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R V Jeffreys

Publications and source records attributed to R V Jeffreys.

At least 19 recordsLinked to original sources
PubMed1998

Effect of cell density on hormonal secretion from human pituitary adenomas in vitro.

UNLABELLED: Cell density effects were investigated on tumorous hormonal secretion from 10 pituitary adenomas: 3 somatotrophinomas secreting GH and PRL; 7 gonadotrophinomas, 3 co-secreted both FSH and LH, all 7 secreted LH. Enzymatically dispersed tissue was plated out in 24-well plates at 5 x 10(5), 10(5), 5 x 10(4) and 10(4) cells/well in serum-free media. Media were collected weekly for 2 weeks. RESULTS: In 3 of 3 somatotrophinomas, GH and PRL secretion was higher (p < 0.05) at both week 1 and 2 from 10(4) cells/well, but similar at other cell densities. In all 3 gonadotrophinomas, the FSH secretory rate was highest at 5 x 10(5) cells/well which fell as cell density decreased. Conversely, in 7 of 7 gonadotrophinomas the LH secretory rate was highest at 10(4) cells/well (p < 0.01) which fell as cell density increased. CONCLUSION: These data suggest that paracrine factors may modulate tumorous GH, PRL, FSH and LH secretion, and show that FSH and LH secretion vary inversely as cell density increases.

Adenoma↗
PubMed1997

Apoptosis and p53 suppressor gene protein expression in human anterior pituitary adenomas.

Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.

Adenoma↗
PubMed1997

A comparison of proliferation indices in human anterior pituitary adenomas using formalin-fixed tissue and in vitro cell culture.

The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1-5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1-100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1-8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9-95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1-2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.

Adenoma↗
PubMed1996

Cytokine expression in human anterior pituitary adenomas.

OBJECTIVE: There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub-types. DESIGN: The reverse transcriptase-linked polymerase chain reaction (PCR) was used to identify the presence of cytokine mRNA within human pituitary adenomas. PATIENTS: Seventeen pituitary adenoma biopsies removed at transsphenoidal surgery were examined: 4 somatotrophinomas, 7 non-functional adenomas, 4 prolactinomas, one case of Cushing's disease and one case of Nelson's syndrome. MEASUREMENTS: RNA was extracted from each adenoma biopsy and reverse transcribed into cDNA. This was specifically amplified in a PCR using oligonucleotide primers complementary to each cytokine. The cytokines investigated were interleukin (IL)-I alpha, IL-I beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and transforming growth factor (TGF)-beta 1, beta 2 and beta 3. The products of each PCR were visualized using agarose gel electrophoresis. RESULTS: All 17 adenomas expressed IL-8 transcripts, but no expression of IL-2, IL-5 or IL-7 was found. IL-6 was expressed in all 4 somatotrophinomas, 3 of 7 non-functional tumours, 2 of 4 prolactinomas and in the single case of Nelson's syndrome. At least one of the 3 isoforms of TGF-beta was found in all but 2 tumours; one prolactinoma and one non-functional adenoma. IL-1 alpha, IL-beta, IL-4, TNF-alpha and TNF-beta were expressed sporadically by individual adenomas. CONCLUSION: These data suggest that whilst IL-8 may be important, the local expression of the cytokines IL-2, IL-5 and IL-7 is not important in human anterior pituitary tumorigenesis.

Adenoma↗
PubMed1995

Ophthalmic manifestations of Rathke's cleft cysts.

PURPOSE: We studied the neuro-ophthalmic features of patients with symptomatic Rathke's cleft cysts, to distinguish features of Rathke's cleft cysts from those of craniopharyngioma. METHODS: Eleven patients who had undergone surgery for symptomatic Rathke's cleft cysts in the Liverpool University Department of Neurological Science were identified from the records. Histopathologic analyses, clinical notes, and radiologic investigations were reviewed. RESULTS: Eight of the 11 patients initially had visual problems. Reduced visual acuity, visual field defect, or both, were detected in nine patients. Optic atrophy was observed in eight patients. Other initial features included headaches, epilepsy, and endocrine disturbance. All patients recovered from surgery, and an improvement in the visual acuity or visual field defect was noted in six patients. CONCLUSIONS: Symptomatic Rathke's cleft cysts often manifest as visual disturbance. Every effort to distinguish Rathke's cleft cysts from craniopharyngiomas should be made preoperatively. Rathke's cleft cysts only require limited surgical intervention, and radiotherapy is not necessary. Early recognition and treatment can lead to improvement in visual function.

Adolescent↗
PubMed1995

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Adenoma↗
PubMed1994

Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro.

OBJECTIVE: IGF-I inhibits GH secretion from normal and some tumorous pituitary tissue, and has been shown to be mitogenic for gonadotrophinoma cells in vitro. It is not known whether IGF-I affects somatotrophinoma cellular proliferation or the secretion of other hormones, such as PRL and alpha-subunit, which are often co-secreted by these tumours. We have therefore examined the effects of IGF-I on proliferation and hormonal secretion of human somatotrophinomas and prolactinomas in vitro. DESIGN: Pituitary adenoma tissue was dispersed to single cells in monolayer culture. The effects of 100 nM IGF-I on GH, PRL and alpha-subunit secretion were determined over 4-hour and over 4-day periods, and a 4-day dose-response study using 1-100 nM IGF-I was performed on two tumours. Adenoma cell S-phase proliferation was determined after bromodeoxyuridine incorporation for 1 hour after 4 days, using a double immunostaining method. RESULTS: Over 4 hours, 100 nM IGF-I had no effect on GH, PRL or alpha-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 somatotrophinomas (range 17-84%, P < 0.05) compared to controls, with tumours responding to IGF-I having lower basal serum and in-vitro GH levels than tumours unaffected by IGF-I (P < 0.05). There was no effect on alpha-subunit secretion in any of the three tumours studied. PRL cosecretion was increased in 3/5 somatotrophinomas compared to control (20, 30 and 37%, P < 0.05), with tumours responding to IGF-I being associated with lower basal serum and in-vitro PRL levels than those tumours unaffected by IGF-I. IGF-I also increased PRL secretion in 2/2 prolactinomas (27 and 32%, P < 0.05) compared with control. GH was inhibited and PRL secretion was stimulated by 1 and 10 nM IGF-I in the two dose-response studies. The proliferative labelling index did not exceed 1.9% in any tumour and no proliferative effect was found with 100 nM IGF-I in any somatotrophinoma. CONCLUSION: IGF-I inhibited tumorous GH in 62% and stimulated PRL secretion in 71% of tumours over 4 days, without affecting alpha-subunit secretion or being mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed over short (4-hour) incubations. IGF-I may be a newly recognized factor directly stimulating tumorous PRL secretion.

Adenoma↗
PubMed1993

Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.

Adenoma↗
PubMed1993

Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas.

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.

Adenoma↗
PubMed1993

Prediction of recurrence in pituitary tumours: a flow cytometric study using in vivo bromodeoxyuridine.

Although most pituitary tumours are regarded as benign, there is a significant risk of local recurrence and a few are frankly malignant. The prediction of clinically aggressive behaviour by histopathological means is inadequate and the selection of patients for postoperative radiotherapy has often been empirical. The flow cytometric analysis of the DNA content of certain intracranial tumours has suggested a correlation between a high proliferative index and a tendency to recur. The in vivo administration of bromodeoxyuridine (BUdR) yields a reliable and accurate S-phase labelling index and evaluation by flow cytometry allows a much greater and therefore more representative number of cells to be examined. We report our results for the flow cytometric evaluation of the S-phase fraction in a group of 11 human pituitary tumours following the preoperative administration of BUdR and discuss the correlation between high values of S-phase fraction and clinically aggressive behaviour. Initial results suggest a correlation between radiological evidence of tumour invasion and an S-phase greater than 2%.

Adenoma↗
PubMed1989

The surgical treatment of large pituitary adenomas.

The problems associated with the treatment of large pituitary adenomas are discussed with reference to 41 patients operated on by the author. All adenomas had either suprasellar extensions greater than 2 cm and/or more than two intracranial extensions. Ninety-five per cent were suffering from chiasmal compression pre-operatively. All underwent transfrontal surgery with 76% being deemed totally excised and 24% being subtotal. After surgery 29% regained normal vision, 53% had improved vision and 18% had unchanged vision. Thirty-four per cent had no postoperative complications and the majority had a variety of complications, some minor and some major. Other aspects, including endocrinology and recurrence, are also discussed.

Adenoma↗
PubMed1987

Successful management of Cushing's disease during pregnancy by transsphenoidal adenectomy.

Pregnancy in patients with Cushing's syndrome is rare. It is associated with a high fetal loss, increased frequency of preterm labour and excessive maternal morbidity. We describe a patient who became pregnant while investigations for hypertension were being done. Cushing's disease was diagnosed and the patient had transsphenoidal pituitary surgery at 22 weeks gestation. To our knowledge this is the first time this operation has been done during pregnancy for this condition. Cushing's disease was controlled, but because of worsening hypertension, she had a caesarean section at 30 weeks gestation. Subsequently her blood pressure fell and her hydrocortisone replacement therapy is being withdrawn. Her daughter is now thriving after initial problems with pneumothoraces.

Adenoma↗
PubMed1986

Failure of prophylactic surgery to avert massive pituitary expansion in pregnancy.

Macroprolactinomas have a well-recognized potential for marked expansion during pregnancy. Measures advocated to minimize this risk include prior treatment with dopamine agonists, radiotherapy and pituitary surgery. We describe a patient who underwent transsphenoidal surgery with the removal of an histologically proven prolactin-secreting adenoma with the intention of rendering subsequent pregnancy safe. The patient remained hyperprolactinaemic and received prolonged therapy with metergoline and bromocriptine which suppressed prolactin to normal and she conceived after induction of ovulation with human menopausal gonadotrophin and human chorionic gonadotrophin. At 3 months gestation she developed headaches, vomiting, reduced visual acuity and bitemporal hemianopia caused by massive pituitary expansion. Reintroduction of bromocriptine rapidly abolished features of tumour expansion and after delivery of a full-term normal female infant, repeat CT scan documented tumour shrinkage.

Bromocriptine↗