Ivan W Caple | University of Melbourne (original) (raw)

Papers by Ivan W Caple

Research paper thumbnail of The Influence of Mineral Deficiencies on Genetic Improvement Programs

Deficiencies of phosphorus, copper, cobalt and selenium are the main mineral deficiencies in sout... more Deficiencies of phosphorus, copper, cobalt and selenium are the main mineral deficiencies in southeastern Australia that are likely to affect lactation, growth, carcass composition and wool production of grazing livestock being compared in genetic improvement programs. Genetic variation in mineral nutrition has been recognized from differences in the incidence of mineral disorders between breeds. The development of diagnostic indicators for measurement of minerals or their associated enzymes in blood, other fluids and tissues, has led to the recognition of genetic variation in mineral metabolism. The heritability for some indicators such as plasma copper is estimated to be as high as 0.4. The opportunities, practical difficulties, and likely benefits from considering genetic variation in mineral metabolism in genetic improvement programs are reviewed. It is concluded that there is an opportunity to select animals on the basis of genetic variation in metabolism of some trace elements...

Research paper thumbnail of WT Kendall MRCVS: Inaugural address to the Mutual Improvement Society on the deck of the SS “Somersetshire”, Friday 2nd January 1880

Published as "Caple, I. (2012). WT Kendall’s inaugural address to the Mutual Improvement Soc... more Published as "Caple, I. (2012). WT Kendall’s inaugural address to the Mutual Improvement Society. Australian Veterinary Journal, 90(9), 28-30.

Research paper thumbnail of John Kendall – WW1 veterinarian

Proceedings of the 4th AVA/NZVA Pan Pacific Conference Brisbane, 2015

access to digitized newspapers which were searched online for "John Kendall". Many letters he had... more access to digitized newspapers which were searched online for "John Kendall". Many letters he had written to friends were published in the Shepparton newspapers. These letters provide a glimpse into his personality, his Australian humour, and how he coped with the conditions. John Kendall was a busy correspondent, and an avid reader. He particularly enjoyed receiving copies of the local newspapers that were sent to him.

Research paper thumbnail of University of Melbourne awards Roger Clarke DVSc (honoris causa)

Australian veterinary journal, 2004

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian veterinary journal, 2010

Research paper thumbnail of Effect of Antidiuretic Hormone on Bile Formation in Sheep

Journal of Endocrinology, 1971

Research paper thumbnail of John Kendall – WW1 veterinarian

Research paper thumbnail of News

Australian Veterinary Journal, 2012

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian Veterinary Journal, Jul 1, 2010

Research paper thumbnail of Metabolic changes associated with the'downer' condition in dairy cows at abattoirs

Australian veterinary journal, 1978

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian veterinary journal, 2010

Research paper thumbnail of Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses

The American journal of physiology, 1993

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to b... more The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34...

Research paper thumbnail of Effects of changes in nutritional copper on erythrocyte superoxide dismutase activity in sheep

Research in veterinary science, 1980

In copper-deficient lambs with serum copper less than 0.30 microgram/ml there was a linear relati... more In copper-deficient lambs with serum copper less than 0.30 microgram/ml there was a linear relationship between erythrocyte superoxide dismutase (SOD) activity and serum copper concentration. When these lambs were fed adequate copper (10-14 mg/kg of feed), SOD increased by 68 per cent over 90 days. The time course of this increase corresponded to the erthrocyte lifespan of lambs. In sheep given excess copper (0.25 g/kg body weight over seven weeks) erythrocyte SOD activity did not differ significantly from that of control sheep. A 40 per cent decrease in erythrocyte SOD activity occurred in sheep fed diets supplemented with molybdenum and sulphate for 90 days. Compared with controls, these sheep stored less copper in their livers and had similar caeruloplasmin activities but higher serum copper concentrations.

Research paper thumbnail of Age-related changes in activities of the superoxide dismutase enzymes in tissues of the sheep and the effect of dietary copper and manganese on these changes

The Journal of nutrition, 1984

Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and M... more Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and MnSOD) were studied in tissues of the sheep to determine the dependence of these activities on sheep age, and their relationship to tissue and dietary mineral concentrations. Tissue samples were obtained from day-old through 16-week-old lambs from flocks grazing pastures normal or high in copper and manganese, and from adult sheep. In liver, lung, heart, kidney and skeletal muscle, activities of CuSOD and MnSOD in day-old and week-old lambs were only half those measured in 16-week-old and adult sheep. Activities in 4-week-old lambs were intermediate between these two groups except for heart tissue, in which activities were not increased until lambs were 16 weeks old. For all age groups, heart and skeletal muscle had low activities of CuSOD. Minimal age-related changes were observed for CuSOD activities in erythrocyte and brain tissues. The low enzyme activities evident in most tissues of ...

Research paper thumbnail of Contribution of cobalamin analogues to plasma vitamin B12 concentrations in cattle

Research in veterinary science, 1984

Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using ... more Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using pig intrinsic factor and a microbiological assay using Euglena gracilis. Both assays provided similar results for samples of cattle plasma containing vitamin B12 concentrations ranging from 0.07 to 3.60 micrograms litre-1 (r = 0.95, P less than 0.001). The addition of excess cobinamide in the radioisotope dilution assay to block non-specific binding in the intrinsic factor preparation due to the presence of R-type binders, was used to determine the presence of cobalamin analogues. Cobalamin analogues accounted for up to 50 per cent of the total vitamin B12 concentration in samples of plasma from cows but were virtually undetectable in plasma from sheep.

Research paper thumbnail of Effect of ethacrynic acid on bile formation in sheep, dogs, rats, guinea pigs and rabbits

The Journal of pharmacology and experimental therapeutics, 1972

... HELEN SHAW, IVAN CAPLE' AND TREVOR HEATH School of Physiology and Pharmacology, The Univ... more ... HELEN SHAW, IVAN CAPLE' AND TREVOR HEATH School of Physiology and Pharmacology, The University of New South Wales, ... SHAw, HELEN, IVAN CAPLE AND TREVOR HEATH: Effect of ethacrynic acid on bile formation in sheep, dogs, rats, guinea pigs and rabbits. ...

Research paper thumbnail of Regulation of output of electrolytes in bile and pancreatic juice in sheep

Australian journal of biological sciences, 1972

Bile and pancreatic juice were collected from conscious, standing sheep with fistulae of the comm... more Bile and pancreatic juice were collected from conscious, standing sheep with fistulae of the common bile duct, before and during infusions of secretin to the portal vein, and during infusion of acid to the duodenum. The output of volume and electrolytes, particularly bicarbonate, in bile and in pancreatic juice increased during infusion of secretin. However, the output of volume and of bicarbonate was three to five times higher in bile than in pancreatic juice. When acid was infused into the duodenum a similar result was obtained, and the increment in total bicarbonate output was similar to the amount of acid infused. Infusions of sodium taurocholate were associated with further increases in the output of volume, bile salts, chloride, sodium, potassium, and bicarbonate in bile, but there were no changes in the volume or composition of pancreatic juice. It is suggested that in normal sheep the entry of acid into the duodenum results in release of secretin, and that this stimulates the output of water, bicarbonate, and other electrolytes, particularly from the liver.

Research paper thumbnail of Parathyroid Hormone-Related Protein: Isolation, Molecular Cloning, and Mechanism of Action

Proceedings of the 1988 Laurentian Hormone Conference, 1989

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, ha... more Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.

Research paper thumbnail of Further evidence for a parathyroid hormone-related protein in fetal parathyroid glands of sheep

Quarterly journal of experimental physiology (Cambridge, England), 1988

Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormo... more Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormone (PTH) which could not be neutralized by antiserum against PTH in a cytochemical bioassay. This substance reacted similarly to human parathyroid hormone-related protein, the humoral hypercalcaemic factor associated with malignancy in man. The ovine fetal PTHrP may be responsible for maintaining the fetus hypercalcaemic relative to the mother.

Research paper thumbnail of Stimulation of ovine placental calcium transport by purified natural and recombinant parathyroid hormone-related protein (PTHrP) preparations

Quarterly journal of experimental physiology (Cambridge, England), 1989

Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been us... more Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo.

Research paper thumbnail of The Influence of Mineral Deficiencies on Genetic Improvement Programs

Deficiencies of phosphorus, copper, cobalt and selenium are the main mineral deficiencies in sout... more Deficiencies of phosphorus, copper, cobalt and selenium are the main mineral deficiencies in southeastern Australia that are likely to affect lactation, growth, carcass composition and wool production of grazing livestock being compared in genetic improvement programs. Genetic variation in mineral nutrition has been recognized from differences in the incidence of mineral disorders between breeds. The development of diagnostic indicators for measurement of minerals or their associated enzymes in blood, other fluids and tissues, has led to the recognition of genetic variation in mineral metabolism. The heritability for some indicators such as plasma copper is estimated to be as high as 0.4. The opportunities, practical difficulties, and likely benefits from considering genetic variation in mineral metabolism in genetic improvement programs are reviewed. It is concluded that there is an opportunity to select animals on the basis of genetic variation in metabolism of some trace elements...

Research paper thumbnail of WT Kendall MRCVS: Inaugural address to the Mutual Improvement Society on the deck of the SS “Somersetshire”, Friday 2nd January 1880

Published as "Caple, I. (2012). WT Kendall’s inaugural address to the Mutual Improvement Soc... more Published as "Caple, I. (2012). WT Kendall’s inaugural address to the Mutual Improvement Society. Australian Veterinary Journal, 90(9), 28-30.

Research paper thumbnail of John Kendall – WW1 veterinarian

Proceedings of the 4th AVA/NZVA Pan Pacific Conference Brisbane, 2015

access to digitized newspapers which were searched online for "John Kendall". Many letters he had... more access to digitized newspapers which were searched online for "John Kendall". Many letters he had written to friends were published in the Shepparton newspapers. These letters provide a glimpse into his personality, his Australian humour, and how he coped with the conditions. John Kendall was a busy correspondent, and an avid reader. He particularly enjoyed receiving copies of the local newspapers that were sent to him.

Research paper thumbnail of University of Melbourne awards Roger Clarke DVSc (honoris causa)

Australian veterinary journal, 2004

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian veterinary journal, 2010

Research paper thumbnail of Effect of Antidiuretic Hormone on Bile Formation in Sheep

Journal of Endocrinology, 1971

Research paper thumbnail of John Kendall – WW1 veterinarian

Research paper thumbnail of News

Australian Veterinary Journal, 2012

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian Veterinary Journal, Jul 1, 2010

Research paper thumbnail of Metabolic changes associated with the'downer' condition in dairy cows at abattoirs

Australian veterinary journal, 1978

Research paper thumbnail of Re: how the profession is tackling rural shortages

Australian veterinary journal, 2010

Research paper thumbnail of Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses

The American journal of physiology, 1993

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to b... more The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34...

Research paper thumbnail of Effects of changes in nutritional copper on erythrocyte superoxide dismutase activity in sheep

Research in veterinary science, 1980

In copper-deficient lambs with serum copper less than 0.30 microgram/ml there was a linear relati... more In copper-deficient lambs with serum copper less than 0.30 microgram/ml there was a linear relationship between erythrocyte superoxide dismutase (SOD) activity and serum copper concentration. When these lambs were fed adequate copper (10-14 mg/kg of feed), SOD increased by 68 per cent over 90 days. The time course of this increase corresponded to the erthrocyte lifespan of lambs. In sheep given excess copper (0.25 g/kg body weight over seven weeks) erythrocyte SOD activity did not differ significantly from that of control sheep. A 40 per cent decrease in erythrocyte SOD activity occurred in sheep fed diets supplemented with molybdenum and sulphate for 90 days. Compared with controls, these sheep stored less copper in their livers and had similar caeruloplasmin activities but higher serum copper concentrations.

Research paper thumbnail of Age-related changes in activities of the superoxide dismutase enzymes in tissues of the sheep and the effect of dietary copper and manganese on these changes

The Journal of nutrition, 1984

Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and M... more Activities of the copper-zinc- and manganese-containing superoxide dismutase enzymes (CuSOD and MnSOD) were studied in tissues of the sheep to determine the dependence of these activities on sheep age, and their relationship to tissue and dietary mineral concentrations. Tissue samples were obtained from day-old through 16-week-old lambs from flocks grazing pastures normal or high in copper and manganese, and from adult sheep. In liver, lung, heart, kidney and skeletal muscle, activities of CuSOD and MnSOD in day-old and week-old lambs were only half those measured in 16-week-old and adult sheep. Activities in 4-week-old lambs were intermediate between these two groups except for heart tissue, in which activities were not increased until lambs were 16 weeks old. For all age groups, heart and skeletal muscle had low activities of CuSOD. Minimal age-related changes were observed for CuSOD activities in erythrocyte and brain tissues. The low enzyme activities evident in most tissues of ...

Research paper thumbnail of Contribution of cobalamin analogues to plasma vitamin B12 concentrations in cattle

Research in veterinary science, 1984

Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using ... more Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using pig intrinsic factor and a microbiological assay using Euglena gracilis. Both assays provided similar results for samples of cattle plasma containing vitamin B12 concentrations ranging from 0.07 to 3.60 micrograms litre-1 (r = 0.95, P less than 0.001). The addition of excess cobinamide in the radioisotope dilution assay to block non-specific binding in the intrinsic factor preparation due to the presence of R-type binders, was used to determine the presence of cobalamin analogues. Cobalamin analogues accounted for up to 50 per cent of the total vitamin B12 concentration in samples of plasma from cows but were virtually undetectable in plasma from sheep.

Research paper thumbnail of Effect of ethacrynic acid on bile formation in sheep, dogs, rats, guinea pigs and rabbits

The Journal of pharmacology and experimental therapeutics, 1972

... HELEN SHAW, IVAN CAPLE' AND TREVOR HEATH School of Physiology and Pharmacology, The Univ... more ... HELEN SHAW, IVAN CAPLE' AND TREVOR HEATH School of Physiology and Pharmacology, The University of New South Wales, ... SHAw, HELEN, IVAN CAPLE AND TREVOR HEATH: Effect of ethacrynic acid on bile formation in sheep, dogs, rats, guinea pigs and rabbits. ...

Research paper thumbnail of Regulation of output of electrolytes in bile and pancreatic juice in sheep

Australian journal of biological sciences, 1972

Bile and pancreatic juice were collected from conscious, standing sheep with fistulae of the comm... more Bile and pancreatic juice were collected from conscious, standing sheep with fistulae of the common bile duct, before and during infusions of secretin to the portal vein, and during infusion of acid to the duodenum. The output of volume and electrolytes, particularly bicarbonate, in bile and in pancreatic juice increased during infusion of secretin. However, the output of volume and of bicarbonate was three to five times higher in bile than in pancreatic juice. When acid was infused into the duodenum a similar result was obtained, and the increment in total bicarbonate output was similar to the amount of acid infused. Infusions of sodium taurocholate were associated with further increases in the output of volume, bile salts, chloride, sodium, potassium, and bicarbonate in bile, but there were no changes in the volume or composition of pancreatic juice. It is suggested that in normal sheep the entry of acid into the duodenum results in release of secretin, and that this stimulates the output of water, bicarbonate, and other electrolytes, particularly from the liver.

Research paper thumbnail of Parathyroid Hormone-Related Protein: Isolation, Molecular Cloning, and Mechanism of Action

Proceedings of the 1988 Laurentian Hormone Conference, 1989

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, ha... more Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.

Research paper thumbnail of Further evidence for a parathyroid hormone-related protein in fetal parathyroid glands of sheep

Quarterly journal of experimental physiology (Cambridge, England), 1988

Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormo... more Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormone (PTH) which could not be neutralized by antiserum against PTH in a cytochemical bioassay. This substance reacted similarly to human parathyroid hormone-related protein, the humoral hypercalcaemic factor associated with malignancy in man. The ovine fetal PTHrP may be responsible for maintaining the fetus hypercalcaemic relative to the mother.

Research paper thumbnail of Stimulation of ovine placental calcium transport by purified natural and recombinant parathyroid hormone-related protein (PTHrP) preparations

Quarterly journal of experimental physiology (Cambridge, England), 1989

Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been us... more Perfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo.