bluuebunny/crossref_metadata_2025 huggingface dataset:
Activin inhibits but inhibin activates mouse placental lactogen-II secretion
Authors: Yamaguchi M , Tasaka K , Ogura K , Sakata M , Mizuki J , Miyake A
Published: December 2008

The regulation of mouse placental lactogen (mPL)-I and mPL-II secretion by activin and inhibin and the expression of activin and inhibin subunit mRNAs in the mouse decidua were examined. Activin-A at a concentration of 10 nm/l significantly inhibited mPL-II secretion by placental cells from days 9 and 12 of pregnancy. However, activin-A did not affect mPL-I secretion by cells from days 7 and 9 of pregnancy nor mPL-II secretion by cells from day 7 of pregnancy. By contrast, 10 nm/l inhibin activated mPL-II secretion by cells from day 12 of pregnancy. These effects of activin and inhibin on mPL-II secretion were dose-dependent. Follistatin, which binds to activin and blocks its bioactivity, completely eliminated the inhibitory effect of activin on mPL-II secretion. Incubation of placental cells from day 12 of pregnancy with activin-A resulted in a significant reduction of the mPL-II mRNA level assessed by Northern blot analysis. Northern blot analysis using poly(A)+ RNA extracted from the decidua indicated that mouse decidua, as well as the placenta, express all activin and inhibin subunits and that their gene expressions increased during gestation. The expression of these mRNAs in the decidua was much higher than those in the placenta. These findings suggest that activin and inhibin regulate mPL-II secretion and suggest the presence of an autocrine or paracrine regulation of mPL-II secretion in mouse placenta by activin and inhibin after mid-pregnancy in vivo.

Journal of Endocrinology (1995) 146, 469–474
GH-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide-6
Authors: Dickson S L , Doutrelant-Viltart O , Leng G
Published: December 2008

In the rat, the synthetic GH secretagogue GH-releasing peptide (GHRP-6) acts centrally to activate a subpopulation of arcuate neurones as reflected by increased electrical activation and by the detection of Fos protein in cell nuclei. Since GHRP-6 also induces GH secretion via a direct action on the pituitary, we set out to determine whether the central actions of GHRP-6 are mediated by GH itself. First, we demonstrated that peripherally administered GHRP-6 induces Fos expression in the arcuate nucleus of GH-deficient animals (dw/dw rats and lit/lit mice). Secondly, in dw/dw rats, neither intracerebro-ventricular injection of 15 μg recombinant bovine GH nor 1 μg recombinant human IGF-I resulted in an increase in the number of cells expressing Fos protein in the arcuate nucleus (or in any other hypothalamic structure studied). These results support our hypothesis that GHRP-6 has a central site and mechanism of action and provide evidence to suggest that the activation of arcuate neurones by GHRP-6 is not mediated by a central action of GH or IGF-I. Furthermore, since the lit/lit mouse pituitary does not release GH following GHRP-6 administration, our finding that the central actions of GHRP-6 remain intact in these animals suggests the possible existence of two subpopulations of putative GHRP-6 receptors.

Journal of Endocrinology (1995) 146, 519–526
Effects of melatonin in the mediobasal hypothalamus on the secretion of gonadotrophins in sheep: role of dopaminergic pathways
Authors: Tortonese D J , Lincoln G A
Published: December 2008

Previous studies have shown that treatment with microimplants of melatonin in the mediobasal hypothalamus (MBH) of sexually inactive Soay rams exposed to long days induces an increase in the secretion of FSH and reactivation of the testicular axis, as normally occurs in response to short days. The current study was conducted to investigate the possible involvement of hypothalamic dopaminergic (DA) systems in this melatonin-induced effect. At 10 weeks under long days, sexually inactive Soay rams were treated in the MBH with micro-implants containing bromocriptine (DA agonist) or sulpiride (DA antagonist), given alone or in combination with melatonin, to establish whether the DA drugs would mimic or negate the effects of melatonin. All micro-implants were inserted bilaterally and left in place for 14 weeks; the study lasted a total of 28 weeks (14 weeks implant period and 14 weeks post-implant period) while the animals remained under long days. The ability of the micro-implants to release bromocriptine and sulpiride for 14 weeks was confirmed by incubating implants in vitro and testing for the presence of the compounds in the incubate using a pituitary cell bioassay. Profiles of FSH, determined in blood samples collected three times weekly, were significantly different among treatments (time × treatment interaction, P<0·001, ANOVA). Melatonin in the MBH induced a marked increase in the concentrations of FSH during the implant period, and a decrease during the post-implant period (P<0·001). Bromocriptine given alone in the MBH induced a decrease in the concentrations of FSH which became statistically different from the control during the post-implant period (P<0·05). Treatment with sulpiride alone also resulted in a suppressive effect during the post-implant period (P<0·01). When given in combination with melatonin, bromocriptine or sulpiride significantly reduced the melatonin-induced increase in the concentrations of FSH observed during the implant period (P<0·001). The results support the view that DA pathways in the MBH play an important role in the inhibitory regulation of gonadotrophin secretion in the ram. The inhibitory effect of bromocriptine is likely to result from the direct activation of the hypothalamic DA receptors linked to GnRH neurones regulating the secretion of FSH. The apparent paradoxical inhibitory effect of sulpiride is thought to be due to enhanced gonadal steroid negative feedback resulting from blockade of the inhibitory DA pathways, as evidenced by significantly increased secretion of testosterone (P<0·05) in the animals receiving sulpiride in combination with melatonin. The observation that DA drugs modified the effects of melatonin in the MBH provides evidence that hypothalamic DA pathways may participate in the mechanism by which melatonin mediates the effects of photoperiod on reproductive function in the ram.

Journal of Endocrinology (1995) 146, 543–552
The role of excitatory amino acid pathways in the control of pituitary function in neonatally oestrogenized male rats
Authors: Pinilla L , Tena-Sempere M , Aguilar E
Published: December 2008

It is well known that in the rat neonatal manipulation of the sex steroid environment results in altered hypothalamic-pituitary function in adulthood which implies an abnormal prolactin secretion and gonadotrophin response to orchidectomy. The present paper analyses the involvement of excitatory amino acid pathways in the disturbed gonadotrophin and prolactin secretion in male rats neonatally injected with oestradiol benzoate (500 μg on the day of birth). In the first experiment, 60-day-old control and oestrogenized male rats (intact or orchidectomized a week before) were killed 15 min after injection of vehicle, N-methyl-d-aspartic acid (NMDA; 15 mg/kg) or kainic acid (KA; 15 mg/kg). In the second experiment, prepubertal males were killed 15 min after injection of vehicle or NMDA. In the third experiment 30-, 45-, 60-and 90-day-old intact control and oestrogenized males were killed 15 min after injection of vehicle or KA. In the fourth experiment, control and oestrogenized males were sham-orchidectomized, orchidectomized or orchidectomized and implanted with Silastic capsules at 30 days of age and killed on day 90, 15 min after vehicle or KA injection.

We found that (1) as previously reported, oestrogenized males showed hyperprolactinaemia and absence of LH and FSH responses after orchidectomy, (2) the stimulatory effect of NMDA on LH secretion was observed in prepubertal control and in prepubertal and adult oestrogenized males, (3) KA stimulated LH secretion only in prepubertal (30-day-old) and peripubertal (45-day-old) control males, whereas stimulation was observed in oestrogenized males at all ages studied, except when they were implanted with testosterone, (4) FSH secretion was only stimulated in oestrogenized orchidectomized males, and (5) prolactin secretion was inhibited by NMDA and KA in control and oestrogenized males.

The greater effectiveness of NMDA and KA on gonadotrophin secretion in oestrogenized males, a finding especially noticeable after orchidectomy, may reflect the existence of a greater pool of releasable GnRH, a consequence of the absence of response to orchidectomy. The decrease in prolactin secretion after NMDA or KA administration in oestrogenized males may be mediated by an increase in dopaminergic tone, presumably reduced in the hyperprolactinaemic oestrogenized males. Finally, the effectiveness of KA on prolactin and LH secretion was maintained in adult oestrogenized males, perhaps because of the permanent decrease in testosterone secretion.

Journal of Endocrinology (1995) 147, 51–57
Interaction between activin A and cAMP in the induction of FSH receptor in cultured rat granulosa cells
Authors: Nakamura M , Nakamura K , Igarashi S , Tano M , Miyamoto K , Ibuki Y , Minegishi T
Published: December 2008

The acquisition of FSH receptor during preantral folliculogenesis is believed to be a key step in the subsequent development of follicles. We examined the interaction between activin and cAMP in FSH receptor induction in rat granulosa cells by measuring 125I-FSH binding and FSH receptor mRNA. In the 125I-FSH binding study, 0·2 mm 8-Br-cAMP and 1 μm forskolin were maximally effective in FSH receptor induction (169 and 220% respectively of control), while higher concentrations gave attenuated responses. It appears that cAMP has ambivalent effects on FSH receptor induction depending on the concentration and length of exposure. Activin alone dramatically increased the number of FSH receptors (314% of control). Moreover, synergistic effects of activin and 8-Br-cAMP or forskolin were observed on FSH receptor induction: a combination of activin (80 ng/ml) and low doses of 8-Br-cAMP (0·2 mm) or forskolin (1 μm) was most effective (160 or 140% of that induced by activin alone) and receptor levels reached a maximum at 24 h. These levels then markedly decreased after 72 h of incubation. Northern blot analysis revealed that the combination of activin (80 ng/ml) and 8-Br-cAMP (0·2 mm) or forskolin (1 μm) increased FSH receptor mRNA to about 140% of that induced by activin alone. These results indicate that activin and cAMP induced FSH receptor synergistically. However, activin did not enhance the production of cAMP induced by forskolin. In addition, a protein kinase A inhibitor (H89) (2 μm), which inhibited the effects of forskolin, had no effect on the action of activin. Taken together, the present findings suggest that the action of activin is not via a cAMP pathway, and that activin works co-operatively with cAMP on folliculogenesis.

Journal of Endocrinology (1995) 147, 103–110
Induced luteal regression in the primate: evidence for apoptosis and changes in c-myc protein
Authors: Fraser H M , Lunn S F , Cowen G M , Illingworth P J
Published: December 2008

There is increasing molecular evidence that apoptosis is involved in the process of structural luteal regression in non-primate species. Apoptosis is dependent upon the activation of certain proto-oncogenes and c-myc protein has an important regulatory role in this process in some cell types. The aim of the present study was to determine the occurrence and localisation of c-myc protein within the primate corpus luteum, determine changes during induction of luteal regression and examine the corpora lutea for morphological evidence of apoptosis. Ovaries were studied from marmoset monkeys in the late follicular, and in the early, mid and late luteal phases. Luteal regression was induced either by treatment with prostaglandin F2α analogue or GnRH antagonist administered during the mid luteal phase and ovaries obtained 24 and 48 h later. Immunocytochemistry was performed using a monoclonal antibody to the c-myc protein. In pre-ovulatory follicles positive staining was found in the nucleus of a few granulosal cells and in the cytoplasm of thecal cells. c-myc was present in all corpora lutea where it was localised predominantly in the cytoplasm. In early corpora lutea, scattered cells with intense staining were observed in the presence of a majority of moderately or weakly stained cells. In the mid and late luteal phases, corpora lutea were uniformly moderately stained for c-myc. Following induction of luteal regression, nuclear degeneration with condensation and fragmentation indicative of apoptosis was observed. In other luteal cells, increased cytoplasmic volume and dissolution of cellular and nuclear membranes suggested necrosis. After luteal regression the overall intensity of staining for c-myc declined, but was present at high signal concentration in the cytoplasm of those cells whose morphological integrity was best maintained following treatment. In a minority of steroidogenic luteal cells, both nuclear and cytoplasmic staining was observed. These results suggest that after ovulation there appears to be a marked increase in c-myc production in the cytoplasm of the luteal cells of the developing corpus luteum and that c-myc is present throughout the luteal phase. During induced luteal regression c-myc may undergo a transitory rise and transfer to the nucleus and both apoptosis and necrosis occur during the process of luteolysis.

Journal of Endocrinology (1995) 147, 131–137
Charge heterogeneity of the AT1 angiotensin II receptor subtype in the rat lung
Authors: Montiel M , Quesada J , Jiménez E
Published: December 2008

In order to obtain more information on the molecular structure of the angiotensin II (Ang II) binding sites from whole rat lung membranes these were characterized by isoelectric focusing (IEF) and SDS-PAGE. Whereas a single population of Ang II receptor sites was identified (Kd=2·2± 0·3 nmol/l; Bmax=203·9± 15·8 fmol/mg protein) by Scatchard analysis, using IEF three Ang II binding isoforms were observed; a major band which migrated to isoelectric point (pI) 6·7, and two minor bands with pI values of 6·5 and 6·3 Specific binding of 125I-Ang II to rat lung membrane preparations was sensitive to Losartan, a non-peptide AT1, receptor subtype antagonist, but was unaffected by the AT2 receptor subtype antagonist CGP42112A. Immunoblotting analyses on SDS gels, using a monoclonal antibody specific to the AT1, receptor, showed two immunoreactive protein species of 45 and 48 kDa. Enzymic deglycosylation using recombinant N-glycanase did not alter the molecular weight patterns of the AT1, receptor subtype. The results of the present study demonstrated that the Ang II receptor population in the whole rat lung consists solely of the AT1, receptor subtype and that the AT2 receptor subtype is absent. In addition, the data showed the existence of charge heterogeneity of the AT1, receptor subtype, and suggest that glycosylation probably does not contribute to its charge heterogeneity.

Journal of Endocrinology (1995) 147, 153–159
Functional luteolysis in response to hydrogen peroxide in human luteal cells
Authors: Vega M , Carrasco I , Castillo T , Troncoso J L , Videla L A , Devoto L
Published: December 2008

To evaluate the effect of reactive oxygen species in human corpus luteum function, we investigated whether hydrogen peroxide (H2O2) affects the in vitro luteal cell production of steroids. H2O2 treatment (1·0–100 μm) of mid and late luteal cell cultures elicited a dose-dependent decrease in basal progesterone production. However, treatment of mid luteal cells with a low concentration of H2O2 0·01 μm) significantly stimulated progesterone secretion (P<0·05). In addition, H2O2 (100 μm) markedly inhibited human chorionic gonadotropin (hCG)-stimulated progesterone and estradiol secretion. cAMP production was enhanced (2·4-fold, P<0·05) by hCG treatment of luteal cells. The addition of H2O2 (0·1–100 μm) to hCG-stimulated luteal cell cultures elicited a decrease in cAMP concentration (P<0·05) and in the specific binding of radiolabeled hCG by luteal cells. Progesterone and estradiol production stimulated by dibutyryl cAMP were significantly inhibited by H2O2 (P<0·05). These findings suggest that H2O2 interferes with basal steroid production and, in hCG-stimulated conditions, it may inactivate the gonadotropin–receptor complex. The anti-steroidogenic action of H2O2 therefore raises the possibility of a modulatory role of H2O2 in human luteal steroidogenesis.

Journal of Endocrinology (1995) 147, 177–182
Pituitary and plasma levels of growth hormone in Booroola sheep that are either homozygous carriers or non-carriers of the FecBB fecundity gene
Authors: Moore L G , McNatty K P , Isaacs K L , Lun S , Ng Chie W , McNatty S , Hudson N L
Published: December 2008

The aim of this study was to examine the effect of the FecBB fecundity gene on plasma concentrations and pituitary content of growth hormone (GH) in sheep. No differences were found between homozygous carriers (BB) and non carriers (++) of the FecBB gene with regard to pituitary GH contents in both ovariectomized and intact ewes. However, ovariectomized ewes had higher levels of pituitary GH than intact ewes (P<0·01). There were no differences between FecBB genotypes with respect to plasma concentrations of GH in 6-year-old ovariectomized ewes bled every 10 min for 12 h or in ram lambs bled weekly during their first year of life. GH levels in the rams decreased until week 27, increased to a peak at week 31 then decreased before increasing again at week 43. Mean plasma GH concentrations in the ewe lambs bled weekly for a year decreased until week 19 then remained at approximately this level for the remainder of the year. Mean GH plasma concentrations in the ram lambs were higher than in the ewe lambs (P<0·001). Ewe lambs that were homozygous for the FecBB gene had lower body weights (P<0·05) and had higher levels of GH (P<0·01) than non carrier ewe lambs during their first year. Before the average age of first behavioural oestrus (36 weeks) GH levels in the ewe lambs were negatively correlated with body weights (r=−0·69, P<0·001, n=22). When body weight was included as a covariate in analysis of variance the genotype difference in ewe lamb plasma GH concentrations was no longer significant. In summary, pituitaries from ovariectomized ewes had higher levels of GH than those from intact ewes. There were no FecBB gene specific differences in pituitary levels of GH, the profile of plasma GH in 6-year-old ovariectomized ewes or in ram lambs during their first year of life. BB ewe lambs had higher levels of GH than ++ ewe lambs during their first year; however, this difference was probably due to the BB ewes having lower body weights than the ++ ewes because body weight was negatively correlated with mean GH levels.

Journal of Endocrinology (1995) 147, 217–223
Immunolocalisation of androgen receptor to interstitial cells in fetal rat testes and to mesenchymal and epithelial cells of associated ducts
Authors: Majdic G , Millar M R , Saunders P T K
Published: December 2008

Androgens are required for the development of male internal and external genitalia. Androgen action is mediated by an intracellular receptor which acts as a transcription factor following activation by ligand binding. The aim of the present study was to define the time of appearance of androgen receptor (AR) in the male fetal rat gonad using immunohistochemistry. Intact fetuses (days 13·5–16·5) or testicular tissue (days 16·5–20·5 and days 3–7 postnatal) were fixed in Bouins' solution and processed into paraffin wax. On day 16·5 nuclear AR were present in mesenchymal cells surrounding the Wolffian duct but those around the Mullerian duct were receptor negative. During the following day (17–18) the abundance of nuclear staining increased, becoming detectable in the epithelial cells of the Wolffian ducts. Within the testis some nuclear staining was apparent at day 17 but was confined to interstitial cells surrounding the seminiferous cords. As development of the testis proceeded the abundance of nuclear AR in peritubular and elongated mesenchymal cells increased. AR were not detected in fetal Leydig cells expressing 3β-hydroxysteroid dehydrogenase nor in the ovaries or associated ducts of female fetuses at the same ages.

In conclusion, in the rat we have found AR expression detectable by immunohistochemistry in mesonephric mesenchyme to be confined to that underlying the Wolffian ducts and to be absent from the area around the degenerating Mullerian duct. On and after day 17 of gestation AR is present in Wolffian duct epithelial cell nuclei and within the testis it is confined to peritubular and interstitial cells which may have migrated from the mesonephros. Fetal Leydig cells were receptor negative. Within the seminiferous cords AR in Sertoli cells remained low until after birth and some perinuclear staining was detected in cells thought to be gonocytes. We believe this to be the first report of immunolocalisation of AR to fetal testicular interstitial cells.

Journal of Endocrinology (1995) 147, 285–293
Differential expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in the developing ovine fetal liver and kidney
Authors: Langlois D A , Matthews S G , Yu M , Yang K
Published: December 2008

In adult mammals, liver and kidney are the two major sites of biosynthesis for 11β-hydroxysteroid dehydrogenase (11β-HSD) 1 and 2 respectively. In the present study, the expression of these two isozymes in the developing ovine fetal liver and kidney was characterized. Livers and kidneys were obtained from fetal sheep at days 85, 100–120 and 140–143 of gestation (term=145 days). Tissue levels of 11β-HSD2 mRNA were assessed by Northern blot analysis. 11β-HSD dehydrogenase and reductase activities in tissue homogenates were determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates respectively. The unidirectional 11β-HSD2 dehydrogenase activity was identified by its distinct co-factor preference (NAD), and by its unique ability to metabolize dexamethasone (Dex). In the liver, 11β-HSD1 dehydrogenase and reductase activities were present by day 85, and their levels did not change between days 85 and 100–120 but increased more than twofold at days 140–143. This was consistent with changes we reported previously in the fetal hepatic 11β-HSD1 mRNA. 11β-HSD1 reductase activity was always higher than the dehydrogenase activity. 11β-HSD2 mRNA and activity were undetectable in the fetal liver at all three ages. By contrast, 11β-HSD2 mRNA was present in the fetal kidney by day 85, and its abundance increased progressively thereafter. There was a parallel increase in the renal 11β-HSD2 activity. Dex was also converted to 11-dehydro-Dex by the fetal kidney. In keeping with the absence of the full-length 11β-HSD1 mRNA, 11β-HSD1 activity was undetectable in the kidney. These results indicate that (1) 11β-HSD1 and 2 genes are differentially expressed and regulated in the fetal liver and kidney during development, (2) since the hepatic 11β-HSD1 reductase activity is always higher than the dehydrogenase activity, the fetal liver may be a potential extra-adrenal source of cortisol, and (3) 11β-HSD2 in the kidney may play a very important role in protecting the fetus from elevated levels of bioactive glucocorticoids.

Journal of Endocrinology (1995) 147, 405–411
Adrenalectomy induces a decrease in the light scatter properties and amylase content of isolated zymogen granules from rat pancreas as analyzed by flow cytometry
Authors: Garcia-Montero A C , De Dios I , Rodriguez A I , Orfao A , Manso M A
Published: December 2008

The effect of glucocorticoid deprivation induced in male rats by adrenalectomy on the pancreatic zymogen granules was studied. Zymogen granules were purified from control, sham-operated and adrenalectomized animals studied 1, 3 and 7 days after surgery. The zymogen granules were characterized by flow cytometry, and in each granule the size (based on the forward or low angle light scatter (FSC) parameter), membrane complexity (based on side or 90° light scatter (SSC) parameter) and amylase content were evaluated. Amylase content/DNA ratio in pancreatic homogenates was also analyzed. The zymogen granules of the control rats were found to be distributed in two populations: a major one – R1 (95·45 ± 1·21%) – containing zymogen granules with a smaller mean size and complexity, and a minor population - R2 (4·45 ± 0·24%) – the granules of which had a mean size which was larger and more complex. At day +1 after adrenalectomy the zymogen granules were significantly (P<0·05) smaller than those of control animals. The R2 zymogen granules were similar to those from R1 as regards their size, but were more complex, suggesting that the immediate effect of glucocorticoid deprivation is to induce a depletion of the larger granules presumably belonging to the R2 population. The amount of amylase per granule did not vary at day +1 after adrenalectomy, although the amylase content/size ratio per granule was significantly (P<0·001) increased. This mechanism could be explained in terms of the existence of a bypass defined in the adrenalectomized animals between the granular content and cytosolic enzymes. Prolongation of the adrenalectomy period to 3 and 7 days resulted in a progressive increase in zymogen granule size and complexity, both parameters showing similar characteristics to those of the controls at day +7 after adrenalectomy. However, the percentage of zymogen granules within the R1 and R2 populations was clearly different from that of controls since the R2 population was much more numerous (11·25 ± 0·75% and 15·25 ± 1·15% (adrenalectomized rats at days +3 and +7 respectively) versus 4·45 ± 0·24% (controls)). An increase in the content of amylase per DNA was observed in adrenalectomized rats at day +1 although this transient effect cannot be related to glucocorticoid deprivation because it was also observed in sham-operated rats (day +1). However, a significant reduction, nearly 64%, in the amylase content/DNA ratio is produced by the absence of glucocorticoids 7 days after adrenalectomy and this is associated with a reduction in the content of amylase in each individual zymogen granule which reaches a minimum 3 days after adrenalectomy. It should be noted that, despite this, the enzyme concentration in each granule remains constant as there is a parallel decrease in the zymogen granule amylase content and size.

Journal of Endocrinology (1995) 147, 431–440
Chloride channels in the apical membrane of thyroid epithelial cells are regulated by cyclic AMP
Authors: Bourke J R , Sand O , Abel K C , Huxham G J , Manley S W
Published: December 2008

Porcine thyroid epithelial cells cultured as a monolayer with their apical membranes facing the medium are known to absorb Na+ and to secrete the anions Cl− and HCO3−. Chloride channels were found in the apical membrane, and displayed a reversal potential close to the resting membrane potential, linear current–voltage relationships, a conductance at physiological temperature of 6·5 pS, and a small but significant permeability to HCO3−. Stimulation of ion transport with prostaglandin E2 or 8-(4-chlorophenylthio) adenosine 3′:5′-cyclic monophosphate promoted activation of Cl− channels in cell-attached patches, and excised patches were reactivated by exposure of their cytoplasmic surface to protein kinase A and ATP. Physiological temperatures were necessary for activation of Cl− channels in cell-attached patches. The channels exhibited sub-states with a conductance exactly half that of the full unit conductance, suggesting a dual-barrelled channel structure. It is concluded that the apical membrane of thyroid epithelial cells contains cyclic AMP-activated Cl− channels controlling anion transport.

Journal of Endocrinology (1995) 147, 441–448
Bioactive oxytocin in human and baboon corpora lutea
Authors: Khan-Dawood F S , Yang J , Anwer K , Dawood M Y
Published: December 2008

Oxytocin has been identified in both non-human primate and human corpora lutea of the menstrual cycle by RIA, immunocytochemistry and HPLC. Evidence for the transcription of the oxytocin gene in this tissue using PCR is available. Oxytocin receptors have been characterized by biochemical procedures. However, there is some debate as to whether the oxytocin identified in these tissues is biologically active and has a role in luteal function. In this study we have demonstrated that oxytocin isolated by gel chromatography of tissue extracts from the baboon and the human corpus luteum is biologically active as determined in a rat uterine bioassay. Since both oxytocin and its receptors are present in these tissues, it is suggested that oxytocin in the human and non-human primate corpora lutea has a functional role.

Journal of Endocrinology (1995) 147, 525–532
Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat
Authors: Streck Randal D. , Rajaratnam Veeraramani S. , Fishman Renata B. , Webb Peggy J.
Published: December 2008

Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.
Contractors’ experiences of integrated management systems
Authors: Griffith A. , Bhutto K.
Published: December 2008

Integrated management systems (IMS) are an innovative method of handling the multitude of management functions and procedures that are applied throughout major construction projects. Quality, safety and environment are at the forefront of management systems evolution where the integration of these traditionally independent and dedicated organisational systems is expected to deliver a range of benefits through efficiency gains and operational effectiveness at both the company and project level. Building and civil engineering contracting organisations are implementing management integration in different ways and this makes the potential benefits of successful systems application difficult to identify and share widely throughout the industry. This paper reports on a government-funded PhD project that examined IMS developments in the construction industry. The research involved data obtained from a survey of 30 UK-based building and civil engineering companies together with interviews and case studies provided by five principal contractors at the leading-edge of management systems integration. The research found that IMS has the potential to deliver greater organisational effectiveness and efficiency and can improve project performance. It also identified that difficulties in system configuration and implementation are commonplace. The challenge is to establish a generic framework for IMS development which contractors can apply to their activities within the context of their core business.
Tubing Buckling—The State of the Art
Authors: Mitchell Robert F.
Published: December 2008

Almost unique in engineering analysis is the problem of tubing buckling in wellbores. In general, structures loaded above their critical load fail catastrophically. Yet, both tubing and drillstrings are commonly operated above the critical load. These tubing strings do not fail because the wellbore provides the necessary support for "post-buckling" equilibrium.

The two fundamental questions about tubing buckling are

What is the critical load? What is the post-buckled configuration?

The critical load tells us if the tubing will buckle. Euler solved the problem for "short" columns, but these results rarely have application in a wellbore because the pipes in a wellbore are usually very long (Timoshenko and Gere 1961). The first stability criterion that considered the stabilizing effect of weight on long pipes in inclined wellbores was developed by Dawson and Paslay (1984).

The post-buckled configuration tells us about tubing movement, bending stresses, contact forces, and axial-load distributions. The original buckling analysis by Lubinski et al. (1962) proposed a helical configuration in a vertical wellbore and used the method of virtual work to determine a specific constant pitch for that helix as a function of the axial force and bending stiffness.

These two works set the following themes for further analysis of tubing buckling:

What is the critical buckling load in curved, 3D wellbores? How does torque affect the critical buckling load? How do tapered strings affect the critical buckling load? What is the buckling configuration in inclined wellbores? How do the boundary conditions affect the configuration? How do tapered strings buckle? How does torque affect the buckling configuration? What effect does friction play in tubing buckling?

Many of these questions have been, at least, partly answered in the past three decades. This paper will examine the technical fundamentals of the tubing-buckling problem; summarize the most useful, new results from these papers, and discuss the remaining challenges in tubing-buckling analysis.
Casing-Collapse Strength Reduction Under Lateral Loads From Yielding Shales in the Daqing Oilfield
Authors: Ai Chi , Zhao Wanchun , Guo Boyun
Published: December 2008

Casing failure has been found in nearly 20% of production wells in the Daqing oil field after 45 years of oil-production history. Plastic failure of casing strings has been recognized in the zones of yielding shales overlying reservoir pay zones in the field. This type of casing failure is one of the most costly problems in the field. No research has been conducted to study the resistance of the casing string to the lateral loads from the yielding shales. This paper offers results from such research.

Assuming a lateral load uniformly distributed along a casing section from a clay zone clamped between an upper and a lower sandstone zone, a mechanistic model was developed in this study. Results of the model indicate that the resistance of casing string to the lateral loads drops sharply in the early stage of development of radial deformation. The resistance of the casing string to the lateral loads is not very sensitive to the longitudinal deformation. The remaining strength of the casing string also depends on properties of the casing string.

A calculation example is illustrated in this paper. This work provides an analytical tool that can be used for optimizing casing programs against lateral loads from yielding-clay zones to minimize casing failure and field-operation cost.
Real-Time Digital Interpretation of Subsea-Blowout-Preventer Tests
Authors: Winters Warren J. , Burns Tim A. , Livesay Ronald B.
Published: December 2008

A computer-based method expedites interpretation of pressure data during subsea blowout-preventer (BOP) tests. This can reduce the time and cost of current subsea-BOP testing practices in a safe and objective manner.

Currently, individual tests can require more than 1 hour of shut-in time, and a complete series of subsea-BOP tests may comprise at least 12 individual tests.

The digital method employs computer software to produce an accurate model of the pressure-decline behavior relatively early in each test. The model can thus predict if future pressures will stabilize at an acceptable level. With regulatory approval and a reliable method to forecast pressure, the duration of subsea-BOP tests can be reduced significantly.

Comparison of the digital method to conventional subsea-BOP testing on numerous field trials shows excellent agreement. If implemented, the digital method could save hours of valuable critical-path rig time during every series of subsea-BOP tests.

Working in concert with regulatory authorities to gain endorsement of this method is integral to the project. Functionality of the software, example results, and implementation status are reported.
Glycogen Synthase Kinase-3 and Mammalian Target of Rapamycin Pathways Contribute to DNA Synthesis, Cell Cycle Progression, and Proliferation in Human Islets
Authors: Liu Hui , Remedi Maria S. , Pappan Kirk L. , Kwon Guim , Rohatgi Nidhi , Marshall Connie A. , McDaniel Michael L.
Published: December 2008

OBJECTIVE—Our previous studies demonstrated that nutrient regulation of mammalian target of rapamycin (mTOR) signaling promotes regenerative processes in rodent islets but rarely in human islets. Our objective was to extend these findings by using therapeutic agents to determine whether the regulation of glycogen synthase kinase-3 (GSK-3)/β-catenin and mTOR signaling represent key components necessary for effecting a positive impact on human β-cell mass relevant to type 1 and 2 diabetes.

RESEARCH DESIGN AND METHODS—Primary adult human and rat islets were treated with the GSK-3 inhibitors, LiCl and the highly potent 1-azakenpaullone (1-Akp), and with nutrients. DNA synthesis, cell cycle progression, and proliferation of β-cells were assessed. Measurement of insulin secretion and content and Western blot analysis of GSK-3 and mTOR signaling components were performed.

RESULTS—Human islets treated for 4 days with LiCl or 1-Akp exhibited significant increases in DNA synthesis, cell cycle progression, and proliferation of β-cells that displayed varying degrees of sensitivity to rapamycin. Intermediate glucose (8 mmol/l) produced a striking degree of synergism in combination with GSK-3 inhibition to enhance bromodeoxyuridine (BrdU) incorporation and Ki-67 expression in human β-cells. Nuclear translocation of β-catenin responsible for cell proliferation was found to be particularly sensitive to rapamycin.

CONCLUSIONS—A combination of GSK-3 inhibition and nutrient activation of mTOR contributes to enhanced DNA synthesis, cell cycle progression, and proliferation of human β-cells. Identification of therapeutic agents that appropriately regulate GSK-3 and mTOR signaling may provide a feasible and available approach to enhance human islet growth and proliferation.
m.3243A>G Mutation in Mitochondrial DNA Leads to Decreased Insulin Sensitivity in Skeletal Muscle and to Progressive β-Cell Dysfunction
Authors: Lindroos Markus M. , Majamaa Kari , Tura Andrea , Mari Andrea , Kalliokoski Kari K. , Taittonen Markku T. , Iozzo Patricia , Nuutila Pirjo
Published: December 2008

OBJECTIVE—To study insulin sensitivity and perfusion in skeletal muscle together with the β-cell function in subjects with the m.3243A>G mutation in mitochondrial DNA, the most common cause of mitochondrial diabetes.

RESEARCH DESIGN AND METHODS—We measured skeletal muscle glucose uptake and perfusion using positron emission tomography and 2-[18F]fluoro-2-deoxyglucose and [15O]H2O during euglycemic hyperinsulinemia in 15 patients with m.3243A>G. These patients included five subjects with no diabetes as defined by the oral glucose tolerance test (OGTT) (group 1), three with GHb <6.1% and newly found diabetes by OGTT (group 2), and seven with a previously diagnosed diabetes (group 3). Control subjects consisted of 13 healthy individuals who were similar to the carriers of m.3243A>G with respect to age and physical activity. β-Cell function was assessed using the OGTT and subsequent mathematical modeling.

RESULTS—Skeletal muscle glucose uptake was significantly lower in groups 1, 2, and 3 than in the control subjects. The glucose sensitivity of β-cells in group 1 patients was similar to that of the control subjects, whereas in group 2 and 3 patients, the glucose sensitivity was significantly lower. The insulin secretion parameters correlated strongly with the proportion of m.3243A>G mutation in muscle.

CONCLUSIONS—Our findings show that subjects with m.3243A>G are insulin resistant in skeletal muscle even when β-cell function is not markedly impaired or glucose control compromised. We suggest that both the skeletal muscle insulin sensitivity and the β-cell function are affected before the onset of the mitochondrial diabetes caused by the m.3243A>G mutation.
Chain and network science: A research framework
Authors: (Onno) Omta S.W.F. , Trienekens Jacques H. , Beers George
Published: December 2008

In this first article of the Journal on Chain and Network Science the base-line is set for a discussion on contents and scope of chain and network theory. Chain and network research is clustered into four main ‘streams’: Network theory, social capital theory, supply chain management and business economics and organizational theory. Furthermore a research agenda is formulated. The article ends with management implications of the different contributions to this first issue.
E-Commerce Transition Model for Supply Chain Management
Authors: Lefebvre Louis A. , Cassivi Luc , Lefebvre Élisabeth
Published: December 2008

The creation of Internet-based companies is changing the way business is being carried out and increasing the pressure on traditional firms, which now need to adapt to the new challenges brought about by the so-called digital economy. Successful electronic commerce activities depend on the partners involved in the product or service being delivered. Firms able to communicate with their partners electronically for procurement, sales, or supply chain management have become what many call clicks-and-mortar companies.

An empirically based technological model that helps organizations understand the requirements of moving towards the seamless integration of intra- and inter- organizational processes is proposed. This five-wave transitional model accompanies key decision-makers through progressive steps that correspond to different business-to-business e-commerce needs and specifications. As organizations move along these technological waves, we can witness the gradual opening-up of new opportunities for carrying out business. This paper presents the model, its requirements and its technological and organizational underpinnings. The model is illustrated with examples from organizations in a major industrial sector.
Determinants of a firm’s likelihood to innovate and intensity of innovation in the Brazilian food industry
Authors: Cabral José E.O. , Bruce Traill W.
Published: December 2008

This paper defines the relative role of firms’ characteristics on both their likelihood to innovate and the intensity of innovation (innovative outputs). Using Christensen´s (1995; 1996) and Teece’s (1986) proposals for analysing assets (resources and capabilities) and inter-asset linkages in order to produce and commercially exploit technological innovation, a conceptual framework is defined suitable to identify the variables affecting the probability of a firm to innovate and those affecting a greater count of innovations, once the firm has decided to innovate.

Thus, a “double-hurdle” approach involving censored and truncated models was applied. The findings confirm that firms innovative assets investment in external technology, investment in R&D, and external alliances, alongside firm size are the significant variables in determining firms’ likelihood to innovate, whereas external alliances, firm size and market orientation are related to intensity to innovate in the Brazilian Food Industry.
A Contingency model of quality management and business-to-business relationships
Authors: Fynes Brian , de Búrca Seán , Ennis Sean
Published: December 2008

This paper aims to contribute to, and link the areas of quality management and business-to-business relationships. To date, there has been limited empirical work at the interface of these areas. Accordingly, this study proposes and tests an integrated model based on both research areas. In doing so, we seek to address the following research question: what is the relationship between quality practices, quality performance and business-to-business relationships? To address this question, we develop a conceptual model, which draws on the contingency approach to research that is common in the strategy literature. We then test model with data collected from suppliers in the electronics sector in the Republic of Ireland. Data analysis of the data indicated considerable support for the conceptual model. We conclude with some reflections of the implications of our findings for both theory and practice.
Food retailers’ buying behaviour: An analysis in 16 European countries
Authors: Skytte Hans , Blunch Niels J.
Published: December 2008

This paper presents results from a study on food retailer buying behaviour, i.e., how the retailers judge product and vendor attributes when choosing a new supplier of a product category that is already well known to them. A conjoint analysis was conducted in 16 Western European countries. The study encompassed the retailers’ buying behaviour for fish and cheese products. The results demonstrate that the traditional four P’s are losing ground to some previously neglected attributes, which now demand consideration by retail suppliers of products and services and by researchers.
Innovation in chains and networks
Authors: (Onno) Omta S.
Published: December 2008

In this editorial contribution I will sketch a theoretical framework for research on innovation in chains and networks. Interested research groups around the world can use this information to determine whether it is of interest for them to participate in cooperative research with our group in Wageningen. For it is our ambition to build a worldwide virtual knowledge centre on innovation in chains and networks.
Weight Loss Prevention in Nursing Home Residents: A Pilot Study to Determine Administrative Strategies
Authors: Dyck Mary J.
Published: December 2008

Weight loss is a common problem for nursing home residents. Although clinical interventions to prevent and treat weight loss are readily available, administrative interventions to prevent weight loss are not identified in the literature. The purpose of this study was to identify administrative strategies that Directors of Nursing could use to prevent weight loss in nursing home residents. A modified three-round Delphi method with a mailed survey was used to develop consensus on administrative strategies. Percentage of panel agreement was determined for each intervention on each round. Eighteen administrative strategies were determined by the panel members, with 85% agreement; these strategies were identified and categorized. The categories and implications for further research are discussed.
Isolated Orbital Pseudotumor as the Presenting Sign of Systemic Lupus Erythematosus
Authors: Amirlak Iradj , Narchi Hassib
Published: December 2008

A 9-year-old girl presented with an orbital pseudotumor a few years prior to developing clinical features of systemic lupus erythematosus. Because the few similar cases previously reported were all adults, this patient is the first pediatric case described. The authors also review the relevant literature, especially in the pediatric age group.