorption time-of-flight mass spectrometry (LD/TOF-MS) is evaluated for the determination of stable metal isotope ratios. The isotope ratios of five metal ions (Cu, Ca, Mg, Fe, Zn) in atomic absorption standard solutions and two metal ions (Ca, Mg) in human serum samples are determined. With an existing LD/TOF-MS instrument we show that the technique can overcome the difficulties of the most commonly used methods for measuring metal isotope ratios: (1) all metals are ionizable without surface treatment, thus overcoming the major drawback of thermal ionization mass spectrometry (TIMS); (2) there is no matrix involved to interfere with the metal ion detection, thus overcoming the major disadvantage of inductively coupled plasma mass spectrometry (ICPMS); (3) there is no interference from hydride ions, a major disadvantage of fast atom bombardment secondary ionization mass spectrometry; (4) a mixture of metals can be detected simultaneously using a single laser wavelength, overcoming the major disadvantage of resonance ionization mass spectrometry; (5) accuracy and precision comparable to ICPMS can be achieved with the current instrumentation; (6) precision comparable to TIMS is feasible; and most importantly (7) high precision can be achieved on very small quantities of material because the LD/TOF-MS instrument permits all masses to be monitored simultaneously and very small differences in isotope ratio can be detected.

Calcium↗
PubMed1995

Extraction of serum and urine calcium with ion exchange membrane filters for isotope enrichment determination using thermal ionization mass spectrometry.

The extraction of calcium from water, serum, and urine using Bio-Rex 25 mm ion exchange membrane filters was compared with the oxalate precipitation procedure currently used in our laboratory. Total recoveries of a known quantity of calcium loaded onto the membrane filters for water, serum and urine were as follows: (a) cation exchange filter, 85%, 74%, and 66%; (b) Chelex, 65%, 98%, and 20%; and (c) oxalate precipitation, 93%, 100%, and 96%, respectively. Regression analysis for precipitation versus ion exchange isotope ratio measurements of standards prepared using highly enriched calcium-44 showed slopes of unity. An improvement of automated sample analysis was observed for water and urine calcium samples extracted with ion exchange filters.

Calcium↗
PubMed1995

Calcium tracer kinetics show decreased irreversible flow to bone in glucocorticoid treated patients.

Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function.

Adolescent↗
PubMed1995

Precise determination of the absorptive component of urinary calcium excretion using stable isotopes.

Some patients with hypercalciuria are thought to have enhanced enteric calcium absorption, with a major component of recent diet contributing to urinary calcium. This mechanism has been difficult to test with the usual calcium loading procedures. We employed dual stable calcium isotope tracers to quantitate the components of urinary calcium excretion in 38 healthy female children. The mean urinary calcium excretion in these girls was 2.4 mg/kg per day. The contribution of recent diet to this total was a mean of 0.2 mg/kg per day. The maximum dietary contribution to urinary calcium excretion was 0.86 mg/kg per day. Recent diet contributes a mean of 8% to total dietary calcium excretion. This novel method permits precise quantitation of the contributions of recent diet and tissue stores to urinary calcium excretion. In these healthy girls, the fraction of urinary calcium derived from diet is trivial.

Absorption↗
PubMed1995

Direct determination of human urinary cortisol metabolites by HPLC/CRIMS.

Feasibility of using high performance liquid chromatographic input to the chemical reaction interface mass spectrometry system was assessed by measuring the profile of hydrolyzed urinary metabolites of [9,12,12-2H3] cortisol in six human subjects with no preparation other than hydrolysis and solid phase extraction. Relative amounts of tetrahydrocortisol, tetrahydrocortisone, and cortolones (as the sum of alpha- and beta-) were 0.417 +/- 0.047, 0.523 +/- 0.036 and 0.059 +/- 0.019, respectively. The constant reproducibility of the measurements coupled with a profile consistent with that observed by other workers shows that the technique represents an important tool in the determination of metabolites of endogenous molecules.

Adolescent↗
PubMed1995

A three-hour measurement to evaluate bone calcium turnover.

It is well established that short-term clearance of an intravenous calcium load in vivo reflects bone uptake. Using results from isotope-dilution experiments with 42Ca, a 3-h test has been developed to measure a quantity, gamma, related to bone accretion. This test is proposed as a useful, clinically applicable measure of bone status. For early times, t, after a bolus of 42Ca, plasma tracer dilution was well approximated by t-gamma, where gamma is related to the fractional rate of loss of tracer, q, from blood into bone (1/q)(dq/dt) = -gamma/t). Gamma was evaluated from kinetic measurements on 91 normal female children, adolescents, and adult women in the age range 4-50 years. For t < or = 3 h, all clearance curves were well fit by a power function. Gamma was found to vary from 0.244 +/- 0.031 for adult premenopausal women (N = 22) to 0.392 +/- 0.056 for prepubertal children (N = 29). Using the Spearman rank-order correlation test, gamma was correlated with bone accretion measured from classic calcium kinetic studies with a correlation coefficient of 0.721, significant at p < 0.005. In those cases in which accretion and resorption remain tightly linked, gamma also provides information on the state of calcium loss from bone. Gamma was evaluated in 14 subjects with bone disease characterised by increased resorption (osteoporosis, Paget's disease) and in 27 subjects with decreased accretion (osteogenesis imperfecta, types I, III, IV; steroid-treated juvenile dermatomyositis). All subjects with Paget's disease and with osteoporosis showed increased gamma, consistent with high bone turnover. The osteoporotic patients furthermore exhibited gamma increasing monotonically by approximately 1% per year after age 55.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Use of stable isotopic tracers in studies of whole body calcium metabolism.

Stable isotopic tracers of calcium have been used to characterize the absorption of dietary calcium and the subsequent distribution of this element through the body. For a group of 7 healthy children, ages 4-14, and 7 children with osteogenesis imperfecta (OI), types I, III and IV, ages 6-17, there were no detectable differences in the fractional absorption of dietary calcium, 0.29+/-0.11 and 0.28+/-0.16, respectively. The total exchangeable pool of calcium was found to be 161+/-52 mg/kg for the healthy children and 95+/-29 mg/kg for the 3 children with Type I OI, 250+/-75 mg/kg for the 3 children with Type III OI and 216 mg/kg for the child with Type IV OI.

Administration, Oral↗
PubMed1994

Extraction of magnesium from biological fluids using 8-hydroxyquinoline and cation-exchange chromatography for isotopic enrichment analysis using thermal ionization mass spectrometry.

The use of 8-hydroxyquinoline to precipitate magnesium was evaluated as a method for preparing biological samples for isotopic enrichment analysis using thermal ionization mass spectrometry (TIMS). Standard curves in matrices of water, serum, and urine were prepared using varying amounts of 25Mg. The 25Mg/24Mg isotope ratio was measured by TIMS using a silica gel/phosphoric acid technique. Although the total Mg recovered by precipitation from the matrices varied considerably and was dependent on matrix, recovery was sufficient for isotopic enrichment analysis. Urine samples required cation-exchange chromatography (Bio-Rex AG 50W-X8 filter membrane, Bio-Rad Laboratories) prior to precipitation to remove contaminants which interfered with the thermal ionization process. The observed versus expected 25Mg/24Mg enrichments were evaluated using linear regression analysis: water, y = 0.016 + 1.022x; serum, y = 0.5 + 1.097x; urine, y = -0.004 + 0.943x. This method has proven useful for the isolation of magnesium from the biofluids tested.

Body Fluids↗
PubMed1994

Issues in constant tracer infusion and mineral metabolism.

The preceding discussion focussed on two aspects of the application of tracer kinetics to studies of endogenous metabolism. It is recognized that the discussions were more directed to theoretical aspects of tracer studies, but it is hoped that, as such, they will lead to some new experimental investigations, particularly in the area of metal metabolism.

Calcium↗
PubMed1994

Influence of age on effects of endogenous 1,25-dihydroxyvitamin D on calcium absorption in normal women.

Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH2)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30 +/- 1 year) and 15 elderly (74 +/- 1 year) women (mean +/- SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)2D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (44Ca mixed with food and 42Ca given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P = 0.01) whereas serum 1,25(OH)2D concentration and true FCA were similar. In both groups, serum 1,25(OH)2D concentrations increased (P < 0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)2D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40 +/- 3 versus 40 +/- 4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods.

Absorptiometry, Photon↗
PubMed1994

A non-Markovian model for calcium kinetics in the body.

We present a new generalized compartmental model for calcium kinetics as measured by tracer concentration in blood plasma. The parameter measuring incorporation of calcium in bone discriminates between different levels of physical development in female teenagers and between teenagers and adults.

Adolescent↗
PubMed1994

Calcium kinetics in lactating women with low and high calcium intakes.

Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption.

Adult↗
PubMed1994

Determination of fractional absorption of dietary calcium in humans.

Four dual-isotopic label methods for determining true fractional absorption of dietary calcium were compared in 23 subjects. The ratio of the integrals of oral label in a 24-h pooled urine to intravenous label in the same urine is called alpha 24h and was taken as the standard against which the others were compared. alpha Spot is the ratio of the fraction of oral label to the fraction of intravenous label in a single urine specimen; alpha Lag is the ratio of the level of oral label in blood 4 h after administration to the level of intravenous label in blood 2 h after administration. alpha Dec is obtained by deconvoluting response to the intravenous label from the response to the oral tracer. Results were as follows: alpha 24h = 0.273 +/- 0.124, alpha Dec = 0.300 +/- 0.101 (n = 14), alpha Spot = 0.359 +/- 0.179, and alpha Lag = 0.271 +/- 0.103. The Bland-Altman approach for comparison of methods was used to show that results for alpha Spot and alpha Lag can be expected, with a 95% confidence limit, to differ from the value of alpha 24h by 60 and 69%, respectively. The results for alpha Dec were shown to be not only indistinguishable from alpha 24h but identical from a theoretical perspective.

Administration, Oral↗