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Biomedical subjects

K Mashiter

Publications and source records attributed to K Mashiter.

At least 19 recordsLinked to original sources
PubMed1987

Ectopic corticotrophin-releasing-factor and growth hormone releasing factor secretion: diagnosis using human pituitary cell culture.

Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing's syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing's syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.

Acromegaly↗
PubMed1987

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Adolescent↗
PubMed1986

Subcellular distribution of rat pituitary homogenates by poly(ethylene glycol)-dextran countercurrent partitioning.

Rat pituitary homogenates were subjected to two phase countercurrent partition in a poly(ethylene glycol)-dextran mixture using a simple apparatus with enhanced gravity to facilitate the phase separations. Assay of the fractions for organelle marker enzymes and prolactin after 17 transfers showed similar distributions for endoplasmic reticulum, lysosomes, prolactin granules and plasma membrane at the lowest dextran concentrations. Increasing the dextran concentrations had a differential effect on the various organelles. Excellent resolution of endoplasmic reticulum from the other organelles was obtained and marked organelle heterogeneity was demonstrated. Two-phase countercurrent partition thus offers an alternative approach to the subcellular fractionation of pituitary homogenates and should prove useful in separating endoplasmic reticulum from plasma membrane and other cell components.

Acetylglucosaminidase↗
PubMed1985

Role of cell and explant culture in the diagnosis and characterization of human pituitary tumours.

The pattern of hormone secretion by human pituitary tumours in cell or explant culture has been shown to be of value in establishing the nature of the tissue. There was complete agreement between the diagnosis reached by conventional immunocytochemical techniques and by examining the secretion of hormones in culture. Culture techniques, however, have some advantages over immunocytochemical analysis. In particular, immunocytochemical techniques can only be used to examine a small, possibly unrepresentative, portion of the pituitary tissue, whereas the in vitro culture systems make use of the whole tissue. In addition, in vitro culture is simpler to employ and can be carried out relatively rapidly. Cell and explant culture was therefore used to examine the nature of human pituitary tumours. To determine the incidence of mixed GH-PRL secreting pituitary tumours in acromegaly, the pattern of hormone secretion in vitro by 98 somatotrophic tumours was examined. Thirty-seven per cent were found to be pure somatotrophic tumours and 59.2% secreted both GH and PRL, but no other hormone, indicating that these tumours were of mixed nature. This latter group could be divided into those removed from patients with hyperprolactinaemia (35.7% of all tumours) and those from patients with normal pre-operative serum PRL levels (23.5%). A further small group (3.1%) of tumours secreted only GH in culture, despite elevated pre-operative serum PRL levels, indicating that the hyperprolactinaemia in these patients was due to pituitary stalk compression by the somatotrophic tumour, thereby preventing prolactin release inhibiting factor reaching the lactotrophs and allowing uncontrolled PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Culture Techniques↗
PubMed1985

Ovine corticotrophin releasing factor stimulates ACTH release from human corticotrophinoma cells in culture; interaction with hydrocortisone and arginine vasopressin.

We have investigated the effects of ovine corticotrophin releasing factor (oCRF) and its interaction with hydrocortisone (HC), and arginine vasopressin (AVP) on ACTH release from human corticotrophinoma cells in culture. Tumour tissue was obtained from six patients (three with active Cushing's disease and three with Nelson's syndrome). Cultures were maintained for periods of up to six months. Ovine CRF (21 nmol) significantly (P less than 0.01) stimulated ACTH release from all tumours. Dose response (21 pmol-21 nmol) effects were observed for the three tumours investigated over 2 and 4 h. Cortisol (20 mumol) significantly (P less than 0.01) inhibited basal ACTH release from one tumour (Nelson's syndrome) by 75% over 4 h, and completely prevented the stimulatory effects of oCRF. AVP directly stimulated ACTH release from two tumours (Nelson's syndrome), and also potentiated the stimulatory action of oCRF during 30 min incubations. These data show corticotrophinoma cells from subjects with Cushing's disease and Nelson's syndrome can be directly stimulated by hypothalamic oCRF and may be potentiated by AVP. Cortisol and oCRF have been shown in one tumour to have antagonistic actions at the pituitary level.

Adrenocorticotropic Hormone↗
PubMed1985

Effect of nivazol on ACTH secretion by human pituitary corticotrophic tumours in cell culture.

The effects of nivazol, a novel steroid which lacks glucocorticoid activity, on ACTH secretion by cell cultures of human pituitary corticotrophic tumours has been investigated. Nivazol (0.002-20 mumol/l) inhibited ACTH secretion by 50-80%, after 4 and 24 h of incubation. (Trilostane (0.3-30 mumol/l) did not affect basal or stimulated ACTH secretion.) The potency of nivazol was comparable with that of hydrocortisone, and less than dexamethasone. The stimulatory effects of oCRF and AVP were reduced or completely blocked by nivazol in a similar manner to that previously described for hydrocortisone. It is concluded that nivazol may be of benefit in the direct treatment of Cushing's disease, particularly since it lacks glucocorticoid activity.

Adrenocorticotropic Hormone↗
PubMed1985

Repeat pituitary ablation for advanced prostatic cancer.

An elderly male patient with advanced prostatic adenocarcinoma, requiring increasing analgesia, underwent interstitial pituitary irradiation by implantation of yttrium-90. He was temporarily relieved of his pain. Assessment of his anterior pituitary function showed only partial ablation. He therefore underwent a second implantation. This achieved complete ablation, and only when this was achieved did he experience full and sustained pain relief. We recommend assessment of anterior pituitary function in patients treated by pituitary ablation for carcinoma of the prostate, and especially in those in whom the disease progresses after initial success response.

Adenocarcinoma↗
PubMed1985

Dopamine in the pituitary adaptation to starvation in man.

To investigate the role of the dopaminergic system in the pituitary adaptation to energy deprivation, the effect of metoclopramide, a dopamine receptor blocker, on prolactin (PRL), TSH, FSH and LH secretion was investigated in 6 healthy men in the fed state and at 36 h starvation. All underwent a further 36 h of starvation on a separate occasion to assess the effect of starvation on the TSH and PRL responses to TRH and the LH and FSH responses to gonadotrophin releasing hormone (GnRH). In all subjects starvation produced the expected reduction in serum T3 and an average decrease of 53% in the cumulative TSH response to TRH. The basal serum PRL and its response to TRH and metoclopramide remained unchanged with 36 h starvation. The FSH response to GnRH also remained unchanged, but the LH response was significantly greater during starvation. We conclude that factor(s) other than dopamine influence not only thyrotrophic activity but also other aspects of pituitary function during energy deprivation.

Adaptation, Physiological↗
PubMed1985

Follicle-stimulating hormone-secreting pituitary adenomas.

This retrospective study concerns 40 patients with an apparently nonsecretory pituitary adenoma who were operated on during an 11-yr period from 1971 to 1981. Among them, 6 men had elevated serum FSH levels. LH levels were normal in 5 and slightly elevated in 1. Testosterone levels were low in 2 patients and within normal limits in 2 others. Sexual impotency had developed from 6 months to 1 yr before surgery in all patients. Primary hypogonadism could be eliminated on clinical grounds (recent onset of hypogonadism, previous fertility of 5 of the 6, and postoperative improvement). After transsphenoidal adenomectomy, FSH levels returned to normal values in all, and clinical recovery occurred in most patients. Tumor tissue obtained at operation stained positively for the gonadotropins, but was negative for other pituitary hormones in all patients. The most probable explanation for these findings was that the tumors were responsible for the elevated FSH secretion. This explanation is supported by the immunocytochemical identification of gonadotropin-containing cells in the tumors. We conclude that these 6 men from a series of 40 patients who presented with pituitary tumor but no GH, PRL, or ACTH hypersecretion had primary gonadotropinomas.

Adenoma↗
PubMed1984

Effects of high-dose fentanyl anaesthesia on the established metabolic and endocrine response to surgery.

The effect of the administration of fentanyl 50 micrograms/kg body weight on the established metabolic response to pelvic surgery was investigated. In comparison with a control group of patients in whom anaesthesia was supplemented with halothane, fentanyl was associated with a significant decrease in only blood lactate concentrations and heart rate. There were no significant differences in blood glucose, plasma non-esterified fatty acids, and plasma cortisol values between the two anaesthetic techniques. It is concluded that the administration of high-dose fentanyl has little effect on the established metabolic response to surgery, compared with the marked changes observed when the same dose is given before the onset of surgical stimulation.

Adult↗
PubMed1984

The levels and subcellular distribution of hormones and marker enzymes in pituitaries from control subjects and patients with prolactinomas, acromegaly or functionless pituitary tumours.

Pituitary homogenates were prepared from patients undergoing pituitary ablation for breast or prostatic carcinoma (controls) and from patients with either PRL- and GH-secreting pituitary adenomas or from patients with 'functionless' pituitary tumours. The principal subcellular organelles, plasma membrane, lysosomes, mitochondria, endoplasmic reticulum, cytosol and hormone-containing granules were characterized by sucrose density gradient centrifugation. Tissue from patients with prolactinomas showed hormone granules, lysosomes and endoplasmic reticulum of lighter density than controls; cytosol, mitochondria and plasma membrane were similar. PRL-secreting tumours showed a 2-fold increase in PRL content with significant reduction of LH, FSH and GH. Activities of various lysosomal enzymes, except for PRL proteolytic activity, were significantly reduced. Similar conclusions were found for GH-secreting pituitary adenomas with a striking reduction in PRL proteolytic activity. Functionless tumours showed significant amounts, though reduced compared to control tissue, of all hormones. In contrast to the hormone-secreting adenomas, the activity of the lysosomal enzyme N-acetyl-beta-glucosaminidase was significantly increased compared to control tissue.

Acetylglucosaminidase↗
PubMed1984

Effect of pancreatic growth hormone releasing factors on GH secretion by human somatotrophic pituitary tumours in cell culture.

Human pancreatic growth hormone releasing factors (hpGRF(1-40) and hpGRF(1-44) significantly stimulated GH secretion when added to cell cultures of human somatotrophic pituitary tumours for 2 h. There was little difference in potency between the two peptides, and the response of different tumours varied, ranging from 30% to 500% increases in GH secretion over control levels. This stimulatory effect was blocked by somatostatin (SRIF) and bromocriptine. The suppressive effect of bromocriptine, but not of SRIF, was overcome by high doses of hpGRF(1-44). TRH stimulated GH secretion by one of three somatotrophic tumours in cell culture, and it was found to potentiate the stimulatory effects of hpGRF(1-44). These results demonstrate that hpGRFs increase serum GH levels in man by a direct action at the pituitary somatotroph level.

Adult↗
PubMed1984

High serum prolactin associated with poor prognosis in carcinoma of the prostate.

Seventy patients with carcinoma of the prostate have had regular estimations of serum prolactin levels during a 10-month period, and were followed up for a further 6 months. Of 21 patients who recorded at least one high serum prolactin, 10 (48%) died during these 16 months, while of 50 with normal prolactin, only 2 (4%) died. Ten (21%) of the 47 patients on oestrogen or anti-androgen therapy died, and 9 of these had a high prolactin. This contrasts with 2 (14%) deaths of 14 who had had either bilateral orchiectomy or radiotherapy to the prostate. One of the 2 who died had a high prolactin. It is concluded that an elevated serum prolactin in treated carcinoma of the prostate is associated with progression of the disease and a poor prognosis.

Humans↗
PubMed1984

Effects of bromocriptine on pituitary organelle marker enzyme activities in lactating and postlactating rats: selective activation of lysosomal prolactin proteolytic activity.

Effects of the dopamine agonist 2-bromo-alpha-ergocryptine (bromocriptine) on plasma and pituitary PRL and enzyme activities in lactating and postlactating rats have been investigated. Lactating rats which had been suckling their young for 3 days were given a single sc injection of bromocriptine or solvent. The treated and control animals were divided into 2 further groups. One group (lactating rats) was permitted to suckle their pups for a further 12 or 24 h; the young were removed from the other group (postlactating rats). Homogenates were prepared from the anterior pituitaries and assayed for organelle marker enzyme activities. When 0.5-500 micrograms bromocriptine were administered to lactating rats for 24 h, pituitary PRL was increased by all doses, but only the 500-micrograms dose significantly reduced plasma PRL. Total protein was unchanged, lysosomal acid PRL proteolytic activity increased 8-fold, N-acetyl-beta-glucosaminidase and beta-glucuronidase (lysosomes) were unchanged, acid phosphatase (lysosomes and endoplasmic reticulum) was increased by three of four doses, 5'-nucleotidase and alkaline phosphatase (plasma membrane) were increased 4-fold, neutral-alpha-glucosidase (endoplasmic reticulum) and malate dehydrogenase (mitochondria) were unchanged, and catalase (peroxisomes) was significantly increased. Bromocriptine (500 micrograms) administration to lactating and postlactating rats for 12 and 24 h significantly decreased the pituitary DNA but not the total protein content of the pituitaries in all animals. The lysosomal acid PRL proteolytic activity and the lysosomal enzyme activities, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were increased by suckling withdrawal alone. Acid PRL proteolytic activity was further increased (to 18-fold) by coadministration of bromocriptine, whereas the increase in the activities of the other lysosomal marker enzymes was blocked. Malate dehydrogenase activity (mitochondria) was also increased by litter removal and blocked by bromocriptine. The activity of the plasma membrane markers 5'-nucleotidase and alkaline phosphatase were increased by litter removal, and bromocriptine further increased both enzyme activities. The activity of neutral-alpha-glucosidase (endoplasmic reticulum) was unchanged by any treatment. The results demonstrate that bromocriptine produces significant changes in the activities of lysosomal marker enzymes, particularly acid PRL proteolytic activity, as well as marker enzymes of plasma membranes and other organelles in pituitaries of lactating and postlactating rats.

5'-Nucleotidase↗
PubMed1983

Analytical subcellular fractionation of rat pituitary homogenates with special reference to the subcellular localization and properties of alkaline phosphatases.

Alkaline phosphatase activities of the virgin rat anterior pituitary were studied with a highly sensitive fluorometric assay. Tissue whole homogenates were fractionated on sucrose density gradients in a Beaufay automatic zonal rotor and the gradient fractions assayed for alkaline phosphatase, prolactin and various organelle marker enzymes. Alkaline phosphatase was distributed between two peaks on the gradient. The low-density (1.10-1.15 g . cm-3) alkaline phosphatase component co-sedimented with the plasma membrane marker, 5'-nucleotidase, had an apparent Km for 4-methylumbelliferyl phosphate of approx. 59 microM, and was inhibited by levamisole. The high-density (1.20-1.25 g . cm-3) peak was resistant to levamisole-inhibition, had an apparent Km of approx. 30 microM and its distribution was distinct from plasma membrane, Golgi, lysosome, endoplasmic reticulum, mitochondria and prolactin granule markers on the isopycnic gradients.

Alkaline Phosphatase↗
PubMed1983

Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF (1-44) ) in acromegaly and hypopituitarism.

Human pancreatic growth hormone releasing factor (GRF (1-44)) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly. GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose. Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further advantage of being free of side effects and readily performed in outpatients. Hence it seems likely to become the standard test and take the place of the insulin stress test.

Acromegaly↗
PubMed1983

Advanced carcinoma of the prostate: treatment with a gonadotrophin releasing hormone agonist.

Ten patients with advanced progressive adenocarcinoma of the prostate were treated with a long acting analogue of gonadotrophin releasing hormone. Eight of these patients responded to treatment in terms of pain relief and clinical regression of tumour. Serum gonadotrophin and testosterone concentrations were significantly suppressed by the end of the second week of treatment, testosterone concentrations being comparable with those achieved by castration. The two patients who failed to respond had both relapsed previously when receiving conventional treatment, and neither showed any endocrine response to the analogue. Superagonists of gonadotrophin releasing hormone may be the treatment of choice in adenocarcinoma of the prostate, but further trials are required to establish long term safety and efficacy.

Acid Phosphatase↗