bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the insulin-like growth factor-binding proteins by follicle size in the human ovary
Authors: Hughes S C Cwyfan , Mason H D , Franks S , Holly J M P 
Published: December 2004

Abstract
The IGFs are believed to play an important role in the regulation of steroidogenesis and follicular maturation in the human ovary. The activities of the IGFs are regulated by a family of binding proteins (IGFBPs) which are subject to a number of potential post-translational modifications. The aim of this study was to investigate both the production and modification of the IGFBPs in follicular fluid and in medium conditioned by granulosa cells and theca from individual follicles at different stages of maturation.
In follicular fluid from healthy, dominant follicles there was an increase in the amount of IGFBP-2, -3 and -4 present as lower molecular weight forms (23 kDa, 29 kDa and 16·5 kDa respectively) in comparison to that seen in atretic follicles from the same ovary. Furthermore for IGFBP-4, this fragmentation was confirmed to be attributable to the presence of a specific protease which could be inhibited not only by the addition of metal ion chelators or serine protease inhibitors, but also by the addition of other recombinant unsaturated IGFBPs, particularly IGFBP-3. IGF-I did not modulate the activity of the IGFBP-4 protease in solution but was able to prevent the inhibition seen with IGFBP-3.
Analysis of granulosa cell conditioned medium from the same series of healthy and atretic follicles revealed that IGFBP-2 and -4 were the predominant IGFBPs with no fragments seen on immunoblotting. In contrast, IGFBP-3 in conditioned medium from theca of atretic follicles was always found as an intact doublet, but was found partially fragmented (30 and 32 kDa) in medium conditioned by theca from healthy, dominant follicles with the proportion of IGFBP-3 in this lower molecular weight or fragmented doublet increasing with follicular maturation. A similar situation was also found for IGFBP-4 with the progressive increase in the amount of the 15 and 16·5 kDa fragments. IGFBP-2 was always found to be intact. Finally, IGFBP production from stroma explants was also examined. This revealed a wide variation in IGFBP pattern between different ovaries, although there was a remarkable degree of consistency between different stroma explant cultures from the same ovary. Immunoblotting for IGFBP-3 revealed that, where present, it existed as both an intact and a lower molecular weight doublet and that IGFBP-2 was again always found to be intact.
In conclusion we have demonstrated alterations in the proteolytic modification of the IGFBPs which differ in the various follicular compartments and are closely linked to the stage of follicular development.
Journal of Endocrinology (1997) 154, 35–43
Effects of vasopressin and elimination of corticotropin-releasing hormone-target cells on pro-opiomelanocortin mRNA levels and adrenocorticotropin secretion in ovine anterior pituitary cells
Authors: van de Pavert S A , Clarke I J , Rao A , Vrana K E , Schwartz J 
Published: December 2004

Abstract
Although arginine-vasopressin (AVP) is reported to produce greater ACTH biosynthetic and secretory responses than does corticotropin-releasing hormone (CRH) in sheep anterior pituitary cells, neither factor appears to increase pro-opiomelanocortin (POMC) mRNA levels, as does CRH in the cells of some other species. Since only a fraction of cells that express POMC mRNA may be able to respond to AVP, the aim of this study was to further delineate the regulation of POMC mRNA in ovine anterior pituitary corticotrophs, as a whole and in functional subpopulations of corticotrophs. We measured the effects of AVP, CRH or activation of protein kinase C by phorbol myristate acetate (PMA) in cultured cells. We compared responses in intact populations with those of cultures from which CRH-target cells were pharmacologically eliminated. Dissociated adult ovine anterior pituitary cells were cultured overnight, treated with either vehicle (intact) or a CRH-toxin conjugate that specifically eliminates CRH-target cells (CRH-target-depleted), washed, returned to culture and subsequently challenged with vehicle, AVP (100 nm), CRH (10 nm) or PMA (1 μm) for 5 h. The media were assayed for ACTH by RIA and the cells for POMC mRNA by Northern blot analysis. In intact populations, AVP and CRH increased ACTH secretion from 6·5 ±1·2 to 216 ±22 and 81 ± 14 ng/well respectively, but only AVP caused an increase in steady-state POMC mRNA levels (+48 ± 10%). Direct activation of protein kinase C with PMA mimicked the effect of AVP on ACTH secretion (318 ± 16 ng/well), but did not alter POMC mRNA levels. In CRH-target-depleted populations, control ACTH secretion (11 ± 3 ng/well) and POMC mRNA (+69 ±7%) were elevated, compared with intact populations. AVP (55 ± 8 ng/well) and PMA (120 ± 17 ng/well), but not CRH, increased ACTH secretion; POMC mRNA was not significantly elevated by any of the treatments. Taken together, these data provide further support for the notion of dissociation between secretion of ACTH and expression of POMC mRNA, and demonstrate that AVP increases steady-state POMC mRNA levels in ovine anterior pituitary cells. The data are also consistent with the concept that complex interactions, possibly including those between cells, influence ACTH secretion and steady-state POMC mRNA levels.
Journal of Endocrinology (1997) 154, 139–147
Tri-iodothyronine increases insulin-like growth factor binding protein-4 expression in rat hepatocytes
Authors: Demori I , Bottazzi C , Voci A , Gallo G , Scharf J-G , Fugassa E 
Published: December 2004

Abstract
Previous in vivo studies demonstrated significant variations in insulin-like growth factor binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-4 hepatic mRNAs and/or serum levels depending on the rat thyroid status. In this study we employed cultured hepatocytes from adult rats to demonstrate a possible direct regulation of these genes by tri-iodothyronine (T3). Northern blot analysis revealed that IGFBP-1 and -4 messages were clearly expressed, whereas IGFBP-2 signal was barely detectable.
No significant effects on IGFBP-1 mRNA level or on peptide secretion were detected in T3-cultured hepatocytes. In contrast, significant increases in IGFBP-4 mRNA steady-state levels as well as in IGFBP-4 secretion were observed in hepatocytes cultured for 12–24 h in the presence of T3. The T3 effect on IGFBP-4 transcript levels appears to consist of enhanced gene transcription and is independent of ongoing protein synthesis.
The T3-increased IGFBP-4 expression in cultured hepatocytes is consistent with our in vivo experiments demonstrating an increase in hepatic IGFBP-4 mRNA and serum IGFBP-4 levels in T3-treated rats. Furthermore, significant decreases in hepatic IGFBP-4 message and serum IGFBP-4 levels were observed in hypothyroid rats compared with euthyroid controls.
Our data establish an important direct role for thyroid hormone in regulating IGFBP-4 expression and consequently IGF activity.
Journal of Endocrinology (1997) 154, 155–165
Thyroid hormone induces protein secretion and morphological changes in astroglial cells with an increase in expression of glial fibrillary acidic protein
Authors: Lima F R S , Trentin A G , Rosenthal D , Chagas C , Neto V Moura 
Published: December 2004

Abstract
Thyroid hormone (T3) induces in vitro differentiation of astrocytes from the developing rat brain. T3 treatment induced the appearance of long processes in cultured cerebral hemisphere and mesencephalon astrocytes from embryonic and newborn rats. T3 treatment also produced a change in the morphology of cultured cerebellar astrocytes from 10-day-old rats, but not in cerebellar astrocytes from newborn rats. An increased expression of glial fibrillary acidic protein (GFAP) was also seen in the T3-treated newborn cerebral hemisphere and mesencephalic astrocytes. The morphological changes were induced earlier when the astrocytes were treated with conditioned medium (CM) obtained from cultures previously exposed to T3. Our results show that astrocytes from the developing rat brain are not homogenous in their responsiveness to T3. Furthermore, the fact that CM produces a response similar to that obtained with T3 treatment but in less time, suggests that T3 might induce the secretion of factors by cultured astrocytes. These factors might, by an autocrine/paracrine effect, induce the expression of GFAP and differentiation in developing brain astrocytes.
Journal of Endocrinology (1997) 154, 167–175
The effect of maternal protein deficiency during pregnancy and lactation on glucose tolerance and pancreatic islet function in adult rat offspring
Authors: Wilson M R , Hughes S J 
Published: December 2004

Abstract
To test the hypothesis that poor foetal–neonatal nutrition predisposes adult animals to impaired glucose tolerance or diabetes, pregnant and lactating rats were fed a low (5%) protein diet and glucose tolerance and pancreatic islet function then assessed in the adult offspring. To expose any underlying defects the offspring were allowed access to a sucrose supplement (35%) or fed a high fat diet. Offspring born to low protein-fed females had significantly lower body weights than controls. In islets from previously malnourished rats, insulin release in batch incubations or perifusion was not significantly different to controls. In islets from previously malnourished animals fed sucrose, glucose-stimulated insulin release was reduced in perifusion by 66% (P<0·01) and batch incubations by 26–52% (6–16 mmol/l glucose, (P<0·01). Similarly, impaired secretory responses were found in islets from previously malnourished animals fed a high fat diet. These did not result from a reduced pool of releasable insulin, as arginine-stimulated secretion was not impaired. Rats previously malnourished showed a normal glucose tolerance. Glucose tolerance was impaired, however, in previously malnourished rats fed sucrose (area under the glucose tolerance test curve was increased by 42%, P<0·05) but despite the reduced islet secretory responses was not significantly different to sucrose-fed controls (area increased by 54%, P<0·05). Glucose tolerance was impaired in previously malnourished animals fed high fat diet (area increased by 48%, P<0·05) more so than in high fat fed-controls (28% increase, NS). These data support the hypothesis that poor foetal–neonatal nutrition leads to impaired pancreatic β-cell function which persists into adult life. Alone this is not sufficient to produce diabetes, but an inability to respond to a highly palatable fat diet may tip the balance towards impaired glucose tolerance.
Journal of Endocrinology (1997) 154, 177–185
Arachidonic acid release from rat Leydig cells depends on the presence of luteinizing hormone/human chorionic gonadotrophin receptors
Authors: Moraga P F , Llanos M N , Ronco A M 
Published: December 2004

Abstract
In this work, the involvement of arachidonic acid (AA) in the luteinizing hormone and human chorionic gonadotrophin (LH/hCG) action on Leydig cells was studied. Experiments were first designed to evaluate [14C]AA incorporation into membrane phospholipids. Subsequently, time-course, pulse-chase and dose–response studies of the effect of hCG on [14C]AA release were performed. Results indicated that 4 h was optimal for maximal incorporation of [14C]AA into membrane phospholipids of viable Leydig cells. Pulse-chase experiments and studies performed to evaluate the effect of different doses of hCG on [14C]AA release demonstrated that this hormone stimulates [14C]AA release in a dose–response and time-dependent manner. Furthermore, using a desensitised animal model, a link between the presence of LH/hCG receptors and LH/hCG-stimulated [14C]AA release in Leydig cells could be established. In fact, the amount of [14C]AA released was significantly dependent on, and directly proportional to, the concentration of LH/hCG binding sites. Thus [14C]AA released from intact rat Leydig cells decreased when animals had been previously injected with a high single dose of hCG (desensitised animals), which is known to cause a dramatic decrease in the number of LH/hCG binding sites. These results demonstrate that the mechanism of AA release in Leydig cells depends on LH/hCG–receptor interaction and also suggest that AA could act as an additional intracellular messenger associated with the hormonal action of LH/hCG.
Journal of Endocrinology (1997) 154, 201–209
Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells
Authors: Baumgartner-Parzer S M , Wagner L , Reining G , Sexl V , Nowotny P , Müller M , Brunner M , Waldhäusl W 
Published: December 2004

Abstract
Hyperthyroidism is associated with elevated plasma levels of endothelium-derived proteins such as von Willebrand factor (vWF), fibronectin (FN) and endothelin-1 (ET-1). This study was designed to characterize the mechanisms involved in this phenomenon at the cellular level. vWF, FN and ET-1 secretion and mRNA expression were measured in human umbilical vein endothelial cells (HUVECs) exposed to tri-iodothyronine (T3) for 13 ± 1 days, using ELISA, Western blot, RIA and Northern blot analysis respectively. Exposure of HUVECs to T3 significantly increased vWF secretion (50 ng T3/ml: 117 ± 5%, P<0·01; 100 ng T3/ml: 127 ± 26%, P<0·01) as well as vWF mRNA expression (50 ng/ml: 116 ± 13%, P<0·001; 100 ng/ml: 136 ± 30%, P<0·002) (results are means ± s.d. analysed by the Wilcoxon signed rank test). FN secretion was significantly affected by 50 (145 ± 42% of control, P<0·05) and 100 (116·8 ± 16% of control, P<0·05) ng T3/ml, and FN mRNA expression by 50 ng T3/ml (123 ± 20%, P<0·05). Long-term incubation with T3 increased both ET-1 secretion (25 ng/ml: 124 ± 25%, P<0·001; 50 ng/ml: 165 ± 53%, P<0·05; 100 ng/ml: 116 ± 17%, P<0·05) and prepro-ET-1 mRNA expression (25 ng/ml: 112 ± 16%, P<0·05; 50 ng/ml: 134 ± 43%, P<0·02; 100 ng/ml: 120 ± 20%, P<0·02). Protein kinase C (PKC) isoforms ε and βII were not significantly affected by T3, whereas PKC α was increased in whole cell lysates and in membrane fractions of cells incubated with 100 but not 50 ng T3/ml. Prepro-ET-1 mRNA stability, cell numbers and proliferation, measured by [3H]thymidine assays, remained unaffected in HUVECs after exposure to T3. These data indicate thyroid hormone-induced upregulation of mRNA expression and protein synthesis of vWF, FN and ET-1, by PKC α-, βII- and ε-independent pathways, explaining, at least in part, increased plasma concentrations of endothelial proteins and peptides in the hyperthyroid state.
Journal of Endocrinology (1997) 154, 231–239
Estrogen increases in vivo leptin production in rats and human subjects
Authors: Shimizu H , Shimomura Y , Nakanishi Y , Futawatari T , Ohtani K , Sato N , Mori M 
Published: December 2004

Abstract
The decrease in estrogen in menopausal women increases body fat. The present studies were undertaken to investigate the involvement of estrogen in leptin production in vivo. In the first study, expression of ob gene mRNA in white adipose tissue was measured at 2 and 8 weeks after ovariectomy in rats. In the second, serum leptin concentration was measured in total body fat of 87 weight-matched human subjects (29 men, 29 premenopausal and 29 postmenopausal women). In the third, changes in serum leptin concentration with the menstrual cycle were determined, ob gene expression decreased in subcutaneous and retroperitoneal white adipose tissue of ovariectomized rats 8 weeks after the operation, while ovariectomy increased ob gene expression in mesenteric white adipose tissue. Serum leptin concentration was decreased by ovariectomy. Estradiol supplement reversed the effect of ovariectomy on ob gene expression and circulating leptin levels. In humans, serum leptin concentration was higher in premenopausal women than in men, and in postmenopausal women it was lower than in premenopausal women, but still higher than in men. In 13 premenopausal women, serum leptin levels were significantly higher in the luteal phase than in the follicular phase. The present studies strongly indicate that estrogen regulates leptin production in rats and human subjects in vivo. Regional variation in the regulation of ob gene expression by estrogen was found.
Journal of Endocrinology (1997) 154, 285–292
Effect of chronic ethanol on reproductive and growth hormones in the peripubertal male rat
Authors: Steiner J C , LaPaglia N , Hansen M , Emanuele N V , Emanuele M A 
Published: December 2004

Abstract
Ethanol (EtOH) has previously been shown to have profound effects on various endocrine systems. The present study further investigates the action of EtOH on testosterone and on the GH–IGF-I axis. Since these hormones are particularly important in male rats progressing through puberty, we examined the effect of 10 days of EtOH treatment at three different ages (35, 50 and 65 days old) as male rats progressed through puberty into adulthood. After 10 days of feeding a 6% EtOH liquid diet, serum testosterone levels were markedly decreased in all three ages (P<0·02 at 35 days, P<0·01 at 50 days and P<0·03 at 65 days). IGF-I was assessed and was differentially affected at each age. At 35 days IGF-I levels were suppressed by EtOH (P<0·0002), at 50 days no change was apparent, and at 65 days levels were significantly higher in EtOH-treated (P<0·01) compared with liquid-fed controls. The levels of IGF-I in the EtOH-treated animals paralleled pituitary GH mRNA levels with a significant fall in the expression of GH mRNA levels noted at 35 days (P<0·04), no change at 50 days and a significant rise observed at 65 days (P<0·03). At the hypothalamic level, GH-releasing hormone (GRF) mRNA was significantly reduced in the two younger EtOH-treated age groups compared with controls (P<0·04 at 35 days; P<0·02 at 50 days). At 65 days of age, EtOH did not alter GRF mRNA levels. No EtOH-induced changes were seen in GRF content at any age. These observations indicate definite age-related alterations in hormonal gene expression and circulating serum hormone levels and emphasize the importance of studying these critical peripubertal ages after chronic EtOH exposure.
Journal of Endocrinology (1997) 154, 363–370
Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets
Authors: Zawalich W S , Yamazaki H , Zawalich K C , Cline G 
Published: December 2004

Glucose and the combination of leucine and glutamine were used to stimulate insulin secretion from rat islets during a dynamic perifusion and the responses obtained were compared with those elicited from mouse islets under identical conditions. In rat islets, glucose (15 mM) or the amino acid combination of 10 mM glutamine plus 20 mM leucine were most efficacious and peak second-phase insulin release responses were 20- to 30-fold above prestimulatory rates. In contrast to rat islet responses, sustained second-phase insulin secretory responses to the same agonists were minimally increased 1- to 2-fold from mouse islets. Parallel studies demonstrated that phospholipase C (PLC) was markedly activated in rat, but not mouse, islets by both high glucose concentrations and the amino acid combination.
Additional studies documented that glucose and amino acid responses of both rat and mouse islets were amplified by carbachol or forskolin. However, wortmannin, a phosphatidylinositol 3-kinase inhibitor, amplified only the responses to glucose leaving the responses to the amino acid mixture unaltered. These observations support the concept that mitochondrial metabolism alone is minimally effective in stimulating insulin secretion from islets. The activation of the supplementary second messenger systems (PLC and/or cAMP) appears essential for the emergence of their full secretory potential. The mechanism regulating the potency and specificity of wortmannin’s impact on glucose-induced secretion remains to be identified; however a unique mechanism is supported by these findings.
Additional case of Tsukahara's syndrome or new syndrome: Further delineation of the association of microcephaly and radio‐ulnar synostosis
Authors: Selicorni Angelo , Ferrarini Alessandra , Cagnoli Giacomo , Fratoni Alessia , Bottigelli Michaela , Milani Donatella 
Published: December 2004

AbstractIn 1994, Giuffrè et al. reported two unrelated families in which some of the members had microcephaly and radio‐ulnar synostosis, suggesting a new condition. Since this first report, Tsukahara et al. and Udler et al. described two distinct patients with a different condition characterized by radio‐ulnar synostosis, short stature, microcephaly, scoliosis, and mental retardation. Here we report on a new case of microcephaly and radio‐ulnar synostosis and discuss the possible relationship between Tsukahara's syndrome and the phenotype described by Giuffrè et al. © 2004 Wiley‐Liss, Inc.
Hand involvement in Schmid metaphyseal chondrodysplasia
Authors: Elliott Alison M. , Field Fiona M. , Rimoin David L. , Lachman Ralph S. 
Published: December 2004

AbstractSchmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by mutations in the COL10A1 gene and is clinically characterized by short stature, bowed legs, and a waddling gait. Radiographic findings include anterior cupping, sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed the radiographs of Schmid MCD patients at the International Skeletal Dysplasia Registry in Los Angeles for evidence of hand involvement. We found hand involvement in 47% (7/15) of cases included in our analysis. These changes were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals. Mild hand involvement is a common feature of Schmid MCD. © 2004 Wiley‐Liss, Inc.
A semi‐supervised active learning algorithm for information extraction from textual data
Authors: Wu Tianhao , Pottenger William M. 
Published: December 2004

AbstractIn this article we present a semi‐supervised active learning algorithm for pattern discovery in information extraction from textual data. The patterns are reduced regular expressions composed of various characteristics of features useful in information extraction. Our major contribution is a semi‐supervised learning algorithm that extracts information from a set of examples labeled as relevant or irrelevant to a given attribute. The approach is semi‐supervised because it does not require precise labeling of the exact location of features in the training data. This significantly reduces the effort needed to develop a training set. An active learning algorithm is used to assist the semi‐supervised learning algorithm to further reduce the training set development effort. The active learning algorithm is seeded with a single positive example of a given attribute. The context of the seed is used to automatically identify candidates for additional positive examples of the given attribute. Candidate examples are manually pruned during the active learning phase, and our semi‐supervised learning algorithm automatically discovers reduced regular expressions for each attribute. We have successfully applied this learning technique in the extraction of textual features from police incident reports, university crime reports, and patents. The performance of our algorithm compares favorably with competitive extraction systems being used in criminal justice information systems.