bluuebunny/crossref_metadata_2025_split huggingface dataset:
CORTICOTROPHIN‐LIKE INTERMEDIARY LOBE PEPTIDE AS A MARKER OF ALTERNATE PRO‐OPIOMELANOCORTIN PROCESSING IN ACTH‐PRODUCING NON‐PITUITARY TUMOURS
Authors: VIEAU DIDIER , MASSIAS JEAN‐FRANCIS , GIRARD FRANÇOIS , LUTON JEAN‐PIERRE , BERTAGNA XAVIER 
Published: March 2008

SUMMARYIn order to evaluate which of human (h) corticotrophin‐like intermediary lobe peptide (CLIP) or hβ‐melanocyte stimulating hormone5–22 (hβMSH5–22) was the better marker of alternate pro‐opiomelanocortin (POMC) processing, both peptides were simultaneously sought in the same tissue extracts from a normal human pituitary, six corticotrophic adenomas, and four non‐pituitary tumours responsible for an ectopic ACTH syndrome. Human CLIP was detected using a combination of gel exclusion chromatography and two different radioimmunoassays (RIAs): a mid‐ACTH RIA which recognized ACTH but not CLIP, and a COOH‐ACTH RIA which recognized both molecules. Human βMSH5–22 had been measured previously. Neither hCLIP nor hβMSH5–22 were detected in the normal or tumoural pituitaries. The four non‐pituitary tumours, in contrast, contained both peptides; the hCLIP and hβMSH5–22 ratios (CLIP/ CLIP + ACTH and hβMSH5–22/ hβMSH5–22+ hγLPH) ranged from 40 to 94% and from 24 to 46%, respectively. In a given tissue the hCLIP ratio was always higher than the hβMSH5–22 ratio. hCLIP is therefore the better marker of alternate POMC processing.
DIET‐INDUCED CHANGES IN SEX HORMONE BINDING GLOBULIN AND FREE TESTOSTERONE IN WOMEN WITH NORMAL OR POLYCYSTIC OVARIES: CORRELATION WITH SERUM INSULIN AND INSULIN‐LIKE GROWTH FACTOR‐I
Authors: KIDDY D. S. , HAMILTON‐FAIRLEY D. , SEPPÄLÄ M. , KOISTINEN R. , JAMES V. H. T. , REED M. J. , FRANKS S. 
Published: March 2008

SUMMARYThe purpose of this study was to investigate the effect of calorie restriction on serum concentrations of sex hormone binding globulin (SHBG) in women with normal or polycystic ovaries (PCO) and to examine the possible role of insulin and insulin‐like growth factor‐I (IGF‐I) in mediating changes in SHBG levels. Six normal subjects with mean (SD) body mass index (BMI) 25.5 (2.2) and five subjects with PCO (BMI 36.1 (3.7)) were studied before and after 2 or (PCO only) 4 weeks of a very low calorie diet (330 kcal/day; Cambridge Diet). In both normal women and patients with PCO there was a twofold increase in SHBG concentrations after 2 weeks and this was sustained in the PCO subjects for a further 2 weeks. The rise in SHBG was accompanied by a fall in free testosterone concentrations. There were parallel changes in serum insulin and IGF‐I concentrations which decreased during the diet and there were significant negative correlations of SHBG with insulin in both normal subjects (r =−0.62) and women with PCO (r =−0.60). In addition, serum concentrations of an insulin‐dependent small molecular weight (34 kDa) binding protein for IGF‐I (IGF‐BPI) increased significantly during dieting in both groups and were negatively correlated with serum insulin (controls, r =−0.56; PCO, r =−0.68) and positively correlated with serum SHBG levels (controls, r = 0.69; PCO, r = 0.63).In summary, these data indicate that in both normal subjects and those subjects with PCO, calorie restriction results in a highly significant increase in SHBG concentrations. Data from this study and related experiments in vitro suggest that the changes in SHBG may be mediated by a fall in insulin and/or IGF‐I.
DIFFERENT HEPATIC RESPONSES TO THYROXINE REPLACEMENT IN SPONTANEOUS AND 131I‐INDUCED PRIMARY HYPOTHYROIDISM
Authors: GOW S. M. , CALDWELL G. , TOFT A. D. , BECKETT G. J. 
Published: March 2008

SUMMARYThe serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n= 9) had spontaneous hypothyroidism whilst in the second (group 2; n= 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 μg increments each month to 200 μg/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose‐dependent increases in glutathione S‐transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 μg (P > 0.01) and the 200 μg (P > 0.005) doses of T4, and they had higher activities of ALT (P > 0.01) and GGT (P > 0.02) at the 200 μg dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine‐induced primary hypothyroidism when given oral doses of thyroxine < 150 μg/day.
VASOPRESSIN AND OXYTOCIN RESPONSES TO HYPERTONIC SALINE INFUSION: EFFECT OF THE OPIOID ANTAGONIST NALOXONE
Authors: SECKL J. R. , JOHNSON M. R. , LIGHTMAN S. L. 
Published: March 2008

SUMMARYEndogenous opioids inhibit the release of oxytocin (OT) when vasopressin (AVP) is secreted in response to acute pharmacological stimuli in man and to a variety of physiological and pharmacological stimuli to animals. We have investigated the effect of naloxone on the AVP and OT responses to hypertonic saline in man. In two separate studies, six male subjects were infused with hypertonic saline (675 mmol/l, 0.05 ml/kg/min for 2 h) and either naloxone (4 mg bolus and 6 mg/h) or normal saline in random order. Hypertonic saline resulted in similar significant rises of plasma osmolality and AVP in both groups and a small but significant decrease in OT. Thirst sensation was not altered by naloxone. Endogenous opioids do not play an important role in the suppression of OT release when AVP is secreted in response to an osmotic stimulus in man.
CHOLINERGIC BLOCKADE WITH PIRENZEPINE IMPROVES CARBOHYDRATE TOLERANCE AND ABOLISHES THE GH RESPONSE TO MEALS IN NORMAL SUBJECTS
Authors: PAGE M. D. , BEVAN J. S. , DIEGUEZ C. , PETERS J. R. , SCANLON M. F 
Published: March 2008

SUMMARYPretreatment of normal male volunteers with the cholinergic muscarinic receptor‐blocking drug pirenzepine (200 mg p.o.) abolishes the delayed GH response to a meal stimulus. In addition, the glycaemic and insulin responses to meals are significantly reduced following this dose of pirenzepine. The data suggest that the effect of pirenzepine on the glucose response to meals is at least partly independent of the inhibition of GH release. Our findings are of relevance to the further investigation of cholinergic muscarinic antagonist in diabetes mellitus.
PULSATILE GnRH‐THERAPY IN OLIGOZOOSPERMIC MEN DOES NOT IMPROVE SEMINAL PARAMETERS DESPITE DECREASED FSH LEVELS
Authors: BALS‐PRATSCH M. , KNUTH U. A. , HÖNIGL W. , KLEIN H. M. , BERGMANN M. , NIESCHLAG E. 
Published: March 2008

SUMMARYIn order to evaluate GnRH administration for the treatment of infertile men with elevated serum FSH levels we administered GnRH in pulses via portable electronic infusion pumps initially to seven patients with low sperm counts and high FSH values over 12 weeks and later to nine further patients over 24 weeks who also underwent testicular biopsies. Fifty microlitres containing 5 pg GnRH were infused subcutaneously for 1 min every 120 min in the short‐term study and every 90 min in the long‐term study. Although FSH levels could be lowered in both groups of patients, none showed any improvement in sperm count or other seminal parameters. Therefore, pulsatile GnRH treatment cannot be recommended for therapy of severe oligozoospermia with elevated FSH levels.
PLASMA ACTH RESPONSES TO CORTISOL INFUSION ARE SIMILAR IN PATIENTS WITH PRIMARY HYPOADRENALISM AND PATIENTS STUDIED SOME YEARS AFTER BILATERAL ADRENALECTOMY FOR CUSHING'S SYNDROME
Authors: ATKINSON A. B. , BEACOM R. , KENNEDY A. L. , HADDEN D. R. , SHERIDAN B. 
Published: March 2008

SUMMARYIt has been suggested that the first‐phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary‐directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first‐phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.
SALIVARY TESTOSTERONE LEVELS AND THE PROGRESS OF PUBERTY IN THE NORMAL BOY
Authors: BUTLER G. E. , WALKER R. F. , WALKER R. V. , TEAGUE P. , RIAD‐FAHMY D. , RATCLIFFE S. G. 
Published: March 2008

SUMMARYSalivary testosterone (ST) levels were measured in 84 boys aged 7.3–16.2 from the Edinburgh Growth Study. The correlation coefficient between matched plasma/saliva samples was 0.88. Six samples were collected over the course of one day from 0900 to 2100 h each month in the majority of the children for 4 consecutive months. Mean daily ST levels showed a significant rise between each pubertal stage (genital (G) and pubic hair (PH)). The rise in ST became more rapid once a mean testicular volume (MTV) of 10 ml had been reached. The diurnal rhythm was assessed by individual curve fitting on the log scale and by cosinor analysis. A rhythm was present prepubertally and developed into a pattern similar to that of the adult rhythm by stage G3. The monthly rate of rise of ST was greatest at stage G4. A significant rise in ST levels was detectable immediately prior to an increase in MTV to 3 ml. This allowed earlier recognition of the clinical onset of puberty at testicular volume of 3 ml, which in this group occurred at 10.9 (SD 0.9) years. ST is a non‐invasive and sensitive method for the serial monitoring of gonadal function in the prepubertal and adolescent boy.
EFFECTS OF PROTRACTED HYPOTHYROIDISM ON PITUITARY FUNCTION AND STRUCTURE IN ENDEMIC CRETINISM
Authors: BOYAGES STEVEN , HALPERN JEAN‐PIERRE , MABERLY GLEN F. , EASTMAN CRESWELL J. , CARR PETER , DEZHONG YU , CHUAN‐YI YOU , CHENEN JIN 
Published: March 2008

SUMMARYPituitary function and structure were assessed in 69 endemic cretins from western China. In hypothyroid cretins (TSH > 10 mIU/1), CT imaging of the pituitary revealed adenoma in five of 20 (25%) and partially empty sella (PES) in a further eight of 20 (40%). The majority of tumours were microadenomas and showed a relation with higher levels of serum TSH but not with duration of hypothyroidism. Dynamic pituitary testing with TRH and GnRH in four patients with adenoma on CT gave a flat TSH response but significant rises in serum PRL, GH, LH and FSH concentrations. Hyperprolactinaemia (> 350 mIU/1) was present in hypothyroid cretins only (13 of 26; 50%) and serum PRL showed a curvilinear relation with serum TSH levels (r = 0.7, P< 0.0001). Hypogonadism was seen in approximately half the cretins with high PRL levels. Our data suggest that severe protracted thyroid hormone deficiency may result in thyrotrophin adenomas of the pituitary gland. Disturbances of growth, puberty, and sexual function in endemic cretins are explained by the secondary effects of thyroid hormone deficiency on pituitary function.
HEREDITARY LOCALIZED PRURITUS IN AFFECTED MEMBERS OF A KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A (SIPPLE'S SYNDROME)
Authors: NUNZIATA V. , GIANNATTASIO R. , DI GIOVANNI G. , D'ARMIENTO M. R. , MANCINI M. 
Published: March 2008

SUMMARYWe describe a kindred with medullary thyroid carcinoma and phaeochromocy‐toma (MEN 2A or Sipple's syndrome) in which a cutaneous manifestation is only present in affected members. These members felt an intense itching in an area 5–10 cm in length and passing through the scapular region where, after long‐term scratching, the skin appears hyperkeratotic and pigmented. Cutaneous biopsies proved negative for dermis nerve abnormality. This restricted itching strongly suggests dominant transmitted hereditary localized pruritus which was described many years ago in a family which was apparently free from inherited diseases. In the examined kindred this skin peculiarity was said to have appeared before the patients reached 10 years of age and, therefore, prior to the biochemical manifestation of the thyroid tumour. Three children of the last generation, aged 4 to 11 years, all of whom presented this cutaneous manifestation, were considered unaffected because of normal basal and stimulated calcitonin, but thyroid C‐cell hyperplasia was recently proved in the eldest. In this MEN 2A kindred the presence of such a characteristic hereditary itch in affected members may be considered as a phenotypic marker giving advance warning of medullary thyroid carcinoma.
GROWTH HORMONE‐RELEASING FACTOR INCREASES SERUM PROLACTIN CONCENTRATIONS IN NORMAL SUBJECTS AND IN PATIENTS WITH PITUITARY ADENOMAS
Authors: SERRI O. , SOMMA M. , RASIO E. , BRAZEAU P. 
Published: March 2008

SUMMARYWe have examined the serum growth hormone (GH) and prolactin (PRL) response to growth hormone releasing factor (hGRF‐(l‐44)NH2: (GRF) I μg/ kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinae‐mic), 13 patients with microprolactinoma, and 14 healthy subjects. The GH responses to‐TRH and to the somatostatin analogue SMS 201–995 were also studied in acromegalic patients. In these, and in patients with microprolactinoma, GH responses after GRF (P<0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 ± 920 μg/l min), or in patients with microprolactinoma (1322 ± 279 μg/l min) was not different from that in controls (2238 ± 633 μg/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P<0.01), in patients with microprolactinoma and in normal subjects (P<0001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r= 0.99, P <0.001) and in patients with microprolactinomas (r = 0.61, P<0.05). Furthermore, a significant correlation was found between GH rise after GRF and basal GH, and between GH rise after GRF and GH decrement after SMS in patients with acromegaly. These results suggest that GRF can stimulate PRL release by actions on the normal pituitary and on pituitary adenomas, including microprolactinomas. Moreover, the data suggest that in acromegaly there is a relative functional deficiency of hypothalamic somatostatin.
IS THE POLYCYSTIC OVARY A CAUSE OF INFERTILITY IN THE OVULATORY WOMAN?
Authors: EDEN J. A. , PLACE J. , CARTER G. D. , ALAGHBAND‐ZADEH J. , PAWSON M. 
Published: March 2008

SUMMARYOvulatory women with polycystic ovaries (PCO) were compared with ovulatory women with normal ovaries, using high‐resolution ultrasound and biochemical parameters to compare precise points in the menstrual cycle taking the day of ovulation as day 0. The PCO group had higher median follicular phase LH (days ‘menses’, −5, −3), FSH (days −5, −3) testosterone (days −3, −2) and free androgen index (days −5, −3, −1) than the controls. Women with PCO had a longer follicular phase and larger follicles. These results suggest that abnormal secretion of LH and free testosterone may contribute to the subfertility of women with PCO, possibly by premature activation of the oocyte or by interfering with folliculogenesis.
BODY COMPOSITION IN ACROMEGALY
Authors: BENGTSSON BENGT‐ÅKE , BRUMMER ROBERT‐JAN M. , EDEN STAFFAN , BOSAEUS INGVAR 
Published: March 2008

SUMMARYTotal body water (TBW) and potassium (TBK) were measured in untreated acromegalic patients seen between 1956 and 1984 and the results were compared to values predicted from height (BH), weight (BW), age and sex, using data from a large number of healthy subjects (n= 476). Normal body weight for each patient (BWnorm) was predicted from BH and sex, the regression equations being derived from a representative population sample (n= 4017). The BH for each patient was compared with data on BH in 15 000 Swedes. The patients were significantly taller than the control population (P<0.001). In 107 (70%) of the 156 patients BH was above the median. Patients with an early onset of the disease were taller than those with a later onset. TBK and TBW were significantly higher than predicted from observed BW (P< 0.001) and so was the quotient extracellular water (ECW)/intracellular water (ICW). Body fat (BF), on the other hand, was lower than predicted (P< 0.001).Observed BW in male acromegalics was 8–1 kg higher than predicted from healthy subjects of the same BH (BWnorm), a difference explained by an average increase of 4.7 kg in body cell mass (BCM) (P<0.001) and 7.1 kg in extracellular water (P<0.001) simultaneously with a mean decrease of 3.7 kg in BF (P<0.01). Female acromegalics weighed on average 6.4 kg more than healthy women, a difference explained by an increase in BCM of 3.3 kg (P<0.001) and in ECW of 4.6 kg (P<0.001) concomitantly with a decrease in BF of 1.5 kg.Mean hGH concentration at diagnosis correlated inversely with the quotients observed/predicted BF (P< 0.01) and B W/BWnorm (P<0.05) but not with the quotients observed/predicted TBK, TBW or ECW/ICW.
PROLACTIN‐INHIBITING ACTIVITY OF GnRH ASSOCIATED PEPTIDE IN CULTURED HUMAN PITUITARY CELLS
Authors: WORMALD PATRICIA J. , ABRAHAMSON MARTIN J. , SEEBURG PETER H. , NIKOLICS KAROLY , MILLAR ROBERT P. 
Published: March 2008

SUMMARYThe 56‐amino‐acid extension of GnRH in the human GnRH precursor (pHGnRH 14–69 or GAP) has previously been shown to inhibit PRL secretion from cultured rat pituitary cells. We have studied the effect of GAP and shorter sequences on prolactin secretion from human and rat pituitary cells. Bacterially synthesized GAP inhibited PRL secretion from human pituitary cells. At 10−6 M GAP inhibition of prolactin release was 67.7% which was similar to that observed in rat pituitary cells (65.5%). A series of shorter peptide sequences (pHGnRH 14–26, pHGnRH 14–36, pHGnRH 14–37·NH2, pHGnRH 28–36, pHGnRH 38–49 and pHGnRH 51–66) which are potentially processed from GAP at basic amino acid residues had no effect on prolactin secretion from human or rat pituitary cells at doses up to 10−5 M.
RETURN OF OVARIAN FUNCTION FOLLOWING SPONTANEOUS ABORTION
Authors: DONNET M. L. , HOWIE P. W. , MARNIE M. , COOPER W. , LEWIS M. 
Published: March 2008

SUMMARYAssays of first morning urine samples for oestrone‐3‐glucuronide, LH and pregnanediol‐3‐glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post‐partum (range 13–103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P < 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68–8 IU/g C; P <0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P < 0.02). The mean luteal phase length of 12–9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P < 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.
HLA ANTIGENS IN ASIAN INDIAN PATIENTS WITH Graves'DISEASE
Authors: TANDON N. , MEHRA N. K. , TANEJA V. , VAIDYA M. C. , KOCHUPILLAI N. 
Published: March 2008

SUMMARYA study of 57 Asian Indian patients with Graves'disease revealed a significant increase in the frequency of HLA‐DQW2 (61.4%) as compared to the control population (22.6%) giving a relative risk of 5.4. Less prominent but statistically significant increase in the frequency of HLA‐A10 (29.8% patients as opposed to 10.5% controls) and HLA‐B8 (28.1% patients as opposed to 8.7% controls) was also observed. Further, patients carrying the phenotypes HLA‐A10 and HLA‐B8 were more prone to develop the disease at a younger age. Two HLA haplotypes, namely A10‐B8 and B8‐DR3, were found in significant linkage disequilibrium in our patients with Graves'disease. Patients carrying these haplotypes also had a tendency to develop the disease at an earlier age.
RAPID ESCAPE OF CORTISOL FROM SUPPRESSION IN RESPONSE TO I. V. DEXAMETHASONE IN ANOREXIA NERVOSA*
Authors: ESTOUR B. , PUGEAT M. , LANG F. , LEJEUNE H. , BROUTIN F. , PELLET J. , ROUSSET H. , TOURNIAIRE J. 
Published: March 2008

SUMMARYThe suppressive effect of dexamethasone (Dex) on plasma cortisol and β‐ lipotrophin (βLPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and βLPH levels during oral or i. v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P < 0.0001) during oral or i. v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i. v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (< 50 nmol/1) by 0800 h on the day following infusion. In the patients who were reinvestigated after re‐feeding and weight gain (n = 9), a normal suppression of cortisol in response to i. v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.
ANALYSIS OF HLA‐DQB AND HLA‐DPB ALLELES IN Graves'DISEASE BY OLIGONUCLEOTIDE PROBING OF ENZYMATICALLY AMPLIFIED DNA
Authors: WEETMAN A. P. , ZHANG LI , WEBB SANDRA , SHINE B. 
Published: March 2008

SUMMARYWe have tested the possible association of HLA‐DQB and HLA‐DPB alleles with Graves'thyrotoxicosis, with or without severe ophthalmopathy, by polymerase chain amplification of genomic DNA and allele‐specific oligonucleotide probing. There was no significantly abnormal distribution of DQB alleles compared to 50 control subjects except for a reduced prevalence of DQw 3.1 in the Graves'patients with severe ophthalmopathy (x2= 6.23, P < 0.02). HLA‐DPB 2.1/8 was found in only 1 of 40 of these patients compared with 15 of the controls (x2= 11.49, P <0‐001). Ten of 48 patients with Graves'disease but without clinically significant eye involvement were HLA‐DPB 2.1/8 positive, not significantly different from controls, but significantly different from the ophthalmopathy group (x2= 6.70, P < 0.01). The other DPB alleles in both groups of Graves'disease patients were the same as controls. These results suggest that HLA‐DPB 2.1/8 may confer a protective effect in Graves'disease with respect to ophthalmopathy.