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Biomedical subjects

J F Whitfield

Publications and source records attributed to J F Whitfield.

At least 163 records · Page 9Linked to original sources
PubMed1982

Oncomodulin--a widely distributed, tumour-specific, calcium-binding protein.

The seemingly de novo appearance of oncomodulin and increased levels of calmodulin were observed (using specific radioimmunoassays) in several types of mouse, rat and human tumours. Oncomodulin could not be found in any normal (adult or fetal) rodent or human tissue. Tryptic peptide mapping showed that oncomodulin in rat and mouse tumours was identical, and was not a fragment of either calmodulin or troponin C. A possible role for oncomodulin in the deregulated cell proliferation of cancer cells was suggested by its ability to stimulate DNA synthesis in isolated rat liver cells.

Animals↗
PubMed1981

Stimulation of autophosphorylation of liver cell membrane proteins by calcium and partial hepatectomy.

Partial hepatectomy in the rat stimulated the phosphorylation of three proteins (Mr 100,000, 48,000, and 35,000) in the plasma membranes of the proliferatively activated cells of the liver remnant. The autophosphorylation of these plasma membrane proteins began to rise about 8 hours after surgery, peaked at 14 hours, and then returned to the original low level by 24 hours. This increase in autophosphorylation was not evident in isolated plasma membranes from other proliferatively activated liver cells, such as those in fetal liver or hepatomas. The protein kinase responsible for the phosphorylation of the three membrane proteins was activated by calcium but appeared both cyclic-AMP- and calmodulin-independent.

Animals↗
PubMed1981

The reversible inability of isoproterenol-activated parotid gland cells to initiate DNA synthesis in the hypocalcemic thyroparathyroidectomized rat.

An intraperitoneal injection of the beta-adrenergic drug dl-isoproterenol hydrochloride (100 mg/kg body weight) into male (190-210 g) albino rats caused two cyclic AMP surges (peaking at 10 minutes and again between 8 and 12 hours) and the initiation of DNA synthesis (between 16 and 20 hours) in the parotid glands. The parotid cells in hypocalcemic thyroparathyroidectomized rats still responded to isoproterenol injection by generating the two cyclic AMP surges, but they did not initiate DNA synthesis unless a blood calcium-elevating combination of parathyroid hormone (50 USP units/100 g of body weight) and 1 alpha,25(OH)2 vitamin D3 (200 pmoles/100 g of body weight) was injected along with the isoproterenol.

Animals↗
PubMed1981

Regulation of the prereplicative changes in the synthesis and transport of messenger and ribosomal RNA in regenerating livers of normal and hypocalcemic rats.

Partial hepatectomy induces increases in the synthesis of both messenger (poly(A)+) and ribosomal (poly(A)-) RNA, which precede the initiation of DNA synthesis. The increase in poly(A)+RNA, which commences soon after surgery and reaches a peak 1-3 hours later is particularly striking. Disruption of this early increase in poly(A)+RNA synthesis by colchicine (and other microtubule disrupters) or indomethacin results in a failure to initiate DNA synthesis. This suggests that prostaglandins and the microtubules are involved in the mechanism of proliferative activation. Hypocalcemia, which also prevents the initiation of DNA synthesis, has no effect on the prereplicative changes in either messenger or ribosomal RNA synthesis. These results help to define the critical stages of prereplicative development and give some insight into their regulation.

Animals↗
PubMed1981

The calcium-dependent stimulation of the proliferation of neonatal rat hepatocytes by imidazole and indomethacin.

Low concentrations (e.g. 10(-12) and 10(-11) mol/l) of imidazole and indomethacin strongly stimulated DNA synthesis and mitosis of hepatocytes in 4-day-old primary cultures of neonatal rat liver. These agents seem to have acted by inducing quiescent hepatocytes to begin cycling rather than by affecting already cycling cells, because they did not shorten the total cell cycle time. Neither compound stimulated DNA synthesis by hepatocytes cultured in low (0.010 mol/l) calcium medium. Nevertheless, hepatocytes in calcium-deficient medium must have been mitogenically activated by these compounds and, hence, been able to reach a late stage of prereplicative development because they did initiate DNA synthesis very soon after the addition of calcium.

Animals↗
PubMed1981

Oncogenic transformation and the reductions of insulin secretion and proliferative calcium dependence during repeated passage of pancreatic islet cells in vitro.

Islet cells were isolated from 2 fetal bovine pancreas glands and cultivated in vitro. During the course of repeated passage in vitro, the B-cells in these cultures retained the ability to synthesize insulin, but rapidly lost the ability to secrete it. The cells also became progressively more able to proliferate in calcium-deficient medium which did not support the proliferation of cells from primary cultures. The reductions of insulin secretion and proliferative calcium dependence were accompanied by the acquisition of the ability to produce tumors in nude mice.

Animals↗
PubMed1980

Cyclic AMP surges during the dihydrotestosterone-induced growth-division cycle of rat seminal vesicle cells.

A single subcutaneous injection of the active androgen DHT (5 alpha-androstan-17 beta-ol-3-one or 5 alpha-dihydrotestosterone; 5 mg/Kg body weight) into rats 7 days after orchidectomy stimulated DNA synthesis in the seminal vesicle, which began between 30 and 35 hr after injection and peaked at 48 hr. Mitotic activity began between 35 and 45 hr after DHT injection and peaked around 55 hr. These proliferative responses appeared to be confined mainly to the epithelial cells of the seminal vesicles. The DHT injection did not rapidly (between 5 min and 2 hr) increase the cyclic AMP level, but it did result in two small later surges of the cyclic nucleotide; the first of which peaked between 18 and 28 hr, but well before the onset of DNA synthesis, and the second of which peaked between 48 and 60 hr, when both the DNA-synthetic and mitotic activities were near or at their peak values.

Animals↗
PubMed1980

Regulation of proliferation of normal and neoplastic rat liver cells by calcium and cyclic AMP.

Calcium and cyclic AMP control the proliferation of nontumorigenic liver cells. These agents seem to be cogenerators of a signal to start synthesizing deoxyribonucleotides, the earliest of the DNA synthetic processes. By contrast, calcium has little or no effect on the proliferation of tumorigenic cells in vitro. Some possible reasons for this loss of control are presented, and the usefulness of this property as a tool for the detection of carcinogens is discussed.

Animals↗