bluuebunny/crossref_metadata_2025_split huggingface dataset:
VARIABILITY IN PRODUCTION and IMMUNOREACTIVITY OF IN‐VITRO SECRETED HUMAN THYROGLOBULIN
Authors: FELDMAN A. , SINGH A. , DIAMOND E. J. , SCHWARTZ A.E. , FRIEDMAN E. W. , DAVIES T. F. 
Published: March 2008

SUMMARYWe examined basal and bTSH‐stimulated human thyreoglobulin (hTg) secretion by autologous normal and abnormal (benign and malignant) human thyroid cell monolayers. Basal and bTSH‐stimulated hTg secretion was highly variable and ranged from 50‐700 ng/ml/105 cells over a 6 day period. All normal and benign ‘non‐functioning’ adenoma cells demonstrated a dose and time related stimulation of hTg secretion in response to bTSH. Comparison of hTG secretion by autologous normal and abnormal cells showed that in six of eight pairs, the normal thyroid cells had a greater output of hTg than the benign adenoma cells in contrast to our previous studies using non‐autologous cells. Malignant thyroid cell hTg production was less predictable than that obtained with normal and benign thyroid cells varying from absent to normal responses to bTSH. Characterization studies of the secreted hTg showed no difference between normal, benign and malignant thyroid cell hTg with reference to molecular weight. However, hTg secreted in vitro was non‐iodinated and had a marked reduction (up to 200‐fold) in immunoreactivity assessed by both polyclonal and monoclonal antibodies to hTg when compared to hTg standard prepared from intact thyroid tissue (which had 4.58 μg iodine/mg). This reduction in hTg immunoreactivity was greatest for hTg secreted by malignant thyroid cells. These data demonstrate the wide variability in the hTg secretory capacity of human thyroid cell monolayers and indicate, when compared to autologous normal cells, that abnormal human thyroid epithelial cells may be relatively deficient in their ability to secrete hTg in vitro. There were also qualitative differences in the immunoreactivity, and iodine content, of in‐vitro secreted hTg. These observations suggest that there may be much greater heterogeneity in hTg secreted in vitro than previously realized, perhaps secondary to differences in iodine content and/or degree of glycosylation.
IODIDE ADMINISTRATION ENHANCES THYROTROPHIN RESPONSIVENESS TO THYROTROPHIN‐RELEASING HORMONE DURING FASTING: EVIDENCE FOR NORMAL PITUITARY FEEDBACK REGULATION
Authors: BURMAN K. D. , SMALLRIDGE R. C. , BURGE J. R. , O'BRIAN J. T. , WARTOFSKY L. 
Published: March 2008

SUMMARYShort‐term fasting in humans is associated with diminished Δ TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 μU/ml; normal range 0.66‐2.98 μU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide‐treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 ± 0.3 μU/ml (mean ± SEM) in the fed state and increased to 14.7 ± 3.5 μU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 ± 0.3 μU/ml was significantly decreased (P < 0.01) compared to control, as was the level of 8.8 ± 2.3 μU/ml (P < 0.01) obtained 20 min after TRH. In the iodide‐treated group the basal TSH level was 1.4 ± 0.2 μU/ml during feeding which increased (P < 0.025) to 2.9 ± 0.7 μU/ml during fasting; the TSH value 20 min after TRH was 12.6 ± 2.5 μU/ml while feeding and 17.3 ± 2.9 μU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups. That free T4 (pmol/l) rose significantly during fasting (28.7 ± 1.3 vs 33.8 ± 1.3, P < 0.01) in the control group but was unaltered in the iodide‐treated group (23.8 ± 1.3 vs 26.2 ± 2.5) suggests an aetiological role for free T4 in blunting TSH responsiveness. The abolition by iodide of the fasting‐related changes in TSH further suggests that normal pituitary feedback regulation is maintained during fasting.
HYPOTHALAMIC FUNCTION IN WOMEN WITH SECONDARY HYPOGONADISM AND UNRESPONSIVE TO CLOMIPHENE THERAPY
Authors: WILLIAMS C. A. VAUGHAN 
Published: March 2008

SUMMARYSeven women with secondary hypogonadism who had been previously unresponsive to two 5‐d courses of clomiphene citrate, were treated with clomiphene citrate 100 mg daily for 10 d. LH and FSH concentrations were measured in serum collected at 15‐min intervals for 5 h before and on the 10th day of treatment and oestradiol was measured in the first two samples on each day. Four women responded with an increase in the amplitude of LH pulses and in mean LH values and in three there was a marked increase in serum oestradiol concentrations. Three women who showed no gonadotropin response were subsequently unresponsive to pulsatile LHRH therapy. These preliminary data are consistent with the hypothesis that hypothalamic hypogonadotrophism may result from hypersensitivity of the hypothalamus to oestrogen negative feedback and that the hypothalamic potential for secretion of LHRH is unimpaired. Prolonged treatment with clomiphene may provide a simple test of hypothalamic function in women with normal pituitary function.
CLINICAL EVALUATION OF A TWO‐SITE IMMUNORADIOMETRIC ASSAY FOR ADRENOCORTICOTROPIC IN UNEXTRACTED HUMAN PLASMA USING MONOCLONAL ANTIBODIES
Authors: WHITE A. , SMITH H. , HOADLEY M. , DOBSON S. H. , RATCLIFFE J. G. 
Published: March 2008

SUMMARYWe have developed a sensitive two‐site immunoradiometric assay (IRMA) for intact ACTH and its precursors, pro‐opiomelanocortin and 22 kDa peptide in unextracted human plasma. The assay uses two monoclonal antibodies. Antibody 1A12, specific for ACTH 10–18, is radiolabelled and antibody 2A3 specific for the C‐terminal region (ACTH 24–39), is coupled to Sephacryl S300 for the solid‐phase. Samples are incubated for 18 h with labelled antibody followed by 2 h with solid‐phase antibody. Separation employs the sucrose layering technique. Using human pituitary ACTH 1–39 (code 74/555) in diluent containing 10% horse serum to standardize the assay, the sensitivity (upper 99% confidence limit of zero standard) is 3.5 ± 0.8 ng/l (n= 7). The mean coefficient of variation is 5.9% within‐assay and 6.7% between‐assay and is less than 10% between 22 and >5000 ng/l. Mean recovery of ACTH 1–39 added to dexamethasone‐suppressed human plasma is 109% and endogenous ACTH behaves indistinguishably from standard ACTH on dilution. In normal subjects, mean plasma ACTH levels are 30 ng/l at 0730 h, and 15 ng/1 at 1630 h at rest. ACTH concentrations are between 60 and 330 ng/l, 8–10.5 h after metyrapone (2 g orally at 2300 h), between 140 and 320 ng/1, 30–60 min after insulin‐induced hypoglycaemia, and < 4 ng/1, 8 h after dexamethasone (1.5 mg orally at 2300 h). In a range of pathological conditions ACTH concentrations accurately reflect the disorders of the pituitary‐adrenal axis. Endogenous ACTH immunoactivity is stable in vitro at 22°C for at least 1 h in whole blood and at least 4 h in plasma. It is concluded that this two‐site IRMA for ACTH in unextracted plasma offers a reliable assay for clinical purposes.
EFFECTIVE LONG‐TERM TREATMENT OF ACROMEGALY WITH A LONG‐ACTING SOMATOSTATIN ANALOGUE (SMS 201–995)
Authors: SANDLER L. M. , BURRIN J. M. , WILLIAMS G. , JOPLIN G. F. , CARR D. H. , BLOOM S. R. 
Published: March 2008

SUMMARYNine acromegalic patients, six previously untreated, were studied before and after 3–15 months of treatment with a long‐acting somatostatin analogue (SMS 201–995; 100 μg injected s.c. three times daily). During treatment, the mean (± SEM) 24‐h GH concentration fell from 82 ± 22 mIU/1 to 33 ± 7 mIU/1 (P < 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin‐like growth factor (IGF‐1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side‐effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 ± 0.3 vs 5.5 ± 0.3 mmol/l), mean 24‐h plasma glucose concentration was higher with SMS (6.6 ± 0.5 mmol/l vs 6.0 ± 0.4 mmol/l; P < 0.02). Mean 24‐h plasma insulin concentration fell from 87 ± 11 mIU/1 before treatment to 39 ± 6 mIU/1 during treatment (P < 0005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long‐term treatment for certain patients with acromegaly.
CHANGES IN THE RESPONSIVENESS OF LUTEINIZING HORMONE SECRETION TO INFUSION OF THE OPIOID ANTAGONIST NALOXONE THROUGHOUT MALE SEXUAL MATURATION
Authors: ULLOA‐AGUIRRE A. , MENDEZ J. P. , GONZALEZ‐CASTILLO A. , CARRANZA‐LIRA S. , GARZA‐FLORES J. , PERES‐PALACIOS G. 
Published: March 2008

SUMMARYThe present study investigated the time of male sexual maturation during which hypothalamic inhibitory opioid activity can be detected. Normal prepubertal (Tanner stage G 1 (Ts‐G1) (n=4)), early pubertal (Ts‐G2 (n=5)), pubertal (Ts‐G3 (n=4), and Ts‐G4 (n=2)) and adult subjects (Ts‐G5 (n=4)) receives a rapid infusion of the selective opiate antagonist nalocone (NAL) (20 mg over 10 min). LH secretion was assessed by frequent (every 10 min for 2 h) venous sampling before and after administration of the opiate blocker, as well as by the LH response to exogenous GnRH. All but one (a Ts‐G2 subject) pubertal boys showed a prompt and sustained increase in serum LH concentrations after NAL administration, as disclosed by the areas under the LH curve (aLHc) calculated from samples obtained before and after NAL infusion (aLHc in four Ts‐G2 responders, 162·20 (mean ± SEM) vs 314·56 mIU/ml/min before and after NAL respectively, P>0·025; Ts‐G3, 227·35 vs 362·56 mIU/ml/min, P>0·025; Ts‐G4 and Ts‐G5, 432·77 vs 687·91 mIU/ml/min, P>0·05). In contrast, none of the prepubertal children had significant changes in LH secretion after the NAL challenge (154·17 vs 154·9 mIU/ml/min). Although all NAL responders exhibited serum testosterone (T) levels above 5 nmol/1, a positive correlation between individual T values and magnitude of LH responses to NAL was not found. All subjects had significant serum LH increments after GnRH administration. In a second series of studies, additional groups of Ts‐G1 subjects were primed during 5 days either with GnRH alone or with GnRH plus sex steroids (ethinyl oestradiol 12·5 μg/12 h or testosterone enanthate 1·8 mg/kg body weight (single dose)), before NAL administration, to investigate whether hypothalamic opioid activity might be unmasked by additional sex steroids. None of the priming schemes significantly modified the pituitary LH responses to NAL infusion (GnRH‐primed group, 145 & 48 us 139 f 43 mIU/ml/min before and after NAL, respectively; GnRH plus ethinyl oestradiol‐primed group, 124 f 42 us 107 f 34 mIU/ml/min; GnRH plus testosterone enanthate‐primed group, 64 f 10 us 57 f 24 mIU/ml/min). This study suggests that the development and/or maturation of the opioid control of LH secretion is temporally related with the onset of puberty. This surge of opioid inhibitory signals at early puberty might be reflecting a further stage of hypothalamic maturation and the re‐establishment of an additional biological system for the control of the maturing reproductive functions.
REVERSIBLE TRABECULAR BONE DENSITY LOSS FOLLOWING INDUCED HYPO‐OESTROGENISM WITH THE GnRH ANALOGUE BUSERELIN IN PREMENOPAUSAL WOMEN
Authors: MATTA W. H. , SHAW R. W. , HESP R. , EVANS R. 
Published: March 2008

SUMMARYThirteen premenopausal women who each received 400 μg three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid‐shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2–4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months’ buserelin treatment and after 6 months off treatment. Significant hypo‐oestrogenism (P>0·001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5·9% (P>0·02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P=0·07) reduction of only 0·9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo‐oestrogenism and the corresponding change in vertebral TBD, (r=0·20; P>0·10).
CHANGES IN THE QUALITATIVE AND QUANTITATIVE SECRETION OF LUTEINIZING HORMONE (LH) FOLLOWING ORCHIDECTOMY IN MAN
Authors: TSATSOULIS A. , SHALET S. M. , ROBERTSON W. R. 
Published: March 2008

SUMMARYThe effect of orchidectomy and thus withdrawal of testicular hormones on the biological and immunological properties of plasma LH was studied. Plasma samples were obtained from five men (mean age 71, range 65–81 years) with advanced carcinoma of the prostate, before orchidectomy and 1, 4, 8 and 16 weeks after surgery. LH bioactivity was estimated by a mouse Leydig cell bioassay and immunoreactivity by radioimmunoassay, using the same human pituitary LH standard 68/40. FSH and testosterone were measured by radioimmunoassay. Similar baseline data were obtained from a group (n = 17) of normal adult men (26, 19–36 years).Baseline bioactive (40 IU/l, median) and immunoreactive (10.8 IU/l) LH levels in the patients were higher (p>0.01) than in the controls (15.1 and 5.7 IU/l respectively), but bioactive to immunoreactive (B:I) LH ratios (3.4 ± 0.2 versus 2.8 ± 0.7) and testosterone levels (15.3 vs 18.7 nmol/l) were no different, consistent with compensated Leydig cell failure in the elderly men. After orchidectomy there was a greater increase in immunoreactive (46.6 IU/1 at 16 weeks) than bioactive (80.3 IU/l) LH levels i.e. a fourfold vs two fold increase from baseline values. Consequently the B:I LH ratio decreased significantly (1.8 ± 0.4 at 16 weeks) from the baseline ratio (P> 0.0001) and that of the controls (P> 0.01).These data indicate that acute withdrawal of testicular sex steroids results not only in quantitative change in LH secretion but also in qualitative change that decreases the biopotency of the LH molecules.
SEX HORMONE BINDING GLOBULIN IN SALIVA
Authors: SELBY C. , LOBB P. A. , JEFFCOATE W. J. 
Published: March 2008

SUMMARYMeasurement of salivary steroid hormone concentrations has frequently been advocated as a convenient alternative to plasma measurements. This is partly due to the belief that salivary steroid concentrations are a reliable reflection of the plasma free hormone level, a belief reinforced by earlier inability to demonstrate the presence of significant quantities of steroid binding proteins. Recent reports confirm that such quantities of these proteins are present in saliva and that they retain their steroid binding activity. We have measured sex hormone binding globulin (SHBG) and albumin in saliva from 14 men, 21 non‐pregnant women and 36 pregnant women. No differences in the concentration of salivary albumin was evident in any of the groups studied whereas a significant difference in the concentration of SHBG was evident between men and non‐pregnant women, and non‐pregnant and pregnant individuals. Although much lower, salivary SHBG and albumin concentrations broadly reflect those found in plasma. Furthermore, a highly significant correlation existed between salivary SHBG and albumin concentrations in all groups studied. It now seems generally accepted that the albumin present in saliva arises from contamination by either traces of blood or gingival fluids. The close relationship between the concentrations of albumin and SHBG in saliva suggests that they both gain entry by a similar route. Furthermore, their presence may significantly influence the concentration of certain steroids in saliva, and this may explain the occasional failure of salivary steroid concentrations to accurately reflect the plasma free hormone levels.
GROWTH HORMONE RESPONSE TO GROWTH HORMONE RELEASING FACTOR IN DIABETIC MEN
Authors: KOPELMAN P. G. , MASON A. C. , NOONAN K. , MONSON J. P. 
Published: March 2008

SUMMARYIncreased plasma concentrations of growth hormone (GH) are reported in diabetes and it is suggested that this may be important in the development of complications. We have investigated fasting GH levels and the response to 100 μg i.v. growth hormone releasing factor, GRF(1‐29)NH2, in age‐matched men: six normal weight controls, six obese controls, six insulin‐dependent diabetics, six normal weight non‐insulin dependent diabetics and six obese non‐insulin dependent diabetics. None of the diabetic men had clinical evidence of diabetic complications. Fasting GH values did not differ significantly between the five groups. The peak GH response to GRF was similar in the controls, insulin‐dependent diabetics (IDD) and non‐insulin dependent (NIDD) normal weight diabetics (mean peak±SEM: controls 25.5 ± 5 mU/1, IDD 26‐5 + 6 mU/1, NIDD 19.7 ± 5 mU/1) but was significantly reduced in the two obese groups (obese 6.4 ± 3mU/l, obese diabetics 4.5 ± 1 mU/1, P<001). This impairment of GH secretion was unrelated to either fasting plasma insulin or glucose concentration. We conclude that our results do not confirm the previous reports of abnormal GH secretion in diabetes but do demonstrate a markedly impaired GH response to GRF to be a feature of obesity.
IODINE IN MILK AND THE INCIDENCE OF THYROTOXICOSIS IN ENGLAND
Authors: PHILLIPS D. I. W. , NELSON M. , BARKER D. J. P. , MORRIS J. A. , WOOD T. J. 
Published: March 2008

SUMMARYBecause iodine is added to cattle feed, milk and dairy products have become a major source of dietary iodine in Britain. The mean iodine concentrations of milk supplied to seven towns in England were measured each month throughout 1 year. Values were more than twice those recorded 20 years ago. There were large differences between the towns, with average annual concentrations ranging from 130 to 200 μ/l. Within the towns there were up to four‐fold variations between the peak values in February/March and lowest values in June. The similarity between the monthly variations in milk iodine and seasonality in the onset of thyrotoxicosis suggests that iodine concentrations in milk and dairy products may now have reached harmful levels. Control of high winter levels in areas of Britain which were previously iodine deficient may now be necessary.
THE MECHANISM OF THE ADOLESCENT GROWTH SPURT INDUCED BY LOW DOSE PULSATILE GnRH TREATMENT
Authors: STANHOPE R. , PRINGLE P. J. , BROOK C. G. D. 
Published: March 2008

SUMMARYWe have used GnRH administered in a pulsatile fashion to treat 26 patients (12M:14F) with delayed puberty. Treatment was for a mean of 1.05 years (range, 0.3‐1.6). Mean age at the onset of treatment was 16.4 years in the girls (range, 12.7‐28.2) and 15.8 years in the boys (range, 13.8‐17.8). At different stages of sexual maturation, overnight serum samples for growth hormone (GH) were taken at 15 min intervals between 2000 h and 0600 h. The girls had a peak growth velocity which occurred between breast stages 2 and stage 3 (B2/3). GH secretion (both sum of the GH peaks and area under the GH pulse) increased at B2 and reached a peak at B3. Growth acceleration in the boys started at the attainment of a 9‐10 ml testicular volume and reached a peak at 11‐15 ml. The boys demonstrated an initial fall in GH secretion with the onset of treatment until the attainment of 9‐10 ml testicular volume; peak GH secretion occurred at the attainment of 11‐12 ml testicular volume. There was no change in GH pulse frequency during treatment in either sex. These observations and the maintenance of the normal relationship of the growth spurts to the appearance of secondary sexual characteristics are relevant to the mechanisms and timing of the adolescent growth spurts in normal girls and boys.
THE RESPONSE OF PLASMA OXYTOCIN TO SURGICAL STRESS
Authors: NUSSEY S. S. , PAGE S. R. , ANG V. T. Y. , JENKINS J. S. 
Published: March 2008

SUMMARYRecent evidence suggests that oxytocin (OXT) and arginine vasopressin (AVP) are involved in the response to stress. We have examined the changes in peripheral plasma OXT during abdominal surgery Hhin eight patients (six males, two female; ages 60‐82 years) undergoing hemicolectomy and compared the results with those for AVP to the same stimulus. There was no significant change in systolic blood pressure, blood haematocrit or plasma sodium, osmolality or glucose. AVP rose significantly after premedication (from 1‐8 ±0‐3 pmol/1 to 5‐5 ±2‐3 pmol/1; P<0‐05) but the greatest increase (to 35‐8 ±6‐6 pmol/1) occurred after gut manipulation. Plasma OXT concentrations fell slightly with premedication (from 5‐7 ± 2‐0 pmol/1 to 3‐3 ± 0‐9 pmol/1; .P<0‐05) but rose markedly (to a peak of 33‐5 ± 11‐4 pmol/1) after gut manipulation. The data support the concept that OXT like AVP may play a role in the neuroendocrine response to surgery. The stimulus to OXT release and its function remain to be determined.