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T H Jones

Publications and source records attributed to T H Jones.

At least 73 records · Page 4Linked to original sources

Should thyroid function be assessed before cardiopulmonary bypass operations?

Thyroid function is depressed during and after cardiopulmonary bypass surgical procedures, and this may adversely affect myocardial performance. There is known to be a high prevalence of thyroid abnormalities in the elderly population, and many patients undergoing cardiac operations fall into this category. We have assessed thyroid function in 116 patients admitted for elective open heart procedures to determine the value of preoperative testing. Abnormalities in thyroid function were present in 13 (11.2%) of the patients studied, 3 of whom were receiving thyroxine therapy. One patient who had overt hypothyroidism died postoperatively of a large cerebral infarct; 11 had elevated thyrotropin levels with normal serum thyroxine levels; and 1 who had overtreated hypothyroidism suffered fast atrial fibrillation postoperatively. No other complications were observed. These findings indicate that thyroid function should be assessed preoperatively in patients already on thyroxine therapy. Whether thyroid function should be evaluated routinely in all patients before operations involving cardiopulmonary bypass is not clear. Although there is a high incidence of abnormal laboratory results, there were no apparent adverse effects on the surgical outcome.

Aged↗

Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Preliminary studies have demonstrated that some pituitary adenomas secrete immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended these studies by investigating 100 pituitary adenomas of different types measuring immunoreactive and bioactive IL-6. Tumors were cultured either as explants without fetal calf serum or as dispersed cells with 10% total calf serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL-6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount of IL-6 released by adenomas in cell culture was generally higher, although the incidence was similar to explant cultures. IrIL-6 was released by 7 of 14 prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2 Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of 49 clinically non-functioning adenomas. Periadenomatous tissue removed from a patient with a corticotrophinoma was found to secrete IL-6 but in much lower concentration than from the adenoma tissue. Tumor necrosis factor-alpha and -gamma-interferon were not detected in the conditioned media. Four IL-6-secreting adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three of these were positive with fluorescence present throughout the tissue examined. We have provided evidence that over half of pituitary adenomas secrete IL-6 which is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.

Adenoma↗

Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration.

When human chorionic gonadotrophin (hCG) is used to stimulate testosterone synthesis and release in males with hypogonadotrophic hypogonadism, it is administered two or three times weekly by intramuscular injection. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular injection and in the second week by self-administered subcutaneous injection. The patients studied had Kallmann's syndrome, isolated idiopathic hypogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrophic hypogonadism. Salivary testosterone was collected twice daily at 08.00 h and 20.00 h, and serum testosterone was collected after 0, 24 h, 72 h, 120 h and 168 h each week. The cumulated serum and salivary testosterone levels were comparable on both intramuscular and subcutaneous hCG. In normal males there is diurnal variation in testosterone, with peak serum levels in the morning falling to a nadir in the evening. The exact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG injections, either subcutaneous or intramuscular, produced a regular testosterone diurnal rhythm. The other four patients had fluctuations in testosterone but with no strict diurnal pattern. This study provides evidence that the luteinizing hormone-like action of hCG is necessary to prime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin production. In conclusion, self-administered subcutaneous hCG is safe and produces comparable levels of serum and salivary testosterone to that administered by the intramuscular route. Moreover, it was very well accepted by the patients and was preferred to conventional treatments. Human hCG in some patients with hypogonadotrophic hypogonadism produces normal physiological changes in daily testosterone levels.

Adolescent↗

Cytokines and hypothalamic-pituitary function.

Several cytokines are now known to affect the release of anterior pituitary hormones by an action on the hypothalamus and/or the pituitary gland. The major cytokines involved are IL-1, IL-2, IL-6, TNF-alpha and interferon-tau. Their predominant effects are to stimulate the hypothalamic-pituitary-adrenal axis and to suppress the hypothalamic-pituitary-thyroid and gonadal axes, and growth hormone release. The relative importance of systemically and locally produced cytokines in achieving these responses and their precise sites of action have not been fully established. There are indeed conflicting reports on the individual effects of each cytokine which need to be clarified. There is now cumulating evidence that there are important interactions between the immune and neuroendocrine systems which may explain in part, some of the effects on growth, thyroid, adrenal and reproductive functions which occur in acute and chronic disease. This article reviews the current knowledge of the effects of some cytokines on hypothalamic-pituitary function.

Adrenocorticotropic Hormone↗

Self-administered subcutaneous human menopausal gonadotrophin for the stimulation of testicular growth and the initiation of spermatogenesis in hypogonadotrophic hypogonadism.

OBJECTIVE: We determined whether or not self-administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis in men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed. DESIGN: Human menopausal gonadotrophin was self-administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n = 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n = 2). Patients were assessed on a monthly basis. PATIENTS: Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism. MEASUREMENTS: Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer. RESULTS: Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of > 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n = 4), mean size increased from 3.25 +/- 0.9 (SD) ml to 12.2 +/- 3.8 ml, (b) an initial testicular volume of > 4 ml mean size (n = 3) increased from 9.2 +/- 3.9 ml to 10.3 +/- 4 ml. In Group II (n = 2) testis size increased from a mean of 3.0 +/- 1.4 ml to 9.0 +/- 1.4 ml over a 6-months treatment period. CONCLUSION: Self-administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism.

Adolescent↗

Pituitary adenomas with high and low basal inositol phospholipid turnover; the stimulatory effect of kinins and an association with interleukin-6 secretion.

OBJECTIVE: We examined basal inositol phospholipid turnover and the response to the kinin, kallidin, in human pituitary adenomas and determined whether or not there was an association between these parameters and interleukin (IL-6) secretion status by the tumours. DESIGN: Pituitary adenoma tissue was dispersed and cells were cultured in monolayer for 96 hours. The medium was then removed and assayed for IL-6 and anterior pituitary hormones. The cells were labelled with 3H-myoinositol for 24 hours and then incubated under basal conditions with kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol phosphate accumulation and pituitary hormone secretion were assessed. PATIENTS: Tissue was collected from 29 consecutive patients being treated surgically for pituitary adenomas. MEASUREMENTS: Total 3H-inositol phosphates, growth hormone, prolactin, LH, FSH, TSH and immunoreactive IL-6. RESULTS: Two groups of pituitary adenomas were identified, one with high and one with low basal inositol phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in seven of the 29 adenomas studied. The kallidin-responsive adenomas were associated with high basal phosphoinositide turnover. All seven kallidin-responsive adenomas secreted IL-6. The adenomas studied with high basal inositol phosphate production were also responsive to TRH and in two tumours to GnRH. Kallidin stimulated GH release in one GH-secreting adenoma but had no effect on hormone secretion from any other tumour. CONCLUSION: Two groups of pituitary adenomas have been identified with high and low basal inositol phosphoinositide turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH in adenomas with high but not low turnover. Kinin-responsive adenomas secreted IL-6 but IL-6 secretor status does not preclude that they will respond to kallidin.

Adenoma↗

Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells.

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-gamma and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.

Adenoma↗

Bradykinin stimulates the production of prostaglandin E2 and interleukin-6 in human osteoblast-like cells.

The effect of bradykinin (BK) on proteinase activity, prostaglandin synthesis, and the production of interleukin-6 (IL-6) was investigated in cultures of human osteoblast-like cells. Bradykinin had no effect on stromelysin activity and plasminogen activator activity produced by human osteoblast-like cells. However, BK stimulated the production of prostaglandin E2, an effect that was markedly enhanced by pre-incubation with recombinant interleukin-1 alpha (rhIL-1 alpha), but was apparently unaffected by BK receptor antagonists types 1 and 2. Bradykinin stimulated the intracellular accumulation of total inositol phosphates suggesting that its effects were mediated by stimulation of phosphoinositide metabolism. Bradykinin within the dose range of 10(-11)-10(-5) M also significantly stimulated the production of IL-6. Bradykinin may, therefore, mediate a variety of responses in bone under both physiological and pathological conditions.

Bradykinin↗

Effect of the GABAA agonist muscimol on prolactin secretion from human prolactin-secreting adenomas and GH3 rat pituitary tumour cells.

The effect of muscimol, a specific potent GABAA receptor agonist, on prolactin release from human prolactin-secreting tissue was investigated using a perifusion system. Perifusion studies on normal rat anterior pituitary tissue, which has identical GABA receptors to those found in normal human pituitary glands, show that muscimol has a specific biphasic effect on prolactin release. This is characterized by an initial transient stimulation (222.3 +/- 21.6% of basal) lasting for 5-10 min followed by a more prolonged inhibitory phase (63.9 +/- 3.1% inhibition of basal). Five human prolactin-secreting adenomas were studied, and in none of the tumours could a biphasic response be demonstrated. One of the prolactin-secreting adenomas had a blunted inhibitory response, but the other 4 showed no inhibitory effect of muscimol on prolactin release. Muscimol had no significant effect on basal or thyrotropin-releasing-hormone (TRH)-stimulated prolactin secretion from GH3 rat pituitary tumour cells. These studies suggest that the GABAergic effect on prolactin secretion is absent or altered in both rat and human prolactin-secreting tumour cells.

Adult↗

Bioregulatory role of the kallikrein-kinin system in the normal pituitary gland and its tumours.

Tissue kallikrein, a serine protease, is present in the prolactin-secreting cells of the normal anterior pituitary gland and pituitary adenomas. It is mainly located in the Golgi apparatus, but is also present in secretory granules. There is a distinct sexual dimorphism, with amount of tissue kallikrein being greater in anterior pituitary tissue from female rats. The intracellular levels of tissue kallikrein are increased by estradiol and in pituitary tumours, and decreased by ovariectomy, dopamine and its agonists. There is preliminary in vitro evidence that tissue kallikrein may be involved in the intracellular processing of the prolactin molecule before secretion. Tissue kallikrein synthesizes kinins which are present in the anterior pituitary and are capable of stimulating prolactin and growth hormone secretion by activating the phosphoinositide second messenger system. Prolactin physiology is uniquely linked to the kallikrein-kinin system in the normal pituitary and its tumours. Tissue kallikrein may have an important role in the pathophysiology of prolactin-secreting pituitary adenomas.

Adenoma↗

Release of interleukin-6 by human thyroid epithelial cells immortalized by simian virus 40 DNA transfection.

Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3). IL-6 release over 24 h was stimulated by TSH (5000 microU/ml), by forskolin (0.01 mmol/l), by fetal calf serum (1-20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with gamma-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1), which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100 mumol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE2 was only threefold. The effect of IL-1 was not inhibited by indomethacin. These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗

Tissue kallikrein is associated with prolactin-secreting cells within human growth hormone-secreting adenomas.

Tissue kallikrein is a serine protease which may be involved in the intracellular processing of prolactin in the anterior pituitary gland. The expression of tissue kallikrein, in the rat, is promoted by oestrogen and inhibited by dopamine. Human and rat prolactinomas contain markedly increased amounts of tissue kallikrein; this is comparatively reduced if patients are pretreated with the dopamine agonist, bromocriptine, before surgery. Some GH-secreting adenomas are mixed and also contain prolactin-secreting cells. We therefore investigated 27 GH-immunostaining human pituitary adenomas for the presence of immunoreactive tissue kallikrein. Sixteen of the adenomas had positive immunostaining for prolactin; eight of these patients had associated clinical hyperprolactinaemia before the tumour was removed. Tissue kallikrein immunoreactivity was found in ten adenomas, all of which also had prolactin immunopositivity. There was a close relationship between the percentage of cells staining for prolactin and tissue kallikrein but not for GH. A further eight adenomas had patchy positivity, i.e. less than 1% of cells immunostained for tissue kallikrein and six of these also had some prolactin-staining cells. Nine out of eleven purely GH-staining adenomas had no tissue kallikrein immunopositivity, the remaining two showing patchy staining. A review of bromocriptine responsiveness, as assessed by mean GH hormone levels during oral glucose tolerance tests before and after therapy was commenced, indicated that patients with adenomas which stained for prolactin and tissue kallikrein were more likely to respond to bromocriptine than those which failed to do so.

Adenoma↗

Tissue kallikrein and the effect of bromocriptine in human prolactin and growth hormone-secreting pituitary adenomas.

Tissue kallikrein (TK) is present and co-localises with prolactin producing cells in human prolactinoma and mixed growth hormone (GH) and prolactin-secreting pituitary adenomas. TK immunoreactivity was reduced or absent in these types of adenomas from patients who had received the dopamine agonist, bromocriptine before surgery. Pure GH secreting adenomas had no TK immunoreactivity.

Adenoma↗

Sodium valproate-induced menstrual disturbance in young women.

Two young girls with epilepsy presented with menstrual disturbances whilst on treatment with sodium valproate. On withdrawing valproate therapy, period cyclicity returned to normal in both individuals. An exaggerated luteinising hormone response to parenterally administered gonadotropin-releasing hormone was present in both subjects. The temporal relationship between normalisatin of periods and stopping the sodium valproate suggests that this drug may possibly affect the control of the menstrual cycle through a GABAergic mechanism.

Adolescent↗

Interleukin-6 secreting human pituitary adenomas in vitro.

Interleukin-6 was found to be secreted from seven out of ten human pituitary tumours cultured in vitro. These tumours included prolactin-secreting, growth hormone-secreting and clinically non-functioning adenomas. The amount of Interleukin-6 secreted was variable from 58 to 10,000 units per ml. in medium removed after a four-day incubation under basal conditions. Four tumours secreted IL-6 in excess of 500U/ml, three of which were clinically non-functioning, but each secreted follicle stimulating hormone in vitro. This is the first report of a cytokine growth factor being released basally by human pituitary tumours.

Adenoma↗