bluuebunny/crossref_metadata_2025_split huggingface dataset:
GROWTH HORMONE SECRETING PITUITARY ADENOMAS ARE HETEROGENEOUS IN CELL CULTURE AND COMMONLY SECRETE GLYCOPROTEIN HORMONE α‐SUBUNIT
Authors: WHITE M. C. , NEWLAND P. , DANIELS M. , TURNER S. J. , MATHIAS D. , TEASDALE G. , KENDALL‐TAYLOR P. 
Published: March 2008

SUMMARYCell culture methods were used to assess whether human pituitary adenomas secreting GH and associated with clinical acromegaly also secreted the structurally unrelated glycoprotein hormone α‐subunit. Thirty‐two tumours, together with peri‐adenomatous tissue from two of them and three normal pituitaries were studied. Anterior pituitary hormones were measured by radioimmunoassay and included PRL, TSH, LH, FSH, and ACTH, as well as GH and α‐subunit. Normal pituitary tissues secreted all hormones assayed. All 32 tumours secreted GH ranging from 241 to 5556 ng/2 × 105 cells/24 h and 12 (37·5%) secreted α‐subunit in amounts which could not be accounted for by cross‐reaction of other hormones or contamination by normal pituitary tissue, and which ranged from 10·3 to 73·5 ng/2 × 105 cells/24 h. Ten other tumours also secreted α‐subunit but in very small amounts, not exceeding 1·8 ng/2 × 105 cells/ 24 h. PRL was secreted from 21 tumours (6679, and small amounts of other hormones, chiefly LH and TSH, were occasionally secreted from tumours. These cell culture studies would suggest that pituitary adenomas causing acromegaly are hormonally heterogeneous and that PRL and glycoprotein a‐subunit are commonly detected in addition to GH.
α‐HUMAN ATRIAL NATRIURETIC POLYPEPTIDE REDUCES THE PLASMA ARGININE VASOPRESSIN CONCENTRATION IN HUMAN SUBJECTS
Authors: FUJIO N. , OHASHI M. , NAWATA H. , KATO K. , IBAYASHI H. , KANGAWA K. , MATSUO H. 
Published: March 2008

SUMMARYThe synthetic α‐human atrial natriuretic polypeptide (α‐hANP) was infused into six normotensive, euvolaemic, healthy volunteers to examine the effect on the plasma arginine vasopressin (AVP) concentration. The intravenous administration of α‐hANP (0·1 μg/kg/min, 20 min) led to a remarkable reduction in mean blood pressure (‐10 mmHg, P>0·05), and there was an increase in pulse rate (+ 10 bpm, P>0·05), in each subject. The urinary volume, sodium excretion and cyclic 3′, 5′‐guanosine monophosphate (cyclic‐GMP) excretion were increased to 3·5 (P>0·05), 2·5 (P>0·05) and eight‐fold (P>0·01), respectively, during the α‐hANP infusion. The dose and duration of the synthetic α‐hANP in the present study was sufficient to induce these cardiovascular and renal effects. The plasma AVP concentrations decreased from 0·39 ± 0·09 pg/ml to the undetectable level during the α‐hANP administration. After infusion, the plasma concentrations of the AVP promptly returned to preinfusion levels (0·46 ± 0·14 pg/ml). However, there was no significant change in plasma AVP concentration during placebo infusion. The marked suppression in plasma AVP concentration may account for the remarkable diuresis, in addition of the direct renal effects of the synthetic α‐hANP.
ANTIPYRINE CLEARANCE IN CONGENITAL ADRENAL HYPERPLASIA
Authors: LOCHE S. , RIFKIND ARLEEN B. , STONER ELIZABETH , CONNEY A. H. , NEW MARIA I. 
Published: March 2008

SUMMARYAntipyrine (AP) metabolism was studied in four adult patients with congenital adrenal hyperplasia (CAH) due to classical 21‐hydroxylase deficiency and in four (adult) patients with CAH due to non‐classical 21‐hydroxylase deficiency. This investigation was prompted by the known biochemical and functional similarities between drug‐ and steroid‐metabolizing enzymes. We hypothesized that a common genetic mechanism may regulate the expression and activity of both the adrenal and hepatic cytochrome P450 enzymes. AP half‐lives (T1/2, mean ± SD) were 10·7 ± 2·1 h in classical CAH patients, 10·1 ± 0·4 h in the non‐classical CAH patients and 10·9 ± 2·2 h in the control group, suggesting that there was no significant difference in AP metabolism among the three groups. Similarly, no significant differences were found in the AP apparent volume of distribution (aVd) and metabolic clearance rate (MCR) among the three groups. These results indicate that despite the deficiency of adrenal cytochrome P450 in patients with 21‐hydroxylase deficiency CAH, these individuals have normal hepatic drug metabolizing activity for the biotransformation of AP.
NURSING BEHAVIOUR, PROLACTIN AND POSTPARTUM AMENORRHOEA DURING PROLONGED LACTATION IN AMERICAN AND KUNG MOTHERS
Authors: STERN JUDITH M. , KONNER M. , HERMAN TALIA N. , † S. REICHLIN 
Published: March 2008

SUMMARYIn order to determine the effects of protracted nursing in American women, blood was collected hourly for 24 h and nursing periods recorded in 20 mothers, 10 amenorrhoeic, 3 3/4 to 17 1/4 months postpartum (PP), and 10 menstruating, 5 1/4 to 46 months PP. These data were compared to the daytime nursing behaviour and 1000–1100 h PRL of women among Kung hunter‐gatherers of Botswana, a non‐contraceptive using population with a birth space interval of < 3 years. Intense nursing behaviour maintained amenorrhoea and hyperprolactinaemia for 1 to nearly 2 years PP in both American and Kung mothers. Among Americans, 80 min of nursing per day, in conjunction with a minimum of six nursing episodes, was highly predictive of remaining amenorrhoeic up to 18 months PP. Amenorrhoea was always accompanied by hyperprolactinaemia, but delay in the onset of menses was related more to nursing behaviour than to a particular 24 h PRL level. The 1000–1100 h sample is equivalent to and about half of the 24 h mean in high and low intensity nursers, respectively. The Kung women were similar to the high intensity nursing American women in 1000–1100 h PRL, percent amenorrhoeic, and the number of minutes of daytime nursing.
TRANSIENT HYPOGONADOTROPHIC HYPOGONADISM AFTER HEAD TRAUMA: EFFECTS ON STEROID PRECURSORS AND CORRELATION WITH SYMPATHETIC NERVOUS SYSTEM ACTIVITY
Authors: WOOLF P. D. , HAMILL R. W. , McDONALD J. V. , LEE LOUYSE A. , KELLY MARY 
Published: March 2008

SUMMARYTransient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1 > 8, Group 2 ≥ 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17‐hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18–95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 ± 105 (SEM) pg/ml; EPI: 191 ± 32 pg/ml and there were highly significant inverse correlations between admission NE (r=−0·52, P > 0·003) and EPI (r=0·44, P > 0·02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P>0·001) in 13 Group la men, but only 25% (P=NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17‐hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8–40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating this response in men.
CHARACTERIZATION OF TSH ANTAGONIST ACTIVITY IN THE SERUM OF PATIENTS WITH THYROID DISEASE
Authors: HASHIM F. A. , CREAGH F. M. , EL HAWRANI A. , PARKES A. B. , BUCKLAND P. R. , SMITH B. REES 
Published: March 2008

SUMMARYThe ability of sera from patients with thyroid disease to block TSH stimulation of cyclic AMP release from isolated porcine thyroid cells has been assessed and the blocking activity characterized. TSH receptor binding activity was also measured. No blocking or receptor binding activity was detectable in patients with primary myxoedema (n= 23), Hashimoto's disease (n= 11), multinodular goitre (n= 6), or rheumatoid arthritis (n= 10). However, analysis of sera from 23 patients (out of an initial screen of 110 patients) with treated Graves' disease which did not stimulate cyclic AMP production in the bioassay showed that two of these sera contained powerful blocking and receptor binding activity. Both these patients had been treated with 131I, Analysis of the two sera by gel filtration on Sephadex G‐200 indicated that blocking and TSH receptor binding activity were associated only with the IgG fraction. Digestion of the IgG with pepsin followed by reduction showed that both (Fab)2 and Fab fragments contained high levels of blocking and binding activity. Antibody divalency was not necessary therefore for TSH antagonist activity. However, our studies suggest that autoantibodies of this type with TSH antagonist activity do not occur frequently in patients from the Cardiff region with primary myxoedema, Hashimoto's or treated Graves' disease.
PROLONGED TREATMENT OF HYPERTHYROIDISM WITH SODIUM TYROPANOATE, AN ORAL CHOLECYSTOGRAPHIC AGENT: A RE‐EVALUATION OF ITS CLINICAL UTILITY
Authors: NOGUCHI K. , SUZUKI H. , NAKAHATA M. , KUROSAWA S. , NAKAGAWA S. 
Published: March 2008

SUMMARYTo re‐evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1·5 g daily) alone for 14 weeks, and six patients (TP+MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an ‘escape’ occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment.In the TP+MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4–14 weeks (7·3±5·0 weeks on the average), TP was withdrawn and replaced by MMI. A rebound of TI and serum T3 occurred within a week. These data suggest that, in the chronic treatment of hyperthyroidism, doses of combined TP and thionamide drug may have the advantage over those of TP alone both for achieving a more significant improvement of thyrotoxicosis and for precluding the recurrence of hyperthyroidism after cessation of TP therapy.
SERUM IODOTHYRONINE CONCENTRATIONS DURING INTRODUCTION OF THYROXINE REPLACEMENT THERAPY IN HYPOTHYROIDISM
Authors: PEARCE C. J. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYSerum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 μg at intervals of 4 weeks to a total of 200 μg daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1·35 + 0·23FT4, r = 0·916, P> 0·001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0·195 TT4, (r=0·936, P>0·001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 μg of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = ‐ 0·022 + 0·0027TT4, r= 0·921, P > 0·001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r= 0·927, −0·917 and −0·900 respectively). These correlations were significantly better (P > 0·05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised. During incremental treatment with T4 there was no disproportionate increase in rT3 as TT4 and FT4 rose, nor was there evidence of a changing relation between the concentrations of FT3 and FT4 over the range of concentrations encountered. The findings suggest that the deioidination of T4 does not change with the availability of T3.
MEASUREMENT OF TSH IN HUMAN AMNIOTIC FLUID: DIAGNOSIS OF FETAL THYROID ABNORMALITY IN UTERO
Authors: YOSHIDA K. , SAKURADA T. , TAKAHASHI T. , FURUHASHI N. , KAISE K. , YOSHINAGA K. 
Published: March 2008

SUMMARYUsing a highly sensitive immunoradiometric assay kit for human TSH, we measured TSH concentrations in unconcentrated amniotic fluids in normal pregnancies and those complicated for example by maternal hyper‐ and hypothyroidism, and compared them with those in maternal and cord sera. In normal pregnancies the mean concentration of TSH in amniotic fluid samples was 0·129 μU/ml, ranging from 0·065 to 0·278 μU/ml. In patients with premature delivery, the amniotic fluid TSH concentration was higher at 0·218 μU/ml. In four patients with abnormal thyroid function, TSH in amniotic fluid changed in parallel to that in cord serum, and there was a significant positive correlation between the two. No such correlation was observed between the concentrations of TSH in amniotic fluid and maternal serum. These results suggest that TSH in human amniotic fluid reflects fetal rather than maternal thyroid function and that the determination of TSH levels in amniotic fluid is useful in the diagnosis of abnormal thyroid function in fetuses.
THE LEUCOCYTE SODIUM PUMP IN HEALTHY AND OBESE SUBJECTS: THE ASSOCIATION OF INSULIN WITH ITS ACTIVITY
Authors: NG L. L. , HOCKADAY T. D. R. 
Published: March 2008

SUMMARYLeucocyte ouabain‐sensitive 22Na+ efflux was studied in 35 normal and 12 obese subjects. This efflux rate constant was raised in the obese (2·72 ± SEM 0·13 vs 2·31 ± 0·08 h‐1, P>0·006), indicating a higher activity of the sodium pump in vivo. There was a significant correlation between this efflux rate constant and fasting insulin level in both the whole population and in the normals alone (rs= 0·36, P > 0·007, and rs= 0·40, P > 0·009 respectively). A hyperinsulinaemiceuglycaemic clamp was performed on seven normal volunteers. After 2 h, there was a significant stimulation of the leucocyte efflux rate constant (from 2·86 ± 0·17 to 3·33 ± 0·18 h‐1, P> 0.01). In‐vitro incubation of leucocytes with insulin produced a maximal stimulation of the Na+‐K+‐ATPase activity of about 35% at 2 h with half‐maximal stimulation achieved at 46 mU/1. Insulin (100 mU/1) also stimulated the leucocyte ouabain‐sensitive 22Na+ efflux rate constant in vitro by about 11 % with or without 1 h of preincubation with the insulin. These findings may explain the hypokalaemic and sodium retaining effects of insulin in man; they may also partially explain the raised Na+ efflux rate constants in obesity.
AUTOIMMUNE CRANIAL DIABETES INSIPIDUS: ITS ASSOCIATION WITH OTHER ENDOCRINE DISEASES AND WITH HISTIOCYTOSIS X
Authors: SCHERBAUM W. A. , WASS J. A. H. , BESSER G. M. , BOTTAZZO G. F. , DONIACH DEBORAH 
Published: March 2008

SUMMARYThirty‐nine patients with idiopathic cranial diabetes insipidus (DI) and 81 secondary to hypothalamic lesions were investigated for the presence both of associated autoimmune diseases and autoantibodies. Eleven (28%) of the idiopathic but none of the secondary DI cases had an overt autoimmune disease. A further two patients with idiopathic DI had associated organ‐specific autoantibodies. Autoantibodies to vasopressin (AVP)‐secreting hypothalamic cells were detected in 12 patients with idiopathic DI (31 %). Seven out of 13 cases of DI secondary to histiocytosis X (HX) were also positive (54%), whereas only two (3%) of the other 68 sera from patients with secondary DI reacted with AVP cells. Of the 13 patients with DI associated with frank organ‐specific autoimmune diseases or autoantibodies alone, eight (62%) were positive for AVP‐cell antibodies. The finding of associated autoimmune diseases in a patient with idiopathic DI is therefore suggestive of an autoimmune origin of DI, and this can be supported by the detection in the serum of AVP cell antibodies. In cases of HX, the new finding of the presence of AVP‐cell antibodies reflects hypothalamic infiltration by HX cells, and suggests that these DR+‘Langer‐hans‐like’ cells play more than a passive role in the hypothalamic lesion.
AN ANALOGUE OF MET‐ENKEPHALIN ATTENUATES THE PITUITARY‐ADRENAL RESPONSE TO OVINE CORTICOTROPHIN RELEASING FACTOR
Authors: GROSSMAN A. , DELITALA G. , MANNELLI M. , AL‐DAMLUJI S. , COY D. H. , BESSER G. M. 
Published: March 2008

SUMMARYThe met‐enkephalin analogue, DAMME, suppresses the pituitary‐adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF‐41) 100 μg i.v. to a group of normal male subjects, with or without pretreatment with DAMME 250 μg i.v., and monitored the response of plasma ACTH and serum cortisol. CRF‐41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF‐41 on the pituitary.
DOPAMINE EFFECTS ON 11‐DEOXYCORTICOSTERONE CONCENTRATIONS IN PATIENTS WITH CUSHING'S SYNDROME AND IN VITRO
Authors: CONNELL J. M. C. , DAVIES D. L. , FRASER R. , KENYON C. J. 
Published: March 2008

SUMMARYThe effect of dopamine (1 μg/kg /min by i.v. infusion) on corticosteroid levels was studied in five patients with cortisol excess caused by increased ACTH secretion. In four of the five subjects dopamine, when compared with placebo infusion, caused plasma concentrations of 11‐deoxycorticosterone to rise without affecting levels of cortisol, corticosterone or aldosterone. In a parallel in‐vitro study using incubations of bovine adrenal zona glomerulosa cells, dopamine (10‐9 mol/1–10‐5 mol/l) had no effect on basal or ACTH stimulated secretion of aldosterone, cortisol or 11‐deoxycorticosterone. However, dopamine (10‐5 mol/l) partially inhibited angiotensin II (10‐7 mol/l) stimulated secretion of aldosterone (4.36 ng/106 cells/h ± 0·28 vs 2·90 ± 0·20, P>0·05) but did not alter 11‐deoxycorticosterone secretion in the same incubations. These data suggest that the effect of dopamine on 11–deoxycorticosterone secretion in vivo may not be due to its direct action on the adrenal to inhibit corticosteroidogenesis. An alternative explanation is that dopamine may alter extra‐adrenal synthesis of 11‐deoxycorticosterone, possibly by increasing substrate availability to tissues capable of 11‐hydroxylation reactions.
THYROID FUNCTION IN PATIENTS WITH HYPERPROLACTINAEMIA: RELATIONSHIP TO DOPAMINERGIC INHIBITION OF TSH RELEASE
Authors: DIEGUEZ C. , PETERS J. R. , PAGE M. D. , JOHN R. , HALL R. , SCANLON M. F. 
Published: March 2008

SUMMARYIt has been reported recently that patients with hyperprolactinaemia may develop hypothyroidism as a consequence of the increased inhibition of TSH release by dopamine which occurs in the majority of such patients. In this study we have evaluated thyroid function in a large number of hyperprolactinaemic patients in order to delineate more precisely the relationship between thyroid status, free thyroid hormone levels and the control of TSH release by dopamine. Biochemical euthyroidism was present in the majority of the hyperprolactinaemic patients. Our data indicate that the increased dopaminergic inhibition of TSH release does not lead to hypothyroidism. Instead, the slightly elevated basal TSH levels and TSH responses to TRH (within the normal range) may reflect the operation of a compensatory mechanism to maintain euthyroidism in the face of the increased inhibition of TSH release by hypothalamic dopamine.
PROTEIN‐A PURIFIED HUMAN IMMUNOGLOBULINS: A COMPARISON OF THYROID STIMULATING AND THYROTROPHIN RECEPTOR BINDING ACTIVITIES IN THYROTOXICOSIS
Authors: READER S. C. J. , DAVISON B. , BEARDWELL C. , RATCLIFFE J. G. , ROBERTSON W. R. 
Published: March 2008

SUMMARYProtein‐A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein‐A Sepharose CL‐4B from sera of euthyroid subjects had little effect in this system. The majority of Protein‐A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in porcine thyrocytes in a dose‐dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4·35 (0·8 to 7·5, % stimulation over control) and 2·7 (–9·3 to 8·6, TBII index) for the bioassay and radioreceptor assay respectively. A value of < 10·0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83·6%) compared to 60 in the radioreceptor assay (82·2%). There was a positive correlation between the two assays (r = 0·821, P>0·001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine‐131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P>0·05) in the iodine‐131 group than in the patients treated with carbimazole.Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related.