Immunochemical heterogeneity of calcitonin in man: Effect on radioimmunoassay

Snider, Richard H.; Silva, Omega L.; Moore, Charles F.; Becker, Kenneth L.

doi:10.1016/0009-8981(77)90113-9

Cited by 60 publications

(24 citation statements)

References 28 publications

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“…One possible explanation is that relating to immunoheterogeneity of circulating iCT with the generation of fragments and(or) aggregates not recognized by our antiserum. These forms of CT could either arise from the C-cell or from peripheral metabolism (23)(24)(25)(26). In addition, possible differences in patient populations with regard to sex (4), degree of hypercalcemia, or renal function (1) might explain the conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Pre- and Postoperative Studies of Plasma Calcitonin in Primary Hyperparathyroidism

Lambert¹,

Heath²,

Sizemore³

1979

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Pre- and Postoperative Studies of Plasma Calcitonin in Primary Hyperparathyroidism

Lambert¹,

Heath²,

Sizemore³

1979

J. Clin. Invest.

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“…Urine iCT is expressed as ng iCT per mg creatinine to eliminate the necessity for collecting urine during a timed period. Gel filtration studies were done using G-75 superfine Sephadex (3 x 110 cm columns, pH 7.5) as we have previously described (12). Urines containing <0.5 ng/ml of iCT were concentrated before gel filtration.…”

Section: Methodsmentioning

confidence: 99%

Urine Calcitonin in Normal Children

et al. 1981

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SummaryAlthough it is known that calcitonin decreases bone resorption, lowers serum calcium and phosphate, and influences the urinary excretion of these ions, its effect upon skeletal maturation in growing children has not been elucidated. Conceivably, the higher serum calcitonin levels that have been reported in children may promote bone formation and growth.To study immunoreactive urine calcitonin (iCT) in normal children, we used the radioimmunoassay (RIA) which we had developed previously to measure the hormone in normal adults and to screen persons at risk for medullary thyroid carcinoma (MTC). The measurement of urine iCT by RIA is particularly useful for children at risk for this thyroid malignancy because it obviates the need for venipunctures. Two antisera, one having region specificity for the midportion of CT (Ab-IIIb) and the other having carboxyl terminal recognition (Ah-IV), were utilized for the assay.For the carboxylterminal antiserum (Ab-IV), boys of ages 7 to 12 years (mean urine iCT, (ng/mg + S.D.), 0.29 f 0.18) had urine iCT levels significantly higher than girls the same age (0.13 f 0.05) and higher than both adult males (0.16 f 0.07) and adult females (0.084 + 0.034). Boys ages 13 to 15 years (0.12 f 0.03) had urine iCT concentrations which were not different from adult males. Girls of ages 7 to 12 years (0.13 + 0.05) had iCT levels significantly lower than boys of the same age (0.29 2 0.18), but significantly higher than adult females (0.084 + 0.034). Girls ages 13 to 15 (0.11 f 0.05) had urine iCT levels not significantly different from boys of the same age (0.12 f 0.03). For the midportion antiserum (Ab-IIIb), children ages 7 to 15 (0.58 + 0.384) had urine iCT concentrations greater than adults (0.26 f 0.10), but there were not significant differences in levels between boys and girls of the same age. Gel filtration studies revealed greater amounts of higher molecular weight fractions (pU-2, -14,600 daltons; pU-3, -11,000) of urine calcitonin than were found in the urine of most normal adults and all patients with MTC.

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“…Gel filtration Gel filtration studies of serum were carried out as previously described (Snider et al 1975(Snider et al , 1976(Snider et al , 1977. Immunoreactive calcitonin in serum and extracts were deter¬ mined by radioimmunoassay following gel filtration.…”

Section: A Radioimmunoassaymentioning

confidence: 99%

“…Ab-II has the same region specificities as Ab-I, but in diflerent pro¬ portions; 65 % of the binding sites recognize the midportion, and 35°/o recognize the carboxyl terminal portion. Ab-III, which was obtained by saturation ot Ab-I with the synthetic 17-32-NH¡) fragment of calcitonin1), recognizes the midportion of calcitonin (Snider et al 1977). Ab-IV was obtained by saturation of Ab-I with the 11-28-OH fragment!)…”

Section: A Radioimmunoassaymentioning

confidence: 99%

“…We, as well as other investigators, have determined that there is a multipli¬ city of immunoreactive forms (iCT) of human calcitonin (Deftos et al 1975;Singer 8c Habener 1974;Sizemore 8c Heath 1975;Snider et al 1975Snider et al , 1976Snider et al , 1977. In order to determine if there is an appreciable difference between the iCT of bronchogenic cancer and medullary thyroid cancer, we undertook a comparative investigation of the immunochemical heterogeneity of this hor¬ mone in patients with these neoplasms.…”

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Calcitonin Heterogeneity in Lung Cancer and Medullary Thyroid Cancer

Becker

Snider

Silva

et al. 1978

Acta Endocrinologica

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An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Endogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I ([2267] 30 000 molecular weight (MW)) to fraction V ([ 223C] 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i. e. fractions I and II A). Following in vitro incubation of the serum, the typical large MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.When calcitonin (HCT), the hypocalcaemic hormone normally secreted by the thyroidal C-cells, was found to be greatly increased in the serum of patients with medullary thyroid cancer (Clark et al. 1969), it was assumed that hypercalcitonaemia would prove to be a marker exclusively for this tumour. Indeed.

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Immunochemical heterogeneity of calcitonin in man: Effect on radioimmunoassay

Cited by 60 publications

References 28 publications

Pre- and Postoperative Studies of Plasma Calcitonin in Primary Hyperparathyroidism

Pre- and Postoperative Studies of Plasma Calcitonin in Primary Hyperparathyroidism

Urine Calcitonin in Normal Children

Calcitonin Heterogeneity in Lung Cancer and Medullary Thyroid Cancer

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