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J M Jacobi

Publications and source records attributed to J M Jacobi.

16 recordsLinked to original sources
PubMed1995

DNA synthesis by pituitary tumours, with reference to plasma hormone levels and to effects of bromocriptine.

BACKGROUND AND OBJECTIVE: In parathyroid adenomas and experimentally in the normal rat pituitary gland, cell replication and secretory activity were previously shown to be correlated. A similar relationship has now been investigated in human pituitary tumours, since this could have relevance to their growth and aetiology. The effect of bromocriptine on the two variables was examined. PATIENTS: Data were derived from 50 patients undergoing operation for pituitary tumour, including 15 with acromegaly and 11 with prolactinoma. MEASUREMENTS: Preoperative plasma levels of GH, PRL and gonadotrophins were measured by radioimmunoassay. DNA synthesis, an index of cell replication, was measured in vitro in freshly removed tumour tissue. Nuclear diameter of tumour cells was measured in histological sections and immunostaining for relevant hormones was carried out on tumour tissue. RESULTS: DNA synthesis was correlated (P < 0.05) with plasma hormone levels in cases of prolactinoma, both treated and not treated with bromocriptine, and in a group of putative FSH secreting tumours from male patients. The correlation was not significant in cases of acromegaly. Comparisons of mean values between groups treated and not treated with bromocriptine showed significantly lower DNA synthesis and mean nuclear diameter in prolactinomas under treatment but not in GH secreting tumours. CONCLUSIONS: The findings in prolactinomas suggest a close relationship between secretion and tumour cell replication dependent on still undefined agents, but including dopamine, affecting both variables, and isoforms of PRL, which may stimulate or inhibit replication of PRL secreting cells. The basis of the relationship in FSH secreting tumours is unknown. The relationship was absent in the non-homogeneous group of GH secreting tumours. When secretion and growth are correlated, the secretory process may be the site of the primary abnormality in the tumour cell. Evidence that bromocriptine inhibits tumour cell replication was obtained for prolactinomas but not for GH secreting tumours.

Acromegaly↗
PubMed1993

Apoptosis in the anterior pituitary gland of the rat: studies with estrogen and bromocriptine.

Apoptosis was investigated by electron and light microscopy in the anterior pituitary gland of the male Fischer rat in which hyperplasia of prolactin-secreting cells had been induced by estrogen implanted subcutaneously for 6 weeks. Counts by light microscopy of apoptotic cells and cells containing phagocytosed apoptotic bodies increased during a period of 44 h after estrogen withdrawal. Necrosis was present but was not prominent. Administration of bromocriptine after estrogen withdrawal increased apoptotic counts to nearly double those in the absence of bromocriptine. Bromocriptine caused some increase in necrosis. Apoptosis occurred in prolactin-secreting cells identified by immunostaining and in other cells. Phagocytosed apoptotic bodies were seen in folliculo-stellate and not in other cells. It is concluded that apoptosis occurs in the anterior pituitary gland and is induced by bromocriptine. Phagocytosis of apoptotic bodies is a function of the folliculo-stellate cells.

Animals↗
PubMed1993

Blunted parathyroid response to correction of hypercalcemia in subjects with squamous cell carcinoma.

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.

Calcitriol↗
PubMed1991

Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin.

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.

Aged↗
PubMed1989

The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia.

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.

DNA↗
PubMed1986

Nuclear diameter in parathyroid carcinomas.

Nuclear diameter was measured and mean nuclear diameter calculated in 18 parathyroid carcinomas. In 11 of the 18 tumours mean nuclear diameter was above the range previously reported for 55 parathyroid chief cell adenomas and provides a useful discriminant in histological diagnosis.

Adenoma↗
PubMed1982

Nuclear diameter in the anterior pituitary gland of the rat: effects of estrogen, bromocriptine, and haloperidol.

Nuclear diameter, DNA synthesis, and mitotic index in the pituitary cells of male rats and serum prolactin were measured after a period of 8 days of treatment with a dopamine agonist and an antagonist given with and without estrogen. In the absence of estrogen, the dopamine agonist, bromocriptine, diminished the mean nuclear diameter of the pituitary cells and lowered pituitary DNA synthesis, and the dopamine-blocking agent haloperidol had no effect. Estrogen increased the mean nuclear diameter, pituitary mitotic index, and DNA synthesis. Bromocriptine prevented the estrogen-induced increase in mean nuclear diameter and pituitary DNA synthesis and mitotic index were lowered. Haloperidol augmented the estrogen-induced increase in mean nuclear diameter, pituitary DNA synthesis, and mitotic index. Positive correlations were obtained between mean nuclear diameter and DNA synthesis and serum prolactin. It was concluded that nuclear diameter was influenced by both DNA synthesis and secretory activity in pituitary cells.

Animals↗
PubMed1981

Modulation by dopamine antagonists of DNA synthesis in the pituitary gland of the male rat.

Pituitary DNA synthesis and serum and pituitary concentrations of prolactin were measured in male rats given the dopamine antagonist haloperidol or pimozide, and the dopamine agonist bromocriptine. Increased DNA synthesis was observed 25h after a single injection of haloperidol and on each day of the 5-day period of pimozide administration. Haloperidol and pimozide increased serum prolactin levels. Pituitary prolactin concentrations fell 12h after haloperidol, recovering b6 24h, and 24 and 48h after pimozide, recovering by 72 h. Bromocriptine lowered pituitary DNA synthesis and serum prolactin levels and induced a transient rise in pituitary prolactin concentrations. The results indicate that dopamine agonists and antagonists modulate DNA synthesis in the pituitary gland of the rat.

Animals↗
PubMed1981

DNA synthesis and secretory activity in parathyroid adenomas.

DNA synthesis was measured in vitro by incorporation of [3H]thymidine into DNA in 42 parathyroid chief cell adenomas immediately after surgical removal. The results ranged from 18 to 185 DPM/microgram DNA and showed a positive correlation with pre-operative values for serum immunoreactive parathyroid hormone (r = + 0.47; P < 0.001) and plasma calcium (r = + 0.35; P < 0.05). There was no correlation between DNA synthesis and tumour weight or mean diameter of tumour cell nuclei. The results suggest that DNA synthesis and cell division in parathyroid adenomas are determined in part by the secretory activity of the tumour. DNA synthesis measured on one occasion is not necessarily an overall index of tumour growth.

Adenoma↗
PubMed1979

Nuclear diameter in parathyroid adenomas.

Nuclear diameter was measured in 55 parathyroid chief-cell adenomas to determine its value in histological diagnosis and to assess its relationship to other features of primary hyperparathyroidism. Mean nuclear diameter for the whole group of adenomas was significantly greater than that for the accompanying normal glands. Mean nuclear diameter in individual adenomas was significantly greater than that in the accompanying normal gland in 27 out of 34 cases. Nuclear diameter was correlated with tumour weight and with plasma calcium but was not correlated with duration of history. It was significantly greater in the group of patients with overt bone disease than in those with kidney stones and in those with neither kidney stones nor overt bone disease. Assessment of nuclear diameter is of value in histological diagnosis of parathyroid adenoma. The rate of growth of the adenoma may be a factor determining nuclear diameter.

Adenoma↗
PubMed1978

DNA synthesis and depletion of prolactin in the pituitary gland of the male rat.

Haloperidol, bromocriptine and diethylstilboestrol dipropionate were given in various régimes to male rats to determine their effects on pituitary DNA synthesis, prolactin secretion and growth hormone secretion. Haloperidol increased serum prolactin but did not stimulate pituitary DNA synthesis or reduce pituitary prolactin concentrations. Haloperidol potentiated the effects of oestrogen on serum prolactin and on pituitary DNA synthesis; pituitary prolactin concentrations were greatly reduced, and growth hormone secretion was slightly inhibited. The inhibitory effects of bromocriptine in oestrogen-stimulated rats were demonstrated by smaller pituitary weights and decreased DNA synthesis; serum prolactin levels were lowered and pituitary prolactin concentrations were increased. Haloperidol, given to rats treated with oestrogen and bromocriptine, reversed the inhibitory effects of bromocriptine on DNA synthesis and serum prolactin; pituitary prolactin concentrations fell to well below normal. The results suggest that the haloperidol potentiation of oestrogen-induced pituitary DNA synthesis may depend upon stimulation of prolactin secretion together with reduction of intracellular prolactin levels.

Animals↗
PubMed1970

Failure of a pure progestogen contraceptive to affect serum levels of iron, transferrin, protein-bound iodine, and transaminase.

Medroxyprogesterone acetate, a pure progestational agent which is not metabolized to oestrogen, was given to 30 women and shown to have no effect on the serum levels of iron, total iron-binding capacity, transferrin, and protein-bound iodine. Eighteen of these women had previously taken oral contraceptives of the combined oestrogen-progestogen "sequential" type, and during that time these serum levels were raised. Nevertheless, the levels all fell significantly after medroxyprogesterone acetate was given and the "sequential" oral contraceptive was stopped. In a further 12 postpartum women the serum levels did not change significantly after medroxyprogesterone acetate.These observations strongly suggest that raised plasma protein levels resulting from the administration of oral contraceptives are due to the oestrogen component.

Adolescent↗