bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG THYROTROPHIN RECEPTOR ANTIBODY ACTIVITY IN GRAVES' DISEASE; A STUDY OF TSH AGONIST AND ANTAGONIST ACTIVITIES BY ISOELECTRIC FOCUSING
Authors: CREAGH FIONUALA M. , HOWELLS R. D. , WILLIAMS SUSAN , DIDCOTE SUZANNE , HASHIM F. A. , PETERSEN V. B. , SMITH B. REES 
Published: March 2008

SUMMARYThe distribution of TSH receptor antibody activity in the 7S and 19S fractions of Graves' sera has been re‐evaluated. Serum fractions were obtained by gel filtration from 12 Graves' sera and assayed for TSH receptor binding activity in a radioreceptor assay. Thyroid stimulating activity was determined in a cultured porcine thyroid cell bioassay. In apparent contrast to the findings of Baker et al. (1983) TSH receptor binding activity was confined to the 7S gel filtration fraction, containing IgG, and was not detected in the 19S fraction, containing IgM. Similarly thyroid stimulating activity was detected only in the 7S fraction. 7S fractions from seven Graves' sera were fractionated by isoelectric focusing and the fractions analysed for TSH receptor binding activity and TSH agonist and antagonist activities. Five of the IgGs showed TSH agonist activity and in all five, the peak thyroid stimulating activity (measured by stimulation of cyclic AMP release from isolated porcine thyroid cells) was in fractions with a pI of between 8.0 and 9.5. In four of these five IgGs, TSH receptor binding activity showed similar isoelectric distribution to the thyroid stimulating activities. High levels of TSH receptor binding activity without associated TSH agonist or antagonist activity were however observed in some isoelectric fractions of the fifth stimulating Graves’IgG studied. All the isoelectric fractions from the fifth IgG with thyroid stimulating activities contained TSH receptor binding activity. Two of the Graves' IgGs showed TSH antagonist activity and both the TSH receptor binding and TSH antagonist activities of these IgGs showed similar isoelectric distribution with the peak activities at a pI of around 9.0. Consequently, it was not possible to separate TSH agonist or TSH antagonist activities from TSH receptor binding activity in seven Graves' sera by isoelectric focusing although in one IgG several isoelectric fractions contained isolated receptor binding activity. These findings are in keeping with the hypothesis that the biological activities of Graves' IgGs are intimately related to their ability to bind to the TSH receptor.
GENETIC FACTORS IN GRAVES' OPHTHALMOPATHY
Authors: FRECKER MAXINE , STENSZKY VALERIA , BALAZS C. , KOZMA L. , KRASZITS E. , FARID N. R. 
Published: March 2008

SUMMARYWe investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA‐DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P < 00005). HLA‐DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8‐ DR7‐ as reference, the odds ratios were 16.7 for B8+ DR7 +, 8.7 for B8 + DR7‐ and 0.26 for B8‐ DR7 +. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA‐B8; the odds ratios were 20.9 for B8+ Gmfb homozygo‐zity (fb +), 15.3 for B8+ fb‐ and 1.7 for B8‐ fb+ (B8‐ fb‐ =1.00). We conclude that the genetic factors contributing to Graves ‘ophthalmopathy are different from those related to liability for Graves’ hyperthyroidism.
POSTURAL SUPPRESSION OF PLASMA ATRIAL NATRIURETIC POLYPEPTIDE CONCENTRATIONS IN MAN
Authors: SAKURAI H. , NARUSE M. , NARUSE K. , OBANA K. , HIGASHIDA T. , KURIMOTO F. , DEMURA H. , INAGAMI T. , SHIZUME K. 
Published: March 2008

SUMMARYThe effects of sequential changes in posture, from recumbency, to sitting and then to the upright position, each for 60 min, respectively, on the levels of plasma immunoreactive atrial natriuretic polypeptide (ANP) in healthy human subjects were studied using a radioimmunoassay (RIA) method. At the end of each change in posture, plasma ANP levels were respectively 150±16‐4 pg/ml (recumbent), 103±11‐2 pg/ml (sitting), and 78‐1±7–90 pg/ml (upright). In contrast, plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) determined concomitantly with ANP showed a significant increase in response to the sitting and upright postures. Plasma ANP levels determined in normal subjects who remained in the recumbent posture for the same period did not show any significant change. This suggests that ANP is involved in the maintenance of haemodynamic homeostasis under physiological conditions and emphasizes that postural factors must be taken into account and controlled in order to evaluate plasma ANP levels properly, as well as those of PRC and PAC.
GONADOTROPHIN RESPONSES TO GnRH PULSES IN HYPOGONADOTROPHIC HYPOGONADISM: LH RESPONSIVENESS IS MAINTAINED IN THE PRESENCE OF LUTEAL PHASE CONCENTRATIONS OF OESTROGEN AND PROGESTERONE
Authors: NIPPOLDT T. B. , KHOURY S. , BARKAN A. , KELCH R. P. , MARSHALL J. C. 
Published: March 2008

SUMMARYLH pulse secretion changes during the menstrual cycle from a rapid regular pattern in the follicular phase to a slower and irregular pattern in the luteal phase. To determine whether the irregular LH pulse pattern in the luteal phase reflects altered GnRH secretion or altered pituitary responsiveness to GnRH, we gave low dose GnRH pulses (25 ng/kg i.v.) every 2 h or every hour for 10 or 12 d to three women with isolated GnRH deficiency. After 4 d of GnRH alone, oestradiol (E2) was given and after 6 d progesterone (P) was added to mimic the hormonal milieu of the luteal phase. LH and FSH were measured every 4 h throughout and also every 20 min for 6 or 12 h, before and after GnRH alone (day 0 and day 4), after E2 (day 6), and after E2+ P (day 10 and day 12). Both GnRH pulse frequencies resulted in a rapid increase in plasma FSH to peaks on day 4 (every 2 h) and day 2 and 3 (every hour). FSH concentrations then declined as plasma E2 rose to 50–80 pg/ml reflecting the selective inhibitory effect of E2 on FSH release. Plasma LH was also increased after the hourly GnRH injections and this regimen was associated with a more rapid rise in E2 reflecting follicular maturation. In contrast to the differences in mean hormone concentrations, administration of GnRH at both frequencies resulted in sustained one‐on‐one responsiveness of LH that was maintained in the presence of both oestrogen and progesterone at mid‐luteal phase concentrations. We conclude that the slow frequency of LH pulses observed during the luteal phase reflects decreased GnRH pulse frequency rather than impaired pituitary responsiveness to GnRH.
ADDITIVE EFFECTS OF GROWTH HORMONE RELEASING FACTOR AND INSULIN HYPOGLYCAEMIA ON GROWTH HORMONE RELEASE IN MAN
Authors: PAGE M. D. , KOPPESCHAAR H. P. F. , EDWARDS C. A. , DIEGUEZ C. , SCANLON M. F. 
Published: March 2008

SUMMARYWe have measured GH and PRL changes following separate and combined administration of insulin and GH releasing factor (GRF) in six normal males. Peak GH responses to separate administration of insulin and GRF were comparable (71 4 ± 10.2 vs 70.1 ± 27.7 mU/1; mean ± SEM). However, the peak GH response following combined administration was significantly higher (120.8 ± 29.7, P < 0.05) as was the total GH released as calculated by measuring the area under the curve (P <005). In contrast the PRL response to hypoglycaemia was not altered by the combined administration of insulin and GRF. This effect was not due to any direct action of hypoglycaemia or insulin at pituitary level since basal and 10−8 M GRF stimulated GH release from rat anterior pituitary cells in vitro was not influenced by varying glucose and insulin levels. Our findings support the hypothesis that GRF and insulin‐induced hypoglycaemia release GH via different pathways which are, at least in part, additive.
CUSHING'S SYNDROME IN PREGNANCY: THE TIMING OF DEFINITIVE TREATMENT
Authors: BEVAN J. S. , GOUGH M. H. , GILLMER M. D. G. , BURKE C. W. 
Published: March 2008

SUMMARYCushing's syndrome in pregnancy is rare but associated with a high fetal loss rate, premature labour and excessive maternal morbidity. There has been controversy regarding the safety and efficacy of surgical treatment during pregnancy. We describe two further cases, both due to adrenal adenomas, in whom the diagnosis was made at 28 and 31 weeks gestation. Both cases suffered from severe myopathy. The first case was not treated during pregnancy and developed wound and urinary infections after caesarean section and subsequent adrenalectomy. An incisional hernia in the caesarean section scar has been repaired twice. The second had an adrenalectomy when 29 weeks pregnant with rapid resolution of the features of Cushing's syndrome, particularly the myopathy, and had an uneventful vaginal delivery. The second case, and a review of those previously described, indicates that surgical treatment during pregnancy is safe and significantly reduces fetal losses, premature labour and maternal morbidity.
AMIODARONE AND THYROID HORMONE EFFECTS ON ANTERIOR PITUITARY HORMONE GENE EXPRESSION
Authors: FRANKLYN J A. , GAMMAGE M. D. , SHEPPARD M. C. 
Published: March 2008

SUMMARYAmiodarone therapy results in marked changes in circulating thyroid hormone and TSH concentrations in man. In the present study we have demonstrated that amiodarone treatment of the rat increases serum TSH and pituitary cytoplasmic concentrations of TSH β and a subunit messenger RNAs (mRNAs) and reduces PRL mRNA as measured by cytoplasmic dot hybridization with specific complementary (c) DNA probes. The fall in circulating TSH and TSH mRNA resulting from thyroid hormone treatment was less marked in animals receiving amiodarone in addition to T3 and T4. In contrast, in the hypothyroid state, increases in serum TSH, TSH β and α mRNA, and reductions in PRL and GH mRNA were less marked in rats treated with amiodarone. In studies of rat anterior pituitary cells in primary monolayer culture we demonstrated a direct effect of amiodarone on PRL gene expression which was antagonized by T3. Changes in circulating thyroid hormone concentrations and deiodination of T4 and T3 induced by amiodarone in vivo may be important in the regulation of pituitary hormone gene expression but we have, in addition, shown a direct interaction between amiodarone and T3 effects on the anterior pituitary cell.
ULTRASENSITIVE ASSAY OF THYROID STIMULATING HORMONE IN PATIENTS WITH ACUTE NON‐THYROIDAL ILLNESS
Authors: BOLES J.‐M. , MORIN J.‐F. , GARRE M. A. 
Published: March 2008

SUMMARYSerum TSH in critically ill euthyroid patients is generally within the normal range when measured with conventional radioimmunoassays. Sensitive immunoradiometric assays allow detection of low levels of serum TSH. We assessed this method in a prospective study of 34 euthyroid patients admitted to our critical care unit. Serum TSH ranged from 0.12 to 3.60 mU/1 and was significantly lower for the whole group than in the controls (P< 0‐001), as also were serum total T4 and T3 values (P<0.001). However, 21 patients had a serum TSH within the normal range (group 1) and 13 patients (33%) had a serum TSH < 0.40 mU/1 (group 2). The two groups did not differ in age, sex, type and severity of illness, outcome, and serum T4 and T3 levels. However, the magnitude of TSH increase from the baseline value after the i.v. injection of 200 μg of TRH, assessed by the 30 min TSH/basal TSH ratio was significantly higher in group 2 (P< 005). These results suggest that a substantial proportion of patients with acute illness have a clearly low serum TSH, unaccounted for by age, sex, type or quantified severity of illness, serum T4 and T3 levels. In addition, the secretory capacity of the pituitary to exogeneous TRH is significantly enhanced in those patients with low basal TSH.
GROWTH HORMONE SECRETION IN CHILDREN DETERMINED BY TIME SERIES ANALYSIS
Authors: HINDMARSH P. C. , MATTHEWS D. R. , BROOK C. G. D. 
Published: March 2008

SUMMARYMid childhood growth has been studied in 26 short children (18M;8F) aged between 5·2 and 11·9 years growing with height velocity standard deviation score (SDS) between 0 and — 0·8 and 24 short children (17M;7F) growing with height velocity SDS >0·8. Twenty‐four hour GH profiles were analysed by an iterative method of pulse detection and subjected to time series analysis to determine dominant periodicity within the data arrays. Children aged >7 years displayed no dominant periodicity but after this age a periodicity of 200 min emerged. In the whole sample, differences between growth rate could be explained entirely by pulse amplitude. Nevertheless, the normal decline in height velocity over this age period occurred despite a significant shift in periodicity and an increase in GH pulse amplitude. This modulation of childhood growth by GH pulse amplitude perisisted into puberty and the pubertal growth spurt of 14 tall girls was shown to be amplitude modulated with the periodicity unchanged. We conclude that mid childhood and pubertal growth is GH pulse amplitude modulated with a periodicity of approximately 200 min.
GROWTH HORMONE FACILITATES OVULATION INDUCTION BY GONADOTROPHINS
Authors: HOMBURG R. , ESHEL A. , ABDALLA H. I. , JACOBS H. S. 
Published: March 2008

SUMMARYThe addition of biosynthetic human growth hormone (GH) to treatment with human menopausal gonadotrophin (hMG) significantly augmented the ovarian response in four patients treated for in‐vivo and three patients treated for in‐vitro fertilization who had previously been resistant to hMG. The amount, duration of treatment and daily effective dose of hMG were all reduced by growth hormone. This action of growth hormone offers a new approach to ovulation induction.
VERTEBRAL BONE DENSITY IN NON‐AMENORRHOEIC HYPERPROLACTINAEMIC WOMEN
Authors: CICCARELLI E. , SAVINO L. , CARLEVATTO V. , BERTAGNA A. , ISAIA G.C. , CAMANNI F. 
Published: March 2008

SUMMARYRecently, a decrease in bone mineral content (BMC) in hyperprolactinaemic women with long‐lasting amenorrhoea has been reported, and attributed either to a direct effect of PRL on bone or secondary to the oestrogen deficiency. To verify if PRL by itself has a direct effect on bone, we have studied BMC at the lumbar level by double‐photon absorptiometry in 22 patients with hyperprolac‐tinaemia, selected on the basis of normal or near‐normal oestradiol levels. The results were compared with those obtained in 28 healthy closely‐matched women, and seven hyperprolactinaemic patients with long‐lasting amenorrhoea and oestrogen deficiency. No significant difference in BMC was observed between hyperprolactinaemic patients with normal oestrogen levels (mean ± SEM = 3.87 ± 0.10 gHA/cm) and normal subjects (mean ± SEM = 3.76±0.10 gHA/cm). Moreover, no significant change was observed during a 6 month follow‐up in 13 patients. On the other hand, a significant difference (P < 0.05) was detected in BMC between the hyperprolactinaemic patients with normal oestradiol levels and those with long‐lasting amenorrhoea and oestrogen deficiency (mean ± SEM = 3.39 ± 0.18). These results suggest that hyperprolac‐tinaemia by itself is not a risk factor for the development of osteoporosis.
EFFECT OF A NEW SOMATOSTATIN ANALOGUE SMS 201‐995 (SANDOSTATIN) ON THE RENIN‐ALDOSTERONE AXIS
Authors: SIEBER C. , GNÄDINGER M. , DEL POZO E. , SHAW S. , WEIDMANN P. 
Published: March 2008

SUMMARYThe effects of a new somatostatin analogue SMS 201‐995 (H‐D‐Phe‐Cys‐Phe‐D‐Trp‐Lys‐Thr‐Cys‐Thr(ol), Sandostatin) on the orthostatic stimulation of plasma renin activity (PRA) following head‐up tilting and on angiotensin II (Ang‐II) induced aldosterone (PA) release were studied under placebo controlled conditions in separate groups of healthy volunteers consisting of six and 10 subjects, respectively. Head‐up tilting (by 60°) produced the characteristic increases in PRA and PA. Administration of SMS 201‐995 significantly (P < 0.05) inhibited this PRA elevation from 30 min on. Throughout the study period, PA levels were not consistently altered by this analogue. Furthermore, SMS 201‐995 failed to inhibit the stimulation of PA secretion induced by exogenous angiotension‐II (2‐10 ng/kg/min). Results presented here are at variance with data collected with natural somatostatin showing an inhibitory effect on stimulated PA. This discrepancy can be explained by the recently described absence of SMS 201‐995 binding sites in primate adrenal cortex and in human aldosteronomas.
PLASMA GROWTH HORMONE HALF‐LIFE AFTER SELECTIVE REMOVAL OF ADENOMA IN ACROMEGALICS DETERMINES THE OUTCOME OF SURGERY
Authors: ROELFSEMA F. , VAN DER HEIDE D. , LOWRY P. J. , VAN DULKEN H. , SCHRÖDER‐VAN DER ELST J. 
Published: March 2008

SUMMARYWe measured plasma GH levels during transsphenoidal surgery in eight patients with acromegaly. After removal of the adenoma GH levels fell monoexponen‐tially in six subjects while they were still under general anaesthesia, but no decrease was noted for two other subjects. Normal postoperative GH and Somatomedin‐C levels were found for those patients who exhibited a reduction in GH during surgery. During follow‐up studies one patient with a normal GH level exhibited a paradoxical reaction to TRH, attributed to tumour remnants. The plasma half‐life found for five patients was 18‐33 min; for another cured subject it was longer, i.e. 58 min. The major fraction of the circulating GH, as determined by gel‐chromatography, was mol. wt 22000; this applied for six subjects, while the patient with the long plasma half‐life appeared to have a mol. wt 33 000 variant. From this study we conclude that a clear drop in the plasma GH level after removal of the adenoma predicts a favourable outcome of surgery; however, if some tumour remnants are left behind, paradoxical reactions may occur despite normal basal GH levels.
CELL KINETICS, DNA CONTENT AND TSH RECEPTOR‐ADENYLATE CYCLASE SYSTEM IN DIFFERENTIATED THYROID CANCER
Authors: CHANG T. C. , KUO S. H. , LIAW K. Y. , CHANG C. C. , CHEN F. W. 
Published: March 2008

SUMMARYThe purpose of this study was to elucidate the changes of the TSH receptor‐adenylate cyclase system in differentiated thyroid carcinomas, and their relationships with nuclear DNA content, cell kinetics and clinical stage. The results showed that the papillary carcinomas had an impaired TSH receptor‐adenylate cyclase system. The production of cAMP stimulated by TSH was decreased when compared with non‐cancerous tissue and high‐affinity TSH receptors were reduced in number or even completely lost (nine in 24 cases). Follicular carcinomas also showed a reduction in, or even complete loss, of high‐affinity TSH receptor (one in five cases). However, the responses to the stimulation of TSH, Gpp (NH)p and forskoiin were not different from those in non‐cancerous tissue. Papillary and follicular cancer cells showed more proliferative activity than those in non‐cancerous tissue. Follicular carcinomas contained more hyperploid cells (DNA content >2.5 C) than papillary carcinomas. There were no differences in cell kinetics, DNA content or the effects of Gpp (NH)p or forskoiin on adenylate cyclase activity between those papillary carcinomas with high‐affinity TSH receptor and those without. However, the presence of high‐affinity TSH receptors had higher cAMP generation stimulated by TSH. The patients having papillary carcinomas in the absence of high‐affinity TSH receptors were all in clinical stage'III. These studies suggest that TSH receptors are the major sites influenced in the TSH receptor‐adenylate cyclase system in papillary carcinomas. The TSH receptor‐adenylate cyclase system of papillary carcinomas differs more from normal than does that of follicular carcinomas. That follicular carcinomas are usually more aggressive than papillary carcinomas may be partly explained by more hyperploid cells in follicular carcinomas. The absence of high‐affinity TSH receptor in papillary carcinomas may mean a more advanced clinical stage and poorer prognosis.
CHARACTERIZATION OF HUMAN CORTICOTROPHIN‐RELEASING HORMONE AND PRO‐OPIOMELANOCORTIN‐RELATED PEPTIDES IN A THYMIC CARCINOID TUMOUR RESPONSIBLE FOR CUSHING'S SYNDROME
Authors: DEMAY M. C. RAUX , PROESCHEL M. F. , DE KEYZER Y. , BERTAGNA X. , LUTON J. P. , GIRARD F. 
Published: March 2008

SUMMARYSevere Cushing's syndrome developed in a man of 35 years. Plasma ACTH and lipotrophin hormone levels were supranormal, and dexamethasone failed to stop their production. An ACTH‐producing thymic carcinoid tumour was found to be responsible for the Cushing's syndrome. The tumour tissue contained pro‐opiomelanocortin (POMC)‐mRNA and POMC‐related peptides. In addition, human corticotrophin‐releasing hormone (h‐CRH) (0.25 ng/ mg wet tissue) was identified in the tumour extract. Among a series of extracts from two normal and three tumoral (Nelson's syndrome) pituitary glands, six non‐pituitary POMC‐producing tumours and five normal thymuses examined, only the extract from the thymic tumour of our patient contained h‐CRH. The molecule isolated had the same properties as synthetic h‐CRH (dilution, Sephadex G 50 chromatography). Circulating h‐CRH levels, however, were normal. The possible involvement of such ectopic CRH production in the aetiology of Cushing's syndrome remains uncertain.
LOW SERUM TSH WITH NORMAL TOTAL THYROID HORMONE LEVELS: AN INDICATOR OF FREE T4 EXCESS
Authors: O'MALLEY B. P. , ROSENTHAL F. D. , EXLEY A. , FALCONER‐SMITH J. F. , MAHABIR J. , WOODS K. L. 
Published: March 2008

SUMMARYWe have studied 18 patients with low serum thyrotrophin (TSH) levels accompanied by normal thyroxine (T4) and triiodothyronine (T3) levels in order to clarify whether or not they are thyrotoxic. Serum T4, T3, free T3, free T4 and TSH were estimated three times weekly for 3–4 weeks. Thyroxine binding globulin (TBG) levels were estimated on one occasion only. Thyroid hormone data were expressed as the cumulative probability of having at least one result above the relevant normal range by the nth sample (Pn). For free T4 this probability was 61% by the 10th sample. Free T4 values were confined to the upper half of the normal range or above throughout the study. In contrast, free T3 values were distributed evenly within the normal range (P10= 12%). For total T4 and total T3, P10 was 34 and 11% respectively. Thus, subjects with subnormal TSH levels but normal T4 and T3 levels have been shown to have elevated serum free T4 levels, an indicator of biochemical hyperthyroidism.