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K J Quelch

Publications and source records attributed to K J Quelch.

6 recordsLinked to original sources

The metabolic clearance rate of osteocalcin in sheep.

Plasma osteocalcin has been proposed as a useful and convenient biochemical marker of bone formation. However, the effect on plasma osteocalcin due to variations in the rate of its removal from the circulation has been little investigated. We have measured the metabolic clearance rate of plasma osteocalcin in adult oophorectomized sheep. Two methods were used: intravenous bolus injection (six animals) and 6 hour constant intravenous infusion (four animals) of 125I-ovine osteocalcin. Using the bolus injection method, the plasma clearance of osteocalcin was found to be 3.3 liters/h. With the constant infusion method, the calculated value was 2.8 liters/h; based on this value and the mean ovine plasma osteocalcin concentration of 26.9 ng/ml (N = 29), a plasma production rate of 1.8 mg/day was derived. Osteocalcin clearance was relatively constant among animals in a basal state. Hence, the present approach should permit us to evaluate the relative contributions to changes in circulating osteocalcin levels from altered osteocalcin plasma clearance and production under various physiological and pathological conditions.

Animals↗

Plasma osteocalcin in man.

A radioimmunoassay for bovine osteocalcin has been developed. Human osteocalcin reacted identically with the bovine standard, allowing the use of this assay to measure human plasma osteocalcin. Levels were determined in 212 healthy subjects (124 men, 88 women) with an age range of 20 to 66 years. The distribution of these was skewed to the right, with the mean being 14.7 ng/ml (range 4 to 40) and the geometric mean 12.2 ng/ml. There was no alteration with age and no difference between males and females. High levels were found in chronic renal failure, Paget's disease of bone, and in primary hyperparathyroidism with severe bone disease, and there was a significant positive correlation of osteocalcin with plasma alkaline phosphatase. Low levels were found in pregnancy. Evidence is presented which suggests that the high levels measured probably reflect intact osteocalcin and not immunoreactive fragments. Our data are compared with those reported by others. Areas of disagreement are noted and discussed.

Adult↗

Noncollagenous proteins in normal and pathological human bone.

The concentrations of alpha 2HS-glycoprotein, albumin, and sialic acid were measured in the bone of 28 normal individuals and 6 patients with osteogenesis imperfecta, 3 patients with Paget's disease, and 4 patients with either renal osteodystrophy, osteoporosis, osteomalacia, or osteopetrosis. The concentration of alpha 2HS-glycoprotein in neonatal bone was 3 X higher than in bone from children and 7 X higher than in adult bone. The concentrations of albumin and sialic acid in neonatal bone were 1.5 X higher that in bone from children and twice the levels in adult bone. The concentrations of alpha 2HS-glycoprotein, albumin and sialic acid were above the normal mean values in the patients with osteogenesis imperfecta, and 4 patients had significantly raised levels of one or more of these proteins. The concentrations of these noncollagenous proteins were also significantly raised in Paget's disease, and the alpha 2HS-glycoprotein was significantly raised in renal osteodystrophy. The lowest level of alpha 2HS-glycoprotein was in osteopetrotic bone and the lowest levels of albumin and sialic acid were in osteoporotic bone. The results of this study suggest that the concentrations of alpha 2HS-glycoprotein, albumin, and sialic acid in bone are related to the rate of bone turnover.

Adolescent↗

Analysis of collagen from normal and abnormal human bone.

Using cyanogen bromide digestion of bone collagen, we have studied the type of collagen in normal bone, and in samples from patients with Paget's disease of bone, osteomalacia, osteoporosis and renal osteodystrophy. Despite extensive extraction with ethylene diamine tetraacetic acid and guanidine hydrochloride, not all of the glycoproteins could be removed from bone collagen. Upon electrophoresis on sodium dodecyl sulphate polyacrylamide gels, the cyanogen bromide peptides of insoluble bone collagen showed the pattern of type I collagen only in all samples, both normal and abnormal. Amino acid composition of the insoluble collagens and the ratio of hydroxylated and non-hydroxylated amino acids were similar for all adult bone samples. These results suggest that the type of collagen in bone is not altered in the bone diseases examined.

Adult↗

Chemical composition of human bone.

The mineral and non-collagenous organic components of normal human femoral cortex were examined following powdering, demineralization with EDTA and digestion with bacterial collagenase. The protein, hexose, sialic acid and uronic acid contents of the matrix were determined. Neonatal bone had lower levels of mineral and calcium and higher levels of organic material and sialic acid than adult bone, suggesting increased glycoprotein content in neonatal bone. The soluble non-collagenous matrix of human femoral cortex was examined by gel filtration on Sephadex G100 and by ion-exchange chromatography on DEAE-cellulose. Four fractions were eluted off Sephadex-G100: a large molecular weight fraction, a shoulder on the descending portion of this, both of which contained sialic acid and two smaller molecular weight fractions. The material eluted off DEAE-cellulose was separated into 6 fractions which were similar to those found for beef and rabbit bone matrix. Human bone matrix appeared more resistant to collagenase digestion than beef bone, soluble collagen eluted later off DEAE-cellulose than beef bone; sialic acid gave 3 peaks: a major and two lesser ones. The sialic acid-containing material in the fifth fraction was probably bound to proteoglycan. Rabbit bone has 2 to 3 sialic acid peaks whereas beef bone has one, indicating species differences in cortical bone matrix.

Adolescent↗

The demonstration of sialic acid in kidney stone matrix.

1. The organic matrices of 12 kidney stones containing calcium and two composed of uric acid were solubilized, with ethylenediaminetetra-acetate for the former and sodium hydroxide for the latter. 2. The solubilized matrices and residual fine particulate material were examined for sialic acid by the thiobarbituric acid method. 3. Sialic acid was found in every stone in either the soluble and/or insoluble material. 4. The identity of sialic acid was confirmed by the absorption spectrum of the colour produced and by its release from the protein by neuraminidase. 5. The presence of sialic acid in all stones despite widely varying composition suggests that it may be passively deposited.

Hexoses↗