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Biomedical subjects

R A Melick

Publications and source records attributed to R A Melick.

At least 19 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

Hypokalemic periodic paralysis of thyrotoxic origin.

A 50-year-old Vietnamese man suffered recurrent episodes of hypokalemic periodic paralysis during treatment for thyrotoxicosis. Suspected precipitants of the paralysis were oral prednisolone, strenuous exertion and poor compliance with medications. Propranolol prevented the periodic paralysis. Control of the thyrotoxicosis was complicated by a florid skin reaction attributed to carbimazole, and was ultimately achieved using radioiodine.

Australia

Metabolism of osteocalcin.

After intravenous injection, labeled bovine osteocalcin was rapidly removed from rat plasma and taken up mainly by kidney, liver, and bone. The rate of disappearance was slowed by nephrectomy but not as much by ureteric ligation, suggesting renal destruction of osteocalcin rather than renal excretion. Both liver and kidney tissue rapidly degraded osteocalcin, both in vivo and in vitro. The enzyme activity was found in microsomal, mitochondrial, and supernatant fractions. EDTA was the most potent inhibitor, suggesting that metalloenzymes are involved. Comparison of three methods of analysis--trichloroacetic acid precipitation, gel filtration on Sephadex G-50, and SDS polyacrylamide gel electrophoresis--showed that the last gave a much faster rate of degradation of osteocalcin and suggests that osteocalcin and/or fragments bind to larger proteins in the tissue homogenates.

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

Hypercalcaemia in adult hospital population: comparison of inpatients of 1966 with those of 1976.

During 1976, inpatients with hypercalcaemia at The Royal Melbourne Hospital were identified from the worksheets of the Department of Biochemistry and compared with those discovered in a similar study in 1966. In 1966, the estimation of plasma calcium level had to be ordered specifically, whereas in 1976, for technical reasons, the measurement of plasma calcium level was frequently performed when not requested. Despite a six-fold increase in plasma calcium in the rate of detection of hypercalcaemia. In both studies, malignant disease was the most common casue of hypercalcaemia, but primary common cause of hypercalcaemia, but primary hyperparathyroidism was found slightly more frequently in 1976. This study suggests that screening inpatients for hypercalcaemia is of little value.

Clinical Laboratory Techniques

Osteomalacia due to unusual causes presenting in adults.

Severe osteomalacia due to causes other than malabsorption and, where renal function was impaired, disproportionate to the degree of renal failure, is described in 15 adults. Only one was younger than 46 years, the median age being 59 years. The diagnosis was not made for months in most patients. After investigation, the patients were grouped as follows: nutritional three cases, "renal" six cases, hypophosphataemia three cases, neurofibromatosis and primary hyperparathyroidism one each. The last patient was poorly nourished and had taken anticonvulsants and analgesics. Most patients responded well to treatment with calciferol. These cases indicate the need to be aware that osteomalacia may occur in previously healthy middle-aged or elderly subjects.

Adult

Metabolic properties of hormonally responsive osteogenic sarcoma cells.

There is sufficient impetus from the clinical nature of osteogenic sarcoma to stimulate basic studies of the effects of hormones on tumor growth and differentiation. This can probably best be done first by the use of in vitro studies to determine precisely the effects of certain hormones on tumor cell growth and biochemical function. Such investigations would hopefully indicate the direction of in vivo work. The differentiated transplantable tumor described in this paper is clearly hormone-responsive, and offers a means of investigating the effects of other hormones, including growth hormone, androgens, estrogens and glucocorticoids, on specialized function of the osteogenic sarcoma cells, and on the growth of the tumor.

Adenylyl Cyclases

The effects of digestive enzymes on characteristics of placental insulin receptor. Comparison of particulate and soluble receptor preparations.

The role of the surrounding membrane structure on the binding characteristics of the insulin receptor was studied by using several digestive enzymes. The effects observed with particulate membrane preparations are compared with those from soluble receptor preparations. beta-Galactosidase and neuraminidase had no effect on insulin binding to either particulate or soluble receptors from human placentae. Exposure to 2 units of phospholipase C/ml increased insulin binding to particulate membranes, but was without effect on the soluble receptor preparation. The increase in binding to particulate membranes was shown to be due to an increase in apparent receptor number. After 5 min exposure to 500 microgram of trypsin/ml there was an increase in insulin binding to the particulate membrane fraction, owing to an increase in receptor affinity. After 15 min exposure to this amount of trypsin, binding decreased, owing to a progressive decrease in receptor availability. In contrast, this concentration of trypsin had no effect on the solubilized receptor preparation. Because of the differential effects of phospholipase C and trypsin on the particulate compared with the solubilized receptor preparations, it is concluded that the effects of these enzymes were due to an effect on the surrounding membrane structure. Changes in receptor configuration due to alterations within the adjoining membrane provide a potential mechanism for mediating short-term alterations in receptor function.

Cell Membrane

The effect of growth retardation and of osteomalacia on the uptake of albumin by bone.

125I-labeled rat albumin injected intravenously into rats was taken up by growing bone. Some of this radioactive albumin could be removed from bone by washing with saline, the proportion so removed decreasing from 82.5% at 1 day to 7.4% at 8 days. Both the total radioactivity, and that remaining in bone after saline wash, were reduced when growth was slowed by alteration or restriction of the diet. Although the amount of 125I albumin in rachitic bone was reduced, autoradiography showed that radioactivity was present in rachitic osteoid. Immunoprecipitation using anti-rat-albumin serum showed that about half of the radioactivity released from normal bone by EDTA was still attached to albumin. These results suggest that albumin plays some part in the growth of bone.

Albumins

Clinical, biochemical and histological observations on the effect of porcine calcitonin in Paget's disease of bone.

The response to porcine calcitonin has been assessed in 38 patients with Paget's disease, observed during 44 treatment periods of from three to 42 months. In 36 of the treatment courses significant relief of pain was achieved but the contribution of placebo effect could not be determined. Serum alkaline phosphatase and urinary hydroxyproline levels reached normal in a few patients, but the grouped data indicated a plateau effect above the range of normal. The acute hypocalcaemic response to calcitonin was lost only in those patients whose bone turnover was restored to normal. Quantitative histology on iliac crest bone biopsy samples showed no statisically significant lowering of osteoclast counts. No antibody-based clinical resistance occurred and the incidence of side effects was low. The results indicate that porcine calcitonin is a useful treatment of Paget's disease, and the experience of the study helps in arriving at patient selection and treatment schedules. Treatment is recommended for bone pain and for active disease in the relatively young, using intermittent therapy with course of at least six months duration. Resumption of therapy is based on clinical and biochemical indications.

Adult

Renal calculi and their management.

Any patient presenting with renal colic requires the taking of a detailed history-- with inquiries about diet and drugs, an examination of the urine, intravenous pyelography and measurement of the calcium concentration in serum and urine. Any stone passed should be analysed. Recurrent stone formation warrants more comprehensive metabolic investigation. The cause of renal calculi in most patients is still not known. When a cause is found, specific treatment can prevent or control stone formation. For the majority in whom no abnormality is detected, various methods of reducing stone formation have been tried but results are disappointing. The most important points in management are the early detection and effective treatment of urinary tract infection or obstruction and the maintenance of a high fluid intake.

Bacteriuria