bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal antibodies reveal circulating growth hormone of high molecular weight not detectable by conventional assays
Authors: Luthman Marguerite , Jónsdóttir Ingileif , Skoog Bo , Wivall Inga-Lena , Roos Paul , Werner Sigbritt 
Published: June 2009

Abstract.
A radioimmunoassay based on a monoclonal antibody, Mc-ab 1, which was raised against growth hormone but cross-reacted with human placental lactogen yielded higher GH immunoreactivity levels in serum than one based on a polyclonal antiserum. This discrepancy was noted in subjects with normal GH secretion as well as in patients with GH insufficiency. To characterize this GH immunoreactivity detected by Mc-ab 1, affinity purification and molecular sieve chromatography of serum were performed. High molecular weight proteins with GH immunoreactivity were found with both techniques. These proteins were associated with carbohydrates. Affinity cross-linking showed specific binding of radiolabelled GH to high molecular weight proteins in the serum. After fractionation of serum, the GH immunoreactivity became detectable by the polyclonal antiserum assay as well as by an immunoradiometric assay. GH immunoreactive material with an approximate mass of 80 kD was subjected to isoelectric focusing. When GH immunoreactive fractions at pH 5 were re-chromatographed, GH immunoreactivity was recovered in the elution volume corresponding to monomeric GH. Our results show that sera from normal subjects as well as from patients with deficient GH secretion contain notable amounts of high molecular weight GH which is undetectable by antibodies generally used for GH measurements, but which can be revealed after fractionation of serum.
The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: A comparison with the lysine-vasopressin test
Authors: Tabarin A. , Galli F. San , Dezou S. , Leprat F. , Corcuff J.-B. , Latapie J.-L. , Guerin J. , Roger P. 
Published: June 2009

Abstract.
The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.
Influence of growth hormone on the immunosuppressive effect of prednisolone in mice
Authors: Franco P. , Marelli O. , Lattuada D. , Locatelli V. , Cocchi D. , Müller E. E. 
Published: June 2009

Abstract
Growth hormone can be used to counteract some catabolic effects of long-term administration of glucocorticoids, such as impairment of growth in children and osteoporosis. However, owing to its immunostimulatory properties the hormone may counteract the effect of glucocorticoids on the immune system. To investigate this question we administered different doses of hGH (4, 8, 40 IU/kg) to C57/B1/6J mice treated for two days with prednisolone, and evaluated thymus and spleen parameters and natural killer activity. Growth hormone at the dose of 4 and 8 IU/kg reversed prednisolone-induced reduction of spleen and thymus weight and cellularity, whereas the highest dose showed to be immunosuppressive in itself. Two days after treatment withdrawal, a recovery of spleen parameters was evident, whereas the thymus was still suppressed by preceding prednisolone or hGH (40 IU/kg) treatments. The pattern of natural killer activity displayed by the splenocytes resembled that present under treatment. In a second experiment prednisolone, administered for 10 days, drastically reduced the number of viable spleen and thymus cells as well as the relative spleen and thymus weights, an effect reversed by concomitant administration of hGH (0.8, 4, 8 IU/kg). Natural killer activity, which was significantly depressed by prednisolone, was restored by the intermediate GH dose only. The 8 IU/kg GH dose was immunosuppressive in itself.
Evidence for LH-inhibiting activity in ovine peripheral and testicular blood
Authors: Papapdopoulos V. , Kamtchouing P. , Boujrad N. , Pisselet C. , Perreau C. , Locatelli A. , Drosdowsky M. A. , de Reviers M. T. Hochereau , Carreau S. 
Published: June 2009

Abstract.
Intracellular cyclic AMP and testosterone productions by purified mature rat Leydig cells were stimulated by oLH (25 μg/l) 18- and 12-fold, respectively, after a 5-h incubation period. The replacement of the incubation medium by charcoal-treated testicular venous plasma (40%, v/v) from adult rams in the breeding season induced an inhibition of cyclic AMP and testosterone productions (82 and 66%, respectively, of oLH-stimulated values). Testicular arterial plasma is less effective than testicular venous plasma, even when it originates from non-breeding season rams; in that case, testicular venous and arterial plasma strongly inhibit testosterone productions (84 and 67%, respectively of oLH-stimulated values), which probably indicates that the inhibitory activity is higher in the non-breeding season. The addition of peripheral plasma leads to a testosterone production equal to 35 and 65% of the oLH-stimulated values, respectively, for ram blood collected in non-breeding and breeding seasons. The same concentration of ovine testicular lymph or rete testis fluid is without significant effect on cyclic AMP production; however, testosterone is slightly decreased by lymph but enhanced by rete testis fluid. Increasing amounts of venous or arterial testicular blood induce a dose-related decrease of the specific binding of labelled hCG in both rat and ram testicular membranes. This inhibiting factor is present in peripheral and testicular blood of either control or hypophysectomized or castrated rams, is a protein in nature, heat-sensitive, and has an apparent molecular weight higher than 10 000 daltons. These results suggest the existence of a control of LH-specific binding to its receptors and of Leydig cell cyclic AMP and testosterone outputs; these activities are not species-specific and are more concentrated in testicular venous than in arterial blood. The origin of this inhibiting factor remains to be determined, since it is not confined to the testis and not of pituitary origin.
The source of cholesterol for progesterone synthesis in cultured preovulatory human granulosa cells
Authors: Endresen Marit J. , Haug Egil , Åbyholm Thomas , Henriksen Tore 
Published: June 2009

Abstract.
There are three possible sources of cholesterol for immediate use in progesterone production by preovulatory human granulosa cells: follicular fluid high-density lipoprotein, de novo synthesis of cholesterol, and preformed intracellular cholesteryl ester stores. In the present study these three alternatives were investigated. First, an in vitro model was established that mimics the preovulatory environment, including short-term cultures and use of autologous follicular fluid in the culture medium, instead of serum. Using this model it was found that the presence of high-density lipoprotein from follicular fluid in the culture medium did not affect the synthesis of progesterone by the granulosa cells. Next, addition of inhibitors of de novo sterol synthesis, like low-density lipoprotein, 25-OH cholesterol and compactin to the culture medium, did not reduce [14C]acetate incorporation into sterols and steroids by the cells. The sterol synthesis was accordingly interpreted to be at a low and therefore uninhibitable level. Finally, the content of free and esterified cholesterol in freshly isolated granulosa cells was found to be 50±7 and 52±13 pmol/mg cell protein, respectively. We suggest that neither follicular high-density lipoprotein nor endogenous synthesis is the imim- cholesterol source for the progesterone production in preovulatory human granulosa cells. However, granulosa cells have a large store of cholesteryl esters that may provide free cholesterol for the preovulatory progesterone production.
Steroid hydroxylase gene expression in the ovine fetal adrenal gland following ACTH infusion
Authors: Tangalakis Kathy , Coghlan John P. , Crawford Robert , Hammond Vicki E. , Wintour E. Marelyn 
Published: June 2009

Abstract.
Between 90 and 120 days of gestation (term = 147±5), when plasma cortisol concentrations in the fetus are at a minimum, levels of mRNA encoding the steroidogenic enzymes 17α-hydroxylase (P-45017α) and cholesterol side-chain cleavage (P-450scc) are also very low. Over the following 30 days, P-45017α and P-450scc gene expression increases concurrent with increasing fetal cortisol concentration. The hypothesis tested in this study was that cortisol biosynthesis is minimal in the period 90-120 days because of insufficient ACTH. Fetuses were cannulated between 98-102 days of gestation. Following recovery, 7 fetuses received 24-h ACTH infusions (12 μg/24 h) and 5 fetuses received 24-h vehicle infusions; 4 ACTH-infused and 4 vehicle-infused fetuses were then sacrificed immediately after cessation of the infusion. The other fetuses were left in utero for 3 days prior to sacrifice. Fetal blood samples were analysed for ACTH and cortisol and the adrenals processed for hybridization histochemistry and Northern blot analysis. ACTH, but not vehicle, induced significant increases in the width of the adrenal cortex and in the levels of P-45017α and P-450scc mRNA. Concurrently, fetal plasma ACTH and cortisol concentrations also increased significantly. In adrenals from fetuses left in utero for 3 days after cessation of the ACTH infusion, P-45017α and P-450scc mRNA levels returned to control levels. Plasma ACTH and cortisol levels also approximated basal values. P-450c21 mRNA levels did not vary significantly at any time with the treatments. It can be concluded that the major regulatory influence on ACTH in the 90-120 day fetus is via increased gene expression of P-45017α and P-450scc but not P-450c21.
Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH
Authors: Laron Z. , Klinger B. , Silbergeld A. , Lewin R. , Erster B. , Gil-Ad I. 
Published: June 2009

Abstract.
Recombinant IGF-I was administered as an iv bolus of 75 μg/kg to 10 patients with Laron type dwarfism (3 children aged 9, 11 and 12 years and 7 adults aged 30.6 ± 3.5 years) and to 8 healthy subjects (mean age 19.9 ± 12.1 years) and determinations of IGF-I, GHRH, hGH, TSH, and glucose were made before and at 2, 5, 15, 30, 60, 90, and 120 min. The following effects were observed: a. an immediate, marked and sustained drop in blood glucose (p < 0.001), more prolonged in the patients; b. in both groups, a dramatic rise in plasma hGH (p<0.01) which peaked at 60-90 min; in the patients this occurred after an initial immediate fall in plasma hGH (p<0.01); c. a progressive decrease of plasma GHRH and TSH (p<0.05, 0.02) in both patients and healthy controls. An hypothesis is put forward that acute and time-limited release of somatostatin by IGF-I is the main cause of the hormonal changes registered. As the IGF-I bolus also suppressed circulating insulin levels, the hypoglycemia is considered to be a direct effect of IGF-I.
Thyroid size and function in healthy pregnant women with thyroid autoantibodies. Relation to development of postpartum thyroiditis
Authors: Rasmussen Nini G. , Hornnes Peter J. , Høier-Madsen Mimi , Feldt-Rasmussen Ulla , Hegedüs Laszlo 
Published: June 2009

Abstract.
In a study of postpartum thyroiditis, thyroid function and ultrasonically determined thyroid size were evaluated in 36 thyroid autoantibody positive healthy women during pregnancy and the first postpartum year. Twelve women (33%) developed postpartum thyroiditis with permanent thyroid dysfunction in three. However, only one woman had symptoms and needed treatment. The most common type of thyroid dysfunction was a transient hyperthyroid phase as seen in 7 women. A significant increase by 20-30% in mean thyroid volume during pregnancy was demonstrated independent of development of postpartum thyroiditis. We conclude that initial thyroid volume or changes during pregnancy and post partum are not useful indicators of the development of postpartum thyroiditis. The fact that the condition is oligosymptomatic suggests that screening procedures are necessary if one wants to diagnose the earliest phases of postpartum thyroiditis.
Parathyroid localization by 201Tl-99mTc subtraction scintigraphy: Results in secondary hyperparathyroidism
Authors: Rademaker Paul , Meijer Sijtze , Piers Do A. 
Published: June 2009

Abstract.
Subtraction scintigraphy with 201Tl and 99mTc for parathyroid localization was performed preoperatively in 13 patients with chronic renal failure and secondary hyperparathyroidism. Twenty of the 37 examined pathological glands were predicted correctly (sensitivity 54%). In 3 patients with recurrent hyperparathyroidism after surgery all pathological glands found at second operation had been detected correctly by subtraction scintigraphy. We conclude that this localization method has a limited value when used prior to first neck exploration in secondary hyperparathyroidism. In persistent hyperparathyroidism after surgery it may play a useful role in localizing missed and ectopic glands.
Changes in thyroid volume during antithyroid drug therapy for Graves' disease and its relationship to TSH receptor antibodies, TSH and thyroglobulin
Authors: Yamaguchi Yoshiyuki , Inukai Toshihiko , Iwashita Akira , Nishino Michio , Yamaguchi Takahiko , Shohda Yoshihito , Shimomura Yohnosuke , Ohshima Kihachi , Kobayashi Setsuo , Kobayashi Isao 
Published: June 2009

Abstract.
Changes in thyroid volume during antithyroid drug therapy for Graves' disease compared with circulating thyroid parameters were evaluated. One hundred and forty-four patients with Graves' disease were treated with methimazole. Thyroid volume was measured by ultrasonography (thyroid volume = Π abc/6, where a is length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins, thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and antithyroglobulin antibodies were also measured. In the whole group of patients, thyroid volume correlated significantly with thyroglobulin (p<0.01) and TSH-binding inhibitory immunoglobulins (p<0.01), but not with TSH, antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a positive correlation was found between thyroglobulin and TSH-binding inhibitory immunoglobulins (p<0.01). In 11 patients the mean thyroid volume decreased significantly after one year of therapy (p<0.01), associated with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten patients experienced transient hypothyroidism with an overdose of methimazole, and the mean thyroid volume increased significantly (p<0.01) with increasing serum TSH levels. In conclusion, it is suggested that TSH receptor antibodies may have a thyroid growth-stimulating effect. In addition, circulating thyroglobulin levels reflect thyroid volume in Graves' disease.
Incidence of intratubular germ cell neoplasia in androgen insensitivity syndrome
Authors: Cassio Alessandra , Cacciari Emanuele , D'Errico Antonia , Balsamo Antonio , Grigioni Franco W. , Pascucci Maria G. , Bacci Francesco , Tacconi Moreno , Mancini Antonio M. 
Published: June 2009

Abstract.
Gonadal histology was investigated by means of conventional microscopy in 6 patients with complete androgen insensitivity syndrome, in 11 with incomplete androgen insensitivity syndrome, and in 3 with 5α-reductase syndrome. Twelve subjects were prepubertal and 8 pubertal. In all patients gonadal tissue was removed as a prophylactic measure and no patients gave rise to any clinical suspicion of a tumour. Eight patients with incomplete androgen insensitivity syndrome, 5 of whom (62.5%) were prepubertal, showed intratubular germ cell neoplasia and in 6 of them it was bilateral. Histochemical and immunohistochemical analysis showed considerable agreement between atypical morphological aspects and positive response to Schiff's periodic acid and to staining with the anti-placenta alkaline phosphatase antibody. Our patients were characterized by one of the highest reported incidences of intratubular germ cell neoplasia, particularly at prepubertal age. These findings would seem to indicate that a rethink is needed concerning the general opinion that patients with androgen intensivity syndrome have practically no risk of developing malignancy, and that orchidectomy is not advisable before puberty is completed.
A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease: Prediction of outcome
Authors: Arnott Richard D , Pestell Richard G , McKelvie Penelope A , Henderson J Keith , McNeill Peter M , Alford Frank P 
Published: June 2009

Abstract.
Twenty-eight patients underwent transsphenoidal pituitary surgery for Cushing's disease. Selective surgical procedures were performed in 26. In 19 patients pituitary adenoma was confirmed histologically and 5 had clumps or clusters of ACTH-staining cells. At follow-up after 22.3 (range 5-56) months 21 (75%) patients remained in clinical and biochemical remission. The 24-h urinary free cortisol performed between 1 and 4 weeks postoperatively while patients took replacement doses of dexamethasone (0.5 to 0.75 mg per day) was found to predict outcome. All patients with suppressed urinary free cortisol excretion have remained in remission, 3 with levels in the normal range have suffered late relapse after initial remission, and 4 with elevated urinary free cortisol excretion were regarded as having failed to remit. Furthermore, all patients with unsuccessful outcomes had no pituitary adenoma and 3 had features consistent with corticotrope nodular hyperplasia at histological examination compared to only 2 and 1, respectively, of patients still in remission. We conclude that 24-h urinary free cortisol performed at 1 to 4 weeks postoperatively whilst on low-dose dexamethasone and the histological findings may predict outcome following transsphenoidal pituitary surgery in Cushing's disease.
Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis
Authors: Bogner Ulrich , Kotulla Peter , Peters Harm , Schleusener Horst 
Published: June 2009

Abstract.
Cytotoxic activity in sera of patients with Hashimoto's thyroiditis was measured with an antibody-dependent cell-mediated cytotoxicity assay. Cytotoxicity was determined in a 51chromium release assay using human thyroid cell targets incubated with heat-inactivated serum or IgG from patients with Hashimoto's thyroiditis. Effector cells were obtained from peripheral mononuclear cells of normal subjects. Cytotoxicity was significantly increased in patients with Hashimoto's thyroiditis (median specific lysis 20.2%, range 2.1-58.8) compared with normals (median specific lysis 8.1%, range 0-19.5; p<0.00001). The amount of percent specific lysis did not correlate with the titres of microsomal antibodies determined by different methods: passive hemagglutination technique (r=0.2), enzyme immunoassay with microsomal antigen (r=0.16), and radioimmunoassay for thyroid peroxidase antibody (r=0.02). The cytotoxic activity was located in the IgG fraction, both in microsomal antibody positive and negative sera. After pre-incubation of microsomal antibody/thyroid peroxidase antibody positive or negative sera with purified thyroid peroxidase followed by analysis in the antibody-dependent cell-mediated cytotoxicity assay, cytotoxicity decreased in only 2 cases but was unchanged in the remaining sera. Western blot experiments with solubilized thyroid membranes and immunoblotting with cytotoxic-positive/microsomal antibody negative sera showed no binding to thyroid peroxidase. Our data suggest that cytotoxicity in sera from patients with Hashimoto's thyroiditis is not mediated by antibodies against thyroid peroxidase, but by antibodies not yet identified.
Not all insulin secretagogues sensitize pancreatic islets to recombinant human interleukin 1β
Authors: Johannesen Jesper , Helqvist Steffen , Nerup Jørn 
Published: June 2009

Abstract.
The purpose of this study was to test the influence of different insulin secretagogues on interleukin 1β mediated injury to isolated rat pancreatic islets. Islets were exposed to interleukin 1β for 6 days. During exposure, beta-cells were stimulated with glucose ( 11 mmol/l vs 3.3 mmol/l or with non-nutrients as tolbutamide (250 μmol/l), iso-butyl 1-methyl-xanthine (50 μmol/l), or glucagon (10 mg/l). At 3.3 mmol/l of glucose, 60 000 U/l of interleukin 1β caused an inhibition of medium insulin accumulation to 62±5% of control from 48 h to 6 days of exposure, whereas islet DNA content was unaffected. At 11 mmol/l of glucose, interleukin 1β dose-dependently decreased medium insulin accumulation (e.g. 60 000 U/l of interleukin 1β, 12±3% of control) and islet content of DNA (60 000 U/l of interleukin 1β, 60±8% of control). During beta-cell stimulation with tolbutamide, interleukin 1β caused inhibition of insulin accumulation to 36±9% of control. In contrast, on islets stimulated with iso-butyl 1-methyl-xanthine or glucagon, the effects of interleukin 1 β were equivalent to those on non-stimulated islets. These differences were paralleled by differences in the interleukin 1β effect on islet morphology. In conclusion, high beta-cell activity (as measured by islet insulin release) may increase islet susceptibility to interleukin 1β, however, depending upon the intracellular pathway through which insulin secretion is activated.
Diurnal variation in melatonin effect on adenosine triphosphate and serotonin release by human platelets
Authors: Del Zar María de las M. , Martinuzzo Marta , Cardinali Daniel P. , Carreras Luis O. , Vacas María I. 
Published: June 2009

Abstract.
The effect of the pineal hormone melatonin on adenosine diphosphate-induced human platelet aggregation and adenosine triphosphate release was assessed in platelet-rich plasma obtained from normal volunteers at 08.30 and 20.30 h. In 10−7-10−5 mol/l concentrations melatonin inhibited ADP-induced platelet aggregation only in the evening (p<0.05). ADP-induced ATP release, an index of platelet secretory processes, showed a generally greater, dose-dependent inhibition after adding melatonin (10−9-10−5 mol/l) at 20.30 h as compared with 08.30 h. The inhibitory activity of melatonin (10−9-10−5 mol/l) on [3H]serotonin release elicited by thrombin in washed human platelets obtained from normal volunteers was dose-dependent; the effect was generally greater at 20.30 h. The activity of the potent platelet anti-aggregating agent prostacyclin did not exhibit diurnal differences with respect to impairing ADP-induced platelet-rich plasma aggregation. These results indicate the existence of a diurnal variation of sensitivity to melatonin in human platelets.