bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLASMA CONTAMINATION ACCOUNTS FOR THYROID HORMONE BINDING IN NUCLEAR PROTEIN EXTRACTS FROM HUMAN MONONUCLEAR CELLS
Authors: MABERLY G. F. , EASTMAN C. J. , SMITH H. C. , WAITE K. 
Published: March 2008

SUMMARYPlasma protein contamination accounted for high affinity thyroid hormone binding to a nuclear protein extract from human blood mononuclear cells. The degree of contamination was directly related to the number of times the cells were washed before the nuclear protein was extracted. After three washes, no specific binding was detected. Plasma contamination was estimated to be 0·3–0·5 μl/assay tube. The TBG concentration in this volume of plasma was consistent with the concentration of 0·2 μg/ml measured by RIA in the nuclear extract. Total specific binding of [125I] T4 and [125I] T3 can be attributed to plasma contamination, as 0·3 μl of plasma gave identical binding. Furthermore, a TBG antiserum abolished specific T4 and T3 binding to the nuclear protein extract. These data are consistent with TBG being the major plasma contaminant. In fourteen normal, euthyroid subjects, the higher mean maximum binding capacity (MBC) for T4 (1·63 ± 0·27 SD) compared to T3 (0·25 ± 0·21 pmol/mg protein; P < 0·001) and the same binding affinity (Ka, 2·0 ± 0·7 × 109/mol) for both T4 and T3 are the same as found in plasma. The higher MBC for T4 (5·8 ± 1·0) and T3 (0·69 ± 0·2 pmol/mg protein) in two hypothyroid subjects are consistent with the higher mean TBG concentration of 28 ± 5 μg/ml compared to the level in ten normal subjects (19·2 ± 1·8 μg/ml; P < 0.001). In two subjects with low normal TBG concentrations of 15 μg/ml, the T4 maximum specific binding of 9% was lower than found in normal subjects 16·6 ± 7·6%. We conclude that the methodology described previously and used in this study is invalid for measuring thyroid hormone nuclear receptor status in humans.
NUCLEAR BINDING AND CELLULAR METABOLISM OF THYROXINE IN A EUTHYROID PATIENT WITH HYPERTHYROXINAEMIA
Authors: KVETNY J. 
Published: March 2008

SUMMARYThe receptor mechanism and intracellular T4 deiodination were studied in a patient, who was euthyroid despite high T4 levels. Serum T3 and serum reverse T3 levels were normal and the TRH tests produced a normal rise in TSH. Protein binding capacities for T4 in serum were found to be normal. The T4 bound to a single set of binding sites in the patient's lymphocyte nuclei with a Ka which was depressed as compared with that of normals (Ka= 2·8 × 1010 l/mol) and a maximum specific binding capacity (MSBC = 1·9 fmol T4/10 μg DNA) which was increased as compared with normals (msbc = 1 × 10−16 mol/l T4/10 μg DNA). The cellular deiodination of T4 was found to be normal, whereas T3 accumulation was increased and the nuclear T3 concentration raised. In conclusion, these results suggest that in this patient the syndrome of peripheral tissue resistance to thyroid hormone action is due to a defect at the level of the nuclear receptor and not to a defective intracellular T4 to T3 conversion.
AN INTRACRANIAL METASTASIS FROM A PRL SECRETING PITUITARY TUMOUR
Authors: COHEN D. L. , DIENGDOH J. V. , THOMAS D. G. T. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYA 70‐year‐old man developed panhypopituitarism and was found to have hyperprolactinaemia and a locally invasive pituitary tumour. The visual fields were unaffected and therefore the patient was treated with hormone replacement only. After 3±5 years during which time the pituitary tumour had not enlarged further, the patient developed a mass in the left cerebello‐pontine angle. This mass was subsequently shown to be entirely separate from, but histologically identical to, the pituitary tumour and the cells of both contained PRL. Evidence was obtained to show that the tumour had spread by a vascular route. This is the second reported case of a malignant prolactinoma.
DOPAMINERGIC MODULATION OF TSH AND ITS SUBUNITS: IN VIVO AND IN VITRO STUDIES
Authors: COOPER D. S. , KLIBANSKI ANNE , RIDGWAY E. CHESTER 
Published: March 2008

SUMMARYWe have studied the effects of dopamine on the secretion of TSH and its subunits in vivo and in vitro. Four normal controls, seven patients with primary hypothyroidism, two patients with peripheral resistance to thyroid hormone (PRTH), and two patients with α‐secreting pituitary tumours underwent a 3‐h dopamine infusion (4 μg/kg/min). Serial blood samples were drawn for TSH, PRL, α, and TSH‐β subunit. In normal subjects, TSH fell from 2·1 ± 0·9 (±SE) to 0·7 ± 0·1 μU/ml (P < 0·05), and α declined from 1·5 ± 0·4 to 1·0 ± 0·1 ng/ml (P < 0·01). TSH‐β was at or slightly above the detection limits of the assay before and after dopamine. In hypothyroidism, basal serum TSH was 81 ± 14 μ/ml. With dopamine, TSH fell to 35 ± 8 μU/ml (P < 0·001), while α decreased from 3·2 ± 0·4 to 2·0 ± 0·3 ng/ml (P < 0·001). Serum TSH‐β also declined from 0·97 ± 0·06 to 0·57 ± 0·05 ng/ml (P 0·001). A similar fall in TSH and α was seen in the two patients with PRTH. In normals and hypothyroid patients, the percentage change in α concentration was significantly less than that observed for intact TSH. This is due presumably to the contribution of the gonadotrophs to the circulating α pool. TSH and TSH‐β were undetectable in the two pituitary tumour patients, and α declined only slightly in each patient after dopamine. The in vitro effects of dopamine were studied using cultured bovine anterior pituitary cells. Dopamine (10−4‐10−8 mol/l) did not change basal TSH, α, or TSH‐β release. However, dopamine at all doses significantly blunted TRH (10−7 mol/l)‐stimulated TSH and TSH‐β release, and blunted TRH‐mediated α release at the two highest dopamine doses. These data suggest that dopamine modulates both TSH and TSH subunit secretion. These effects may be exerted directly at the level of the thyrotroph.
THE PLACE OF PRL IN HUMAN LACTATION
Authors: MARTIN R. H. 
Published: March 2008

SUMMARYPlasma PRL levels were measured during an episode of breast feeding in fourteen women on the eighth and 42nd post‐partum days. The results show that as lactation continues so the importance of absolute values of PRL diminishes, but the capability to secrete PRL in response to the suckling stimulus is maintained.
THE ACUTE AND LONG TERM EFFECT OF THE H2‐RECEPTOR ANTAGONISTS CIMETIDINE AND RANITIDINE ON THE PITUITARY‐GONADAL AXIS IN MEN
Authors: KNIGGE U. , DEJGAARD A. , WOLLESEN F. , INGERSLEV O. , BENNETT P. , CHRISTIANSEN P. M. 
Published: March 2008

SUMMARYWe have investigated the effect on the human pituitary–gonadal axis of the H2‐receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1·5 months followed by 400 mg/day for 4·5 months) or ranitidine (200–400 mg/day for 1·5 months followed by 100–200 mg/day for 4·5 months). Administration of the H2‐antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long‐term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre‐treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre‐treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2‐antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2‐receptors. It is possible that cimetidine, having anti‐androgen properties, blocks pituitary or hypothalamic androgen receptors.
CYCLE INITIATION IN AMENORRHOEA; THE EFFECT OF PROGESTERONE AND OESTROGEN ADMINISTRATION ON THE PULSATILE RELEASE OF GONADOTROPHINS
Authors: EL SHEIKH M. A. A. , MOLLOY B. G. , CHAPMAN C. , OAKEY R. E. , HANCOCK K. W. , GLASS M. R. 
Published: March 2008

SUMMARYThe modulation of pulsatile gonadotrophin release by endogenous ovarian steroids during the normal menstrual cycle may be involved in the initiation of the following menstrual cycle. The absence of this cyclical variation may, in some cases, be the cause of, or contribute to the cause of, amenorrhoea. To assess this the modulatory effect of gonadal steroid administration on the pulsatile release of gonadotrophins was studied in fourteen amenorrhoeic and four oligomenorrhoeic women. Pulsatility was assessed by samples collected at 10 min intervals during a 4 h morning period before and after treatment with either progesterone or micronized oestradiol or a sequential combination of both.Ten patients with intact positive oestrogen‐gonadotrophin feedback responded to progesterone treatment by both a significant reduction in LH pulse frequency, from a mean of 4·1 to a mean of 2·1 pulses within the 4 h study period and an increase in pulse amplitude. Progesterone therapy did not affect mean LH concentrations but there was a significant reduction in mean FSH concentrations. In the eight patients with absence of positive feedback, none of the treatment regimes elicited significant changes in LH release. No definable FSH pulses were detected before or after treatment in either group.Both the changes in LH and FSH concentrations and their release observed in this study, support the concept that cycle initiation may be related to a reduced pituitary exposure to LHRH associated with elevated progesterone concentration in the luteal phase of the cycle. This selectively induces FSH synthesis and storage. Release of this stored FSH may occur as a result of failure of the corpus luteum and falling progesterone concentrations.
SUPPRESSION OF RESIDUAL OESTROGEN PRODUCTION WITH AMINOGLUTETHIMIDE IN WOMEN FOLLOWING SURGICAL HYPOPHYSECTOMY OR ADRENALECTOMY
Authors: SAMOJLIK E. , SANTEN R. J. , WORGUL T. J. 
Published: March 2008

SUMMARYIn postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy. Plasma and urinary oestrogens were measured with radioimmunoassays developed to provide appropriate sensitivity. In five women treated after initial hypophysectomy (hypox), plasma oestrone fell from 66·28 pg/ml (hypox) to 9·1 ± 2·4 pg/ml (hypox and AG) and oestradiol decreased from 8·3 ± 1·8 pg/ml to 2·5 ± 0·69 pg/ml. Similar decrements in urine oestrone (U‐E1) and ostradiol (U‐E2) were observed (U‐E1 hypox: 2·25 ± 0·71 μg/24 h and 0·071·0±015 μg/24 h hypox and AG; U‐E2 0·47 ± 0·12 μg/24 h hypox to 0·124 ± 0·015 hypox and AG, P<0·05 for all). Similar significant reductions in plasma oestrone and oestradiol were observed in four women treated with aminoglutethimide following surgical adrenalectomy. While the levels of urinary oestrogens also fell in these patients, the differences were not statistically significant. In response to the decrements in oestrogen levels induced by AG, 2/5 women in the post‐hypophysectomy group and 2/4 in the post‐adrenalectomy group experienced partial objective tumour regression. These observations indicated that the residual oestrogens produced after surgical adrenalectomy or hypophysectomy, even though made in small quantities, were nonetheless biologically active. We conclude that endogenous production of oestrogens in extragonadal and extra‐adrenal sites occurs after major surgical endocrine
CORTICOTROPHIN RELEASING FACTOR: RESPONSES IN NORMAL SUBJECTS AND PATIENTS WITH DISORDERS OF THE HYPOTHALAMUS AND PITUITARY
Authors: LYTRAS N. , GROSSMAN A. , PERRY L. , TOMLIN S. , WASS J. A. H. , COY D. H. , SCHALLY A. V. , REES L. H. , BESSER G. M. 
Published: March 2008

SUMMARYSynthetic CRF‐41 has been given to 43 patients with hypothalamic, pituitary or adrenal diseases and contrasted with the responses in 20 normal subjects. In the normal subjects the mean increment in serum cortisol (± SE) was 276 ± 38 nmol/l; the increments showed a significant negative correlation with the basal serum cortisol levels (r= ‐0·56; P<0·02). The mean peak serum cortisol was 662 ± 34 nmol/1 and the mean peak corticosterone was 28·6 ± 3·8 nmol/1. There was a significant positive correlation between the peak serum corticosterone and cortisol concentrations (r= 0·84; P<0·0001). Dexamethasone pretreatment abolished the rise in cortisol in response to CRF‐41. The peak serum cortisol following CRF‐41 was not significantly different between the normal subjects and those patients with pituitary disease who had normal cortisol responses to insulin‐induced hypoglycaemia. However, in individual patients the peak cortisol levels induced by hypoglycaemia were greater than, but significantly correlated with, those induced by 100 μg of CRF‐41. Seven patients were ACTH deficient in response to hypoglycaemia, and of these six responded normally to CRF‐41. Only one of these patients had a lesion clearly originating in the hypothalamus; four had pituitary tumours with suprasellar extensions and the remaining patient had idiopathic GH and ACTH deficiency. Our data suggest that these patients have a functional defect of ACTH secretion due to the failure of CRF to reach the corticotroph. Of the four patients with pituitary‐dependent Cushing's disease who were on no treatment at the time of testing, three showed an exaggerated and one a normal response to CRF‐41. These normal or enhanced responses of hypercortisolaemic patients with Cushing's syndrome contrast with the complete inhibition of the responses to CRF‐41 in normal subjects given dexamethasone. In the treated patients with Cushing's syndrome
STUDIES OF THE ANDROGEN RECEPTOR IN DISPERSED FIBROBLASTS: INVESTIGATION OF PATIENTS WITH ANDROGEN INSENSITIVITY
Authors: EVANS B. A. J. , JONES T. R. , HUGHES I. A. 
Published: March 2008

SUMMARYThe practical application of a simple, reproducible androgen receptor assay using dispersed fibroblasts is described for the investigation of patients with the androgen insensitivity syndrome (AIS). The concentration of androgen receptors (Bmax) in genital skin fibroblasts derived from normal subjects is 814 ± 168 ×−18 moles/μg DNA (mean ± SD) and the binding affinity (Kd) is 0·91 ± 0·26 × 10±10M at 37°C, using [3H]‐5α‐dihydrotestosterone (DHT) as the labelled ligand. Studies in patients with phenotypic signs of complete or partial AIS showed either absent (receptor‐negative), decreased (receptor‐deficient) or normal/increased (receptor‐positive) specific binding of DHT to the receptor. In some mutant cell lines, there was evidence of thermolability and increased rate constant of dissociation of the androgen‐receptor complex, suggesting a possible structural abnormality of the receptor protein. This simple receptor assay can be used to delineate quantitative and qualitative defects of the androgen receptor in a significant number of patients with a wide spectrum of phenotypic abnormalities associated with androgen resistance.
MEASUREMENT OF FREE THYROXINE AND FREE TRIIODOTHYRONINE IN THYROTOXICOSIS AND HYPOTHYROIDISM
Authors: FRANKLYN J. A. , SHEPPARD M. C. , RAMSDEN D. B. , WILKINSON R. , HOFFENBERG R. 
Published: March 2008

SUMMARYFree T4 and free T3 concentrations in thyrotoxic and hypothyroid patients at presentation differentiated those with thyroid disease from euthyroid control subjects and were closely correlated with T4/TBG ratio. A further group of thyrotoxic patients was followed serially during treatment with carbimazole. Measurements of free T4 and free T3 against closely reflected thyroid status with changes in the hormone measurements being paralleled by changes in T4/TBG ratio.
PLASMA SOMATOMEDIN ACTIVITY AFTER INJURY IN MAN AND ITS RELATIONSHIP TO OTHER HORMONAL AND METABOLIC CHANGES
Authors: FRAYN K. N. , PRICE D. A. , MAYCOCK P. F. , CARROLL S. M. 
Published: March 2008

SUMMARYPlasma somatomedin activity was measured in 12 patients who had sustained non‐fatal musculo‐skeletal injuries. It was depressed for 2‐3 d after injury, but this depression bore no relationship to the catabolic response to injury which, as judged by urinary nitrogen excretion, was maximal at about one week. The depression of somatomedin activity may have been related to the high plasma cortisol concentrations observed during the first few days after injury. Plasma growth hormone concentrations were high acutely after injury but rapidly returned to normal. The changes in plasma somatomedin activity were thus unrelated to those in growth hormone, but were very similar to those in plasma insulin concentrations. A marked positive relationship was observed between plasma insulin concentrations and urinary nitrogen excretion, indicating unresponsiveness of protein metabolism to the normal anabolic effects of insulin. The study showed, however, that this was not as a result of low somatomedin activity.
ELEVATED SERUM THYROGLOBULIN AS A MANIFESTATION OF ACUTE HAEMORRHAGE INTO THE THYROID GLAND
Authors: KAWAMURA S. , KISHINO B. , TAJIMA K. , MASHITA K. , TARUI S. 
Published: March 2008

SUMMARYClinical observations and serial determinations of serum thyroglobulin (Tg) were made in five patients with acute haemorrhage into the thyroid gland. Fever, local pain and acceleration of erythrocyte sedimentation rate were minimal or were not observed, and serum T4 and T3 were normal. Although all patients showed an increase in serum Tg, this was most obvious in three subjects and it gradually decreased as the nodule became smaller. There was no correlation between the serum Tg concentration and the nodular size. Acute haemorrhage into the thyroid gland should be added as one of the causes to increase serum Tg concentrations.
EFFECTS OF THE GABAERGIC DRUG, SODIUM VALPROATE, ON THE PROLACTIN RELEASE EVOKED BY PHARMACOLOGICAL STIMULI IN NORMAL WOMEN
Authors: MELIS G. B. , FRUZZETTI F. , PAOLETTI A. M. , MAIS V. , BENEVENTI F. , TRIMARCHI G. , FIORETTI P. 
Published: March 2008

SUMMARYSodium valproate (DPA or Na‐dipropylacetate), an anticonvulsant drug activating the endogenous GABAergic system, was administered orally at the dose of 400 mg to seventeen normal women 1 h before intravenous injections with three drugs which stimulate prolactin (PRL) release: TRH (200 ųg bolus; six subjects); domperidone (5 mg bolus; six subjects); and sulpiride (5 mg bolus; five subjects). DPA pretreatment significantly blunted PRL response to both domperidone and sulpiride injections without affecting the PRL response to TRH. In particular, the quantitative PRL secretion (areas under curves) following domperidone and sulpiride tests appeared significantly reduced after DPA treatment in comparison to placebo (P < 0·02 and P <0·01 for domperidone and sulpiride respectively). These results indicate that the pharmacological enhancement of the endogenous GABAergic system by DPA may blunt PRL response to both central and peripheral dopamine receptor blockade. These observations suggest that a GABAergic pathway inhibiting PRL secretion at the hypothalamic level competes, at least in part, with the dopaminergic system. Conversely, the lack of any effect of DPA on PRL response to TRH seems to suggest that pituitary TRH receptors are independent of any GABAergic control.
SALMON AND HUMAN CALCITONIN‐LIKE PEPTIDES IN MAN
Authors: TOBLER P. H. , TSCHOPP F. A. , DAMBACHER M. A. , FISCHER J. A. 
Published: March 2008

SUMMARYCalcitonin‐like peptides have been identified in the serum of normal subjects and of medullary thyroid carcinoma (MTC) patients. Using specific homologous radioimmunoassays (RIA) in combination with reversed‐phase high performance liquid chromatography and gel permeation chromatography under denaturing conditions, we have recognized major components which coeluted with human calcitonin‐(1–32), PDN‐21, a carboxyl‐terminal flanking peptide derived from the calcitonin mRNA sequence, and salmon calcitonin‐(1–32). An additional 12000 molecular weight peak possibly represents a human calcitonin‐PDN‐21 polyprotein. In both the human calcitonin‐(1–32) (normal value < 0·043 ngEq/ml; MTC 140·80 ngEq/ml, mean value±SEM) and the PDN‐21 (normal value <0·050 ngEq/ml; MTC 33·6±16·5 ngEq/ml) RIAs, serum levels were increased in MTC patients. Circulating levels of the salmon calcitonin‐like peptide were indistiguishable between normal subjects (0·038 ± 0·006 ngEq/ml) and MTC patients (0·037 ± 0·011 ngEq/ml).
LEVELS OF THE OXYTOCIN‐ASSOCIATED AND VASOPRESSIN‐ASSOCIATED NEUROPHYSINS IN PLASMA AND THEIR RESPONSES IN ESSENTIAL HYPERTENSION
Authors: AMICO JANET A. , CORDER C. N. , McDONALD R. H. , ROBINSON A. G. 
Published: March 2008

SUMMARYA group of 89 individuals with essential hypertension was evaluated with several measurements including the neurophysin believed to be the human oxytocin neurophysin (OT‐Np), and the human vasopressin neurophysin (VP‐Np). The neurophysins are proteins synthesized within cells of the supraoptic and paraventricular nuclei in conjunction with their respective hormones oxytocin and vasopressin as part of a common precursor molecule and so may reflect the simultaneous presence in plasma of their associated hormones. A poor but statistically significant correlation was noted between levels of OT‐Np and renin activity in plasma (PRA) either supine (r= 0·248) or erect (r= 0·255). Levels of OT‐Np averaged 1·75 ng/ml and were inversely correlated with creatinine (r= ‐ 0·252), supine blood pressure (r= ‐ 0·450), plasma volume (r= ‐ 0·327), and 24‐hour urine sodium (r= ‐ 0·313). Levels of Ot‐Np could be suppressed by infusion of physiologic saline. Levels of OT‐Np were lower in the volume expanded state and were positively correlated with the quantity of sodium excreted into a 24‐hour urine collected after the infusion (r= 0·426) and inversely correlated with the supine systolic (r= ‐ 0·379) and supine diastolic (r= ‐ 0·455) blood pressures recorded after the infusion of saline. Oestrogen, a stimulus to the secretion of OT‐Np, did not account for the elevation of OT‐Np observed in the study, since mean levels of oestradiol (E2) in a subset of the patients with elevated OT‐Np (E2= 36 pg/ml) were not different from levels in subjects with lower values of OT‐Np (E2= 45 pg/ml). Levels of VP‐Np averaged 0·85 ng/ml and correlated positively with PRA (r= 0·353) and 24‐hour urine excretion of dopamine (r= 0·44), and inversely with age (r= ‐ 0·263), blood pressure, and 24‐hour urine excretion of sodium (r= ‐ 0·226). Erect posture caused an elevation of VP‐Np. Therefore, levels of OT‐Np and VP‐Np respond to certain physiological stimuli and levels of OT‐Np are elevated in a subgroup of subjects with essential hypertension.
THYROTOXIC MYOPATHY ASSOCIATED WITH SUBACUTE THYROIDITIS
Authors: TAJIMA K. , MASHITA K. , YAMANE T. , YOSHIKAWA H. , KAWAMURA S. , KANG J. , KAJIYAMA Y. , MORIWAKI K. , TARUI S. 
Published: March 2008

SUMMARYWe report a case of subacute thyroiditis complicated by thyrotoxic myopathy. Previously thyrotoxic myopathy has been described as being associated with GRAVES' disease. The patient in this study was a 35‐year‐old man who developed proximal dominant muscular weakness and atrophy during the course of subacute thyroiditis. His myopathic symptoms regressed as his serum thyroxine and triiodothyronine levels returned to normal, however it took a relatively long period of time for them to do so. This suggests that marked myopathy may develop even in cases of subacute thyroiditis if the thyrotoxic state persists for a long period of time.