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1

Tilapia follicle-stimulating hormone (FSH): immunochemistry, stimulation by gonadotropin-releasing hormone, and effect of biologically active recombinant FSH on steroid secretion.  

PubMed

In fish, FSH is generally important for early gonadal development and vitellogenesis. As in mammals, FSH is a heterodimer composed of an alpha subunit that is noncovalently associated with the hormone-specific beta subunit. The objective of the present study was to express glycosylated, properly folded, and biologically active tilapia FSH (tFSH) using the Pichia pastoris expression system. Using this material, we aimed to develop a specific ELISA and to enable the study of FSH response to GnRH. The methylotrophic yeast P. pastoris was used to coexpress recombinant genes formed by fusion of mating factor alpha leader and tilapia fshb and cga coding sequences. Western blot analysis of tilapia pituitary FSH, resolved by SDS-PAGE, yielded a band of 15 kDa, while recombinant tFSH beta (rtFSH beta) and rtFSH beta alpha had molecular masses of 17-18 kDa and 26-30 kDa, respectively. Recombinant tFSH beta alpha was found to bear only N-linked carbohydrates. Recombinant tFSH beta alpha significantly enhanced 11-ketotestosterone (11-KT) and estradiol secretion from tilapia testes and ovaries, respectively, in a dose-dependent manner (similar to tilapia pituitary extract, affinity-purified pituitary FSH, and porcine FSH). Using antibodies raised against rtFSH beta, FSH-containing cells were localized adjacent to hypothalamic nerve fibers ramifying in the proximal pars distalis (PPD), while LH cells were localized in a more peripheral region of the PPD. Moreover, FSH is under the control of hypothalamic decapeptide GnRH, an effect that was abolished through the use of specific bioneutralizing antisera, anti-rtFSH beta. It also reduced basal secretion of 11-KT. PMID:17192515

Aizen, Joseph; Kasuto, Harel; Golan, Matan; Zakay, Hila; Levavi-Sivan, Berta

2006-12-27

2

Hypothalamic, pituitary and gonadal regulation of FSH.  

PubMed

FSH is a key reproductive hormone involved in the control of ovarian folliculogenesis and steroidogenesis. Multiple regulatory mechanisms govern the release of FSH. These regulatory mechanisms appear to work in concert to modulate the level, pattern and biological potency of circulating FSH, thereby adjusting the gonadotrophic stimulus to meet the challenge of a changing physiological need. This review (i) summarizes various neuroendocrine, autocrine and paracrine mechanisms involved in the control of FSH production and secretion; (ii) identifies possible mechanisms by which LH and FSH are differentially released from the same gonadotrophs; (iii) considers the means by which changes in the quality of the FSH signal are regulated and the implication of such changes; and (iv) emphasizes how large animal models have helped to advance our understanding of FSH control. PMID:12698974

Padmanabhan, V; Karsch, F J; Lee, J S

2002-01-01

3

A 66-kDa protein of bovine hypophyseal Pars tuberalis induces luteinizing hormone release from rat Pars distalis.  

PubMed

In this study, evidence for a factor secreted by bovine hypophyseal pars tuberalis that stimulates luteinizing hormone (LH) release from rat pars distalis cells is shown. The secretion products of bovine pars tuberalis cells into the culture medium were assayed on dispersed rat pars distalis cells in 30 min incubations and superfusion experiments. The culture medium from pars tuberalis total cell populations, added at a dose of 6 microg per tube, induced the greater LH release from pars distalis cells, without effect on follicle stimulating hormone (FSH) release. After pars tuberalis cells separation on a discontinuos Percoll gradient, only the culture medium of cells from 50 and 60% strength Percoll were able to release LH from rat pars distalis cells. Therefore, cell fractions from 50 and 60% strenght Percoll were cultured together. To elicit maximal LH release (6 times the basal output), with the addition of 2 microg of pars tuberalis protein was required, suggesting that these cells produce the factor or factors which affect pars distalis gonadotrope cells. After applying the pars tuberalis culture medium on 12% SDS-PAGE, the band with biological activity was that of 66-kDal. Fifty ng protein of its eluate released almost 9 times the basal output of LH from pars distalis cells. Results suggest a modulating effect of a protein from the bovine pars tuberalis on rat cultured gonadotrope cells from the pars distalis. PMID:19181183

Lafarque, Martha; Oliveros, Liliana

2008-12-01

4

Par4  

Microsoft Academic Search

Prostate apoptosis response-4 (Par-4) is a 38-kDa protein initially identified as the product of a gene upregulated in prostate\\u000a tumor cells undergoing apoptosis. Par-4 contains both a death domain and a leucine zipper domain, and has been shown to interact\\u000a with several proteins known to modulate apoptosis, including protein kinase C?, Bcl-2, and caspase-8. A rapid increase in\\u000a Par-4 levels

Mark P. Mattson; Wenzhen Duan; Sic L. Chan; Simonetta Camandola

1999-01-01

5

eFSH in clinical equine practice.  

PubMed

Equine follicle stimulating hormone (eFSH) has been used to induce follicular development in transitional mares and problem acyclic mares, as well as superovulate cycling mares. The most efficacious protocol is to administer 12.5 mg eFSH, intramuscularly, twice daily beginning 5 to 7 days after ovulation when the diameter of the largest follicle is 20 to 25 mm. Prostaglandins are to be administered on the second day of eFSH therapy. Treatment with eFSH is continued for 3 to 5 days until follicle(s) are >or=35 mm in diameter. The mare is subsequently allowed to 'coast' for 36 h, after which human chorionic gonadotropin is administered to induce ovulation. PMID:17548106

McCue, P M; LeBlanc, M M; Squires, E L

2007-06-04

6

Expression of FSH and its co-localization with FSH receptor and GnRH receptor in rat cerebellar cortex.  

PubMed

The expression of follicle-stimulating hormone (FSH) and its receptor in extrapituitary and non-HPG axis tissues has been demonstrated and their non-reproductive functions in these tissues have been found. However, there have been no reports concerning the expression and function of FSH and its receptor in the cerebellum. In our study, immunofluorescence staining and in situ hybridization were used to detect the expression of FSH, double-labeled immunofluorescence staining was used to detect co-localization of FSH and its receptor and co-localization of FSH and gonadotropin-releasing hormone (GnRH) receptor in the rat cerebellar cortex. Results showed that some cells of the Purkinje cell layer, granular layer, and molecular layer of the cerebellar cortex showed both FSH immunoreactivity and FSH mRNA positive signals; not only for FSH and FSH receptor, but also for FSH and GnRH receptor co-localized in some cells throughout the Purkinje cell layer, granular layer, and molecular layer of the cerebellar cortex. These suggested that rat cerebellum could express FSH; cerebellum is a target tissue of FSH; FSH may exert certain functions through FSH receptor in a paracrine or autocrine manner; GnRH may regulate FSH positive cells through GnRH receptor in the cerebellum. Our study provides morphological evidence for further functional research on FSH and related hormones in the cerebellum. PMID:22972435

Chu, Chenyu; Zhou, Jing'an; Zhao, Yaqun; Liu, Ce; Chang, Pengfei; Zhou, Qing; Zhao, Li; Huang, Weiquan

2012-09-13

7

Clinical Pharmacology of Recombinant Human Follicle-Stimulating Hormone (FSH). I. Comparative Pharmacokinetics with Urinary Human FSH  

Microsoft Academic Search

Objective: To assess and compare the pharmacokinetics of recombinant human FSH with those of a reference preparation of urinary human FSH.Design: Urinary human FSH and recombinant human FSH (Metrodin and Gonal-F; Laboratoires Serono, Aubonne, Switzerland) were administered in a balanced, random order, crossover sequence as a single IV dose of 150 or 300 IU separated by 1 week of washout

Jean-Yves le Cotonnec; Hervé Claude Porchet; Vanya Beltrami; Azhar Khan; Steeve Toon; Malcolm Rowland

1998-01-01

8

Can cycle day 7 FSH concentration during controlled ovarian stimulation be used to guide FSH dosing for in vitro fertilization?  

PubMed Central

Background When stimulating a patient with poor ovarian response for IVF, the maximal dose of gonadotropins injected is often determined by arbitrary standards rather than a measured response. The purpose of this study was to determine if serum FSH concentration during an IVF stimulation cycle reflects follicular utilization of FSH and whether serum FSH values may inform dose adjustments of exogenous FSH. Methods In this retrospective cross sectional study we studied 155 consecutive IVF cycles stimulated only with recombinant human FSH. We only included long GnRH agonist protocols in which endogenous FSH levels were suppressed. We correlated the serum concentration of cycle?day (CD) 7 FSH with the number of oocytes retrieved, cleaving embryos and pregnancy rate. Results We found that a CD7 FSH concentration above 22?IU/L was associated with poor response regardless of the daily dose of FSH injected and a lower pregnancy rate. Conclusions We concluded that CD7 FSH concentration during stimulation could be used to guide FSH dosing in poor responders. If the CD7 FSH concentration is above 22?IU/L increasing the dose of FSH in an attempt to recruit more growing follicles is unlikely to be successful.

2013-01-01

9

Pulsatile release of FSH for superovulation in cattle  

Microsoft Academic Search

The studies reported here were directed towards the development of an implantable microcapsule which “pulses” release of follicle stimulating hormone, FSH, for application to superovulating cows. Final dose forms were administered using membrane-coated cylinders. The “pulse” of the FSH is achieved by membrane encapsulation of an effervescent\\/swelling core containing citric acid, sodium bicarbonate, glucose and FSH. Entry of water results

A. G. Jimoh; D. L. Wise; J. D. Gresser; R. H. Foote; R. C. Rhodes; L. H. Underbill; D. J. Trantolo

1995-01-01

10

Transcriptome analysis of FSH and FSH variant stimulation in granulosa cells from IVM patients reveals novel regulated genes  

Microsoft Academic Search

FSH is crucial for oocyte maturation and fertility and is the main component in infertility treatment in assisted reproduction. The granulosa cells expressing the FSH receptor interact with the oocyte and provide nourishing substrates controlling the oocyte maturation. Thus, transcriptome analysis of granulosa cells stimulated by FSH is of major importance in understanding the com- munication between oocytes and granulosa

S. Perlman; T. Bouquin; B. van den Hazel; T. H. Jensen; H. T. Schambye; S. Knudsen; J. S. Okkels

2006-01-01

11

Impact of highly purified urinary FSH and recombinant FSH on haemostasis: an open-label, randomized, controlled trial  

Microsoft Academic Search

BACKGROUND: It has recently been suggested that recombinant FSH administration may result in an increased risk of venous thrombosis. An open-label, randomized, controlled trial was carried out to compare the impact of urinary and recombinant FSH on haemostasis. METHODS: Fifty infertile women were randomized, using a random number generator on a personal computer, to receive either highly purified urinary FSH

G. Ricci; F. Cerneca; R. Simeone; C. Pozzobon; S. Guarnieri; A. Sartore; R. Pregazzi; S. Guaschino

2004-01-01

12

Selective modulation of FSH and LH secretion by steroids.  

PubMed

Significant divergence between the pattern of FSH and LH secretion has been observed in the ovulatory cycle, after ovariectomy and during puberty. The presence of an FSH-releasing factor, gonadal FSH inhibiting and releasing peptides and changes in the pulsatile pattern of LHRH secretion are among the postulates used to explain the divergent secretion of FSH and LH. Experiments in our laboratory have shown considerable evidence of differential regulation of FSH and LH secretion by steroids in the absence of gonadal regulatory peptides. Natural and synthetic estrogens show significant differences in the suppression of FSH and LH in the ovariectomized rat using a standard uterine response to the estrogen as the end point. In the immature ovariectomized rat treated with a low dose of estradiol that is sufficient for the synthesis of progesterone receptors to ensure progesterone sensitivity, but not large enough to induce estrogen triggered LH surges, progesterone administration resulted in a pattern of LH and FSH secretion similar to that observed on the day of proestrus in the cycling rat. Selective secretion of FSH was induced in the estrogen primed immature rat model by the administration of progesterone metabolite 5 alpha-dihydroporgesterone (5 alpha-DHP) while selective LH secretion was induced by 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP). The selective secretion of FSH and LH induced by progesterone metabolites was confirmed in the immature female rat primed with PMSG and maintained in constant light. 5 alpha-DHP was also able to induce a greater release of FSH when administered to the adult cycling rat on proestrus. The priming of the pituitary gonadotrope in secreting a high baseline level of FSH or responding to LHRH in releasing a greater amount of FSH appeared to be an important factor in selective FSH release and such priming can be brought about by 5 alpha-DHP in the absence of gonadal regulatory peptides. PMID:3124517

Mahesh, V B; Murphy, L L; O'Conner, J L

1987-01-01

13

Further evidence for direct pro-resorptive actions of FSH.  

PubMed

We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive G(i)-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNFalpha, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid peri-menopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade. PMID:20171951

Sun, Li; Zhang, Zhiyuan; Zhu, Ling-Ling; Peng, Yuanzhen; Liu, Xuan; Li, Jianhua; Agrawal, Manasi; Robinson, Lisa J; Iqbal, Jameel; Blair, Harry C; Zaidi, Mone

2010-02-19

14

Further Evidence for Direct Pro-Resorptive Actions of FSH  

PubMed Central

We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive Gi-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNF?, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid perimenopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade.

Sun, Li; Zhang, Zhiyuan; Zhu, Ling-Ling; Peng, Yuanzhen; Liu, Xuan; Li, Jianhua; Agrawal, Manasi; Robinson, Lisa J.; Iqbal, Jameel; Blair, Harry C.; Zaidi, Mone

2011-01-01

15

Breed differences in clearance of porcine FSH in hypophysectomized rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

Extracts of anterior pituitary (AP) glands were infused iv into hypophysectomized male rats followed by sequential sampling of blood for 120 min. Determination of follicle-stimulating hormone (FSH) concentrations established that FSH from Chinese Meishan males decreased in the circulation of rats mo...

16

Follicle-stimulating hormone (FSH) unmasks specific high affinity FSH-binding sites in cell-free membrane preparations of porcine granulosa cells  

SciTech Connect

The purpose of these studies was to determine whether changes in FSH receptors correlated with FSH-induced attenuation of FSH-responsive adenylyl cyclase in immature porcine granulosa cells. Cells were incubated with FSH (1-1000 ng/ml) for up to 24 h, treated with acidified medium (pH 3.5) to remove FSH bound to cells, and incubated with (125I)iodo-porcine FSH to quantify FSH-binding sites. FSH increased binding of FSH in a time-, temperature-, and FSH concentration-dependent manner. FSH (200 ng/ml) increased binding approximately 4-fold within 16 h. Analysis of equilibrium saturation binding data indicated that the increase in binding sites reflected a 2.3-fold increase in receptor number and a 5.4-fold increase in apparent affinity. The increase in binding did not appear to be due to 1) a decrease in receptor turnover, since the basal rate of turnover appeared to be very slow; 2) an increase in receptor synthesis, since agents that inhibit protein synthesis and glycosylation did not block the increase in binding; or 3) an increase in intracellular receptors, since agents that inhibit cytoskeletal components had no effect. Agents that increase intracellular cAMP did not affect FSH binding. The increase in binding appeared to result from unmasking of cryptic FSH-binding sites, since FSH increased binding in cell-free membrane preparations to the same extent as in cells. Unmasking of cryptic sites was hormone specific, and the sites bound FSH specifically. Unmasking of sites was reversible in a time- and temperature-dependent manner after removal of bound FSH. The similarity between the FSH dose-response relationships for unmasking of FSH-binding sites and attenuation of FSH-responsive cAMP production suggests that the two processes are functionally linked.

Ford, K.A.; LaBarbera, A.R.

1988-11-01

17

Avian LH and FSH: comparison of several radioimmunoassays  

SciTech Connect

Comparisons were made between various LH and FSH radioimmunoassays currently being used to measure avian hormones. The two LH assays were the homologous chicken system of Follett et al. (1972) and the turkey assay of Burke et al. (1979). These assays were also used in heterologous arrangement by interchanging the iodinated LH fractions and antisera. Five FSH assays were analyzed: two homologous chicken systems (Scanes et al., 1977; Sakai and Ishii, 1980) an assay based on mammalian materials (rat FSH and anti-ovine FSH antiserum, and one using labelled turkey FSH (Burke et al., 1979) with an anti-chicken FSH antiserum. The potencies of purified chicken and turkey gonadotrophin preparations and of a range of plasma samples from Japanese quail were measured in each assay. The two LH systems showed some degree of species specificity, such that chicken LH was more active than turkey LH in the chicken assay, whereas the reverse was true in the turkey LH assay. The potency estimates of the purified hormones in the various FSH assays were very consistent. The qualitative changes in plasma hormone levels were similar in all assays, although there were some differences in the magnitude of the responses.

Goldsmith, A.R.; Follett, B.K.

1983-04-01

18

Neuroendocrine control of FSH secretion: IV. Hypothalamic control of pituitary FSH-regulatory proteins and their relationship to changes in FSH synthesis and secretion.  

PubMed

The current dogma is that the differential regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and secretion is modulated by gonadotropin-releasing hormone (GnRH) pulse frequency and by changes in inhibins, activins, and follistatins both at the pituitary and at the peripheral level. To date no studies have looked at the overlapping function of these regulators in a combined setting. We tested the hypothesis that changes in GnRH pulse frequency alter the relative abundance of these regulators at the pituitary and peripheral levels in a manner consistent with changes in pituitary and circulating concentrations of FSH; that is, an increase in FSH will be accompanied by increased stimulatory input (activin) and/or reduced follistatin and inhibin. Ovariectomized ewes were subjected to a combination hypothalamic pituitary disconnection (HPD)-hypophyseal portal blood collection procedure. Hypophyseal portal and jugular blood samples were collected for a 6-h period from non-HPD ewes, HPD ewes, or HPD ewes administered GnRH hourly or every 3 h for 4 days. In the absence of endogenous hypothalamic and ovarian hormones that regulate gonadotropin secretion, 3-hourly pulses of GnRH increased pituitary content of FSH more than hourly GnRH, although these differences were not evident in the peripheral circulation. The results failed to support the hypothesis in that the preferential increase of pituitary content of FSH by the lower GnRH pulse frequency could be explained by changes in the pituitary content of inhibin A, follistatin, or activin B. Perhaps the effects of GnRH pulse frequency on FSH is due to changes in the balance of free versus bound amounts of these FSH regulatory proteins or to the involvement of other regulators not monitored in this study. PMID:22423050

Sharma, Tejinder P; Nett, Terry M; Karsch, Fred J; Phillips, David J; Lee, James S; Herkimer, Carol; Padmanabhan, Vasantha

2012-06-07

19

A Markov model of the cost-effectiveness of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH using comparative clinical trial data.  

PubMed

This study compared the cost and effectiveness of highly purified, human-derived follicle-stimulating hormone (FSH) (Bravelle) to recombinant FSH (Follistim) using Markov modeling and Monte Carlo simulation. One IVF treatment cycle resulted in costs of 11,584 dollars +/- 211 dollars for human-derived FSH and 12,762 dollars +/- 170 dollars for recombinant FSH, while three treatment cycles, holding the transition probabilities of the first cycle constant for the next two cycles, resulted in costs of 22,712 dollars +/- 1,107 dollars for human-derived FSH and 24,935 dollars +/- 1,205 dollars for recombinant FSH. PMID:15749525

Hatoum, Hind T; Keye, William R; Marrs, Richard P; Walton, Surrey M; Marshall, Dennis C

2005-03-01

20

Heterogeneity of rat FSH by chromatofocusing: studies on serum FSH, hormone released in vitro and metabolic clearance rates of its various forms.  

PubMed

Rat pituitary FSH was fractionated by chromatofocusing between pH 6 and 3. Ten components were resolved having apparent isoelectric points between 3.1 and 5.1. A comparative study of pituitary FSH and FSH secreted in vitro by quartered pituitary glands in the presence and in the absence of gonadotrophin-releasing hormone (GnRH) revealed similar patterns of charged species of intracellular and released FSH. Although GnRH increased FSH secretion about fourfold, no influence on the pattern of charged species was observed. Utilizing exclusion chromatography and chromatofocusing, pituitary FSH was compared to serum FSH which had been extracted by immuno-affinity chromatography. The results demonstrate for serum FSH a larger molecular size and a relative shift to more acidic components. Metabolic clearance rates of eight FSH components separated by chromatofocusing were measured in adult male rats. Half-lives varied between 13 min and several hours. A correlation existed between decrease of isoelectric points and decrease of metabolic clearance rates. These findings suggest that all hypophysial FSH components are secreted into the circulation at similar rates and the more acidic FSH components which appear to contain increased sialic acid, have a longer circulatory half-life and are more abundant in serum. It is concluded that sialylation may be involved in modulating serum FSH levels. PMID:3921643

Blum, W F; Gupta, D

1985-04-01

21

[From theory to clinical practice: recombinant FSH in daily practice].  

PubMed

The purpose of the present study is to determine the efficacy of induction ovulation with recombinant FSH in patients treated with in vitro fertilization and embryo transfer (IVF-ET) and basic assisted reproductive techniques (ART). One hundred seven cycles were analyzed. The patients were divided in two groups: Group 1, treated with IVF (n = 12) and group 2, treated with basic ART (n = 95). Only recombinant FSH was utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, were administered when one or more dominant follicles with diameter > or = 18 mm were presents; oocyte retrieval was performed 34 hour, while intrauterine insemination was practiced at 36 hours after the hCG injection. The pregnancy rate per IVF cycle was 25.0%, and 16.4% for basic ART. It is concluded that ovulation induction with recombinant FSH is a good and efficient alternative for both variations of ART. PMID:10504796

Kably Ambe, A; Barrón Vallejo, J; Góngora Rodríguez, A; Carballo Mondragón, E; Anta Jaén, E

1999-08-01

22

Localization of follicle-stimulating hormone (FSH) immunoreactivity and hormone receptor mRNA in testicular tissue of infertile men  

Microsoft Academic Search

Testicular biopsies from 82 oligo-or azoospermic male patients were subjected to immunostaining using anti-human FSH antibodies. Histological evaluation showed normal spermatogenesis (nspg) in 7 (FSH: 2.7±0.7), mixed atrophy (ma) in 63 (FSH:5.3±0.5), and bilateral or unilateral Sertoli Cell Only syndrome (SCO) in 12 (FSH:21.7±3.5) patients. For the relationship between FSH values and testicular histology, see Bergmann et al. (1994). FSH

Tobias M. Böckers; Eberhard Nieschlag; Michael R. Kreutz; Martin Bergmann

1994-01-01

23

PAR2 modulates PAR1-driven neointimal hyperplasia  

PubMed Central

Objective Emerging evidence suggests that protease-activated receptors-1 and 2 (PAR1 and PAR2) can signal together in response to proteases found in the rapidly changing microenvironment of damaged blood vessels. However, it is unknown whether PAR1 and PAR2 promote or mitigate the hyperplastic response to arterial injury. Using cell-penetrating PAR1 pepducins and mice-deficient in PAR1 or PAR2, we set out to determine the respective contributions of the receptors to hyperplasia and phenotypic modulation of smooth muscle cells (SMCs) in response to arterial injury. Methods and Results SMCs were strongly activated by PAR1 stimulation as evidenced by increased mitogenesis, mitochondrial activity, and calcium mobilization. The effects of chronic PAR1 stimulation following vascular injury were studied by performing carotid artery ligations in mice treated with PAR1 agonist pepducin, P1pal-13. Histological analysis revealed that PAR1 stimulation caused striking hyperplasia which was ablated in PAR1-/-, and surprisingly in PAR2-/- mice. P1pal-13 treatment yielded an expression pattern consistent with a de-differentiated phenotype in carotid artery SMCs. Detection of PAR1-PAR2 complexes provided an explanation for the hyperplastic effects of the PAR1 agonist requiring the presence of both receptors. Conclusions We conclude that PAR2 regulates the PAR1 hyperplastic response to arterial injury leading to stenosis.

Sevigny, Leila M.; Austin, Karyn M.; Zhang, Ping; Kasuda, Shogo; Koukos, Georgios; Sharifi, Sheida; Covic, Lidija; Kuliopulos, Athan

2011-01-01

24

Poor ovarian response to gonadotrophin stimulation is associated with FSH receptor polymorphism  

Microsoft Academic Search

Similarities in the phenotype observed in women with FSH receptor mutation and in FSH receptor knockout mice have clearly established a critical role of this protein in normal gonadal function. Two common single nucleotide polymorphisms in the exonic region of the FSH receptor gene have been shown to be associated with altered ovarian response in subjects undergoing gonadotrophin treatment. Recent

Swati K Achrekar; Deepak N Modi; Sadhana K Desai; Vijay S Mangoli; Ranjana V Mangoli; Smita D Mahale

2009-01-01

25

Detection and Potential Function of Anti 2FSH Antibodies in Patients with Spermatogenesis Dysfunction  

Microsoft Academic Search

Objective : To detect the anti2FSH antibody using ELISA , and further probe into the role of anti2FSH in infertile patients. Meth2 ods : The anti2FSH antibody was detected using ELISA in the serum of patients with spermatogenesis dysfunction , of infertile patients with nor2 mal sperm density and motility , and of normal fertile males. Results : The positive

Yao Bing; Zhang Leilei; Cui Yingxia; Wang Yongmei; Huang Yufeng

2004-01-01

26

Intrafollicular Antimullerian Hormone (AMH) Levels Predict Follicle Responsiveness to FSH in Normoandrogenic Ovulatory Women Undergoing GnRH analog/Recombinant Human FSH Therapy for IVF-ET  

PubMed Central

Objective To investigate the relationship between antimullerian hormone (AMH) and steroidogenesis in follicles of normoandrogenic ovulatory women undergoing FSH therapy for IVF-ET. Design Prospective cohort. Setting Institutional/private practice. Patients 26 normoandrogenic ovulatory women. All women received GnRH analog and ovarian stimulation for IVF-ET. Interventions Follicle fluid was aspirated at oocyte retrieval from the first follicle of each ovary. Main Outcome Measures Follicle fluid was assayed for AMH, E2, P, androstenedione, T, dihydrotestosterone, insulin and FSH. Results Intrafollicular AMH levels positively and negatively correlated with E2 and FSH concentrations in follicles, respectively, causing a positive relationship between follicle fluid AMH levels and E2/FSH ratios as a measure of follicle sensitivity to FSH. A positive relationship also existed in follicles between AMH levels and E2/androgen ratios as a marker of aromatase activity. Conclusions AMH levels in follicles of IVF patients positively correlate with follicle sensitivity to FSH.

Dumesic, Daniel A.; Lesnick, Timothy G.; Stassart, Jacques P.; Ball, G. David; Wong, Ashley; Abbott, David H.

2009-01-01

27

Par Pond water balance  

SciTech Connect

A water budget for the Par Pond hydrologic system was established in order to estimate the rate of groundwater influx to Par Pond. This estimate will be used in modeling exercises to predict Par Pond reservoir elevation and spillway discharge in the scenario where Savannah River water is no longer pumped and discharged into Par Pond. The principal of conservation of mass was used to develop the water budget, where water inflow was set equal to water outflow. Components of the water budget were identified, and the flux associated with each was determined. The water budget was considered balanced when inflow and outflow summed to zero. The results of this study suggest that Par Pond gains water from the groundwater system in the upper reaches of the reservoir, but looses water to the groundwater system near the dam. The rate of flux of groundwater from the water table aquifer into Par Pond was determined to be 13 cfs. The rate of flux from Par Pond to the water table aquifer near the dam was determined to be 7 cfs.

Hiergesell, R.A.; Dixon, K.L.

1996-06-01

28

Development of a sensitive enzymeimmunoassay (EIA) for FSH determination in bovine plasma.  

PubMed

A highly sensitive enzymeimmunoassay (EIA) procedure for FSH determination in bovine plasma on microtiterplates using the biotin-streptavidin amplification system and the second antibody coating was developed. Biotin was coupled to FSH and used to bridge between streptavidin-peroxidase and the immobilized antiserum in the competitive assay. The EIA was carried out directly in 50 microl of bovine plasma and compared with an established radioimmunoassay (RIA) employing 100 microl plasma. Same FSH standards and FSH specific antiserum were used in both procedures. FSH standards prepared in hormone free plasma were used. The sensitivity of the EIA procedure was 6.25 pg/well FSH which corresponded to 125 pg/ml plasma; the 50% relative binding sensitivity was seen at 200 pg/well. In comparison to RIA, the EIA was at least four times more sensitive besides requiring 6 times less FSH specific antiserum. Plasma volumes for the EIA ranging from 12.5 to 50 microl did not influence the shape of the standard curve even though a slight drop in the OD450 was seen with higher plasma volumes. When both EIA and RIA methods were used to measure FSH in cows, the levels were detectable only by the EIA procedure. The assay detects high and low plasma FSH levels within the physiological variation as well as changes in plasma FSH after stimulation with a GnRH analog. In conclusion, in addition to being non-radioactive and low cost in nature, the method offers several advantages over the conventional FSH RIA procedure; these are (a) higher sensitivity, (b) less labour and time saving, (c) more economical use of precious FSH antiserum and (d) long shelf-life of the biotinyl-FSH label (in contrast to the short half life of iodinated FSH in RIA). PMID:10379671

Prakash, B S; Wallenhorst, S; Metten, M; Holtz, W; Wuttke, W

29

FSH stimulation of DNA synthesis in Sertoli cells in culture.  

PubMed

The incorporation of [2H]thymidine into nuclear DNA was investigated in cultured Sertoli cells prepared from testes of 20-day-old rats. Addition of follicle-stimulating hormone (FSH) or dibutyryl cyclic, 3',5'-adenosine monophosphate (DBCAMP) to the culture medium greatly increased incorporation, expressed either as total amounts of [3H]thymidine incorporated per mug DNA or as the percentage of Sertoli cells with labeled nuclear DNA. No stimulation was observed in cells cultured in the presence of testosterone, insulin or cyclic 3',5'-GMP (cGMP). Light and electron microscopic autoradiographic analysis was employed to establish the identity of Sertoli cells having labeled nuclear DNA. Contaminating spermatogonia, which also took up labeled [3H]thymidine, were excluded from cell counts. In addition, Sertoli cells prepared from testes of irradiated 20-day-old germinal cell depleted rats were also observed to incorporate more [3H]thymidine into nuclear DNA when cultured in a chemically defined medium in the presence of FSH. DNA synthesis was abolished by prior treatment of cells with cytosine arabinoside. In separate experiments, the incorporation of [3H]thymidine into DNA of peritubular myoid cells was shown to be independent of FSH or dbcAMP. PMID:174964

Griswold, M D; Mably, E R; Fritz, I B

1976-02-01

30

Effect of porcine and ovine FSH on nuclear maturation of pig oocytes in vitro.  

PubMed

The effect of porcine or ovine FSH on the maturation rate of porcine oocytes and on the time course of meiotic progression was studied. Groups of 20 grade-A cumulus oocyte complexes, aspirated from slaughterhouse cycling-gilt ovaries, were cultured in vitro in 400 mul of Modified Parker's Medium supplemented with oestrous cow serum and porcine FSH (Folltropin(R)-V, 0.50 mg/ml) or ovine FSH (Ovagen(TM), 0.44 iu/ml), in four-well dishes under mineral oil, at 38.5 degrees C, 5% CO(2) in humidified air. At the end of each 3-h interval, from 3 to 42 h of culture, the nuclear status of oocytes was assessed microscopically (1000x), after fixation (methanol/acetic acid: 3/1) and orcein (2%) staining. Oocytes were classified as (i) immature (IMM), i.e. oocytes at germinal vesicle stage, germinal vesicle break down and prophase I, (ii) metaphase I (MI) and (iii) metaphase II (MII), i.e. oocytes at anaphase I, telophase I and metaphase II. Data were analysed using regression analysis, chi-square and t-test. Nuclear status was assessed in 1610 oocytes (porcine FSH: 787, ovine FSH: 823). Most of the oocytes were at MI from 24 to 33 h (porcine FSH 60.27%, ovine FSH 42.80%, p < 0.001) and at MII from 36 to 42 h (porcine FSH 80.38%, ovine FSH 67.45%, p < 0.01) of culture. Significantly higher maturation rate was observed in porcine FSH than in ovine FSH treated oocytes (86.69 +/- 12.97%, 71.34 +/- 9.86%, mean +/- SD, p < 0.05), after 42 h of culture. In conclusion, under the specific culture conditions, porcine FSH seems to support pig oocyte maturation better than ovine FSH. PMID:18325004

Samartzi, F; Tsakmakidis, I; Theodosiadou, E; Vainas, E

2008-04-01

31

Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome  

Microsoft Academic Search

Background: Boys with prepubertal onset of hypogonadotropic hypogonadism (HH) are at a risk of poor testis growth and impaired spermatogenesis. One potential cause for this is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH. Objective: To evaluate the effects of recombinant human FSH (r-hFSH) and human chorionicgonado- tropin (hCG) on testicular function

Taneli Raivio; Anne M Wikstrom; Leo Dunkel

2007-01-01

32

FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3.  

PubMed

Recent studies have suggested that FSH plays an important role in ovarian epithelial carcinogenesis. We demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis and facilitates neovascularisation. Our previous work has shown that transient receptor potential channel C3 (TRPC3) contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between FSH and TRPC3. We found that FSH stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. siRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and blocked apoptosis in ovarian cancer cell lines. FSH stimulation was associated with the up-regulation of TRPC3, while also facilitating the influx of Ca(2)(+) after treatment with a TRPC-specific agonist. Knockdown of TRPC3 abrogated FSH-stimulated Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1-? and VEGF. Ovarian cancer specimens were analysed for TRPC3 expression; higher TRPC3 expression levels correlated with early relapse and worse prognosis. Association with poor disease-free survival and overall survival remained after adjusting for clinical stage and grade. In conclusion, TRPC3 plays a significant role in the stimulating activity of FSH and could be a potential therapeutic target for the treatment of ovarian cancer, particularly in postmenopausal women with elevated FSH levels. PMID:23580589

Tao, Xiang; Zhao, Naiqing; Jin, Hongyan; Zhang, Zhenbo; Liu, Yintao; Wu, Jian; Bast, Robert C; Yu, Yinhua; Feng, Youji

2013-05-30

33

Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction  

Microsoft Academic Search

The FSH receptor shows three single nucleotide polymorphisms (SNPs), one in the promoter and two in exon 10. In addition, the FSH receptor mRNA undergoes extensive alternative splicing. While no physiological role for the SNP in the promoter and for alternative spliced isoforms has been demonstrated so far, the SNPs in exon 10 result in four discrete allelic variants characterized

M. Simoni; E. Nieschlag; J. Gromoll

2002-01-01

34

Anti-Mullerian Hormone Attenuates the Effects of FSH on Follicle Development in the Mouse Ovary  

Microsoft Academic Search

Although ovarian follicle growth is under the influence of many growth factors and hormones of which FSH remains one of the most prominent regulators. Therefore, factors affecting the sensitivity of ovarian follicles to FSH are also important for follicle growth. The aim of the present study was to inves- tigate whether anti-Mullerian hormone (AMH) has an inhib- itory effect on

ALEXANDRA L. L. DURLINGER; MARIA J. G. GRUIJTERS; PIET KRAMER; BAS KARELS; T. RAJENDRA KUMAR; MARTIN M. MATZUK; URSULA M. ROSE; FRANK H. DE JONG; J. UILENBROEK; J. ANTON GROOTEGOED; AXEL P. N. THEMMEN

2010-01-01

35

A study on superovulation using FSH and eCG in Awassi ewes.  

PubMed

The present study was conducted to evaluate superovulatory treatments in Awassi ewes by eCG and FSH. High number of unovulated follicles (P < 0.05) was observed in ewes treated with eCG in non-breeding season. It could be concluded that using FSH to induce superovulation in Awassi ewes is better than eCG. PMID:19882226

Azawi, Osama Ibrahim; Al-Mola, M K M A

2009-11-01

36

Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase-2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis  

Microsoft Academic Search

The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH) and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC) were cultured in a control defined medium supplemented with eFSH

Maria Elena Dell'Aquila; Maud Caillaud; Filippo Maritato; Alain Martoriati; Nadine Gérard; Giulio Aiudi; Paolo Minoia; Ghylène Goudet

2004-01-01

37

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis  

Microsoft Academic Search

BACKGROUND: Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce.

Alberto Revelli; Francesca Poso; Gianluca Gennarelli; Federica Moffa; Giuseppina Grassi; Marco Massobrio

2006-01-01

38

[Ovulation induction with pure FSH in anovulatory patients resistant to clomifene citrate].  

PubMed

The objective was to evaluate the utility of the pure FSH as treatment of women clomiphene-resistant. Seventy two patients clomiphene-resistant were treated with pure FSH. Ovulation induction was started with 75 IU of pure FSH on day 3 of the menstrual cycle, monitoring the follicular growth with transvaginal ultrasonography, additional doses of pure FSH were administered accordingly. Human chorionic gonadotropin (10,000 IU) was administered when the dominant follicle reached a diameter > or = 16 mm. The pregnancy rate per cycle was 18.0%, on the other hand, the cumulate rate of pregnancy was 72.2%. There was not significant difference in the pregnancy rate between patients with primary or secondary infertility. The rate of spontaneous abortions was similar to the general population. As conclusion, it therefore appropriate to offer the treatment with pure FSH to patients clomiphene-resistance. The cases with gonadotropin-resistance, will be candidates to surgical procedures. PMID:8756188

Kably-Ambe, A; Reyes-Cuervo, H; Barrón-Vallejo, J

1996-07-01

39

Identification of Smad Response Elements in the Promoter of Goldfish FSH? Gene and Evidence for Their Mediation of Activin and GnRH Stimulation of FSH? Expression  

PubMed Central

As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH) is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSH? but suppresses LH? expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSH? in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSH? transcription, the present study was undertaken to analyze the promoter of goldfish FSH? gene (fshb) with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the L?T-2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSH? promoter-SEAP (secreted alkaline phosphatase) were co-transfected with an expression plasmid for Smads (2 or 3) followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (AGAC, ?1675/?1672) whereas the proximal site (GACCTTGA, ?212/?205) was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA) highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSH? expression by gonadotropin-releasing hormone and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSH? that are responsible for activin-induced expression of the gene. Since activin stimulation of FSH? expression is functionally conserved in fish and mammals, our findings contribute to the understanding of the fundamental mechanisms of this regulation across vertebrates.

Lau, Man-Tat; Lin, Sze-Wah; Ge, Wei

2012-01-01

40

Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland  

Technology Transfer Automated Retrieval System (TEKTRAN)

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

41

Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland  

Technology Transfer Automated Retrieval System (TEKTRAN)

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

42

Poor ovarian response to gonadotrophin stimulation is associated with FSH receptor polymorphism.  

PubMed

Similarities in the phenotype observed in women with FSH receptor mutation and in FSH receptor knockout mice have clearly established a critical role of this protein in normal gonadal function. Two common single nucleotide polymorphisms in the exonic region of the FSH receptor gene have been shown to be associated with altered ovarian response in subjects undergoing gonadotrophin treatment. Recent in-vitro studies have shown that the A allele at the -29 position in the 5 untranslated region of the FSH receptor gene is associated with impaired transcriptional activity. Differential expression of the FSH receptor and its function may be one of the factors responsible for altered ovarian response. These observations prompted a study of the association between FSH receptor genotype at the -29 position and ovarian response in women undergoing gonadotrophin treatment. Analysis of the data revealed that the subjects with AA genotype at the -29 position required the highest amount of exogenous FSH for ovulation induction, and oestradiol concentrations before the day of human chorionic gonadotrophin administration were significantly lower (P = 0.015) compared with the GA genotype. The number of pre-ovulatory follicles and retrieved oocytes were lowest in the subjects with AA genotype. These results indicate that the AA genotype at position -29 may be associated with the poor ovarian response. PMID:19400992

Achrekar, Swati K; Modi, Deepak N; Desai, Sadhana K; Mangoli, Vijay S; Mangoli, Ranjana V; Mahale, Smita D

2009-04-01

43

Isolated low follicle stimulating hormone (FSH) in infertile males - a preliminary report.  

PubMed

Objectives: High levels of follicle stimulating hormone (FSH) in infertile males received a significant attention and exploration. Studies investigating the isolated deficiency of FSH in males are few, and its real prevalence is still unknown. Therefore, the objectives of the current study was to report the prevalence of isolated low FSH in infertile males and highlight their demographics and standard sperm parameters. Methods: Records of 3335 infertile men were retrospectively checked. Patients with isolated low FSH were retrieved. FSH levels were categorized into 3 groups based on the number of affected sperm parameter (s). Study variables were also arranged into 2 groups in relation to smoking history. A control group was included to document the changes in sperm morphology. Results: Isolated low FSH (1.146 ± 0.219 mIU/mL) was found in 29 (0.87%) patients. All patients showed at least one abnormal sperm parameter. The abnormal parameters were present in different combinations within the same patient but with no significant correlations with the FSH levels. The FSH levels got lower as the number of the affected sperm parameters increased although the decline was insignificant. The most frequent abnormal parameter presented was sperm morphology (86.2%). Anomalous sperm morphology was highly and significantly demonstrated in the head; specifically in acrosome. Abnormal sperm parameters were present in both smoking and nonsmoking groups but with no significant differences in between. Conclusions: Isolated low FSH among infertile males has a low prevalence. This may be associated with abnormality in semen parameters; particularly sperm morphology. These patients are suggested to be found as a primary entity. However, an additional work-up is highly recommended to validate this hypothesis. PMID:24085232

Salama, Nader; El-Sawy, Mohamed

2013-09-26

44

Suppression of the high endogenous levels of plasma FSH in infertile men are associated with improved Sertoli cell function as reflected by elevated levels of plasma inhibin B  

Microsoft Academic Search

BACKGROUND. In vitro continuous stimulation of Sertoli cells with FSH leads to a desensitization of these cells to FSH action. To evaluate the presence of a desensitization of FSH receptor on Sertoli cells in vivo, we performed a controlled clinical study in 97 men affected by severe oligozoospermia. METHODS. On the basis of FSH and inhibin B plasma concentrations, these

C. Foresta; A. Bettella; D. Spolaore; M. Merico; M. Rossato; A. Ferlin

2004-01-01

45

C:\\Sonny files\\Team 1 Files\\FSH\\Follistim\\11099 12.12.03 ...  

Center for Drug Evaluation (CDER)

Text Version... and “Recombinant FSH Follistim – Life source for today's ART successes” are ... without any header or other presentation elements that emphasize to ... More results from www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation

46

FSH: One Hormone with Multiple Forms, or a Family of Multiple Hormones  

Microsoft Academic Search

Follicle stimulating hormone (FSH) is produced within pituitary gonadotroph cells and is a critical component of the reproductive\\u000a process. It has a wide variety of activities in both male and female reproductive tissues including growth, division, and\\u000a differentiation of Sertoli and granulosa cells. As a result, FSH is directly involved in the production of both male and female\\u000a gametes, as

Tim G. Rozell; Rena J. Okrainetz

47

[Embryonic quality in the use of urofolitropin vs recombinant FSH for in vitro fertilization].  

PubMed

There were no differences in both groups as tho the age of the patients; received doses of both types of FSH, nor HMG; but there was as to the amount of captured ovocytes, amount, and quality, embrionary, in special 1+ 2+ in favor of the group that received urofolitropine, specially under 35 years of age. In this study there was better qualy and amount, embrionary, obtained with the use of urofolitropine, as compared with FSH recombinant for in vitro fertilization. PMID:10363424

Contreras Bretherton, C; David Vargas, R; Cedillo, F J; Vilchez, R; Das Neves, D; Bernal, M A; Verez Ruíz, J R; Stern Colin y Nunes, J J; Gutiérrez Nájar, A

1999-05-01

48

Synthesis and characterization of biologically active recombinant elk and horse FSH  

Microsoft Academic Search

The objective of this investigation was to clone and express the elk and horse common ?-subunit and FSH ?-subunit cDNAs, and to produce recombinant FSH from both species in vitro. The RNAs extracted from elk and horse pituitary glands were reverse-transcribed and amplified by polymerase chain reaction. The cDNAs corresponding to both subunits of elk and horse were cloned into

María Victoria Fachal; Mike Furlan; Rena Clark; Claire E. Card; P. Jorge Chedrese

2010-01-01

49

Long-term in vitro culture of ovarian cortical tissue in goats: effects of FSH and IGF-I on preantral follicular development and FSH and IGF-I receptor mRNA expression.  

PubMed

Long-term in vitro culture (16 days) of caprine ovarian cortical tissue was performed to test the effect of FSH and IGF-I on the viability and development of preantral follicles and mRNA expression for FSH and IGF-I receptors. Fragments were cultured in ?-MEM(+) alone or supplemented with different combinations of FSH and IGF-I (sequential medium). The culture period was divided into two parts. Follicles were isolated and classified as normal or abnormal and primordial, primary or secondary. Viability of isolated follicles was determined by staining with Trypan Blue dye. Expression of FSHR and IGFR-1 mRNA was evaluated by qPCR. At day 8 of culture, more (P < 0.05) follicles in treatments containing IGF-I alone or associated with FSH were normal and viable (overall mean, 81 % and 79 % respectively) than the treatments cultured with FSH or ?-MEM(+) alone (68 % and 63 %). At day 16 of culture, treatments with FSH and/or IGF-I had more (P < 0.05) viable follicles (69 %) than ?-MEM(+) (38 %). The percentages of follicular development observed in the IGF-I/FSH, FSH+IGF-I/FSH+IGF-I and FSH/IGF-I treatments were similar but higher (P < 0.05) than the other treatments. FSH and IGF-I during the entire culture period maximized (P < 0.05) follicular and oocyte diameters and the percentage of secondary follicles (28 %). FSHR mRNA expression in the non-cultured control was similar to the treatment supplemented with FSH and IGF-I but higher (P < 0.05) than ?-MEM(+). IGFR-1 expression did not differ among treatments. Association of FSH and IGF-I in long-term in vitro culture promoted follicular development, maintaining FSHR mRNA expression. PMID:23053050

Magalhães-Padilha, D M; Fonseca, G R; Haag, K T; Wischral, A; Gastal, M O; Jones, K L; Geisler-Lee, J; Figueiredo, J R; Gastal, E L

2012-10-09

50

Blocking antibody to the ?-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis  

PubMed Central

Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH ?-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)?/? mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.

Zhu, Ling-Ling; Blair, Harry; Cao, Jay; Yuen, Tony; Latif, Rauf; Guo, Lida; Tourkova, Irina L.; Li, Jianhua; Davies, Terry F.; Sun, Li; Bian, Zhuan; Rosen, Clifford; Zallone, Alberta; New, Maria I.; Zaidi, Mone

2012-01-01

51

The ParPar System: A Software MPP  

Microsoft Academic Search

IntroductionTo place ParPar1. in context, we must first review the different modes of operationcommon on clusters. Probably the most common approach is to view the clusteras a Network Of Workstations (NOW). With this approach, each node is owned bya certain individual, and is usually also physically located in his work area. Theowner uses his workstation for administrative work, such as

Anat Batat; Avi Kavas; David Er-el; Dror G. Feitelson; Gabriel Benhanokh; Marc A. Volovic; Tomer Klainer; Yoav Etsion

1999-01-01

52

Effect of sialylation and complexity of FSH oligosaccharides on inhibin production by granulosa cells.  

PubMed

Granulosa cell (GC) inhibin A and B production is regulated by FSH and gonadal factors. This gonadotrophin is released as a mixture of glycoforms, which induce different biological responses in vivo and in vitro. Our aim was to determine the effect of recombinant human FSH (rhFSH) glycosylation variants on inhibin A and B production by rat GCs. Preparative isoelectro focusing was used to isolate more acidic/sialylated (pH <4.00) and less acidic/sialylated (pH >5.00) rhFSH charge analogues. Concanavalin A was used to isolate unbound and firmly bound rhFSH glycoforms on the basis of their oligosaccharide complexity. GCs, obtained from oestrogen-primed immature rats, were cultured with either native rhFSH or its glycosylation variants. Inhibin A and B were determined using specific ELISAs. Results were expressed as mean±s.e.m. Under basal conditions, inhibin A was the predominant dimer produced (inhibin A: 673±55; inhibin B: 80±4? pg/ml). More acidic/sialylated charge analogues stimulated inhibin B production when compared to inhibin A at all doses studied; by contrast, less acidic/sialylated charge analogues stimulated inhibin A production and elicited no effect on inhibin B. Glycoforms bearing complex oligosaccharides showed a potent stimulatory effect on inhibin B when compared to inhibin A production (i.e. dose 1 ?ng/ml: 4.9±0.5 vs 0.9±0.1-fold stimulation, P<0.001). Glycoforms bearing hybrid-type oligosaccharides favoured inhibin A production (i.e. dose 4? ng/ml 2.9±0.1 vs 1.6±0.1-fold stimulation, P<0.05). These results show that the sialylation degree as well as the complexity of oligosaccharides present in the rhFSH molecule may be considered additional factors that differentially regulate dimeric inhibin production by rat GCs. PMID:23166369

Loreti, Nazareth; Ambao, Verónica; Andreone, Luz; Trigo, Romina; Bussmann, Ursula; Campo, Stella

2013-01-24

53

FSH and LH have common and distinct effects on gene expression in rainbow trout testis.  

PubMed

The general rules established from mammalian species for the regulation of spermatogenesis by gonadotropins may not be fully relevant in fish. Particularly, Fsh is as potent as Lh to stimulate steroidogenesis and the Fsh receptor is expressed in Leydig cells. In seasonal breeders, Fsh is likely the major gonadotropin involved in spermatogenesis onset and Lh is required to support spermatogenesis progression and gamete release. However, the genes that relay the action of Fsh and Lh have been poorly investigated in fish. The present study was aimed at identifying gonadotropin-dependent genes expressed in the testis during fish puberty. We cultured pubertal trout testicular explants for 96?h, with or without gonadotropin, and analyzed transcriptome variations using microarrays. Fsh and Lh had similar effects on a large group of genes while other genes were preferentially regulated by one or the other gonadotropin. We showed that most of the responsive genes were expressed in somatic cells and exhibited relevant patterns during the seasonal reproductive cycle. Some genes preferentially modulated by Lh could be involved in testicular cell fate (pvrl1 and bty) or sperm maturation (ehmt2 and racgap1) and will deserve further examination. Besides Fsh's effects on the steroidogenic pathway, our study demonstrates that Fsh coordinates relevant stimulatory and inhibitory paracrine factors known to regulate early germ cell proliferation and differentiation. Some of these genes belong to major regulatory pathways including the Igf pathway (igf1b/igf3 and igfbp6), the Tgfb pathway (amh, inha, inhba, and fstl3), the Wnt pathway (wisp1), and pleiotrophin (mdka). PMID:23045716

Sambroni, Elisabeth; Rolland, Antoine D; Lareyre, Jean-Jacques; Le Gac, Florence

2012-12-31

54

Par Pond vegetation status 1996  

SciTech Connect

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned.

Mackey, H.E. Jr.; Riley, R.S.

1996-12-01

55

Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF  

PubMed Central

Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N?=?88] or recFSH alone [N?=?99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40?years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40?years and could be of potential benefit for IVF cycles in older infertile women.

2012-01-01

56

FSH is superior to eCG for promoting ovarian response in Chinese Bamei gilts.  

PubMed

The Bamei gilt is a Chinese native breed located in northwest China, which adapts to the extremely dry and cold environment and is distinguished for its excellent reproductive and maternal characters. To ensure sufficient numbers of embryos for transgenic and nuclear transfer research, hormonal induction of gilt estrus and superovulation may be necessary. The objective of this study was to compare the superovulation effects of equine chorionic gonadotropin (eCG, Group A) and FSH (Groups B-D) in Chinese Bamei gilts. The results show that though eCG could produce more corpora lutea (CL, 14.3) than the control (CL, 9.2), and the FSH treatments had significantly increased the number of CL compared with the eCG treatment. Within the different FSH protocols, the numbers of CL were significantly greater in Groups B (CL, 77.8) and C (CL, 66.8) than in Group D (CL, 42.7), however, ovarian cysts were observed in Groups B and C, but not in Group D. These data suggest that Group D (280 IU FSH) is a suitable protocol to facilitate the development of ovarian follicles and increase the number of useful embryos per gilt for embryos recovery. The optimal FSH protocol of superovulation in Bamei gilts appears to be: D13/100 IU, D14/80 IU, D15/60 IU, D16/40 IU plus prostaglandin (PG) 0.2mg, D17/hCG 1000 IU. PMID:21074338

Hu, Junhe; Bao, Jianchang; Ma, Xiaoling; Li, Wei; Lei, Anmin; Yang, Chunrong; Gao, Zhimin; Wang, Huayan

2010-10-11

57

The role of transcription in EGF- and FSH-mediated oocyte maturation in vitro  

PubMed Central

Understanding mechanisms responsible for meiotic resumption in mammalian oocytes is critical for the identification of strategies to enhance developmental competence of in vitro matured oocytes. Improvement of in vitro oocyte maturation systems is dependent on a better understanding of mechanisms that regulate oocyte maturation both in vivo and in vitro as well as on the identification of methods to manipulate the meiotic progression of oocytes matured in vitro in a physiological manner. The purpose of this review is two-fold: first, to examine the mechanisms that underlie the acquisition of oocyte developmental competence and regulation of oocyte maturation in vivo and in vitro; and second, to present data examining the role of transcription in mediating the ability of EGF and FSH to induce oocyte maturation in vitro. Results presented support the conclusions that (1) EGF-induced oocyte maturation does not require nascent gene transcription in both mice and domestic cats; (2) FSH requires gene transcription to induce oocyte maturation in both species; (3) EGF must be present in the maturation medium to optimize the effectiveness of FSH to promote oocyte maturation; and (4) the mechanism used by FSH to induce oocyte maturation in vitro appears to predominate over that used by EGF when both EGF and FSH are present in maturation medium used for either murine or feline cumulus oocyte complexes.

Farin, C.E.; Rodriguez, K.F.; Alexander, J.E.; Hockney, J.E.; Herrick, J.R.; Kennedy-Stoskopf, S.

2007-01-01

58

Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells  

SciTech Connect

Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

1984-01-01

59

Streptococcus pyogenes pSM19035 requires dynamic assembly of ATP-bound ParA and ParB on parS DNA during plasmid segregation  

PubMed Central

The accurate partitioning of Firmicute plasmid pSM19035 at cell division depends on ATP binding and hydrolysis by homodimeric ATPase ?2 (ParA) and binding of ?2 (ParB) to its cognate parS DNA. The 1.83 Å resolution crystal structure of ?2 in a complex with non-hydrolyzable ATP?S reveals a unique ParA dimer assembly that permits nucleotide exchange without requiring dissociation into monomers. In vitro, ?2 had minimal ATPase activity in the absence of ?2 and parS DNA. However, stoichiometric amounts of ?2 and parS DNA stimulated the ?2 ATPase activity and mediated plasmid pairing, whereas at high (4:1) ?2 : ?2 ratios, stimulation of the ATPase activity was reduced and ?2 polymerized onto DNA. Stimulation of the ?2 ATPase activity and its polymerization on DNA required ability of ?2 to bind parS DNA and its N-terminus. In vivo experiments showed that ?2 alone associated with the nucleoid, and in the presence of ?2 and parS DNA, ?2 oscillated between the nucleoid and the cell poles and formed spiral-like structures. Our studies indicate that the molar ?2 : ?2 ratio regulates the polymerization properties of (?•ATP•Mg2+)2 on and depolymerization from parS DNA, thereby controlling the temporal and spatial segregation of pSM19035 before cell division.

Pratto, Florencia; Cicek, Aslan; Weihofen, Wilhelm A.; Lurz, Rudi; Saenger, Wolfram; Alonso, Juan C.

2008-01-01

60

[Low-dose desmopressin (DDAVP) and blood levels of FSH, LH and testosterone in men].  

PubMed

The effect of desmopressin (DDAVP) administration (2.5 micrograms/12 hours) on serum concentrations of FSH, LH and testosterone was studied in six men. No significant changes were observed in serum concentrations of FSH and LH after 9 days with DDAVP therapy. Nevertheless, serum concentrations of testosterone after 12 hours of DDAVP administration were significantly higher than basal concentrations. Three hours after the administration of DDAVP, serum testosterone concentrations decreased significantly. The conclusion reached was that low doses of desmopressin do not change serum concentrations of FSH and LH, but serum concentration of testosterone is decreased within three hours after the administration, although an increase is observed 12 hours later possibly due to a "rebound effect". Desmopressin would therefore directly act upon human testicle. PMID:8650386

García-Pascual, I J; Rozán Flores, M A

1996-03-01

61

Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol Acetic Acid, EGF, and FSH  

PubMed Central

The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To evaluate ultrastructure of primordial follicles cultured in MEM (control) or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6?d were ultrastructurally normal. They had oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain ultrastructural integrity of sheep primordial follicles cultured in vitro.

Andrade, Evelyn Rabelo; Maddox-Hyttel, Poul; Landim-Alvarenga, Fernanda Da Cruz; Viana Silva, Jose Roberto; Alfieri, Amauri Alcindo; Seneda, Marcelo Marcondes; Figueiredo, Jose Ricardo; Toniolli, Ricardo

2011-01-01

62

Cumulus cell-enclosed oocytes acquire a capacity to synthesize GSH by FSH stimulation during in vitro maturation in pigs.  

PubMed

We investigated (i) follicle stimulating hormone (FSH)-modulated changes in the expression of glutathione (GSH) and its rate-limiting enzyme, glutamate cysteine ligase (GCL), in porcine oocytes and cumulus cells, and (ii) the contribution of gap-junctional communications (GJCs) in cumulus-oocyte complexes (COCs) to intraoocyte GSH accumulation. In experiment (i), COCs were cultured for 48 h with (+FSH group) or without FSH (-FSH group). The GSH content of oocytes increased with cultivation time in the +FSH group, but decreased in the -FSH group. The GSH content of cumulus cells at 48 h was also higher in the +FSH group than that in the -FSH group. Expression of GCL subunit mRNAs in oocytes and cumulus cells was increased by FSH stimulation until 12 h, and then fell to the baseline level. On the other hand, the amount of GCL subunit proteins in oocytes and cumulus cells increased gradually throughout the period of culture with FSH. In experiment (ii), blocking of GJCs in COCs during 0-24 h of culture led to a decrease in the GSH content of oocytes at 24 h of culture, whereas the GSH content at 48 h of culture did not differ even after blocking of the GJCs during 24-48 h of culture. These findings indicate that FSH initiates GSH synthesis in cumulus cells and oocytes by modulating the expression of GCL, and that porcine oocytes are able to synthesize GSH without GJC-mediated support from cumulus cells, at least in the later half of maturation culture. PMID:19852067

Ozawa, Manabu; Nagai, Takashi; Somfai, Tamás; Nakai, Michiko; Maedomari, Naoki; Miyazaki, Hitoshi; Kaneko, Hiroyuki; Noguchi, Junko; Kikuchi, Kazuhiro

2010-02-01

63

Development of an enzyme-immunoassay (EIA) for the measurement of follicle-stimulating-hormone (FSH) in Callitrichid primates using a monoclonal antibody against the human-FSH-beta-subunit.  

PubMed

Despite the importance of Callitrichid primates in both biomedical and conservation research, practical and reliable immunoassays for the measurement of follicle-stimulating hormone (FSH) have not yet been described. A panel of monoclonal antibodies against specific peptide fragments within either the alpha or beta subunit of human FSH was evaluated for their ability to recognize FSH from Callitrichid and other New World primates. One of these, monoclonal antibody 46.3h6.b7 raised against human FSH, was selected due to its ability to recognize marmoset monkey FSH and its low crossreactivity with other gonadotrophins. The antibody formed the basis of an enzymeimmunoassay using a highly purified human urinary FSH (Metrodin, Serono) preparation coupled to biotin as label and unmodified as standard. After 24 h incubation, antibody bound label was visualized by addition of streptavidin-peroxidase followed by the appropriate substrate. Parallelism was obtained between the standard and dilutions of pituitary extracts, urine and plasma from the common marmoset (Callithrix jacchus) as well as from two tamarin species (Saguinus fuscicollis and S. oedipus) and one squirrel monkey (Saimiri sciureus). Profiles of plasma and urinary FSH during the follicular phase are shown for two individual marmosets. The ability to measure FSH in Callitrichidae provides new opportunities for studies of the reproductive biology of these New World primate species. PMID:9057964

Rosenbusch, J; Dias, J A; Hodges, J K

1997-01-01

64

Mixed protocols: Multiple ratios of FSH and LH bioactivity using highly purified, human-derived FSH (BRAVELLE) and highly purified hMG (MENOPUR) are unaltered by mixing together in the same syringe  

Microsoft Academic Search

BACKGROUND: The use of mixed or blended protocols, that utilize both FSH and hMG, for controlled ovarian hyperstimulation is increasing in use. To reduce the number of injections a patient must administer, many physicians instruct their patients to mix their FSH and hMG together to be given as a single injection. Therefore, the goal of this study was to definitively

M Joseph Scobey; Elizabeth Raike; Dennis C Marshall

2005-01-01

65

Serum Inhibin B in Combination with Serum Follicle Stimulating Hormone (FSH) Is a More Sensitive Marker Than Serum FSH Alone for Impaired Spermatogenesis in Men, But Cannot Predict the Presence of Sperm in Testicular Tissue Samples  

Microsoft Academic Search

The measurement of serum FSH is useful in the diagnostic workup of the infertile male, but fails to predict the presence of sperm in testicular tissue. We investigated whether inhibin B reflects testic- ular morphology and the presence of sperm more accurately than FSH. Serum inhibin B and gonadotropin levels were determined in 91 infertile men undergoing diagnostic bilateral testicular

SIGRID VON ECKARDSTEIN; MANUELA SIMONI; MARTIN BERGMANN; GERHARD F. WEINBAUER; PAUL GASSNER; ANDREAS G. SCHEPERS; EBERHARD NIESCHLAG

66

FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men  

PubMed Central

BACKGROUND No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters. METHODS A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. RESULTS Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups. CONCLUSIONS The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.

Grigorova, Marina; Punab, Margus; Ausmees, Kristo; Laan, Maris

2008-01-01

67

Development and validation of a sensitive radioimmunoassay procedure for estimating FSH in mithun (Bos frontalis) plasma.  

PubMed

The present study was designed to develop and validate a simple and sensitive radioimmunoassay (RIA) procedure to estimate FSH in mithun (Bosfrontalis) plasma. The assay was carried out in 100 [L of mithun plasma. The bovine FSH standards (10 to 5000 pg/100 microL/tube) in hormone-free plasma were used in the assay. The sensitivity of the assay was 20 pg/100 microL/tube, which corresponded to 0.20 ng/mL plasma. The 50% relative binding sensitivity of the assay was 80 pg/100 microL/tube, which corresponded to 0.80 ng/mL plasma. The intra- and inter-assay coefficients of variation were 4.6% and 12.4%, respectively. The biological validation of the assay was carried out in plasma samples that were collected during different stages of the estrous cycle. In the entire estrous cycle, plasma FSH concentration (p < 0.01) attained two peaks (on day 3 to 4 before estrus 5.1 +/- 0.3 ng/mL and on the day of estrus 6.9 +/- 0.2 ng/mL). FSH concentration remained at basal level (1.3 +/- 0.1 to 1.6 +/- 0.2 ng/mL) during day 4 to 16 of the estrous cycle. The concentration of plasma FSH was found to be significantly (p < 0.05) higher (4.9 +/- 0.3 to 6.8 +/- 0.5 ng/mL) until 48 h following the estrus onset. In conclusion, the RIA procedure that was developed in the current study is sufficiently reliable and sensitive to estimate different physiological levels of FSH in mithun plasma. PMID:17424829

Dhali, A; Mishra, D P; Mech, A; Khate, K; Rajkhowa, C; Karunakaran, M

2007-01-01

68

Progesterone and regulation of the follicle-stimulating hormone (FSH-beta) gene.  

PubMed

Progesterone (P) biphasically modulates follicle-stimulating hormone (FSH) secretion in the rat both in vivo and in vitro with the duration of estrogen priming determining the biphasic nature of the P action, probably through estrogen up-regulation of the anterior pituitary progesterone receptor (PR) levels. P has been also shown to regulate anterior pituitary levels of FSH-beta mRNA in the rat. Although the mechanism of this action has not been determined, steroids may regulate gene expression through the binding of liganded receptors to gene sequences known as hormone response elements (HRE); however, it is not known whether HRE's exist on the rat FSH-beta gene. We have localized a series of progesterone response elements (PRE)-like sequences on the rat FSH-beta gene and have begun testing the hypothesis that P modulates the expression of the rat FSH-beta gene through the direct binding of the P/PR complex to these PRE-like sequences. Electromobility shift assays indicate that these PRE-like sequences bind PR with high affinity and specificity. In addition, when a 361-base pair sequence, which contains the three PRE-like sequences localized in the upstream region of the gene, was cloned into a luciferase expression vector driven by a heterologous promoter and transiently transfected into anterior pituitary cell cultures, progestin stimulation elicited increased luciferase expression. These results indicated that the 361-base pair sequence conferred P-responsiveness to a heterologous promoter. The data further suggest that FSH synthesis in the rat is modulated by direct binding of PR to PRE-like sequences. PMID:10503714

O'Conner, J L; Wade, M F; Edwards, D P; Mahesh, V B

1999-09-01

69

Molecular Analysis of a Mutated FSH Receptor Detected in a Patient with Spontaneous Ovarian Hyperstimulation Syndrome  

PubMed Central

Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event that may result from a FSH-producing pituitary adenoma (FSHoma), activating mutations of the FSH receptor (FSHR), and cross-reactivity of the FSHR to elevated hCG and TSH in the setting of pregnancy or hypothyroidism. The objective of this study was to investigate whether an aberrant FSHR was present in a woman with sOHSS and a non-surgically diagnosed FSHoma whose serum FSH levels and FSH bioactivity were nearly normal. Sequencing of the patient’s FSHR gene revealed a heterozygous novel missense mutation c. 1536G>A resulting in an amino acid substitution M512I. We asked whether this mutant FSHR affected FSHR-mediated signaling pathways involving cAMP/protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog kinase (SRC)/ p42/p44 extracellular signal-regulated protein kinases (ERK1/2). Thus, 293T cells expressing wild-type (FSHRwt), the mutant FSHR (FSHRmt), or both (FSHRwt/mt) were treated with FSH and subjected to measurements of intracellular cAMP, cAMP-induced CRE (cAMP response element)-mediated luciferase assays and immunoblot analyses of phosphorylated PI3K and ERK1/2. There were no differences in luciferase activities or phosphorylation levels of ERK1/2 among FSHRwt, FSHRmt cells and FSHwt/mt cells. However, FSHRmt cells showed a significant reduction in both cAMP production and PI3K phosphorylation levels with unchanged phosphorylation of ERK1/2 upon FSH stimulation in comparison to FSHwt cells. Also, FSH treatment did not provoke PI3K phosphorylation in FSHwt/mt cells. These results indicate that the novel missense M512I FSHR mutation identified herein did not participate in hyperactivation of FSHR-mediated signaling pathways but rather in hypoactivation of the FSH-mediated PI3K/AKT pathway. Thus, this study demonstrates a new functional property of this novel mutatnt FSHR, which, however, might not be involved in the pathogenesis of sOHSS in this FSHoma patient.

Uchida, Sayaka; Uchida, Hiroshi; Maruyama, Tetsuo; Kajitani, Takashi; Oda, Hideyuki; Miyazaki, Kaoru; Kagami, Maki; Yoshimura, Yasunori

2013-01-01

70

Molecular Analysis of a Mutated FSH Receptor Detected in a Patient with Spontaneous Ovarian Hyperstimulation Syndrome.  

PubMed

Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event that may result from a FSH-producing pituitary adenoma (FSHoma), activating mutations of the FSH receptor (FSHR), and cross-reactivity of the FSHR to elevated hCG and TSH in the setting of pregnancy or hypothyroidism. The objective of this study was to investigate whether an aberrant FSHR was present in a woman with sOHSS and a non-surgically diagnosed FSHoma whose serum FSH levels and FSH bioactivity were nearly normal. Sequencing of the patient's FSHR gene revealed a heterozygous novel missense mutation c. 1536G>A resulting in an amino acid substitution M512I. We asked whether this mutant FSHR affected FSHR-mediated signaling pathways involving cAMP/protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog kinase (SRC)/ p42/p44 extracellular signal-regulated protein kinases (ERK1/2). Thus, 293T cells expressing wild-type (FSHRwt), the mutant FSHR (FSHRmt), or both (FSHRwt/mt) were treated with FSH and subjected to measurements of intracellular cAMP, cAMP-induced CRE (cAMP response element)-mediated luciferase assays and immunoblot analyses of phosphorylated PI3K and ERK1/2. There were no differences in luciferase activities or phosphorylation levels of ERK1/2 among FSHRwt, FSHRmt cells and FSHwt/mt cells. However, FSHRmt cells showed a significant reduction in both cAMP production and PI3K phosphorylation levels with unchanged phosphorylation of ERK1/2 upon FSH stimulation in comparison to FSHwt cells. Also, FSH treatment did not provoke PI3K phosphorylation in FSHwt/mt cells. These results indicate that the novel missense M512I FSHR mutation identified herein did not participate in hyperactivation of FSHR-mediated signaling pathways but rather in hypoactivation of the FSH-mediated PI3K/AKT pathway. Thus, this study demonstrates a new functional property of this novel mutatnt FSHR, which, however, might not be involved in the pathogenesis of sOHSS in this FSHoma patient. PMID:24058690

Uchida, Sayaka; Uchida, Hiroshi; Maruyama, Tetsuo; Kajitani, Takashi; Oda, Hideyuki; Miyazaki, Kaoru; Kagami, Maki; Yoshimura, Yasunori

2013-09-13

71

LSH and FSH autonomous secretion in long-term pituitary tissue culture.  

PubMed

Pituitary tissue from 2- to 6-day-old male rats was cultivated for up to 136 days in medium containing fetal bovine serum, but without added steroid or hypothalamic extracts. After 40 to 70 days of sustained release of LH and FSH at a very low level, there was an increase in the quantity of both, and a plateau of depressed secretion. LH was identified by immunoreactivity in two radioimmunological systems and in gel chromatography. Little, if any, alpha-subunits were liberated in these cultures. It is concluded that basal production of LH and FSH is a constitutive activity of the gonadotropic cell. PMID:535914

Loras, B; Sheridan, R; Rocle, B

1979-09-01

72

A Naturally Occurring Basically Charged Human Follicle-Stimulating Hormone (FSH) Variant Inhibits FSH-Induced Androgen Aromatization and Tissue-Type Plasminogen Activator Enzyme Activity in vitro  

Microsoft Academic Search

It is well known that deglycosylation of gonadotropins by enzymatic or chemical procedures or by deletion of sites for N-linked glycosylation produces antagonistic analogs which are able to interact strongly with the receptor and to inhibit binding of the wild-type hormone. In the present study, we analyzed the antagonistic properties of a naturally occurring basic follicle-stimulating hormone (FSH) charge isoform

Carlos M. Timossi; Jorgelina Barrios de Tomasi; Elena Zambrano; Roberto González; Alfredo Ulloa-Aguirre

1998-01-01

73

Some effects of adding pLH in defined amounts to purified p-FSH to modify FSH LH ratios during the superovulatory treatment of anestrous ewes  

Microsoft Academic Search

Nonlactating Leccese ewes (n = 61) were used during seasonal anestrus to investigate the effects on ovarian response and embryo production of adding defined amounts of p-LH to purified p-FSH as well as decreasing the FSHLH ratio during treatment. The ewes were synchronized with FGA-impregnated intravaginal pessaries for 9 days and prostaglandin F2? (Cloprostenol) injected on the seventh day. They

A. D'Alessandro; G. Martemucci; M. A. Colonna; C. Cafueri; F. Toteda

1997-01-01

74

Alterations in Sperm Characteristics of Follicle-Stimulating Hormone (FSH)-Immunized Men Are Similar to Those of FSH-Deprived Infertile Male Bonnet Monkeys  

Microsoft Academic Search

The quality of sperm ejaculated by bonnet monkeys and normal, healthy proven fertile volunteer men, both actively im- munized with ovine follicle-stimulating hormone (oFSH), was ex- amined at different times of study for chromatin packaging and ac- rosomal glycoprotein concentration by flow cytometry. Susceptibility of sperm nuclear DNA to dithiothreitol (DTT)-induced decondensa- tion, as measured by ethidium bromide binding, was

HANUMANTHAPPA KRISHNAMURTHY; K. M. PRASANNA KUMAR; CHIRAG V. JOSHI; HEGGANAHALLI N. KRISHNAMURTHY; RAGHUVEER N. MOUDGAL; M. RAM SAIRAM

75

Elevated basal FSH in normal cycling women is associated with unfavourable lipid levels and increased cardiovascular risk  

Microsoft Academic Search

estradiol levels. We investigated the relationship between basal FSH and an established major risk factor for cardio- vascular disease. METHODS AND RESULTS: We obtained cycle day 3 serum FSH levels and fasting lipoprotein profiles on 40 women between the ages of 29 and 49 years, with normal menstrual cycles and who were not using hormonal medications or statins. Premenopausal women

Micheline C. Chu; Kristina M. Rath; Jennifer Huie; Hugh S. Taylor

76

Cloning and sequence analysis of FSH and LH in the giant panda ( Ailuropoda melanoleuca)  

Microsoft Academic Search

The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. It has been proposed that it has a highly specialized reproductive pattern with low fecundity, but little is known about its basic reproductive biology at the molecular level. In this report the genes encoding gonadotropin subunits ?, follicle-stimulating hormone (FSH) ? and luteinizing hormone (LH) ? of

Ming-Juan Liao; Mu-Yuan Zhu; Zhi-He Zhang; An-Ju Zhang; Guang-Han Li; Fu-Jun Sheng

2003-01-01

77

Screening of FSH receptor gene in Argentine women with premature ovarian failure (POF)  

Microsoft Academic Search

Diverse mutations in FSH-receptor (FSHR) gene have been described as possible cause of premature ovarian failure (POF). To investigate the presence of mutations and\\/or polymorphisms in FSHR gene, DNA from 20 POF, 5 of which were diagnosed as resistant ovary syndrome (ROS), and from 44 controls was isolated from peripheral lymphocytes. The complete coding sequence was analysed by PCR followed

Victoria Sundblad; Violeta A Chiauzzi; Maria Eugenia Escobar; Liliana Dain; Eduardo H Charreau

2004-01-01

78

Interactions of indole acetic acid with EGF and FSH in the culture of ovine preantral follicles  

Microsoft Academic Search

The mechanisms that regulate the gradual exit of ovarian follicles from the non-growing, primordial pool are very poorly understood. The objective of this study was to evaluate the effects of adding indole acetic acid (IAA), epidermal growth factor (EGF) and follicle stimulating hormone (FSH) to the media for in vitro culture of ovine ovarian fragments and determine their effects on

Evelyn Rabelo Andrade; Marcelo Marcondes Seneda; Amauri Alcindo Alfieri; João Ademir de Oliveira; Ana Paula Frederico Rodrigues Loureiro Bracarense; José Ricardo Figueiredo; Ricardo Toniolli

2005-01-01

79

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.  

PubMed

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis. PMID:18028739

Wechowski, Jaroslaw; Connolly, Mark; McEwan, Philip; Kennedy, Richard

2007-11-01

80

FSH induced stimulation of catalase activity in goat granulosa cells in vitro  

Microsoft Academic Search

Reactive oxygen species scavenging enzymes like catalase play diverse role in mammals. The presence of catalase in mammalian ovary is now well established. In the present investigation, changes in catalase activity in granulosa cells isolated from follicles at various stages of differentiation in response to FSH were studied. The follicles were dissected out from goat ovaries and classified as small

Rahul Behl; R. S. Pandey

2002-01-01

81

No significant leukocytosis under controlled ovarian stimulation using the LHRH antagonist Cetrorelix and recFSH  

Microsoft Academic Search

Objective: To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin). Design: Prospective, randomized phase III clinical trial. Setting: Infertility day clinic, Department of Gynecology and Obstetrics. Patients: Thirty patients undergoing IVF\\/intracytoplasmic sperm

M Ludwig; D Strik; R Felberbaum; S Al-Hasani; K Diedrich

2000-01-01

82

Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis.  

PubMed

Follicular differentiation is a tightly regulated process involving various endocrine, autocrine, and paracrine factors. The biosynthesis of progesterone and estradiol in response to FSH involves the regulation of multiple steroidogenic enzymes, such as p450 cholesterol side-chain cleavage enzyme and aromatase. Here we demonstrated that prohibitin (PHB), a multifunctional protein, inhibits FSH-induced progesterone and estradiol secretion in rat granulosa cells. The mRNA abundances of cyp11a (coding p450 cholesterol side-chain cleavage enzyme) and cyp19 (coding aromatase) were also suppressed by PHB in a time-dependent manner. It is known that a novel adipokine chemerin suppresses FSH-induced steroidogenesis in granulosa cells. Chemerin up-regulates the content of PHB, and PHB knockdown attenuates the suppressive role of chemerin on steroidogenesis. In addition, inhibition of phosphatidylinositol 3-kinase/Akt pathway enhances the suppressive action of PHB, whereas expression of constitutively active Akt attenuates this response. These findings suggest that PHB is a novel negative regulator of FSH-induced steroidogenesis, and its action with chemerin may contribute to the dysregulation of steroidogenesis in the pathogenesis of polycystic ovarian syndrome. PMID:23254195

Wang, Qi; Leader, Arthur; Tsang, Benjamin K

2012-12-18

83

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary  

PubMed Central

Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s?t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

2012-01-01

84

Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study  

Microsoft Academic Search

BACKGROUND: Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The

José G Franco Jr; Ricardo LR Baruffi; João Batista A Oliveira; Ana L Mauri; Claudia G Petersen; Paula Contart; Valeria Felipe

2009-01-01

85

Par Pond Fish, Water, and Sediment Chemistry  

SciTech Connect

The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

Paller, M.H. [Westinghouse Savannah River Company, AIKEN, SC (United States); Wike, L.D.

1996-06-01

86

Phosphoinositide 3-Kinase p110? Mediates Estrogen- and FSH-Stimulated Ovarian Follicle Growth.  

PubMed

In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110? isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110? isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development. PMID:23820902

Li, Qian; He, Hui; Zhang, Yin-Li; Li, Xiao-Meng; Guo, Xuejiang; Huo, Ran; Bi, Ye; Li, Jing; Fan, Heng-Yu; Sha, Jiahao

2013-07-02

87

Follicle-Stimulating Hormone (FSH) Transiently Blocks FSH Receptor Transcription by Increasing Inhibitor of Deoxyribonucleic Acid Binding/Differentiation-2 and Decreasing Upstream Stimulatory Factor Expression in Rat Sertoli Cells  

PubMed Central

FSH acts through the FSH receptor (FSHR) to modulate cell processes that are required to support developing spermatozoa. Within the testis, only Sertoli cells possess receptors for FSH and are the major targets for this regulator of spermatogenesis. FSH stimulation of Sertoli cells for 24–48 h is known to induce Fshr mRNA expression through an E-box motif (CACGTG) located 25 bp upstream of the transcription start site. In contrast, FSH stimulation for 8 h inhibits Fshr transcription. DNA-protein binding studies performed using nuclear extracts from Sertoli cells show that protein binding to the Fshr promoter E-box was reduced 68% after 6 h of FSH stimulation but increased 191% over basal levels after 48 h of stimulation. The proteins binding to the Fshr E-box were identified as upstream stimulatory factor (USF)-1 and -2. FSH stimulation transiently decreased USF1 levels and increased the expression of the inhibitor of DNA binding/differentiation (ID)-2 repressor protein with the same kinetics as the decreased USF/E-box interactions. Overexpression of ID2 resulted in a dose-dependent decrease in USF-driven Fshr promoter activity in the MSC-1 Sertoli cell line, and ID2 inhibited USF binding to the Fshr E-box. Together, these studies suggest that stimulation of Sertoli cells with FSH transiently decreases expression of the USF1 activator and induces accumulation of the ID2 repressor, to block USF binding to the Fshr promoter and delay activation of Fshr transcription. This FSH-regulated mechanism may explain the cyclical changes in Fshr expression that occurs in Sertoli cells in vivo.

Viswanathan, Pushpa; Wood, Michelle A.; Walker, William H.

2009-01-01

88

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes  

PubMed Central

Objective The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. Design Cross-sectional study. Methods In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. Results Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull ? analysis. There was no difference between approximate entropy ratios or Weibull ? analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. Conclusion In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.

Aksglaede, Lise; Jensen, Rikke Beck; Carlsen, Elisabeth; Kok, Petra; Keenan, Daniel M; Veldhuis, Johannes; Skakkebaek, Niels E; Juul, Anders

2009-01-01

89

Par proteins and neuronal polarity  

PubMed Central

A hallmark of neurons is their ability to polarize with dendrite and axon specification to allow the proper flow of information through the nervous system. Over the past decade, extensive research has been performed in an attempt to understand the molecular and cellular machinery mediating this neuronal polarization process. It has become evident that many of the critical regulators involved in establishing neuronal polarity are evolutionarily conserved proteins that had previously been implicated in controlling the polarization of other cell types. At the forefront of this research are the partition defective (Par) proteins. In this review, we will provide a commentary on the progress of work regarding the central importance of Par proteins in the establishment of neuronal polarity.

Insolera, Ryan; Chen, She; Shi, Song-Hai

2011-01-01

90

[Comparative analysis of multifollicular development with the application of recombinant FSH vs. urinary FSH in the results of in vitro fertilization].  

PubMed

The interactive function between intrafollicular factors related with ovum competence and embryo development played an important role getting high quality embryos during the embryo transference in in-vitro fertilization programs. Urinary gonadotropins are used widely to get homogeneous follicles during ovarian stimulation. Recombinant technology has been applied in these compounds to correlate with a best egg formation and higher pregnancy rates. We developed a prospective, linear and comparative study to aim the ovum/embryo development using urinary and recombinant FSH. A total of 100 patients were included in the study, 56 patients received rFSH (group I) and 44 hMG (group II). There were not differences in age, weight and body mass index as well as ovarian reserve. However, patients who used urinary gonadotrophins required a higher number of ampoules [31.7 +/- 8.6 vs. 20.7 +/- 6.4 (p < 0.001)]. No differences in peak E2, day of hCG and endometrial thickness. Although, no differences in number of egg mature, the fertilization rate was higher in the recombinant group [5.9 +/- 3.7 vs. 3.4 +/- 2.3 (p < 0.02)]. A higher number of embryo transfer were observed in the same group (3.4 +/- 1.7 vs. 1.9 +/- 2.2 (p < 0.004)]. The pregnancy rates were 34.3% and 29.6% for each group respectively. PMID:11599315

Kably, A; Castelazo, E; Barroso, G

2001-08-01

91

Polymorphism of follicle stimulating hormone beta (FSH?) subunit gene and its association with litter traits in giant panda.  

PubMed

The different SSCP patterns of the follicle stimulating hormone beta (FSH?) gene amplified by three pairs of primers were sequenced. Comparisons among the three nucleotide sequences of three genotypes indicated that three base substitutions (A213T, A91G, and A89C) were detected in FSH? gene, which A213T substitution led to one amino acids mutation (Lys > Met), and the other two substitutions were synonymous mutations. The AA, AB and BB genotypes patterns obtained by FSH? primer1 had evident relation with the litter traits, but the SSCP genotypes patterns obtained by FSH? primer2 and primer3 had no evident relation with the litter traits in giant panda. The giant panda with AA and AB genotype had the largest litter size and multiparity rate compared with the BB genotypes (P < 0.05). We speculated that the giant pandas with the A allele have better litter traits than those with the B allele. PMID:24057246

Huang, Xiaoyu; Li, Desheng; Wang, Jiwen; Huang, Yan; Han, Chunchun; Zhang, Guiquan; Huang, Zhi; Wu, Honglin; Wei, Ming; Wang, Guosong; Hu, Haiping; Deng, Tao; He, Tao; Zhou, Yingming; Song, Shixian; Luo, Bo; Zhang, Heming

2013-09-22

92

Importance of Inhibin B in the Regulation of FSH Secretion in the Human Male  

Microsoft Academic Search

Regulation of FSH secretion in the male involves a complex balance between stimulation by GnRH from the hypothala- mus, inhibitory feedback by sex steroids (T and E2) and in- hibin B (Inh B) from the gonads, and autocrine\\/paracrine mod- ulation by activin and follistatin within the pituitary. The aim of the present study was to delineate the feedback control of

FRANCES J. HAYES; NELLY PITTELOUD; PAUL A. BOEPPLE

93

Correlation of the Day 3 FSH/LH Ratio and LH Concentration in Predicting IVF Outcome  

PubMed Central

Background This study was undertaken to evaluate the role of day 3 FSH/LH ratio and day 3 LH level as predictors of IVF cycle outcomes. Methods This prospective observational study was undertaken in the IVF and Reproductive Biology Centre and Lok Nayak Hospital, affiliated to Maulana Azad Medical College, in New Delhi, India. The study included 105 women who underwent controlled ovarian hyperstimulation for in vitro fertilization. Characteristics of IVF cycles and outcomes were studied in patient subgroups based on day 3 FSH/LH ratio (<2 and ?2) and day 3 LH levels (>3 and ?3 mIU/ml). The student t-test, Bartlett's test, chi-squred (?2) and Fisher's exact test, and linear regression model were used for data analysis. A p-value less than 0.05 was considered as statistically significant. Results Women with an elevated FSH/LH ratio ?2 (n = 31) required higher doses of gonadotrophins (3019.34 vs. 2482.43 IU). The outcome of IVF was poor in these patients and they had fewer number of mature follicles (>16 mm) (5.44 vs. 6.09), less E2/mature follicle ratio (4.65 vs. 6.36), fewer retrieved oocytes (6.67 vs. 9.09) and fewer pregnancy rates (11.1% vs. 33.8%). On the other hand, patients with low basal LH levels (?3 mIU/ml) did not differ significantly in terms of response to controlled ovarian hyperstimulation except for fewer number of retrieved oocytes (7.33 vs. 7.91) but there was a trend towards poor pregnancy rates (7.33 vs. 7.91) but there was a trend towards poor pregnancy rates as compared to subgroup with LH levels >3 mIU/ml. Conclusion Elevated day 3 FSH/LH ratio is associated with inferior outcome in IVF treatment cycles and it could be used as an additional predictor of decreased ovarian reserve.

Prasad, Sudha; Gupta, Teena; Divya, Aabha

2013-01-01

94

Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders  

Microsoft Academic Search

This study investigated whether luteal phase initiation of FSH supplementation would improve oocyte yield compared with follicular phase administration in women with poor ovarian response (POR). A two-arm, randomized, open-label pilot trial was performed at a university-based infertility centre. In nine of 18 infertile women with a history of POR in a previous cycle [10 mm and >16 mm and

Suleena Kansal Kalra; Sarah Ratcliffe; Clarisa R Gracia; Linda Martino; Christos Coutifaris; Kurt T Barnhart

2008-01-01

95

Mechanisms underlying endothelin’s inhibition of FSH-stimulated progesterone production by ovarian granulosa cells  

Microsoft Academic Search

In previous studies in porcine granulosa cell cultures, endothelin-1 (ET-1) was shown to inhibit FSH-stimulated cAMP and progesterone accumulation, and to increase inositol phosphate formation and cytosolic calcium ion concentration. The latter results suggest an action of ET-1 via the activation of phospholipase C. Here we have investigated the following experimental questions. (1) Does ET-1 activate PKC in ovarian cells?

Jorge A Flores; James C Garmey; Michal Lahav; Johannes D Veldhuis

1999-01-01

96

Effect of FSH and cell localization on dimeric inhibin-A secretion from bovine granulosa cells in culture.  

PubMed

We tested the hypotheses that the secretion of dimeric inhibin-A from cultured bovine granulosa cells is stimulated by FSH, and that antral cells secrete more inhibin-A than do mural cells. Cells from the antral or mural compartment of follicles were cultured in defined medium in two culture systems, and dimeric inhibin-A was measured by two-site ELISA or by Western immunoblotting. In the first culture system, dimeric inhibin-A secretion declined with time in culture, but was significantly (P<0.05) higher from antral than from mural cells (as was total inhibin-alpha measured by RIA). The secretion of dimeric inhibin-A and inhibin-alpha from antral but not mural cells was responsive to FSH. In the second culture system, dimeric inhibin-A secretion increased with time in culture, and was significantly stimulated by FSH, but FSH responsiveness was dependent on the concentrations of insulin in the culture medium. The major forms of inhibin-A secreted had molecular masses of approximately 58, 62, 103-116 and >116 kDa; the 32 kDa form was barely detectable. These different forms were all stimulated by FSH, but the >116 and 62 kDa forms were most responsive to FSH. We conclude that (i) FSH stimulates dimeric inhibin-A secretion from bovine granulosa cells, (ii) the 62 kDa form of inhibin-A may be more responsive to FSH than the 58 kDa form, and (iii) the spatial differentiation of granulosa cell function within the follicle previously observed for oestradiol secretion was also observed for inhibin-alpha and dimeric inhibin-A secretion. PMID:10810284

Boudjemaâ, M L; Rouillier, P; Bhatia, B; Silva, J M; Guilbault, L A; Price, C A

2000-05-01

97

Development of specific enzyme-linked immunosorbent assay for determining LH and FSH levels in tilapia, using recombinant gonadotropins  

Microsoft Academic Search

We recently produced Oreochromis niloticus recombinant LH and FSH as single-chain polypeptides in the methylotrophic yeast Pichia pastoris. Glycoprotein subunit ? was joined with tilapia (t) LH? or tFSH? mature protein-coding sequences to form a fusion gene that encodes a ``tethered” polypeptide, in which the gonadotropin ?-subunit forms the N-terminal part and the ?-subunit forms the C-terminal part. Recombinant (r)

Joseph Aizen; Harel Kasuto; Berta Levavi-Sivan

2007-01-01

98

Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study.  

PubMed

The CONSORT dosing algorithm individualizes recombinant human FSH (r-hFSH) doses for assisted reproduction technologies, assigning 37.5 IU increments according to patient characteristics: basal FSH, body mass index, age and antral follicle count. A prospective, uncontrolled, international, 18-centre, pilot study of normo-ovulatory women aged 18-34 years inclusive undergoing a long agonist treatment protocol was performed. Follitropin alfa filled-by-mass (GONAL-f®) dose was assigned by the algorithm and was intended to be altered only for risk of ovarian hyperstimulation syndrome (OHSS). Primary end-point was number of oocytes retrieved. Dose groups containing ?5 patients were analysed: 75 IU (n = 48), 112.5 IU in = 45), 150 IU (n = 34), 187.5 IU (n = 24), 225 IU (n = 10). Cancellations due to inadequate response were higher than expected in the 75 IU group (12/48). Overall, a median of 9.0 oocytes were retrieved (8.5, 8.0, 10.0, 12.0 and 8.0 in the 75, 112.5, 150, 187.5 and 225 IU groups respectively). Clinical pregnancy rates/cycle started were 31.3, 31.1, 35.3, 50.0 and 20.0%, respectively (overall, 34.2%). Two patients had severe OHSS. Use of the CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in this preliminary study. Adjustment of the algorithm could reduce cancellation rates. PMID:21575853

Olivennes, F; Howies, C M; Borini, A; Germond, M; Trew, G; Wikland, M; Zegers-Hochschild, F; Saunders, H; Alam, V

2011-02-01

99

Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study.  

PubMed

The CONSORT dosing algorithm individualizes recombinant human FSH (r-hFSH) doses for assisted reproduction technologies, assigning 37.5 IU increments according to patient characteristics: basal FSH, body mass index, age and antral follicle count. A prospective, uncontrolled, international, 18-centre, pilot study of normo-ovulatory women aged 18-34 years inclusive undergoing a long agonist treatment protocol was performed. Follitropin alpha filled-by-mass (GONAL-f) dose was assigned by the algorithm and was intended to be altered only for risk of ovarian hyperstimulation syndrome (OHSS). Primary end-point was number of oocytes retrieved. Dose groups containing >or=5 patients were analysed: 75 IU (n = 48), 112.5 IU (n = 45), 150 IU (n = 34), 187.5 IU (n = 24), 225 IU (n = 10). Cancellations due to inadequate response were higher than expected in the 75 IU group (12/48). Overall, a median of 9.0 oocytes were retrieved (8.5, 8.0, 10.0, 12.0 and 8.0 in the 75, 112.5, 150, 187.5 and 225 IU groups respectively). Clinical pregnancy rates/cycle started were 31.3, 31.1, 35.3, 50.0 and 20.0%, respectively (overall, 34.2%). Two patients had severe OHSS. Use of the CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in this preliminary study. Adjustment of the algorithm could reduce cancellation rates. PMID:19192339

Olivennes, F; Howles, C M; Borini, A; Germond, M; Trew, G; Wikland, M; Zegers-Hochschild, F; Saunders, H; Alam, V

2009-02-01

100

[Study on anterior-pituitary function during pregnancy and puerperium by radioimmunoassay of human FSH-subunits (author's transl)].  

PubMed

In order to observe the anterior pituitary function of pregnant women in terms of FSH secretion, specific and sensitive radioimmunoassays for human FSH-alpha and -beta subunits were utilized for this study. Blood levels of hFSH-alpha during pregnancy increase acutely and the values of the subunits are as follows: 428.0 +/- 92.64 ng/ml (mean +/- SE., 5-10 weeks of gestation), 962.8 +/- 132.5 ng/ml (11-20 weeks), 1889.0 +/- 137.60 ng/ml (21-30 weeks), 2959 +/- 323.40 ng/ml (31-40 weeks). After child delivery, serum levels of hFSH-alpha decreased to 22.92 ng/ml. In contrast, blood levels of hFSH-beta were not altered significantly through gestation. hFSH-beta subunits: 1.97 +/- 0.74 ng/ml (5-10 weeks of gestation), 2.66 +/- 0.52 ng/ml (11-20 weeks), 2.27 +/- 0.52 ng/ml (21-30 weeks), 2.07 +/- 0.37 ng/ml (31-40 weeks), respectively. PMID:6802910

Sakai, M; Makino, T; Suekane, H; Lin, H; Yokokura, T; Iizuka, R

1981-12-01

101

Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1? signaling in human epithelial ovarian cancer.  

PubMed

Follicle-stimulating hormone (FSH) and the FSH receptor contribute to tumor angiogenesis and are acknowledged risk factors for ovarian epithelial cancer (OEC). Accumulating evidence suggests that FSH can induce vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1? (HIF1?) expression. We previously demonstrated that FSH induces reactive oxygen species (ROS) production and activates Nrf2 signaling. This study was performed to investigate whether FSH induces VEGF expression via a ROS-mediated Nrf2 signaling pathway. In the current study, OET cells were treated with FSH; dichlorofluorescein staining was used to determine ROS generation, western blotting was used to quantify Nrf2 expression and VEGF expression was measured using an ELISA. Nrf2 and HIF1? were knocked down using siRNAs to investigate the role of the Nrf2 and HIF1? signaling pathways in FSH-induced VEGF expression. The chromatin immunoprecipitation assay (ChIP) was used to determine HIF1? binding to the VEGF promoter. Finally, it was found that FSH induced ROS production and activated Nrf2 signaling; elimination of ROS or knockdown of Nrf2 blocked FSH-induced VEGF expression. Knockdown of Nrf2 impaired HIF1? signaling activation. Blockage of the FSH-ROS-Nrf2-HIF1? signaling pathway attenuated FSH-induced binding of HIF1? to the VEGF promoter. Collectively, this study indicates that ROS and aberrant expression of Nrf2 play an important role in FSH-induced angiogenesis in OEC, and provides insight into the mechanisms of FSH-induced VEGF expression. Elimination of ROS or inhibition of Nrf2 may represent potential therapeutic targets for the treatment of ovarian cancer. PMID:23404377

Zhang, Zhenbo; Wang, Qianqian; Ma, Jie; Yi, Xiaofang; Zhu, Yaping; Xi, Xiaowei; Feng, Youji; Jin, Zhijun

2013-02-06

102

Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis  

PubMed Central

BACKGROUND Some studies, but not all, support the hypothesis that trisomy frequency is related to the size of the oocyte pool, with the risk increased for women with fewer oocytes (older ovarian age). We tested this hypothesis by comparing hormonal indicators of ovarian age among women who had trisomic pregnancy losses with indicators among women with non-trisomic losses or chromosomally normal births. The three primary indicators of advanced ovarian age were low level of anti-Müllerian hormone (AMH), high level of follicle-stimulating hormone (FSH) and low level of inhibin B. METHODS The analysis drew on data from two hospital-based case–control studies. Data were analyzed separately and the evidence from the two sites was combined. We compared 159 women with trisomic pregnancy losses to three comparison groups: 60 women with other chromosomally abnormal losses, 79 women with chromosomally normal losses and 344 women with live births (LBs) age-matched to women with losses. We analyzed the hormone measures as continuous and as categorical variables. All analyses adjust for age in single years, day of blood draw, interval in storage and site. RESULTS AMH and inhibin B did not differ between women with trisomic losses and any of the three comparison groups. Mean ln(FSH) was 0.137 units (95% confidence interval (CI): 0.055, 0.219) higher for trisomy cases compared with LB controls; it was also higher, though not significantly so, for trisomy cases compared with women with other chromosomally abnormal losses or chromosomally normal losses. The adjusted odds ratio in relation to high FSH (?10 mIU/ml) was significantly increased for trisomy cases versus LB controls (adjusted odds ratio (OR): 3.8, 95% CI: 1.6, 8.9). CONCLUSIONS The association of trisomy with elevated FSH is compatible with the oocyte pool hypothesis, whereas the absence of an association with AMH is not. Alternative interpretations are considered, including the possibility that elevated FSH may disrupt meiotic processes or allow recruitment of abnormal follicles.

Kline, J.K.; Kinney, A.M.; Levin, B.; Kelly, A.C.; Ferin, M.; Warburton, D.

2011-01-01

103

Anti-Müllerian hormone versus antral follicle count for defining the starting dose of FSH.  

PubMed

This pilot study compared the efficacy and safety of two simple dosing algorithms, one based on anti-Müllerian Hormone (AMH) and the other on the antral follicle count (AFC), to determine the starting dose of recombinant FSH (rFSH) for ovarian stimulation in 348 women. Patients were randomized to a predefined AMH- or AFC-based algorithm. The proportion of cycles with the desired response was similar when rFSH dose was determined using AMH or AFC (35.2% versus 28.4%). There was a significant difference between the groups in the proportion of cycles with a hyperresponse (8.6% and 17.4%, but the incidence of ovarian hyperstimulation syndrome was similar (1.1% and 4.6%). There were no significant differences between two groups in outcomes, including implantation (19.3% versus 19.0%), clinical pregnancy (38.0% versus 46.9%), multiple pregnancy (16.5% versus 15.2%) and miscarriage (7.0% versus 8.3%). However, statistically significant differences in ovarian response were evident among the AMH and AFC subgroups: for AMH, Desired and Hypo; for AFC, Hypo and Hyper. This pilot study provides information for developing protocols to further validate the use of either AMH or AFC to guide the starting dose of rFSH in ovarian stimulation. The ideal outcome for couples undergoing IVF treatment is the birth of a healthy baby. One factor that might influence this is retrieving an adequate number of eggs, which are obtained using various treatment protocols. A group of drugs called gonadotrophins have been used for more than 20years to stimulate the ovaries to produce eggs. However, the dose to start treatment has not been clearly defined. A few studies have looked at ways to use the best gonadotrophin dose for each woman, but to be useful in the clinic any approach needs to be simple and easy to use. This study compared the effectiveness and safety of two simple approaches to determining the starting dose of recombinant FSH (rFSH) for ovarian stimulation in women undergoing IVF. One was based on the concentration of a hormone secreted by developing eggs (anti-Müllerian hormone; AMH) and the other on the number of developing follicles (antral follicle count; AFC). The number of cycles achieving the desired response in terms of number of eggs was similar when rFSH dose was guided using AMH or AFC, and the incidence of ovarian hyperstimulation syndrome was also similar. In addition, rates of clinical pregnancy, multiple pregnancy and miscarriage did not differ between the two groups. However, patients with low AMH concentrations or low AFC had a poor response to ovarian stimulation. This pilot study provides useful information from which new studies can further assess these approaches to personalizing treatment during IVF. PMID:23953069

Lan, Vuong Thi Ngoc; Linh, Nguyen Khanh; Tuong, Ho Manh; Wong, P C; Howles, Colin M

2013-07-23

104

The time interval between FSH-P administration and slaughter can influence the developmental competence of beef heifer oocytes.  

PubMed

Superovulation alone may not be enough to result in developmentally competent oocytes. The objective of this study was to determine if a time interval between FSH administration and slaughter and between slaughter and oocyte recovery could increase the percentage of embryos. Beef heifers (n = 20) were superovulated with 1 bolus injection of 25 mg, im FSH-P diluted in saline and then slaughtered at 24, 48 or 72 h after FSH injection and the ovaries transported to the laboratory at 30 degrees C. For 6 of the heifers that received FSH-P and were then culled at 48 h post treatment, oocytes were recovered 1 to 2 h post slaughter from the first ovary and 4 to 5 h from the second ovary. Ovaries from untreated cows were collected and served as controls. The results indicated that FSH-P and culling at 48 h produced 35% >/= 32-cell embryos, significantly more than FSH-P and culling at 24 and 72 h (19 and 14%, respectively; P < 0.05). Furthermore, FSH-P and culling at 48 h produced 25% >/= 64-cell embryos, significantly more than FSH-P and culling at 24 and 72 h and the nontreatment control group (5, 7 and 15%, respectively; P < 0.05). The FSH-P group culled at 48 h produced more >/= 32-cell embryos, with an average of 84 +/- 5 cells/embryo, than the treated groups culled at 24 and 72 h and the untreated group (52 +/- 6, 60 +/- 5 and 63 +/- 3, respectively; P < 0.01). Finally, oocytes left in the postmortem ovaries for 4 to 5 h resulted in higher rates (51% and 41%) of >/= 32- and >/= 64-cell embryos, respectively, compared with that of the untreated control animals (29 and 18%; P < 0.05), but these rates were not different from oocytes left in ovaries for 1 to 2 h (33 and 24%). It is concluded that culling at 48 h after FSH treatment, as well as the conditioning effect on oocytes in warm postmortem ovaries for 4 to 5 h, increases the number of competent oocytes. PMID:16728173

Blondin, P; Guilbault, L A; Sirard, M A

1997-10-01

105

Changes in plasma concentrations of LH, FSH, estradiol 17-beta and progesterone during oestrus in mithun (Bos frontalis).  

PubMed

The objective of the present study was to establish the changes in plasma concentrations of LH, FSH, estradiol 17-beta (E2) and progesterone (P4), as well as to understand their temporal relationships during oestrus in mithun (Bos frontalis). The experiment was conducted on 11 mithuns during third or fourth postpartum oestrous cycle. Since oestrus onset the jugular vein blood samples were collected every 2 h for 72 and 96 h, respectively from the animals without and with standing heat. The LH, FSH, E2 and P4 concentrations were estimated in plasma. The P4 concentration was fluctuated throughout the oestrus period and the average P4 concentration was found significantly (p<0.05) lower on the day of oestrus onset. The multiple rises in LH and FSH concentrations above the basal level in spike like fashion were observed throughout the oestrus period irrespective of the occurrence of standing heat. A significant (p<0.01) gradual increase in the average daily E2 concentration was observed till day 2 following oestrus onset irrespective of the occurrence of standing heat. A significant (p<0.05) simultaneous increase in LH, FSH and E2 concentrations and a transient increase in P4 concentration at approximately the time of standing heat onset were observed. During investigation a definite temporal coupling between LH and FSH rises was absent throughout the oestrus period. The results suggest that (1) the multiple short-duration low-amplitude LH and FSH surges during oestrus may be crucial for the final maturation of ovulatory follicle and subsequent ovulation in mithun; (2) a differential mechanism for controlling LH and FSH secretions probably exists in mithun. PMID:16519723

Dhali, A; Mishra, D P; Mech, A; Karunakaran, M; Choudhury, H; Khate, K; Rajkhowa, C

2006-04-01

106

Pars plana vitrectomy in ocular Behçet's disease  

Microsoft Academic Search

Purpose: To evaluate the results of pars plana vitrectomy in Behçet patients with dense vitreous opacities, and its effect on intraocular inflammatory episodes and visual prognosis. Methods: The study group consisted of nine patients (one eye in eight patients, both eyes in one) with Behçet's disease who underwent pars plana vitrectomy because of dense vitreous opacification. The indications for vitrectomy,

Merih Soylu; Nihal Demircan; Aysel Pelit

2001-01-01

107

Pars Plana Vitrectomy in Advanced Coats’ Disease  

Microsoft Academic Search

Purpose: To report 5 cases of advanced Coats’ disease managed with pars plana vitrectomy and silicone oil tamponade. Methods: Five patients with advanced Coats’ disease and serous or tractional retinal detachment underwent pars plana vitrectomy with internal drainage, endolaser photocoagulation and silicone oil tamponade. One patient had combined phacoemulsification-vitrectomy surgery. Of the 5 patients, 1 had intravitreal hemorrhage and a

Gulipek Muftuoglu; Gokhan Gulkilik

2011-01-01

108

Par Pond vegetation status Summer 1995 -- Summary  

SciTech Connect

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

Mackey, H.E. Jr.; Riley, R.S.

1996-01-01

109

Validation Studies of the Seven Day Physical Activity Recall (PAR)  

Cancer.gov

Validation Studies of the Seven Day Physical Activity Recall (PAR) Wilkinson et al. 2004 See reference #111 Methods 7-day physical activity recall (PAR), including alternative PAR scoring algorithms compared to pedometer readings (3 days step counts).

110

Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study  

Microsoft Academic Search

Circulating endogenous concentrations of LH are reduced in women undergoing down-regulation with gonadotrophin-releasing hormone agonists (GnRHa) and ovarian stimulation with recombinant human FSH (r-hFSH). The effect of recombinant human LH (r-hLH) supplementation on ovarian response and pregnancy outcome was evaluated in a prospective randomized study (sealed envelopes) including 231 cycles. Normogonadotrophic women were stimulated with either r-hFSH or a combination

P Humaidan; M Bungum; L Bungum; C Yding Andersen

2004-01-01

111

Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia.  

PubMed

The objective of the present study was to determine the effects of bone morphogenetic protein (BMP)-15 and FSH on the growth, viability, and expression of mRNA for FSH (FSH-R) and BMP-15 (BMPR-IB and BMPR-II) receptors in cultured bovine secondary follicles. Secondary follicles were microdissected and cultured for 12 days in minimum essential medium-? alone or supplemented with BMP-15, sequential FSH, both BMP-15 and FSH, or BMP-15 from days 0 to 6, and FSH from days 7 to 12. Thereafter, the effect of these treatments on the follicular volume, viability, and antrum formation and the levels of mRNA for BMPR-IB, BMPR-II, and FSH-R were assessed. Compared with day 0, the follicles cultured with FSH or BMP-15, or both, had a significant and progressive increase in volume (P < 0.05). However, the follicles cultured for 12 days with both BMP-15 and FSH had the greatest volume and a greater rate of antrum formation than those in control medium, but results similar to those cultured with FSH (days 0 to 12) or BMP-15 (days 0 to 6) and FSH (days 7 to 12). Together with their accelerating effect on in vitro follicle growth, the combination of FSH and BMP-15 induced ultrastructural changes in the cultured follicles and increased atresia. However, adding either BMP-15 or FSH to the culture medium, not only promoted follicular growth and follicular antrum formation, but also maintained follicular viability during culture. Except for follicles cultured in minimal essential medium-?, the levels of mRNA for BMPR-IB were reduced, and the levels of mRNA for FSH-R were significantly greater in follicles cultured in medium supplemented with BMP-15. In conclusion, all in vitro follicle treatments supported growth of bovine preantral follicles; however, adding both BMP-15 and FSH to the culture medium (minimal essential medium-?) for 12 days provided the greatest stimulation. Furthermore, the viability and ultrastructural integrity of cultured follicles were only maintained when only BMP-15 or FSH was added to the culture medium. PMID:23582608

Passos, M J; Vasconcelos, G L; Silva, A W B; Brito, I R; Saraiva, M V A; Magalhães, D M; Costa, J J N; Donato, M A M; Ribeiro, R P; Cunha, E V; Peixoto, C A; Campello, C C; Figueiredo, J R; van den Hurk, R; Silva, J R V

2013-04-09

112

Development of specific enzyme-linked immunosorbent assay for determining LH and FSH levels in tilapia, using recombinant gonadotropins.  

PubMed

We recently produced Oreochromis niloticus recombinant LH and FSH as single-chain polypeptides in the methylotrophic yeast Pichia pastoris. Glycoprotein subunit alpha was joined with tilapia (t) LHbeta or tFSHbeta mature protein-coding sequences to form a fusion gene that encodes a ;;tethered" polypeptide, in which the gonadotropin beta-subunit forms the N-terminal part and the alpha-subunit forms the C-terminal part. Recombinant (r) gonadotropins were used to develop specific and homologous competitive ELISAs for measurements of FSH and LH in the plasma and pituitary of tilapia, using primary antibodies against rtLHbeta or rtFSHbeta, respectively, and rtLHbetaalpha or rtFSHbetaalpha for the standard curves. The wells were coated with either rtLHbeta (2ng/ml) or rtFSHbeta (0.5ng/well), and the final concentrations of the antisera were 1:5000 (for tLH) or 1:50,000 (for tFSH). The sensitivity of the assay was 15.84pg/ml for tLH and 0.24pg/ml for tFSH measurements in the plasma, whereas for the measurements in the pituitary, the sensitivity was 2.43ng/ml and 1.52ng/ml for tLH and tFSH, respectively. The standard curves for tFSH and tLH paralleled those of serially diluted pituitary extracts of other cichlids, as well as of serially diluted pituitary extract of seabream, European seabass and hybrid bass. We examined plasma tFSH and tLH levels in the course of one reproductive cycle, between two successive spawnings, in three individual tilapia females. Plasma levels of both FSH and LH increased during the second day after the eggs had been removed, probably related to the vitellogenic phase. LH levels increased toward spawning, which occurred on the 11th day. FSH levels also increased on day of cycle, probably due to recruitment of a new generation of follicles for the successive spawning. The development of specific ELISAs using recombinant gonadotropins is expected to advance the study of the distinct functions of each of these important hormones. PMID:17507016

Aizen, Joseph; Kasuto, Harel; Levavi-Sivan, Berta

2007-04-11

113

Effects of alcohol on pulsatile luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion in the adult male rat  

SciTech Connect

To determine possible hypothalamic actions of alcohol on hormone secretion, the effects of acute intragastric alcohol on plasma LH and FSH pulsations were studied. One jugular and one intragastric cannula were surgically implanted into adult male Sprague Dawley rats. Eight days later, rats were bilaterally castrated at 1400 h and infused intragastrically with either saline or 3 g/kg ethanol between 0700 h 0800 h the next days. Blood samples (300 microliters) were collected every 5 min for 3 h (starting at 0800 h), centrifuged and the plasma was frozen for LH and FSH radioimmunoassay. The blood cells were resuspended in saline and returned to the animal immediately following the next sample collection. While the mean plasma LH or FSH concentration did not vary significantly between the alcohol-treated and saline-treated rats, the mean LH (but not FSH) pulse frequency was lower in ethanol-treated rats (3.3 {plus minus} 0.25 pulses/3 h) than saline-treated controls (7.2 {plus minus} 0.3 pulses/3 h). In addition, mean area under the OH pulses were significantly greater in ethanol-treated than saline controls. These data suggest that: (1) ethanol acts to reduce the frequency of LHRH release for the hypothalamus and increase the area under each LH pulse; and (2) LH and FSH secretion are differentially regulated.

Badger, T.M.; Abdallah, M.M.; Hayden, J.B. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

1989-02-09

114

Pharmacological Estrogen Administration Causes a FSH-Independent Osteo-Anabolic Effect Requiring ER Alpha in Osteoblasts  

PubMed Central

Postmenopausal osteoporosis is characterized by declining estrogen levels, and estrogen replacement therapy has been proven beneficial for preventing bone loss in affected women. While the physiological functions of estrogen in bone, primarily the inhibition of bone resorption, have been studied extensively, the effects of pharmacological estrogen administration are still poorly characterized. Since elevated levels of follicle-stimulating hormone (FSH) have been suggested to be involved in postmenopausal bone loss, we investigated whether the skeletal response to pharmacological estrogen administration is mediated in a FSH-dependent manner. Therefore, we treated wildtype and FSH?-deficicent (Fshb?/?) mice with estrogen for 4 weeks and subsequently analyzed their skeletal phenotype. Here we observed that estrogen treatment resulted in a significant increase of trabecular and cortical bone mass in both, wildtype and Fshb?/? mice. Unexpectedly, this FSH-independent pharmacological effect of estrogen was not caused by influencing bone resorption, but primarily by increasing bone formation. To understand the cellular and molecular nature of this osteo-anabolic effect we next administered estrogen to mouse models carrying cell specific mutant alleles of the estrogen receptor alpha (ER?). Here we found that the response to pharmacological estrogen administration was not affected by ER? inactivation in osteoclasts, while it was blunted in mice lacking the ER? in osteoblasts or in mice carrying a mutant ER? incapable of DNA binding. Taken together, our findings reveal a previously unknown osteo-anabolic effect of pharmacological estrogen administration, which is independent of FSH and requires DNA-binding of ER? in osteoblasts.

Jeschke, Anke; Marshall, Robert P.; Stride, Brenda D.; Wintermantel, Tim; Beil, Frank T.; Amling, Michael; Schutz, Gunther; Tuckermann, Jan; Schinke, Thorsten

2012-01-01

115

Matrix metalloproteases and PAR1 activation.  

PubMed

Cardiovascular diseases, including atherothrombosis, are the leading cause of morbidity and mortality in the United States, Europe, and the developed world. Matrix metalloproteases (MMPs) have recently emerged as important mediators of platelet and endothelial function, and atherothrombotic disease. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that is classically activated through cleavage of the N-terminal exodomain by the serine protease thrombin. Most recently, 2 MMPs have been discovered to have agonist activity for PAR1. Unexpectedly, MMP-1 and MMP-13 cleave the N-terminal exodomain of PAR1 at noncanonical sites, which result in distinct tethered ligands that activate G-protein signaling pathways. PAR1 exhibits metalloprotease-specific signaling patterns, known as biased agonism, that produce distinct functional outputs by the cell. Here we contrast the mechanisms of canonical (thrombin) and noncanonical (MMP) PAR1 activation, the contribution of MMP-PAR1 signaling to diseases of the vasculature, and the therapeutic potential of inhibiting MMP-PAR1 signaling with MMP inhibitors, including atherothrombotic disease, in-stent restenosis, heart failure, and sepsis. PMID:23086754

Austin, Karyn M; Covic, Lidija; Kuliopulos, Athan

2012-10-18

116

GH, ACTH, LH and FSH behaviour in the first seven days of life.  

PubMed

--43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2 +/- 34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p less than 0.01). Minimum level was reached on the 7th day. Plasma hCG-LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5 +/- 16.2 and 33.0 +/- 24.9 mU/ML, respectively). after this, plasma hCG-LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards. PMID:179270

Cacciari, E; Cicognani, A; Pirazoli, P; Dallacasa, P; Mazzaracchio, M A; Tassoni, P; Bernardi, F; Salardi, S; Zappulla, F

1976-05-01

117

Repeated oocyte pick up in prepubertal swamp buffalo (Bubalus bubalis) calves after FSH superstimulation.  

PubMed

The objective in this study was to investigate the effect of repeated oocyte collection by transvaginal, ultrasound-guidance, oocyte pick-up (OPU) in nine, prepubertal (8-12 months), swamp buffaloes. Animals were treated with FSH for 3 days and received GnRH on the third day, 24 h before OPU. This session was repeated on five occasions at 2 weekly intervals. Over the five sessions of hormone treatment followed by OPU, 39/42 (92.9%) animals responded and had 6.6+/-3.6 follicles with a follicular diameter of 5.0+/-2.0 mm. The oocyte recovery rate was 5.4+/-3.7 and averaged 82.8% oocytes, except for session 4, when oocyte recovery was around 75.0%. Most oocytes were denuded (39.5%), whilst 28.8% had a substantial cumulus mass. There were no differences in the ovarian responses and the recovery rates between the collections. It was concluded that five repeat cycles of FSH and OPU did not influence the follicular response to superstimulation or the number of oocytes recovered from prepubertal, buffalo calves. PMID:15019465

Techakumphu, Mongkol; Promdireg, Akachart; Na-Chiengmai, Ancharlie; Phutikanit, Nawapen

2004-06-01

118

Serum gonadotropin concentrations and ovarian response in ewes treated with analogs to LH-RH/FSH-RH.  

PubMed

Serum gonadotropin concentrations and ovarian response in ewes treated with analogs to luteinizing hormone-releasing hormone/follicle s timulating hormone-releasing hormone (LH-RH/FSH-RH) are reported. In Ex periment 1, 32 ewes received either .5, 5, 50 or 500 mcg of des Gly10-LH-RH ethylamide or LH-RH/FSH-RH. Peak LH concentration was signi ficantly higher (p less than .01) in ewes treated with .5 mcg analog than in ewes treated with .5 mcg LH-RH/FSH-RH and there was a greater number (p less than .05) of ovulations in the ewes treated with analog than in ewes treated with LH-RH/FSH-RH. In Experiment 2, 10 ewes were treated either with 500 mcg anlog or saline. All were artificially inse minated 12 hours postinjection. A greater number of ovulations (p less than .05) occurred in ewes treated with the analog than in those treated with saline, but none of the ewes conceived. In Experiment 3, 70 ewes r eceived either the analogs D-ALa6 des Gly10-FH-RH ethylamide, D-leu6 des Gly10-LH-RH-ethylamide or LH-RH/FSH-RH. An increase (p less than .05) in total LH, mean peak LH and duration of the LH release in ewes treated with either .5, 5, 50 mcg D-Ala6 and D-Leu6 analog was seen as compared to ewes which received corresponding doses of LH-RH/FSH-RH. The analogs were 9, 4 and 3 times more potent in total LH releasing ability when compared to LH-RH/FSH-RH at the .5, 4 and 50 mcg doses, respectively. These data indicate that the maximal pituitary response was obtained with 50 mcg of the D-Ala6 or D-Leu6 analog but that 500 mcg of LH-RH/FSH-RH was required before maximal LH release was attained. PMID:773913

Kinder, J E; Adams, T E; Nett, T M; Coy, D H; Schally, A V; Reeves, J J

1976-05-01

119

Comparative cactus architecture and par interception  

SciTech Connect

Because CO{sup 2} uptake by cacti can be limited by low levels of photosynthetically active radiation (PAR) and because plant form affects PAR interception, various cactus forms were studied using a computer model, field measurements, and laboratory phototropic studies. Model predictions indicated that CO{sub 2} uptake by individual stems at an equinox was greatest when the stem were vertical, but at the summer and the winter solstice CO{sub 2} uptake was greatest for stems titled 30{degree} away from the equator. Stem tilting depended on form and taxonomic group. Not only can the shape of cacti be affected by PAR, but also shape influences PAR interception and hence CO{sub 2} uptake.

Geller, G.N.; Nobel, P.S. (Univ. of California, Los Angeles (USA))

1987-07-01

120

COMPARISON OF THE ABILITY OF THE THREE GONADOTROPIN RELEASING HORMONES (GNRH) TO STIMULATE RELEASE OF FOLLICLE STIMULATING HORMONE (FSH) AND LUTEINIZING HORMONE (LH) IN CHICKENS  

Technology Transfer Automated Retrieval System (TEKTRAN)

It is well established that GnRH can stimulate the release of LH and FSH in mammals. Two decapeptide releasing hormones for LH have been found in the chicken hypothalamus, chicken (c) GnRH I and cGnRH II. There is controversy as to whether either peptide can stimulate release of FSH in birds. The pr...

121

Céphalées par abus médicamenteux et addiction  

Microsoft Academic Search

Résumé  \\u000a Objectifs: étude de la comorbidité pour les troubles liés à l’utilisation de substances psychoactives chez les patients souffrant de\\u000a céphalées par abus médicamenteux.Méthode: étude comparative de quarante et un migraineux (MIG) et quarante et un patients souffrant de céphalées par abus médicamenteux\\u000a issus de migraines (CAM).Résultats: les CAM ulilisant des médicaments contenant des substances psychoactives (caféine et codéine) remplissent

F. Radat; C. Creac'h; M. Lafitau; S. Irachabal; V. Dousset; P. Henry

2005-01-01

122

Modified sutureless sclerotomies in pars plana vitrectomy  

Microsoft Academic Search

PURPOSE: To study the effectiveness and safety of a modified sutureless sclerotomy technique in pars plana vitrectomy.METHODS: We rotated the scleral tunnels of the original sutureless sclerotomy technique through 90 degrees, thus rendering them parallel to the corneoscleral limbus. This modified technique was applied to 25 consecutive eyes (25 patients) that had pars plana vitrectomy during a 2-month period.RESULTS: Twenty

Alvin K. H Kwok; Clement C. Y Tham; Dennis S. C Lam; M Li; John C Chen

1999-01-01

123

Maladies émergentes transmises par les tiques  

Microsoft Academic Search

RésuméLes infections transmises par les tiques surviennent dans le monde entier et sont bien connues depuis plus d’un siècle. Certaines d’entre elles sont très courantes alors que d’autres sont extrêmement rares. Les techniques modernes de génétique moléculaire (dont une plus grande disponibilité de la réaction en chaîne par polymérase (PCR) (de l’anglais polymerase chain reaction) ont permis la découverte et

Ingomar Mutz

2009-01-01

124

Radioecological implications of the Par Pond drawdown  

SciTech Connect

The drawdown of the Par Pond reservoir created dramatic alterations in this formerly stable lentic ecosystem. In addition, the radiation environment at Par Pond has changed significantly because of the exposure of Cesium 137-contaminated sediments and the appearance of new transport pathways to the terrestrial environment. In response to this situation, SREL was asked to study the radioecological implications of the reservoir drawdown. This report contains the objectives, methods, and results of the SREL study.

Hickey, H. [Westinghouse Savannah River Co., Aiken, SC (United States); Whicker, F.W. [Savannah River Ecology Lab., Aiken, SC (United States)

1991-12-05

125

Activity of recombinant trypsin isoforms on human proteinase-activated receptors (PAR): mesotrypsin cannot activate epithelial PAR-1, -2, but weakly activates brain PAR-1.  

PubMed

Trypsin-like serine proteinases trigger signal transduction pathways through proteolytic cleavage of proteinase-activated receptors (PARs) in many tissues. Three members, PAR-1, PAR-2 and PAR-4, are trypsin substrates, as trypsinolytic cleavage of the extracellular N terminus produces receptor activation. Here, the ability of the three human pancreatic trypsin isoforms (cationic trypsin, anionic trypsin and mesotrypsin (trypsin IV)) as recombinant proteins was tested on PARs. Using fura 2 [Ca(2+)](i) measurements, we analyzed three human epithelial cell lines, HBE (human bronchial epithelial), A549 (human pulmonary epithelial) and HEK (human embryonic kidney)-293 cells, which express functional PAR-1 and PAR-2. Human mesotrypsin failed to induce a PAR-mediated Ca(2+) response in human epithelial cells even at high concentrations. In addition, mesotrypsin did not affect the magnitude of PAR activation by subsequently added bovine trypsin. In HBE cells, which like A549 cells express high PAR-2 levels with negligible PAR-1 levels (<11%), half-maximal responses were seen for both cationic and anionic trypsins at about 5 nM. In the epithelial cells, mesotrypsin did not activate PAR-2 or PAR-1, whereas both anionic and cationic trypsins were comparable activators. We also investigated human astrocytoma 1321N1cells, which express PAR-1 and some PAR-3, but no PAR-2. High concentrations (>100 nM) of mesotrypsin produced a relatively weak Ca(2+) signal, apparently through PAR-1 activation. Half-maximal responses were observed at 60 nM mesotrypsin, and at 10-20 nM cationic and anionic trypsins. Using a desensitization assay with PAR-2-AP, we confirmed that both cationic and anionic trypsin isoforms cause [Ca(2+)](i) elevation in HBE cells mainly through PAR-2 activation. Desensitization of PAR-1 with thrombin receptor agonist peptide in 1321N1 cells demonstrated that all three recombinant trypsin isoforms act through PAR-1.Thus, the activity of human cationic and anionic trypsins on PARs was comparable to that of bovine pancreatic trypsin. Mesotrypsin (trypsin IV), in contrast to cationic and anionic trypsin, cannot activate or disable PARs in human epithelial cells, demonstrating that the receptors are no substrates for this isoenzyme. On the other hand, mesotrypsin activates PAR-1 in human astrocytoma cells. This might play a role in protection/degeneration or plasticity processes in the human brain. PMID:16231009

Grishina, Zoryana; Ostrowska, Ewa; Halangk, Walter; Sahin-Tóth, Miklós; Reiser, Georg

2005-12-01

126

Activity of recombinant trypsin isoforms on human proteinase-activated receptors (PAR): mesotrypsin cannot activate epithelial PAR-1, -2, but weakly activates brain PAR-1  

PubMed Central

Trypsin-like serine proteinases trigger signal transduction pathways through proteolytic cleavage of proteinase-activated receptors (PARs) in many tissues. Three members, PAR-1, PAR-2 and PAR-4, are trypsin substrates, as trypsinolytic cleavage of the extracellular N terminus produces receptor activation. Here, the ability of the three human pancreatic trypsin isoforms (cationic trypsin, anionic trypsin and mesotrypsin (trypsin IV)) as recombinant proteins was tested on PARs. Using fura 2 [Ca2+]i measurements, we analyzed three human epithelial cell lines, HBE (human bronchial epithelial), A549 (human pulmonary epithelial) and HEK (human embryonic kidney)-293 cells, which express functional PAR-1 and PAR-2. Human mesotrypsin failed to induce a PAR-mediated Ca2+ response in human epithelial cells even at high concentrations. In addition, mesotrypsin did not affect the magnitude of PAR activation by subsequently added bovine trypsin. In HBE cells, which like A549 cells express high PAR-2 levels with negligible PAR-1 levels (<11%), half-maximal responses were seen for both cationic and anionic trypsins at about 5?nM. In the epithelial cells, mesotrypsin did not activate PAR-2 or PAR-1, whereas both anionic and cationic trypsins were comparable activators. We also investigated human astrocytoma 1321N1cells, which express PAR-1 and some PAR-3, but no PAR-2. High concentrations (>100?nM) of mesotrypsin produced a relatively weak Ca2+ signal, apparently through PAR-1 activation. Half-maximal responses were observed at 60?nM mesotrypsin, and at 10–20?nM cationic and anionic trypsins. Using a desensitization assay with PAR-2-AP, we confirmed that both cationic and anionic trypsin isoforms cause [Ca2+]i elevation in HBE cells mainly through PAR-2 activation. Desensitization of PAR-1 with thrombin receptor agonist peptide in 1321N1 cells demonstrated that all three recombinant trypsin isoforms act through PAR-1. Thus, the activity of human cationic and anionic trypsins on PARs was comparable to that of bovine pancreatic trypsin. Mesotrypsin (trypsin IV), in contrast to cationic and anionic trypsin, cannot activate or disable PARs in human epithelial cells, demonstrating that the receptors are no substrates for this isoenzyme. On the other hand, mesotrypsin activates PAR-1 in human astrocytoma cells. This might play a role in protection/degeneration or plasticity processes in the human brain.

Grishina, Zoryana; Ostrowska, Ewa; Halangk, Walter; Sahin-Toth, Miklos; Reiser, Georg

2005-01-01

127

Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling.  

PubMed

Selection of a dominant follicle that will ovulate likely occurs by activation of cell survival pathways and suppression of death-promoting pathways in a mechanism involving FSH and its cognate receptor (FSHR). A yeast two-hybrid screen of an ovarian cDNA library was employed to identify potential interacting partners with human FSHR intracellular loops 1 and 2. Among eight cDNA clones identified in the screen, APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif; also known as APPL or DIP13alpha) was chosen for further analysis. APPL1 appears to coimmunoprecipitate with FSHR in HEK 293 cells stably expressing FSHR (293/FSHR cells), confirming APPL1 as a potential FSHR-interacting partner. The phosphorylation status of members of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway was also examined because of the proposed role of APPL1 in the antiapoptotic PI3K/Akt pathway. FOXO1a, also referred to as forkhead homologue in rhabdomyosarcoma, is a downstream effector in the pathway and tightly linked to expression of proapoptotic genes. FOXO1a, but not the upstream kinase Akt, is rapidly phosphorylated, and FOXO1a is thereby inactivated when 293/FSHR cells are treated with FSH. In addition, FSHR coimmunoprecipitates with Akt. The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive. PMID:15070827

Nechamen, Cheryl A; Thomas, Richard M; Cohen, Brian D; Acevedo, Giselles; Poulikakos, Poulikos I; Testa, Joseph R; Dias, James A

2004-04-07

128

A human FSHB promoter SNP associated with low FSH levels in men impairs LHX3 binding and basal FSHB transcription.  

PubMed

FSH production is important for human gametogenesis. In addition to inactivating mutations in the FSHB gene, which result in infertility in both sexes, a G/T single-nucleotide polymorphism (SNP) at -211 relative to the transcription start site of the 5' untranslated region of FSHB has been reported to be associated with reduced serum FSH levels in men. In this study, we sought to identify the potential mechanism by which the -211 SNP reduces FSH levels. Although the SNP resides in a putative hormone response element, we showed that, unlike the murine gene, human FSHB was not induced by androgens or progestins in gonadotropes. On the other hand, we found that the LHX3 homeodomain transcription factor bound to an 11-bp element in the human FSHB promoter that includes the -211 nucleotide. Furthermore, we also demonstrated that LHX3 bound with greater affinity to the wild-type human FSHB promoter compared with the -211 G/T mutation and that LHX3 binding was more effectively competed with excess wild-type oligonucleotide than with the SNP. Finally, we showed that FSHB transcription was decreased in gonadotrope cells with the -211 G/T mutation compared with the wild-type FSHB promoter. Altogether, our results suggest that decreased serum FSH levels in men with the SNP likely result from reduced LHX3 binding and induction of FSHB transcription. PMID:23766128

Benson, Courtney A; Kurz, Troy L; Thackray, Varykina G

2013-06-13

129

Concanavalin-A induces granulosa cell death and inhibits FSH-mediated follicular growth and ovarian maturation in female rats.  

PubMed

Reproductive success stems from a finely regulated balance between follicular maturation and atresia, in which the role of carbohydrate structure is poorly understood. Here, we describe for the first time a fraction of purified recombinant human FSH that is capable of bringing about the cell death of granulosa cells and preventing follicular maturation in a rat model. Further analysis by mass spectrometry revealed the presence of the lectin Concanavalin-A (Con-A) within this fraction of recombinant FSH. Using both the fractionated FSH and Con-A, the observed cell death was predominantly located to the granulosa cells. Ex vivo culture of rat follicles demonstrated that follicle degeneration occurred and resulted in the release of a denuded and deteriorated oocyte. Moreover, in vivo experiments confirmed an increase in atresia and a corresponding reduction confined to follicle in early antral stage. As a mechanism of action, Con-A reduces ovarian proliferation, Von Willebrand staining, and angiogenesis. Based on the observation that Con-A may induce granulosa cell death followed by follicle death, our results further demonstrate that follicular carbohydrate moiety is changing under the influence of FSH, which may allow a carbohydrate-binding lectin to increase granulosa cell death. The physiological consequences of circulating lectin-like molecules remain to be determined. However, our results suggest a potential exploitation of carbohydrate binding in fertility and ovarian cancer treatment. This work may shed light on a key role of carbohydrates in the still obscure physiological process of follicular selection and atresia. PMID:23515285

Velasquez, Ethel V; Ríos, Mariana; Ortiz, María Elena; Lizama, Carlos; Nuñez, Elizabeth; Abramovich, Dalhia; Orge, Felipe; Oliva, Barbara; Orellana, Renán; Villalon, Manuel; Moreno, Ricardo D; Tesone, Marta; Rokka, Anne; Corthals, Garry; Croxatto, Horacio B; Parborell, Fernanda; Owen, Gareth I

2013-03-20

130

Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols  

PubMed Central

Background The study was designed to test the hypothesis that granulosa cell (GC) gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG) stimulation regimens. Methods Females < 35 years-old undergoing IVF for tubal or male factor infertility were prospectively randomized to one of two stimulation protocols, GnRH agonist long protocol plus individualized dosages of (1) recombinant (r)FSH (Gonal-F) or (2) purified human menopausal gonadotropin (hMG; Menopur). Oocytes were retrieved 35 h post-hCG, and GC were collected. Total RNA was extracted from each GC sample, biotinylated cRNA was synthesized, and each sample was run on Human Genome Bioarrays (Applied Microarrays). Unnamed genes and genes with <2-fold difference in expression were excluded. Results After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11), bone morphogenetic protein receptor II (BMPR2), epidermal growth factor (EGF), insulin-like growth factor binding protein (IGFBP)-4, IGFBP-5, and hypoxia-inducible factor (HIF)-1 alpha. Conclusions Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.

2010-01-01

131

FSH and growth factors affect the growth and endocrine function in vitro of granulosa cells of bovine preantral follicles  

Microsoft Academic Search

The hypothesis was tested that bovine preantral follicles can be stimulated to grow in vitro by FSH and by the mitogens, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), but not by transforming growth factor-? (TGF?), which generally inhibits EGF and bFGF action. Preantral follicles, 60 to 179 ?m in diameter, were isolated from fetal ovaries by treatment

S.-A. Wandji; J. J. Eppig; J. E. Fortune

1996-01-01

132

Modulation of gene expression in small follicle porcine granulosa cells by human follicle stimulating hormone (hFSH)  

SciTech Connect

Small follicle (1-3 mm) porcine granulosa cells (SFPGF) were isolated by puncture, aspiration and cultured under standard conditions in DMEM, HEPES, BSA, MIX. At the start of culture, cells were stimulated with 100ng hFSH/ml. At various times afterwards total cellular RNA was prepared using guanidine-hydrochloride solubilization, phenol extraction and precipitation from 3M NaOAc, pH 6.0. RNA was 5'-end labelled with /sup 32/P in a kinase reaction and hybridized to an excess of clone-specific DNA immobilized on nitrocellulose filters using stringent hybridization and wash conditions. After autoradiography the RNA hybridized to the DNA blot filter were quantitated by microdensitometry. Hybridization to parent plasmid was negative. RNA derived from control cultures showed patterns of hybridization similar to those obtained from freshly obtained cells. Results of these experiments demonstrate hFSh induction of RNA specific for transferrin receptor, ..cap alpha..-interferon, H-ras, and K-ras. Increased RNA levels were apparent within 10 min of treatment and had declined by 180 min. Expression of actin, p53 and for RNAs declined by 10 min of hFSH addition but was enhanced by 160 min. Levels of ..beta..-interferon, myc, mos, abl and yb RNAs were not detectable under these conditions. These results demonstrate specific gene modulation in SFPGC cultured with hFSH.

Calvo, F.O.; Ryan, R.J.; Woloschak, G.E.

1986-03-01

133

Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins three years prior to the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during the late peri-men...

134

FSH receptor gene variants are rarely associated with premature ovarian failure.  

PubMed

FSH receptor (FSHR) gene variants have been associated with premature ovarian failure (POF). Genomic DNA from New Zealand women with POF (n=80) and control women (n=80) was screened for variants in FSHR exons 7 and 10. FSHR exon 7 variants, including the c.566C>T Finnish founder mutation (p.Ala189Val), were not detected. Previously reported FSHR exon 10 polymorphisms were identified in both groups with similar allelic distributions. A novel heterozygous FSHR exon 10 variant c.1411A>T, p.Ile471Phe was observed in one woman with a family history of POF, but not her affected siblings. It is concluded that variants in exons 7 and 10 of FSHR are not frequently associated with the development of POF in the New Zealand population. PMID:23419799

Woad, Kathryn J; Prendergast, Deborah; Winship, Ingrid M; Shelling, Andrew N

2013-01-19

135

MRI Asymmetries of Broca's Area: The Pars Triangularis and Pars Opercularis  

Microsoft Academic Search

Broca's area, which includes the pars triangularis (PTR) and pars opercularis (POP), is a neuroanatomic region important in speech-language production. Previous data demonstrated that PTR asymmetries are highly correlated with language dominance determined by selective hemispheric anesthesia or Wada testing, suggesting that asymmetries of the PTR may, in part, predict language dominance. The POP, however, has not been measured on

Anne L. Foundas; Kathy F. Eure; Laura F. Luevano; Daniel R. Weinberger

1998-01-01

136

The horse pseudoautosomal region (PAR): characterization and comparison with the human, chimp and mouse PARs  

Microsoft Academic Search

The pseudoautosomal region (PAR) is a genomic segment on mammalian sex chromosomes where sequence homology mimics that seen between autosomal homologues. The region is essential for pairing and proper segregation of sex chromosomes during male meiosis. As yet, only human\\/chimp and mouse PARs have been characterized. The two groups of species differ dramatically in gene content and size of the

T Raudsepp; B. P. Chowdhary

2008-01-01

137

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH  

SciTech Connect

Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

Bruheim, Kjersti [Cancer Center, Ullevaal University Hospital, Oslo (Norway)], E-mail: Kjersti.Bruheim@medisin.uio.no; Svartberg, Johan [Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Department of Medicine, University Hospital of North Norway, Tromso (Norway); Carlsen, Erik [Department of Gastrointestinal Surgery, Ullevaal University Hospital, Oslo (Norway); Dueland, Svein [Department of Oncology, Norwegian Radium Hospital, Oslo (Norway); Haug, Egil [Hormone Laboratory, Aker University Hospital, Oslo (Norway); Skovlund, Eva [School of Pharmacy, University of Oslo, Oslo (Norway); Tveit, Kjell Magne; Guren, Marianne G. [Cancer Center, Ullevaal University Hospital, Oslo (Norway)

2008-03-01

138

FSH induces the development of circadian clockwork in rat granulosa cells via a gap junction protein Cx43-dependent pathway.  

PubMed

The present study was designed to assess the relationship between gap junctions and the maturation of a clock system in rat granulosa cells stimulated by follicle-stimulating hormone (FSH). Immature and mature granulosa cells were prepared by puncturing the ovaries of diethylstilbestrol- and equine chorionic gonadotropin (eCG)-treated mouse Period2 (Per2)-dLuc reporter gene transgenic rats, respectively. Mature granulosa cells exposed to dexamethasone (DXM) synchronization displayed several Per2-dLuc oscillations and a rhythmic expression of clock genes. Intriguingly, we observed clear evidence that the FSH stimulation significantly increased the amplitude of Per2 oscillations in the granulosa cells, which was confirmed by the elevation of the Per2 and Rev-erb? (Nr1d1) mRNA levels. FSH also induced a major phase-advance shift of Per2 oscillations. The mature granulosa cells cultured for 2 days with FSH expressed higher mRNA levels of Per2, Rev-erb?, Bmal1 (Arnt1), Lhcgr, and connexin (Cx) 43 (Gja1) compared with the immature granulosa cells. Consistently, our immunofluorescence results revealed abundant Cx43 protein in antral follicles stimulated with eCG and weak or no fluorescence signal of Cx43 in primary and preantral follicles. Similar results were confirmed by Western blotting analysis. Two gap junction blockers, lindane and carbenoxolone (CBX), significantly decreased the amplitude of Per2 oscillations, which further adhered significant decreases in Per2 and Rev-erb? transcript levels. In addition, both lindane and CBX induced a clear phase-delay shift of Per2 oscillations. These findings suggest that FSH induces the development of the clock system by increasing the expression of Cx43. PMID:23299500

Chen, Huatao; Zhao, Lijia; Chu, Guiyan; Kito, Gakushi; Yamauchi, Nobuhiko; Shigeyoshi, Yasufumi; Hashimoto, Seiichi; Hattori, Masa-aki

2013-01-08

139

Metformin Inhibits Follicle-Stimulating Hormone (FSH) Action in Human Granulosa Cells: Relevance to Polycystic Ovary Syndrome  

PubMed Central

Background: Women with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions. Objective: The aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary. Methods: The effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay. Results: Metformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB–CREB-binding protein–CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels. Conclusion: These finding have implications for the use of metformin in the treatment of anovulation in women with PCOS.

Elia, Androulla; Jawad, Zara; Pellatt, Laura; Mason, Helen D.

2013-01-01

140

Metformin Inhibits Follicle-Stimulating Hormone (FSH) Action in Human Granulosa Cells: Relevance to Polycystic Ovary Syndrome.  

PubMed

Background: Women with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions. Objective: The aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary. Methods: The effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay. Results: Metformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels. Conclusion: These finding have implications for the use of metformin in the treatment of anovulation in women with PCOS. PMID:23846817

Rice, Suman; Elia, Androulla; Jawad, Zara; Pellatt, Laura; Mason, Helen D

2013-07-11

141

ParCAT: Parallel Climate Analysis Toolkit  

SciTech Connect

Climate science is employing increasingly complex models and simulations to analyze the past and predict the future of Earth s climate. This growth in complexity is creating a widening gap between the data being produced and the ability to analyze the datasets. Parallel computing tools are necessary to analyze, compare, and interpret the simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools to efficiently use parallel computing techniques to make analysis of these datasets manageable. The toolkit provides the ability to compute spatio-temporal means, differences between runs or differences between averages of runs, and histograms of the values in a data set. ParCAT is implemented as a command-line utility written in C. This allows for easy integration in other tools and allows for use in scripts. This also makes it possible to run ParCAT on many platforms from laptops to supercomputers. ParCAT outputs NetCDF files so it is compatible with existing utilities such as Panoply and UV-CDAT. This paper describes ParCAT and presents results from some example runs on the Titan system at ORNL.

Smith, Brian E [ORNL; Steed, Chad A [ORNL; Shipman, Galen M [ORNL; Ricciuto, Daniel M [ORNL; Thornton, Peter E [ORNL; Wehner, Michael [Lawrence Berkeley National Laboratory (LBNL); Williams, Dean N. [Lawrence Livermore National Laboratory (LLNL)

2013-01-01

142

Identification of ovarian genes regulated by follicle-stimulating hormone (Fsh) in vitro during early secondary oocyte growth in coho salmon.  

PubMed

Follicle-stimulating hormone (Fsh) function in fishes is poorly understood. This study aimed to reveal Fsh-regulated genes in coho salmon previtellogenic ovarian follicles in vitro. Four suppression subtractive hybridization libraries were generated with RNA isolated from Fsh-treated and control follicles or follicle cell-enriched tissue fractions. Fsh induced steroidogenesis and dynamically upregulated several genes predominantly expressed in follicle cells, including WAP domain-containing protease, connexin 34.3, clusterin (clu1, clu2), fibronectin, wilms tumor 2-like, and influenza virus NS1A-binding protein a. Genes downregulated by Fsh included connective tissue growth factor, alcohol dehydrogenase 8-like, and serine/threonine-protein kinase pim-1. This study demonstrates for the first time in fishes that Fsh influences the expression of a unique suite of ovarian genes involved in processes like cell communication, survival and differentiation, and extracellular matrix remodeling. Collectively, these findings suggest that Fsh and/or steroids induce differentiation of granulosa cells and remodeling of the follicle in preparation for onset of vitellogenesis. PMID:23200633

Luckenbach, J Adam; Yamamoto, Yoji; Guzmán, José M; Swanson, Penny

2012-11-27

143

Les Brulures Chimiques Par Le Laurier Rose  

PubMed Central

Summary Le laurier rose ou Nerium oleander est un arbuste qui pousse naturellement dans les régions méditerranéennes. Au Maroc on le trouve dans les lieux humides. Il est réputé par ses risques de toxicité systémique en cas d'empoisonnement à cause de la présence de deux alcaloïdes, surtout l'oléandrine. La littérature illustre des cas d'utilisation locale des feuilles de cette plante contre la gale, les hémorroïdes et les furoncles. Nous rapportons deux cas de brûlures chimiques par le laurier rose de gravité différente. Cela doit aboutir à une information élargie de la population, ainsi qu'une réglementation stricte de sa commercialisation.

Bakkali, H.; Ababou, M.; Nassim Sabah, T.; Moussaoui, A.; Ennouhi, A.; Fouadi, F.Z.; Siah, S.; Ihrai, H.

2010-01-01

144

Effects of FSH and 17beta-estradiol on the transactivation of estrogen-regulated promoters and cell proliferation in L cells.  

PubMed

In the present study, we analyzed human follicle-stimulating hormone (FSH)-induced cell proliferation and transactivation of estrogen-sensitive reporter genes-in L cells stably expressing the human FSH receptor [L-(hFSHR(+)) cells]. In order to dissect the signaling pathways involved in this process, L-(hFSHR(+)) cells were transiently transfected with either the 3X-ERE-TAT-Luc or the ERE-VitA2-TK-CAT reporter genes and treated with FSH or PKA activators (cholera toxin, forskolin and 8-Br-cAMP) in the presence or absence of various kinase inhibitors. We found that FSH and all PKA activators, specifically induced transactivation of both reporter genes. Transactivation of estrogen-sensitive genes by FSH or PKA activators were blocked (approximately 90%) by H89 (PKA inhibitor) and LY294002 but not by Wortmannin (PI3-K inhibitors), 4-OH-tamoxifen, ICI182,780 or SB203580 (p38 MAPK inhibitor); PD98059 (ERK1/2 inhibitor) partially (approximately 30%) blocked the FSH-mediated effect. The combination of FSH and estradiol resulted in a synergistic effect on transactivation as well as on cell proliferation, and this enhancement was attenuated by antiestrogens. We additionally analyzed the participation of the coactivators SRC-1 and cAMP response element binding protein (CREB)-binding protein (CBP) in FSH-evoked estrogen receptor (ER)-dependent transactivation; we found that CBP but not SRC-1 potentiated FSH-induced transcriptional activation of both ER-sensitive reporters, being this effect stronger on the ERE-VitA2-TK-CAT than on the 3X-ERE-TAT-Luc reporter. Thus, in L-(hFSHR(+)) cells FSH induces transcriptional activation of estrogen-sensitive genes through an A-kinase-triggered signaling pathway, using also to a lesser extent the ERK1/2 and p38 pathways. PI3-K is not apparently involved in this FSH-mediated process since LY294002, but not Wortmannin, specifically binds ERs and completely blocks estrogen action. Presumably, CBP cooperates with the ER on genes that contain estrogen responsive elements through mechanisms involving the participation of other proteins and/or basal transcription factors (e.g. CREB), which in turn mediate the transcriptional response of estrogen-sensitive reporter genes to FSH stimulation. PMID:15857748

Pasapera, Ana María; Jiménez-Aguilera, María del Pilar; Chauchereau, Anne; Milgrom, Edwin; Olivares, Aleida; Uribe, Aída; Gutiérrez-Sagal, Rubén; Ulloa-Aguirre, Alfredo

2005-02-12

145

Influence d'une diffusion d'or sur l'activité recombinante des joints de grains dans le silicium  

NASA Astrophysics Data System (ADS)

We have studied by Deep Level Transient Spectroscopie (DLTS) the energy levels introduced by gold diffusion in Polix multicrystalline P type silicon. Diffusion has been carried out at 900 °C for 6 h in argon flow after a gold layer was previously deposited by cathodic sputtering on one side of the sample. Al-Si diodes have been made on the other side of the samples, on the grains and on grain boundaries. The results show that gold atoms reach the other side of the sample (400 ?m). They are in substitutional sites and give the well-known donor level in P type silicon (E_v+0.35 eV). However on the diodes which cover the grain boundaries, an additional level located at 0.43 eV above the valence band is revealed. The enhanced diffusion of gold atoms through the grains could be explained by the kick-out mechanism. In the grain boundaries the additional level might result from the formation of gold-iron or gold-defect complexes. Nous avons étudié au moyen de la technique de spectroscopie capacitive (DLTS) les niveaux d'énergie introduits par l'or dans le silicium multicristallin de type P obtenu selon le procédé Polix. Les diffusions sont réalisées à 900 °C pendant 6 h dans un tube ouvert, parcouru par un flux d'argon, après qu'une couche d'or ait été déposée sur une face des échantillons. Les résultats obtenus à partir des mesures effectuées avec des diodes Al-Si réalisées sur l'autre face et dans les grains, montrent que l'or a traversé toute l'épaisseur de l'échantillon (400 ?m) et s'est placé en site substitutionnel caractérisé par le niveau donneur à E_v+ 0,35 eV. Les analyses effectuées avec les diodes recouvrant les joints de grains font apparaître un niveau donneur supplémentaire situé à 0,43 eV de la bande de valence. La diffusin de l'or selon le mécanisme de “kick-out” permet d'interpréter les résultats obtenus dans les grains. En ce qui concerne le joint de grains, la formation de complexes Au-défaut cristallin ou bien Au-impuretés, telle que le fer, serait à l'origine du niveau situé à E_v+ 0,43 eV .

Pasquinelli, M.

1992-03-01

146

Repeated superovulation using a simplified FSH/eCG treatment for in vivo embryo production in sheep.  

PubMed

This study investigated the efficacy of a simplified repeated superovulation treatment (eCG plus FSH in a single dose, rather than the usual protocol of six decreasing doses of FSH) in the in vivo embryo production in Ojalada donor ewes during the breeding season. In vitro viability after vitrification and warming of embryos recovered from both treatments was also assessed. In addition, the study examined the effects of the concentration of anti-eCG antibodies before each eCG/FSH treatment on in vivo embryo production. Thirty-eight females at the end of their reproductive lives were given the decreasing (n = 19) or simplified (n = 19) superovulatory treatment up to three times at intervals of ? 50 d. The onset of estrus was 5 h earlier (P < 0.05) among ewes that received the eCG/FSH protocol (25.2 ± 0.80 h) than it was among those that received the decreasing superovulatory treatment (30.1 ± 1.0 h), but the two treatments did not differ significantly in ovulation rates or the number and viability of embryos recovered. Both of the superovulatory protocols were significantly (P < 0.05 to P < 0.01) less effective after the first application. After three superovulatory treatments, the average number of viable embryos per ewe was 14.1 ± 2.3 and 13.7 ± 2.5 in the decreasing and simplified protocols, respectively. High anti-eCG antibody concentrations just before the superovulatory treatment with eCG/FSH were associated with a significant decrease (P < 0.05) in the rates of fertilization, viability, and freezability, especially in the second and third recoveries. Repeated superovulatory treatments with eCG/FSH can provide an efficient means of producing high quality embryos in the ewes of endangered breeds at the end of their reproductive lives, although further studies are needed to characterize the response associated with high concentrations of anti-eCG antibodies. PMID:21144569

Forcada, F; Ait Amer-Meziane, M; Abecia, J A; Maurel, M C; Cebrián-Pérez, J A; Muiño-Blanco, T; Asenjo, B; Vázquez, M I; Casao, A

2010-12-07

147

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial  

PubMed Central

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged?FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657

2012-01-01

148

Age, FSH dose and follicular aspiration frequency affect oocyte yield from juvenile donor lambs.  

PubMed

Experiments were conducted to determine the effects of lamb age, frequency of follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on the number of collected oocytes and their maturational competence. In trial 1, the characteristics of follicular population (number and diameter of follicles) were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42 days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs were divided into four groups. group MF lambs (n = 6) had follicular aspiration (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was conducted once during the 12-13, 16-17 and 20-21 week of age, respectively. Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial 3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose, which was administered according to the body weight in a dose of 0.27 mg/kg. The number and the size of follicles, the number and the quality of collected oocytes and the maturational competence of the oocytes were compared between and within groups. In trial 1, the total number and the number of small follicles were greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01). Similarly, the follicular population was greater in group MF1 than in group SF3 (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected in comparison with those from the respective once-aspirated age mates (groups SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute maturational failure was observed in oocytes collected from groups SF2 and SF3. Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions of group MF, but it was more uniform among sessions of group MV (range 12.5-42.9%, p > 0.05). Our results indicate that firstly, the number and the quality of harvested oocytes from juvenile lambs can be much improved if follicular stimulation regime is adjusted to the body weight. Secondly, in terms of follicular population and oocyte quality, 3 and 4-month-old lambs are naturally bad oocyte donors, but this characteristic can be reversed by a previous follicular ablation. PMID:17506799

Valasi, I; Leontides, L; Papanikolaou, Th; Amiridis, G S

2007-06-01

149

A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition  

SciTech Connect

Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

Chaudhuri, Barnali [University of Buffalo, The State University of New York; Gupta, Sayan [Case Western Reserve University; Urban, Volker S [ORNL; Chance, Mark [Case Western Reserve University; D'Mello, Rhijuta [Case Western Reserve University; Smith, Lauren [University of Buffalo, The State University of New York; Lyons, Kelly [University of Buffalo, The State University of New York; Gee, Jessica [University of Buffalo, The State University of New York

2010-01-01

150

A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition Assembly  

SciTech Connect

Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

B Chaudhuri; S Gupta; V Urban; M Chance; R DMello; L Smith; K Lyons; J Gee

2011-12-31

151

Suprachoroidal hemorrhage during pars plana vitrectomy  

Microsoft Academic Search

ObjectiveSuprachoroidal hemorrhage (SCH) is an uncommon but serious complication of pars plana vitrectomy (PPV) that can be associated with a guarded visual prognosis. The purpose of this study is to document the risk factors and outcomes of this complication.

Homayoun Tabandeh; Paul M Sullivan; Peter Smahliuk; Harry W Flynn; Joyce Schiffman

1999-01-01

152

Giant retinal tears after pars plana vitrectomy  

Microsoft Academic Search

Vitreous surgery is used to treat complicated vitreo-retinal pathology. Retinal tears are a serious complication of vitreous surgery. In this report, the development of giant retinal tears in four eyes after pars plana vitrectomy for posterior segment pathology is described. The pathogenesis and implications of this serious and infrequent complication are discussed.

Ahmed M Abu El-Asrar

1997-01-01

153

Transmission par bistabilit e nonlin eaire  

Microsoft Academic Search

R esum e. La nonlin earit e, induite par la d ependance de l'indice de r efraction a l'intensit e, peut ^ etre un moyen de concevoir des d etecteurs de lumi ere sensibles a une tr es faible excitation. Cela provient des propri et es de bistabilit e de l' equation de Schrodinger nonlin eaire soumise a des conditions

D. Chevriaux

154

Positron Accumulator Ring (PAR) power supply.  

National Technical Information Service (NTIS)

The Positron Accumulator Ring (PAR) consists of 8 dipole magnets connected in series. These magnets are energized via one 12-pulse dc power supply. The power supply consists of four phase controlled half-wave wye group converters. Each of the two half-wav...

M. Fathizadeh

1995-01-01

155

Sources of errors in measurements of PAR  

Microsoft Academic Search

Due to optical processes in the atmosphere the spectral distribution of global, direct solar and diffuse radiation is different and depends on solar elevation, atmosphere transparency etc. Because of various optical properties of phytoelements, the spectral distribution of penetrated and reflected radiation differs from that of incoming radiation. Owing to radiative transfer processes, photosynthetically active radiation (PAR) and its proportion

J. Ross; M. Sulev

2000-01-01

156

Using multicast to pre-load jobs on the ParPar cluster  

Microsoft Academic Search

The ParPar system is a high-performance cluster environment supporting a multiuser parallel workload. Its design follows a master-nodes structure, where the master controls all aspects of system activity using a dedicated control network. As nearly all control messages are multicast to a set of nodes, we implemented a reliable multicast protocol for this network based on UDP. This was then

Avi Kavas; David Er-el; Dror G. Feitelson

2001-01-01

157

Glaucoma secondary to pars plana lensectomy for congenital cataract  

Microsoft Academic Search

Background: To identify risk factors related to the onset of secondary glaucoma in eyes that have undergone pars plana lensectomy for congenital cataract. Methods: We investigated intraocular pressure levels after pars plana lensectomy for congenital cataract in 80 eyes of 44 patients who were followed up for at least 36 months. Mean age at the time of pars plana lensectomy

Shinsuke Miyahara; Kentaro Amino; Hidenobu Tanihara

2002-01-01

158

FSH Modulates PKAI and GPR3 Activities in Mouse Oocyte of COC in a Gap Junctional Communication (GJC)-Dependent Manner to Initiate Meiotic Resumption  

PubMed Central

Many studies have shown that cyclic adenosine-5?-monophosphate (cAMP)-dependent protein kinase A (PKA) and G-protein-coupled receptor 3 (GPR3) are crucial for controlling meiotic arrest in oocytes. However, it is unclear how gonadotropins modulate these factors to regulate oocyte maturation, especially by gap junctional communication (GJC). Using an in vitro meiosis-arrested mouse cumulus-oocyte complex (COC) culture model, we showed that there is a close relationship between follicle-stimulating hormone (FSH) and the PKA type I (PKAI) and GPR3. The effect of FSH on oocyte maturation was biphasic, initially inhibitory and then stimulatory. During FSH-induced maturation, rapid cAMP surges were observed in both cumulus cells and oocyte. Most GJC between cumulus cells and oocyte ceased immediately after FSH stimulation and recommenced after the cAMP surge. FSH-induced maturation was blocked by PKAI activator 8-AHA-cAMP. Levels of PKAI regulatory subunits and GPR3 decreased and increased, respectively, after FSH stimulation. In the presence of the GJC inhibitor carbenoxolone (CBX), FSH failed to induce the meiotic resumption and the changes in PKAI, GPR3 and cAMP surge in oocyte were no longer detected. Furthermore, GPR3 was upregulated by high cAMP levels, but not by PKAI activation. When applied after FSH stimulation, the specific phosphodiesterase 3A (PDE3A) inhibitor cilostamide immediately blocked meiotic induction, regardless of when it was administered. PKAI activation inhibited mitogen-activated protein kinase (MAPK) phosphorylation in the oocytes of COCs, which participated in the initiation of FSH-induced meiotic maturation in vitro. Just before FSH-induced meiotic maturation, cAMP, PKAI, and GPR3 returned to basal levels, and PDE3A activity and MAPK phosphorylation increased markedly. These experiments show that FSH induces a transient increase in cAMP levels and regulates GJC to control PKAI and GPR3 activities, thereby creating an inhibitory phase. After PDE3A and MAPK activities increase, meiosis resumes.

Xia, Guoliang

2012-01-01

159

No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH  

Microsoft Academic Search

The association between endogenous LH concentrations during ovarian stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol and pregnancy likelihood was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH and a GnRH antagonist prior to IVF\\/intracytoplasmic sperm injection. Data from 1764 patients from six randomized controlled trials were pooled for retrospective analysis. Ongoing

George Griesinger; Daniel B. Shapiro; Efstratios M. Kolibianakis; Han Witjes; Bernadette M. Mannaerts

2011-01-01

160

Regulation of rat Sertoli cell function by FSH: possible role of phosphatidylinositol 3-kinase\\/protein kinase B pathway  

Microsoft Academic Search

The FSH molecular mechanism of action is best recog- nized for its stimulation of the adenylyl cyclase\\/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K\\/PKB

S B Meroni; M F Riera; E H Pellizzari; S B Cigorraga

2002-01-01

161

FSH Injections and Ultrasonography Determine Presence of Ovarian Components in the Evaluation of Ovotesticular Disorders of Sex Development  

PubMed Central

Three infants with ambiguous genitalia and suspected ovotestes were given recombinant FSH to induce ovarian follicular development. The development of follicles in the gonadal tissue suggested the presence of ovarian tissue in two of the three infants. This method may provide a means to better characterize gonadal anatomy in patients affected by disorders of sex development (DSD). Sonographic information poststimulation provided parents with earlier and more specific education and support concerning the possible need for confirmative gonadal biopsy treatment options.

French, Shannon; Rodriguez, Luisa; Schlesinger, Alan; McCullough, Laurence; Dietrich, Jennifer; Hicks, John; Karaviti, Lefkothea

2009-01-01

162

Lindane, a gap junction blocker, suppresses FSH and transforming growth factor  1-induced connexin43 gap junction formation and steroidogenesis in rat granulosa cells  

Microsoft Academic Search

The present study was designed to explore the role of gap junctions in follicle-stimulating hormone (FSH) and trans- forming growth factor 1 (TGF1)-stimulated steroido- genesis in ovarian granulosa cells of gonadotropin-primed immature rats. There were three specific aims. First, we investigated the effect of FSH and TGF1 as well as lindane (a general gap junction blocker) on the level of

Ferng-Chun Ke; Su-Huan Fang; Ming-Ting Lee; Shiow-Yhu Sheu; Si-Yi Lai; Yun Ju Chen; Fore-Lien Huang; Paulus S Wang; Douglas M Stocco; Jiuan-Jiuan Hwang

2005-01-01

163

Receptor binding activity and in vitro biological activity of the human FSH charge isoforms as disclosed by heterologous and homologous assay systems  

Microsoft Academic Search

Follicle-stimulating hormone (FSH) is produced and secreted in multiple molecular forms. These isoforms differ in their oligosaccharide\\u000a structures, which determine the particular behavior of a given variant in in vitro and in vivo systems. Employing heterologous\\u000a cell assay systems, this and other laboratories have shown that highly sialylated human FSH variants exhibit lower receptor\\u000a binding\\/immunoactivity as well as in vitro

Elena Zambrano; Teresa Zariñán; Aleida Olivares; Jorgelina Barrios-de-Tomasi; Alfredo Ulloa-Aguirre

1999-01-01

164

Isolation, characterization and expression analyses of FSH receptor in protogynous grouper.  

PubMed

Follicle-stimulating hormone (FSH) and its receptor (FSHR) play important roles in spermatogenesis. We cloned and characterized the honeycomb grouper Epinephelus merra FSHR (EmFSHR) to elucidate its role in the protogynous sex change in groupers. Reverse transcription-polymerase chain reaction (RT-PCR) analysis suggested that EmFSHR was expressed exclusively in the gonads. In situ hybridization showed the distribution of EmFSHR in the granulosa cells of previtellogenic oocytes and Leydig cells in the testis. Quantitative reverse transcription PCR (RT-qPCR) analysis of gonadal EmFSHR transcripts during the process of sex change indicated that the lowest levels were found in the female phase before sex change. EmFSHR transcripts increased during the early transitional phase, when oocytes began to degenerate in parallel with the initiation of gonial germ cell differentiation into spermatogonia. A dramatic increase in EmFSHR transcription occurred during the late transitional phase, when the gonad contained numerous proliferating male germ cells and many degenerated oocytes. EmFSHR expression remained high until the transformation from ovary to testis was complete. The data reveal that female to male sex change is associated with the upregulation of EmFSHR transcripts, and that this upregulation may be responsible for the development of testicular tissue and the progression of spermatogenesis. Furthermore, how the upregulation of EmFSHR is controlled in the initiation of sex change remains to be elucidated. PMID:20227511

Alam, Mohammad Ashraful; Kobayashi, Yasuhisa; Hirai, Toshiaki; Nakamura, Masaru

2010-03-20

165

The Human Pseudoautosomal Region (PAR): Origin, Function and Future.  

PubMed

The pseudoautosomal regions (PAR1 and PAR2) of the human X and Y chromosomes pair and recombine during meiosis. Thus genes in this region are not inherited in a strictly sex-linked fashion. PAR1 is located at the terminal region of the short arms and PAR2 at the tips of the long arms of these chromosomes. To date, 24 genes have been assigned to the PAR1 region. Half of these have a known function. In contrast, so far only 4 genes have been discovered in the PAR2 region. Deletion of the PAR1 region results in failure of pairing and male sterility. The gene SHOX (short stature homeobox-containing) resides in PAR1. SHOX haploinsufficiency contributes to certain features in Turner syndrome as well as the characteristics of Leri-Weill dyschondrosteosis. Only two of the human PAR1 genes have mouse homologues. These do not, however, reside in the mouse PAR1 region but are autosomal. The PAR regions seem to be relics of differential additions, losses, rearrangements and degradation of the X and Y chromosome in different mammalian lineages. Marsupials have three homologues of human PAR1 genes in their autosomes, although, in contrast to mouse, do not have a PAR region at all. The disappearance of PAR from other species seems likely and this region will only be rescued by the addition of genes to both X and Y, as has occurred already in lemmings. The present review summarizes the current understanding of the evolution of PAR and provides up-to-date information about individual genes residing in this region. PMID:18660847

Helena Mangs, A; Morris, Brian J

2007-04-01

166

The Human Pseudoautosomal Region (PAR): Origin, Function and Future  

PubMed Central

The pseudoautosomal regions (PAR1 and PAR2) of the human X and Y chromosomes pair and recombine during meiosis. Thus genes in this region are not inherited in a strictly sex-linked fashion. PAR1 is located at the terminal region of the short arms and PAR2 at the tips of the long arms of these chromosomes. To date, 24 genes have been assigned to the PAR1 region. Half of these have a known function. In contrast, so far only 4 genes have been discovered in the PAR2 region. Deletion of the PAR1 region results in failure of pairing and male sterility. The gene SHOX (short stature homeobox-containing) resides in PAR1. SHOX haploinsufficiency contributes to certain features in Turner syndrome as well as the characteristics of Leri-Weill dyschondrosteosis. Only two of the human PAR1 genes have mouse homologues. These do not, however, reside in the mouse PAR1 region but are autosomal. The PAR regions seem to be relics of differential additions, losses, rearrangements and degradation of the X and Y chromosome in different mammalian lineages. Marsupials have three homologues of human PAR1 genes in their autosomes, although, in contrast to mouse, do not have a PAR region at all. The disappearance of PAR from other species seems likely and this region will only be rescued by the addition of genes to both X and Y, as has occurred already in lemmings. The present review summarizes the current understanding of the evolution of PAR and provides up-to-date information about individual genes residing in this region.

Helena Mangs, A; Morris, Brian J

2007-01-01

167

Differentially Expressed miRNAs after GnRH Treatment and Their Potential Roles in FSH Regulation in Porcine Anterior Pituitary Cell  

PubMed Central

Hypothalamic gonadotropin-releasing hormone (GnRH) is a major regulator of follicle-stimulating hormone (FSH) secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs) are small RNA molecules that control gene expression by imperfect binding to the 3?-untranslated region (3?-UTR) of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA) at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSH? mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR). Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSH? mRNA 3?-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially expressed miRNAs resolved in this study provide the first guide for post-transcriptional regulation of pituitary gonadotrope FSH secretion in pig, as well as in other mammals.

Qi, Qien; Cheng, Xiao; Chen, Ting; Li, Hongyi; Kallon, Sanpha; Shu, Gang; Wang, Song-Bo; Jiang, Qing-Yan; Zhang, Yong-Liang

2013-01-01

168

Differentially expressed miRNAs after GnRH treatment and their potential roles in FSH regulation in porcine anterior pituitary cell.  

PubMed

Hypothalamic gonadotropin-releasing hormone (GnRH) is a major regulator of follicle-stimulating hormone (FSH) secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs) are small RNA molecules that control gene expression by imperfect binding to the 3'-untranslated region (3'-UTR) of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA) at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSH? mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR). Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSH? mRNA 3'-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially expressed miRNAs resolved in this study provide the first guide for post-transcriptional regulation of pituitary gonadotrope FSH secretion in pig, as well as in other mammals. PMID:23451171

Ye, Rui-Song; Xi, Qian-Yun; Qi, Qien; Cheng, Xiao; Chen, Ting; Li, Hongyi; Kallon, Sanpha; Shu, Gang; Wang, Song-Bo; Jiang, Qing-Yan; Zhang, Yong-Liang

2013-02-22

169

The MasPar MP1 architecture  

Microsoft Academic Search

The MasPar MP-1 architecture is described. It is a massively parallel SIMD machine with the following key characteristics: scalable architecture in terms of the number of processing elements, system memory, and system communication bandwidth; reduced-instruction-set-computer-like instruction set design which leverages optimizing compiler technology; adherence to industry-standard floating point formats, specifically VAX and IEEE floating point; and an architectural design amenable

Tom Blank

1990-01-01

170

Par Pond refill water quality sampling  

SciTech Connect

This study was designed to document anoxia and its cause in the event that the anoxia caused a fish kill. However, no fish kill was observed during this study, and dissolved oxygen and nutrient concentrations generally remained within the range expected for southeastern reservoirs. Par Pond water quality monitoring will continue during the second summer after refill as the aquatic macrophytes become reestablished and nutrients in the sediments are released to the water column.

Koch, J.W. II; Martin, F.D.; Westbury, H.M.

1996-08-01

171

Pars Plana Vitrectomy in Advanced Coats' Disease  

PubMed Central

Purpose To report 5 cases of advanced Coats’ disease managed with pars plana vitrectomy and silicone oil tamponade. Methods Five patients with advanced Coats’ disease and serous or tractional retinal detachment underwent pars plana vitrectomy with internal drainage, endolaser photocoagulation and silicone oil tamponade. One patient had combined phacoemulsification-vitrectomy surgery. Of the 5 patients, 1 had intravitreal hemorrhage and a retinal macrocyst and 1 had a retinal cyst. Follow-up period was 1–6 years. Results All patients had improved visual acuity after surgery. No intraoperative or postoperative complications were observed in any of the patients. The retina was attached and the disease was stable in all patients during follow-up. Two patients had cataract formation, and in one of them the cataract was successfully managed with phacoemulsification surgery. Conclusion Pars plana vitrectomy, subretinal fluid drainage, and long-term silicone oil tamponade are effective methods in the management of advanced Coats’ disease. Early and prompt management can prevent visual loss and secondary complications.

Muftuoglu, Gulipek; Gulkilik, Gokhan

2011-01-01

172

Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study  

PubMed Central

Background Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The present study aimed to compare the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in r-FSH and GnRH-agonist (GnRH-a) protocol in ICSI cycles. Methods A total of 244 patients without ovulatory dysfunction, aged <40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Down-regulation with GnRH-a + r-FSH and r-LH (beginning simultaneously). Result(s) The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (P = 0.036, P = 0.0014 and P = 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (P = 0.0092 and P = 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (P = 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups. Conclusion These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.

Franco, Jose G; Baruffi, Ricardo LR; Oliveira, Joao Batista A; Mauri, Ana L; Petersen, Claudia G; Contart, Paula; Felipe, Valeria

2009-01-01

173

Effects of different batches of /sup 125/iodine on properties of /sup 125/I-hFSH and characteristics of radioligand-receptor assays  

SciTech Connect

Radioiodination of highly purified human follicle-stimulating hormone (hFSH) (4000 IU/mg) was performed every other week for 23 weeks using 2 mCI carrier free Na/sup 125/I (Amersham Corp., 15 mCi/micrograms I2) in the presence of lactoperoxidase. Incorporation of /sup 125/I into hFSH was determined by the method of R. C. Greenwood, W. M. Hunter, and J. S. Grover (1963) Biochem. J. 89, 114). Hormone binding was studied in vitro under steady-state conditions (16 h, 20 degrees C) using different calf testis membrane preparations having similar receptor characteristics. Each /sup 125/I-hFSH preparation was characterized for maximum bindability, specific activity of bindable radioligand as determined by self-displacement analysis, and by determination of Ka and Rt. Incorporation of /sup 125/I into FSH was relatively constant over the large number of experiments (62.4 +/- 6.4 microCi/micrograms; n = 23). By comparison, however, specific radioactivity of the receptor bindable fraction of /sup 125/I-hFSH was related to the lot of /sup 125/I utilized, and was significantly (P less than or equal to 0.01) lower and more variable (28.7 +/- 10.5 microCi/micrograms). Maximum bindability of /sup 125/I-hFSH was not correlated to specific activity (r = 0.06) but was negatively correlated to hFSH /sup 125/I incorporation (r = -0.47; P less than or equal to 0.05). These observations demonstrate the need to assess the quality of each batch of radioligand before undertaking radioligand-receptor assays and suggest that differences in Na/sup 125/I lots affect specific radioactivity of the radioligand and its receptor binding characteristics.

Melson, B.E.; Sluss, P.M.; Reichert, L.E. Jr.

1987-02-01

174

Production of recombinant channel catfish (Ictalurus punctatus) FSH and LH in S2 Drosophila cell line and an indication of their different actions.  

PubMed

Due to the lack of purified, native gonadotropins (GtH) for almost all species of fish, we designed a system for the production of recombinant bioactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) using the channel catfish (Ictalurus punctatus) as a model animal. The strategy was to produce the three subunits composing FSH and LH, i.e. the common alpha-subunit (alpha-glycoprotein hormone (alpha-GP)), beta-FSH, and beta-LH subunit, individually in stable recombinant insect cells (S2) with C-terminal His-tag. This expression system was also used to co-express the alpha-subunit without the His-tag with each of the His-tagged beta-subunits. The recombinant S2 cells were capable of secreting FSH and LH heterodimers and alpha-GP in abundance; however, expression of the individual beta-subunits was much less successful. The recombinant GtHs were partially purified from the cell medium by immobilized metal affinity chromatography to ~15% purity with a yield of 7 and 4 mg per liter of medium for FSH and LH respectively. These recombinant GtHs activated their receptors in vitro, enhanced estrogen secretion, up-regulated several steroidogenic enzyme genes in channel catfish ovarian follicles, and increased androgen secretion from African catfish testis. Interestingly, the FSH and LH dose-response curves for each of these biological activities clearly demonstrate differences in their cellular action and physiological roles. This expression system may be an important development for the production of species-specific GtHs so that FSH- and LH-specific mechanisms of actions within the reproductive endocrine processes can finally be examined with homologous, albeit recombinant, hormones. PMID:17641288

Zmora, Nilli; Kazeto, Yukinori; Kumar, R Sampath; Schulz, Rüdiger W; Trant, John M

2007-08-01

175

LH and FSH subunit mRNA concentrations during the progesterone-induced gonadotropin surge in ovariectomized estrogen-primed immature rats.  

PubMed

Progesterone is able to bring about an LH and FSH surge in the estrogen-primed ovariectomized rat while dexamethasone brings about selective FSH release. The purpose of this study was to determine if progesterone and desamethasone-induced gonadotropin secretion is accompanied by changes in LHbeta and FSHbeta mRNA levels. Gonadotropin alpha-subunit, LHbeta-subunit, and FSHbeta-subunit mRNA levels in the pituitary of ovariectomized rats were suppressed by estrogen treatment and dexamethasone brought about a significant increase in FSHbeta mRNA within 1 h. Progesterone treatment (0900 h) led to a surge in serum LH levels, with peak values at 1400 h. LHbeta mRNA levels were slightly elevated by progesterone at 1400 h. However, an elevation of LHbeta at 1400 h was also observed in the dexamethasone group which did not show an increase in serum LH. Serum FSH levels were elevated at 1400 and 1600 h in the progesterone group and at 1600 h in the dexamethasone group after an initial fall at 1000 h. No correlation was observed between increases in serum FSH during these times with FSHbeta mRNA levels. In conclusion, the ability of progesterone to induce LH and FSH surges in the estrogen-primed ovariectomized rat was not associated with any clear correlative changes in the mRNAs for these hormones. On the other hand, dexamethasone did increase FSHbeta mRNA levels prior to elevating serum levels of FSH. Nevertheless, as a whole, steroid effects on the temporal secretory pattern of LH and/or FSH in the estrogenprimed ovariectomized rat were not mirrored by correlative changes in the mRNA levels for these hormones. PMID:19912857

Brann, D; O'Conner, J; Wade, M; Mahesh, V

1992-04-01

176

PAR1- and PAR2-induced innate immune markers are negatively regulated by PI3K\\/Akt signaling pathway in oral keratinocytes  

Microsoft Academic Search

BACKGROUND: Protease-Activated Receptors (PARs), members of G-protein-coupled receptors, are activated by proteolytic activity of various proteases. Activation of PAR1 and PAR2 triggers innate immune responses in human oral keratinocytes (HOKs), but the signaling pathways downstream of PAR activation in HOKs have not been clearly defined. In this study, we aimed to determine if PAR1- and PAR2-mediated signaling differs in the

Maryam G Rohani; Dennis H DiJulio; Jonathan Y An; Beth M Hacker; Beverly A Dale; Whasun O Chung

2010-01-01

177

A Conserved Mode of Protein Recognition and Binding in a ParD?ParE Toxin?Antitoxin Complex  

SciTech Connect

Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and binding groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.

Dalton, Kevin M.; Crosson, Sean (UC)

2010-05-06

178

Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila.  

PubMed

The anterior-posterior axis of C. elegans is defined by the asymmetric division of the one-cell zygote, and this is controlled by the PAR proteins, including PAR-3 and PAR-6, which form a complex at the anterior of the cell, and PAR-1, which localizes at the posterior [1-4]. PAR-1 plays a similar role in axis formation in Drosophila: the protein localizes to the posterior of the oocyte and is necessary for the localization of the posterior and germline determinants [5, 6]. PAR-1 has recently been shown to have an earlier function in oogenesis, where it is required for the maintenance of oocyte fate and the posterior localization of oocyte-specific markers [7, 8]. Here, we show that the homologs of PAR-3 (Bazooka) and PAR-6 are also required to maintain oocyte fate. Germline clones of mutants in either gene give rise to egg chambers that develop 16 nurse cells and no oocyte. Furthermore, oocyte-specific factors, such as Orb protein and the centrosomes, still localize to one cell but fail to move from the anterior to the posterior cortex. Thus, PAR-1, Bazooka, and PAR-6 are required for the earliest polarity in the oocyte, providing the first example in Drosophila where the three homologs function in the same process. Although these PAR proteins therefore seem to play a conserved role in early anterior-posterior polarity in C. elegans and Drosophila, the relationships between them are different, as the localization of PAR-1 does not require Bazooka or PAR-6 in Drosophila, as it does in the worm. PMID:11516655

Huynh, J R; Petronczki, M; Knoblich, J A; St Johnston, D

2001-06-01

179

Changes in morphological appearance and functional capacity of recruited follicles in cows treated with FSH in the presence or absence of a dominant follicle.  

PubMed

This study was designed to determine the effect of the presence of a dominant follicle at the beginning of FSH stimulation on the morphological appearance and functional capacity of recruited follicles during FSH stimulation in cattle. Synchronized nonlactating dairy cows were assigned to 1 of 2 groups and treated with FSH in the presence (n = 5) or absence (n = 6) of a dominant follicle between Days 7 and 12 of the estrous cycle (Day 0 = estrus) to stimulate follicular growth. Dominant follicles were identified by daily ultrasonographic observations, beginning on Day 3 of the estrous cycle. Dominant follicle had an ultrasonographic diameter > or = 10 mm and were in a growing phase, or maintaining a constant diameter (> or = 10 mm) for less than 4 d. Ovaries were collected at slaughter on the morning of the third day following initiation of the FSH stimulation. All follicles > 2 mm were dissected, classified according to diameter (Class 1: 2 to 4.4 mm; Class 2: 4.5 to 7.9 mm; Class 3: > 8 mm), and incubated individually for 90 min in medium M-199 (37 degrees C, 5% CO2). Following incubation, integrity of each follicle was evaluated histologically to assess the level of atresia and biochemically to determine the in vitro release of estradiol (E2) and androstenedione in culture media. On Day 3 of the FSH treatment, mean number of follicles in each class was similar (P > 0.1) between the 2 groups. The percentage of atretic follicles in Classes 1 and 3 on Day 3 of the FSH stimulation did not differ (P > 0.1) between the 2 groups. However, the percentage of atretic follicles in Class 2 was higher (P < 0.005) in cows treated with FSH in presence than in absence of a dominant follicle (60.8 vs 38.2%). The release of E2 in culture media by small Class 1 atretic or healthy follicles, by Class 2 atretic and by Class 3 healthy follicles was not affected (P > 0.1) by the ovarian status. However (P < 0.001), the release of E2 in culture media of Class 2 healthy and Class 3 atretic follicles was less for follicles harvested from cows bearing than from those not bearing a dominant follicle. Within each follicular class, concentrations of androstenedione in the culture media did not differ between the 2 groups (P > 0.1). These results suggest that the presence of a dominant follicle at the beginning of FSH stimulation alters the population of follicles recruited FSH stimulation. This may be associated with the reported decrease of the superovulatory response in cows superovulated in presence of a dominant follicle. PMID:16727969

Rouillier, P; Guilbault, L A; Lussier, J G; Matton, P

1996-10-15

180

Onset of lipoprotein-supported steroidogenesis in differentiating granulosa cells of rats: cellular events involved in mediating FSH-enhanced uptake of low-density lipoproteins  

SciTech Connect

Luteal cells use lipoproteins as the main source of cholesterol in steroidogenesis. However, little is known about the mechanisms underlying hormonal control of lipoprotein uptake. Thus, the authors tested the hypothesis that FSH and androgens regulate low density lipoprotein (LDL)-supported steroidogenesis in maturing granulosa cells by affecting receptor-mediated endocytosis of LDL at a cellular level. For this, immature ovarian granulosa cells were cultured with or without hormones, compactin (de novo synthesis inhibitor), or unlabeled or labeled (/sup 125/I or gold particles) LDL. Nonhormone-treated cultures produced little progestin; FSH and FSH/androstenedione stimulated steroid secretion. Progestin production by hormone-, but not nonhormone-, treated cultures was decreased by compactin, suggesting that de novo synthesis provided sterol for steroidogenesis. EM quantitation of cells exposed to gold-LDL at 37/sup 0/C revealed that, compared to nonhormone-treated cells, FSH-treated cells (1) bound and internalized more gold-LDL, (2) had a smaller percentage of gold-LDL at their surfaces, (3) displayed a faster apparent rate of LDL internalization and delivery to lysosomes, and (4) contained more gold-labeled lysosomes. Data from biochemical studies in which /sup 125/I-LDL was used supported the morphological findings. In conclusion, this study demonstrates that FSH has important effects at the cellular level on LDL uptake, which seem to underlie the striking increase in progestin production accompanying granulosa cell differentiation.

Foster, J.D.

1987-01-01

181

Protease-activated Receptor2 (PAR2) in Human Periodontitis  

Microsoft Academic Search

No evidence for the role of protease-activated receptor-2 (PAR2) in human periodontal disease has been demonstrated so far. Thus, we sought to investigate the expression of PAR2 mRNA in chronic periodontitis, and to examine whether its expression is related to the presence of PAR2 potential activators. Microbiological and gingival crevicular fluid samples were collected from individuals with chronic periodontitis and

M. Holzhausen; J. R. Cortelli; V. Araújo da Silva; G. C. Nobre Franco; S. Cavalca Cortelli; N. Vergnolle

2010-01-01

182

Evaluation of the PAR corneal topography system  

NASA Astrophysics Data System (ADS)

The purpose of this study was to evaluate the raster photogrammetry based Corneal Topography System by determining: inter-operator variability, reproducibility of images, effects of defocused and decentered images, and the precision of data at different optical zones. 4 human cadaver eyes were used to study the inter-operator variability. To study the reproducibility of images, 3 human cadaver eyes and a test surface doped with flourescine (provided by PAR Vision Systems Corporation) were focused and their images taken four successive times. Defocused and decentered images were taken of 4 human cadaver eyes and four times of the test surface mentioned above. The precision of defocused/decentered cadaver eyes was evaluated at the following optical zones: 3 mm, 4 mm, 5 mm, and 6 mm. All human cadaver eyes used in the above experiments had their epithelial layer removed before imaging. Average inter-operator variability was 0.06 D. In reproducibility attempts, there was an average deviation of 0.28 D for the human cadaver eyes and 0.04 D for the test surface. The defocused and decentered test surface gave an average deviation of 0.09 D. Defocused and decentered cadaver eyes resulted in an average deviation of 0.52 D, 0.37 D, 0.24 D, and 0.22 D at optical zones of 3 mm, 4 mm, 5 mm, and 6 mm, respectively. The imaging method employed by PAR Vision Systems Corporation virtually eliminates inter-operator variability. The PAR Corneal Topography System's clinical usefulness, however, could be improved by improving the reproducibility of images, decreasing the sensitivity to spatial alignment, and increasing accuracy over smaller optical zones.

Jindal, Prateek; Cheung, Susan; Pirouzian, Amir; Keates, Richard H.; Ren, Qiushi

1995-05-01

183

Pars plana vitrectomy revealed Toxocara canis organism  

Microsoft Academic Search

Background  The Toxocara organism may cause direct injury to the eye, but most commonly, host inflammatory reactions are responsible for the resulting\\u000a compromise. The inflammatory response created by the ocular involvement may result in epiretinal membrane formation, tractional\\u000a or combined tractional-rhegmatogenous retinal detachment. The treatment of choice is pars plana vitrectomy (PPV), which also\\u000a has diagnostic significance.\\u000a \\u000a \\u000a \\u000a Methods  We report a pediatric

Nur Acar; Ziya Kapran; Canan Asl? Utine; Nesimi Büyükbabani

2007-01-01

184

2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) BARRACKS WITH RADAR ATTACHED. - Nike Hercules Missile Battery Summit Site, Battery Control Administration & Barracks Building, Anchorage, Anchorage, AK

185

Mechanism of DNA Segregation in Prokaryotes: Replicon Pairing by parC of Plasmid R1  

NASA Astrophysics Data System (ADS)

Prokaryotic chromosomes and plasmids encode partitioning systems that are required for DNA segregation at cell division. The systems are thought to be functionally analogous to eukaryotic centromeres and to play a general role in DNA segregation. The parA system of plasmid R1 encodes two proteins ParM and ParR, and a cis-acting centromere-like site denoted parC. The ParR protein binds to parC in vivo and in vitro. The ParM protein is an ATPase that interacts with ParR specifically bound to parC. Using electron microscopy, we show here that parC mediates efficient pairing of plasmid molecules. The pairing requires binding of ParR to parC and is stimulated by the ParM ATPase. The ParM mediated stimulation of plasmid pairing is dependent on ATP hydrolysis by ParM. Using a ligation kinetics assay, we find that ParR stimulates ligation of parC-containing DNA fragments. The rate-of-ligation was increased by wild type ParM protein but not by mutant ParM protein deficient in the ATPase activity. Thus, two independent assays show that parC mediates pairing of plasmid molecules in vitro. These results are consistent with the proposal that replicon pairing is part of the mechanism of DNA segregation in prokaryotes.

Jensen, Rasmus Bugge; Lurz, Rudi; Gerdes, Kenn

1998-07-01

186

Historic macrophyte development in Par Pond  

SciTech Connect

Aerial photographs from 1975, 1980, and 1983 were examined to evaluate the changes that have occurred in the wetland vegetation of Par Pond, a reactor-cooling reservoir. Evaluation of the aerial photographs was based on comparisons with ground-level vegetation maps made during July 1984. Comparisons of photographs from August and December of 1983 revealed the main seasonal change in the aerial coverage of wetland vegetation to be the wintertime loss of non-persistent emergent species such as Nelumbo lutea and Nymphaea odorata. Comparisons between September 1980 and August 1983 revealed that the lakeward extent of non-persistent macrophytes has increased by an average of 8.2 m, though not all sites have changed equally. For persistent macrophytes (principally Typha), the average increase in lakeward extent between December 1975 and August 1983 was 3.48 m. The extensive development of wetland vegetation in Par Pond as well as the substantial spread of vegetation over only a few years time indicates the high suitability of this habitat for the growth of wetland plants.

Grace, J.B.

1985-08-01

187

The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells.  

PubMed

WNTs are extracellular signaling molecules that exert their actions through receptors of the frizzled (FZD) family. Previous work indicated that WNT2 regulates cell proliferation in mouse granulosa cells acting through CTNNB1 (beta-catenin), a key component in canonical WNT signaling. In other cells, WNT signaling has been shown to regulate expression of connexin43 (CX43), a gap junction protein, as well as gap junction assembly. Since previous work demonstrated that CX43 is also essential in ovarian follicle development, the objective of this study was to determine if WNT2 regulates CX43 expression and/or gap-junctional intercellular communication (GJIC) in granulosa cells. WNT2 knockdown via siRNA markedly reduced CX43 expression and GJIC. CX43 expression, the extent of CX43-containing gap junction membrane, and GJIC were also reduced by CTNNB1 transient knockdown. CTNNB1 is mainly localized to the membranes between granulosa cells but disappeared from this location after WNT2 knockdown. Furthermore, CTNNB1 knockdown interfered with the ability of follicle-stimulating hormone (FSH) to promote the mobilization of CX43 into gap junctions. We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC. PMID:23843235

Wang, Hong-Xing; Gillio-Meina, Carolina; Chen, Shuli; Gong, Xiang-Qun; Li, Tony Y; Bai, Donglin; Kidder, Gerald M

2013-08-22

188

USGS field activity 09FSH02 on the west Florida shelf, Gulf of Mexico, in August 2009  

USGS Publications Warehouse

From August 17 to 21, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 2,000 data points were collected underway over a 1,320-kilometer (km) track line using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH02 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the second field activity for that study in that calendar year.

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

189

USGS field activity 08FSH01 on the west Florida shelf, Gulf of Mexico, in August 2008  

USGS Publications Warehouse

From August 11 to 15, 2008, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,600 data points were collected underway over a 650-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River southward to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples from approximately 40 locations were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 08FSH01 tells us the data were collected in 2008 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

190

USGS field activity 09FSH01 on the west Florida shelf, Gulf of Mexico, in February 2009  

USGS Publications Warehouse

From February 24 to 28, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,800 data points were collected underway over a 1,300-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH01 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

191

Effects of growth differentiation factor-9 and FSH on in vitro development, viability and mRNA expression in bovine preantral follicles.  

PubMed

The present study investigated the role of growth differentiation factor (GDF)-9 and FSH, alone or in combination, on the growth, viability and mRNA expression of FSH receptor, proliferating cell nuclear antigen (PCNA) and proteoglycan-related factors (i.e. hyaluronan synthase (HAS) 1, HAS2, versican, perlecan) in bovine secondary follicles before and after in vitro culture. After 12 days culture, sequential FSH (100ngmL(-1) from Days 0 to 6 and 500ngmL(-1) from Days 7 to 12) increased follicular diameter and resulted in increased antrum formation (P<0.05). Alone, 200ngmL(-1) GDF-9 significantly reduced HAS1 mRNA levels, but increased versican and perlecan mRNA levels in whole follicles, which included the oocyte, theca and granulosa cells. Together, FSH and GDF-9 increased HAS2 and versican (VCAN) mRNA levels, but decreased PCNA mRNA expression, compared with levels in follicles cultured in ?-minimum essential medium supplemented with 3.0mgmL(-1) bovine serum albumin, 10µgmL(-1) insulin, 5.5µgmL(-1) transferrin, 5ngmL(-1) selenium, 2mM glutamine, 2mM hypoxanthine and 50?gmL(-1) ascorbic acid (?-MEM(+)). Comparisons of uncultured (0.2mm) and ?-MEM(+) cultured follicles revealed that HAS1 mRNA expression was higher, whereas VCAN expression was lower, in cultured follicles (P<0.05). Expression of HAS1, VCAN and perlecan (HSPG2) was higher in cultured than in vivo-grown (0.3mm) follicles. In conclusion, FSH and/or GDF-9 promote follicular growth and antrum formation. Moreover, GDF-9 stimulates expression of versican and perlecan and interacts positively with FSH to increase HAS2 expression. PMID:23241220

Vasconcelos, G L; Saraiva, M V A; Costa, J J N; Passos, M J; Silva, A W B; Rossi, R O D S; Portela, A M L R; Duarte, A B G; Magalhães-Padilha, D M; Campelo, C C; Figueiredo, J R; van den Hurk, R; Silva, J R V

2013-10-01

192

Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group.  

PubMed

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development. PMID:10920087

Schats, R; Sutter, P D; Bassil, S; Kremer, J A; Tournaye, H; Donnez, J

2000-08-01

193

Metabolism of /sup 3/H-estradiol-17 beta by cultures of isolated rat Sertoli cells and the effect of FSH: presence of 16 alpha-hydroxylase  

SciTech Connect

The ability of Sertoli cells to metabolize /sup 3/H-estradiol-17 beta was investigated utilizing Sertoli cell cultures isolated from 18d rat testes. The Sertoli cells converted estradiol-17 beta to estriol as shown by recrystallization of estriol from samples containing cells and media but not from cell-free control media. The effect of FSH treatment on such metabolism was investigated and was shown to be similar to nontreated samples. This is the first demonstration that 16 alpha-hydroxylase is present in Sertoli cells and that this enzyme activity is not under the influence of FSH.

Tcholakian, R.K.; Steinberger, A.; St. Pyrek, J.

1983-07-01

194

Regulative actions of the Chinese drugs for tonifying the kidney on gene expression of the hypothalamic GnRH, pituitary FSH, LH and osteoblastic BGP.  

PubMed

It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate, and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH, pituitary FSH, LH and osteoblastic BGP, indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH, pituitary FSH, LH, and osteoblastic BGP, which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney, regulating ephebic development process andimproving skeletal development in sexual precocity children. PMID:15889526

Cai, Depei; Zhang, Wei

2005-03-01

195

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology.  

PubMed

BACKGROUND: V-betaLH is a common genetic variant of LH caused by two polymorphic base changes in the beta subunit gene, altering the amino acid sequence (Trp8Arg and Ile15Thr). In a previous-preliminary trial performed in women undergoing IVF, it was demonstrated that carriers of v-betaLH show sub-optimal ovarian response to a standard long GnRH-agonist down -regulation protocol when stimulated with pure recombinant FSH (r-hFSH). The aim of this study was to confirm the hypothesis that women with v-betaLH display hypo-sensitivity to exogenous FSH in a larger IVF population and to explore the frequency of this variant in a Danish female population. METHODS: In the present study, the effect of v-betaLH was retrospectively investigated in a larger series of women undergoing controlled ovarian stimulation (COS) and, for the first time, in a Danish IVF population. A total of 220 normogonadotrophic women following a long GnRH-agonist down-regulation protocol received an individualized dose of r-hFSH (100 IU and 375 IU s.c. daily) according to antral follicle count, baseline FSH, body mass index and age. The LH genotype was assessed in all patients by immunofluorometric assay. RESULTS: V-betaLH was present in 11% of patients, whereas the allelic frequency was 12%. The study population was divided into two groups according to their LH genotype. Group A consisted of 196 wt/wt women. Group B included 24 individuals with v-betaLH (21 heterozygous and 3 homozygous). No statistically significant differences in the mean number of oocytes retrieved, fertilization rate and pregnancy rate per cycle were observed between groups. However, Group B received a significantly higher cumulative-dose of r-hFSH than Group A (2435.86 +/- 932.8 IU versus 1959.8 +/- 736.45 p = 0.048). When one-way ANOVA in a within design was applied, the LH genotype had a statistically significant effect (p < 0.01) on the cumulative dose of r-hFSH, showing a progressive increase from wt/wt (1959.8 +/- 736.45 IU) to v-betaLH hetero- (2267.5 +/- 824.3) and homozygotic women (3558.3 +/- 970.9). CONCLUSIONS: These results confirm that carriers exhibit hypo-sensitivity to exogenous FSH during COS, documenting that the frequency of v-betaLH in Denmark is similar to a number of European countries. PMID:23725475

Alviggi, Carlo; Pettersson, Kim; Longobardi, Salvatore; Andersen, Claus Yding; Conforti, Alessandro; De Rosa, Pasquale; Clarizia, Roberto; Strina, Ida; Mollo, Antonio; De Placido, Giuseppe; Humaidan, Peter

2013-06-01

196

BINDING TO PKC-3, BUT NOT TO PAR-3 OR TO A CONVENTIONAL PDZ DOMAIN LIGAND, IS REQUIRED FOR PAR-6 FUNCTION IN C. ELEGANS  

PubMed Central

PAR-6 is a conserved protein important for establishment and maintenance of cell polarity in a variety of metazoans. PAR-6 proteins function together with PAR-3, aPKC and CDC-42. Mechanistic details of their interactions, however, are not fully understood. We studied the biochemical interactions between C. elegans PAR-6 and its binding partners and tested the requirements of these interactions in living worms. We show that PB1 domain-mediated binding of PAR-6 to PKC-3 is necessary for polarity establishment and PAR-6 cortical localization in C. elegans embryos. We also show that binding of PAR-6 and PAR-3 is mediated in vitro by a novel type of PDZ-PDZ interaction; the ?C strand of PAR-6 PDZ binds the ?D strand of PAR-3 PDZ1. However, this interaction is dispensable in vivo for PAR-6 function throughout the life of C. elegans. Mutations that specifically abolish conventional ligand binding to the PAR-6 PDZ domain also failed to affect PAR-6 function in vivo. We conclude that PAR-6 binding to PKC-3, but not to PAR-3 nor to a conventional PDZ ligand, is required for PAR-6 cortical localization and function in C. elegans.

Li, Jin; Kim, Heon; Aceto, Donato G.; Hung, Jeffrey; Aono, Shinya; Kemphues, Kenneth J.

2010-01-01

197

Pars plana vitrectomy for retinal detachment with unseen retinal holes  

Microsoft Academic Search

A study was made of a consecutive series of 47 cases of rhegmatogenous retinal detachment treated by pars plana vitrectomy in which no holes were identified preoperatively. The view of the fundus during preoperative examination varied from being totally clear to completely obscured by media opacities. The role of pars plana vitrectomy in finding retinal holes peroperatively is considered. The

D. Wong; B. M. Billington; A. H. Chignell

1987-01-01

198

Acrylic intraocular lens placement in conjunction with pars plana vitrectomy  

Microsoft Academic Search

PURPOSE: To report the results of placing a foldable acrylic intraocular lens through a clear cornea incision in eyes undergoing pars plana vitrectomy.METHODS: This interventional case series is a retrospective report of 15 eyes of 15 consecutive patients undergoing foldable (acrylic) intraocular lens insertion in conjunction with pars plana vitrectomy in a single academic institution. Outcome measures included visual acuity

William E Smiddy; Medhat Mady; Scott Anagnoste

2001-01-01

199

Complicated retinal detachment and its management with pars plana vitrectomy  

Microsoft Academic Search

Fifty patients with retinal detachment accompanied by vitreous haemorrhage, perforating eye injuries, intraocular foreign bodies, massive preretinal retraction,.giant tears greater than 180 degrees, and proliferative retinopathies underwent pars plana vitrectomy, cryocoagulation, scleral buckling, and intravitreal gas injection. Intraoperative complications included minimal to moderate bleeding and iatrogenic retinal tears, but no retinal dialysis was produced at the pars plana sclerotomy site.

F U Huamont; G A Peyman; M F Goldberg

1977-01-01

200

The Par3/Par6/aPKC complex and epithelial cell polarity.  

PubMed

Apical-basal polarity is the basic organizing principle of epithelial cells, and endows epithelial cells to function as defensive barriers and as mediators of vectorial transport of nutrients in and out of organisms. Apical-basal polarity is controlled by a number of conserved polarity factors that regulate cytoskeletal organizations, asymmetric distributions of cellular components, and directional transports across cells. Polarity factors often occupy specific membrane regions in response to the adhesion forces generated by cell-cell and cell-extracellular matrix interactions. Both internal polarity factors and the external extracellular matrices play fundamental roles in epithelial cell polarity establishment and maintenance. This review focuses on recent developments of the Par3/Par6/aPKC complex and its interacting proteins in epithelial cell polarity. PMID:23535009

Chen, Jia; Zhang, Mingjie

2013-03-25

201

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia  

PubMed Central

This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

2011-01-01

202

Pars plana vitrectomy for asteroid hyalosis.  

PubMed

Asteroid hyalosis is a common, usually asymptomatic, benign vitreous disease affecting older individuals. A case report of an aphakic patient who developed anterior segment complications with no visualization of the fundus is presented. A pars plana anterior and posterior vitrectomy was performed using the Ocutome system. An excellent technical result with moderate restoration of vision was achieved. Preoperative evaluation with ultrasound was helpful. Pathology confirmed the diagnosis of calcium-containing lipids. Other indications for vitrectomy for asteroid hyalosis include retinal detachments in which the tear cannot be seen and diabetic retinopathy in which laser cannot be performed. Differential diagnosis includes synchysis scintillans, which is usually bilateral and seen in younger individuals after severe ocular inflammation, trauma, or hemorrhage. PMID:7348845

Renaldo, D P

1981-01-01

203

Pars plana Baerveldt tube insertion with pars plana vitrectomy for refractory glaucoma  

PubMed Central

Background: Glaucoma drainage implants (GDIs) are used for managing recalcitrant glaucoma and are usually placed in the anterior chamber. This approach may lead to complications such as corneal decompensation, and so a pars plana approach is used in at risk eyes. Aims: To compare functional outcomes and complications of 250 mm2 and 350 mm2 pars plana Baerveldt tube insertion with pars plana vitrectomy (PPV) (both 20- and 23-gauge) for managing refractory glaucoma. Settings and Design: A retrospective chart review of 38 patients (39 eyes) undergoing combined PPV-Baerveldt procedure for glaucoma recalcitrant to maximal medical treatment or previous filtering procedures with >6 weeks of follow-up. Materials and Methods: Main outcome measures were visual acuity, intraocular pressure (IOP), number of glaucoma medications, and postoperative complications. Statistical Analysis Used: A paired ‘t’ test was used to evaluate changes in IOP and glaucoma medications, Fisher's exact test was used to compare complication rates, and Kaplan-Meier survival curves were constructed for comparison of overall outcomes. Results: Mean patient age was 62.2 years. Mean follow-up period was 33.7 months, with 36 (92%) eyes followed for ?6 months. Mean±SD preoperative IOP and number of glaucoma medications were significantly reduced by the combined procedure (P<0.05). Thirty-five (90%) eyes maintained final IOP between 6 and 21 mmHg. Vision improved by ?2 lines in 10 (26%) eyes, remained stable in 15 (38%) eyes, and decreased in 14 (36%) eyes. Two (5.1%) eyes developed no light perception vision, with one (2.6%) eye becoming phthisical. Twenty-four (62%) eyes developed complications managed with conservative measures. Five (13%) eyes required ?1 surgeries within a year of the combined procedure. Conclusions: Pars plana Baerveldt tube implantation with PPV can preserve vision, reduce IOP, and decrease the number of glaucoma medications necessary to achieve target IOP in patients with recalcitrant glaucoma.

Kolomeyer, Anton M.; Kim, H. Jane; Khouri, Albert S.; Lama, Paul J.; Fechtner, Robert D.; Zarbin, Marco A.; Bhagat, Neelakshi

2012-01-01

204

Modélisation par éléments finis des phénomènes couples électromagnéto-thermiques caractérisant le frittage par induction  

NASA Astrophysics Data System (ADS)

An electromagnetic and thermal phenomena coupling model is presented and discussed. Called Direct Coupling Model: MCD, the proposed method is based on a finite element solution of the set of the magnetic vector potential and temperature equations. The MCD is applied to the case of the induction sintering technique, used for the design of the tantalum condenser. The model validity is obtained when comparing the computed and measured data. Un modèle de représentation du couplage réel des phénomènes électromagnétique et thermique est proposé et discuté. Appelé Modèle de Couplage Direct de phénomènes Electro-Mangéto-Thermiques (MCDEMT), ce modèle est basé sur une résolution par éléments finis du système des équations du potentiel vecteur magnétique et de la température. Le MCDEMT est appliqué à la modélisation d'un dispositif axisymétrique utilisé dans le frittage par induction pour l'élaboration de condensateurs au tantale. La validation de la méthode proposée est réalisée par comparaison des profils de température calculé et mesuré sur la surface de l'anode.

Féliachi, M.; Perronnet, A.; Develey, G.

1992-11-01

205

Control of Cleavage Spindle Orientation in Caenorhabditis Elegans: The Role of the Genes Par-2 and Par-3  

PubMed Central

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these division. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2(it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage.

Cheng, N. N.; Kirby, C. M.; Kemphues, K. J.

1995-01-01

206

Novel Role for Proteinase-activated Receptor 2 (PAR2) in Membrane Trafficking of Proteinase-activated Receptor 4 (PAR4)*  

PubMed Central

Proteinase-activated receptors 4 (PAR4) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR4 remain unknown. Here, we report novel features of the intracellular trafficking of PAR4 to the plasma membrane. PAR4 was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit ?-COP1. Analysis of the PAR4 protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R183AR ? A183AA), mutation of which allowed efficient membrane delivery of PAR4. Interestingly, co-expression with PAR2 facilitated plasma membrane delivery of PAR4, an effect produced through disruption of ?-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3?. Intermolecular FRET studies confirmed heterodimerization between PAR2 and PAR4. PAR2 also enhanced glycosylation of PAR4 and activation of PAR4 signaling. Our results identify a novel regulatory role for PAR2 in the anterograde traffic of PAR4. PAR2 was shown to both facilitate and abrogate protein interactions with PAR4, impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR4 in normal physiology and disease.

Cunningham, Margaret R.; McIntosh, Kathryn A.; Pediani, John D.; Robben, Joris; Cooke, Alexandra E.; Nilsson, Mary; Gould, Gwyn W.; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-01-01

207

Sexually dimorphic expression of gonadotropin subunits in the pituitary of protogynous honeycomb grouper (Epinephelus merra): evidence that follicle-stimulating hormone (FSH) induces gonadal sex change.  

PubMed

Recent studies have suggested that the hypothalamic-pituitary-gonadal axis is involved in gonadal sex change in sex-changing teleosts. However, its underlying mechanism remains largely unknown. In this study, we focused on the distinct roles of two gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in the protogynous hermaphrodite teleost, honeycomb grouper (Epinephelus merra). First, we investigated the expression pattern of mRNAs for GTH subunits (cga, fshb, and lhb) in the pituitaries from fish at the different sexual phases. Real-time RT-PCR analyses showed that fhsb mRNA levels in the female pituitary were low. However, fshb transcripts increased dramatically in association with testis development. In contrast, levels of cga and lhb mRNAs did not significantly vary during sex change. In addition, immunohistochemical observations of Fshb- and Lhb-producing cells in the pituitary, through the use of specific antibodies for detections of teleost GTH subunits, were consistent with sexually dimorphic expression of Fshb. In order to identify the role of GTH in gonad of honeycomb grouper, we treated females with bovine FSH (50 or 500 ng/fish) or LH (500 ng/fish) in vivo. After 3 wk, FSH treatments induced female-to-male sex change and up-regulated endogenous androgen levels and fshb transcripts, whereas LH treatment had no effect on sex change. These results suggest that FSH may trigger the female-to-male sex change in honeycomb grouper. PMID:20147735

Kobayashi, Yasuhisa; Alam, Mohammad Ashraful; Horiguchi, Ryo; Shimizu, Akio; Nakamura, Masaru

2010-02-10

208

Initiation of the expression of peroxisome proliferator - activated receptor gamma (PPAR gamma) in the rat ovary and the role of FSH  

Microsoft Academic Search

PPARgamma is highly expressed in granulosa cells by 23 days post-partum (pp) and is down-regulated in response to the LH surge. We tested the hypothesis that high levels of FSH during the neonatal period trigger the expression of PPARgamma. To determine when PPARgamma expression is initiated, ovaries were collected from neonatal rats. Messenger RNA for PPARgamma was undetectable on day

Mary J Long; M Ram Sairam; Carolyn M Komar

2009-01-01

209

Simultaneous evaluation of basal FSH and oestradiol response to GnRH analogue (F-G-test) allows effective drug regimen selection for IVF.  

PubMed

To determine whether preliminary assessment of ovarian reserve by simultaneous evaluation of basal follicle-stimulating hormone (FSH) and oestradiol response to gonadotrophin releasing hormone (GnRH) analogue (F-G-test) can be used to tailor individually the drug regimen for ovarian stimulation, the in-vitro fertilization (IVF) results of 238 patients were retrospectively analysed. Sixty-two women with abnormal response to the test (DeltaE2 <180 pmol/l and/or FSH >9.5 mIU/ml) had commenced buserelin nasal spray in the mid-luteal phase and discontinued it on cycle day 1. Ovarian stimulation was started on cycle day 3 with 375 IU/day of gonadotrophin. Fifty-three patients completed the treatment cycle (group A). A total of 176 women with normal response to the test (DeltaE2 >180 pmol/l and FSH <9.5 mIU/ml) had continued the GnRH analogue throughout the stimulation cycle and a starting dose of 225 IU/day of gonadotrophin was used from cycle day 3. A total of 158 patients completed the treatment cycle (group B). Group A had significantly higher age (34.9 +/- 4.2 versus 33.2 +/- 4.2) (P < 0.05) and basal FSH (9.2 +/- 3.8 versus 7.0 +/- 2.2) (P < 0.05) and required a higher total dose of gonadotrophin. The numbers of oocytes retrieved and embryos transferred were significantly lower. However, fertilization, clinical pregnancies, and implantation rates were similar in both groups. It was concluded that simultaneous evaluation of basal FSH and oestradiol response to GnRH analogue can be useful in identifying subcategories of women with reduced ovarian reserve who may benefit from reduced GnRH analogue administration and a higher starting dose of gonadotrophin. PMID:11278216

Ranieri, D M; Phophong, P; Khadum, I; Meo, F; Davis, C; Serhal, P

2001-04-01

210

A 361 base pair region of the rat FSH-beta promoter contains multiple progesterone receptor-binding sequences and confers progesterone responsiveness.  

PubMed

The rat is frequently used as a model to study the role of progesterone (P) in regulating FSH secretion and synthesis. The ability of P to modulate rat FSH-beta mRNA levels suggests the presence of a functional hormone response element. We have found three PRE-like sequences upstream of the transcription start site in the rat FSH-beta gene. These sequences are herein referred to as PRE-like sequence #1, #2 and #3 with #1 being most distal from the start site. The current studies determined whether these PRE-like sequences bound P receptor (PR) and were functional in regulating the induction of expression by P. Electrophoretic mobility shift assays (EMSA) demonstrated that a single 289 base pair (bp) DNA fragment encompassing all three PRE-like sequences specifically bound PR. Further, PR bound with high affinity to double-stranded oligonucleotides representing individual PRE-like sequences #1, #2 and, with lower affinity to a double-stranded oligonucleotide representing PRE-like sequence, #3. We have cloned a 361 bp sequence from the promoter region of the rat FSH-beta gene encompassing all three PRE-like sequences into a luciferase reporter vector (pGL3-promoter) yielding pFSHbeta361-luc+ which when transiently transfected into primary rat pituitary cell cultures, conferred P-responsiveness to a heterologous promoter. P-responsiveness was dependent upon the presence of PR and was blocked by the PR antagonist RU-486. These data strongly suggest the presence of functional PRE's in the rat FSH-beta gene promoter. PMID:9510069

O'Conner, J L; Wade, M F; Prendergast, P; Edwards, D P; Boonyaratanakornkit, V; Mahesh, V B

1997-12-31

211

Clinical outcomes following repair of the pars interarticularis.  

PubMed

Spondylolysis is a source of back pain in adolescents and young adults. The purpose of this study was to report clinical outcomes in 49 patients treated with isolated motion-sparing repair of the pars interarticularis. Patients who underwent direct repair of the pars interarticularis between 2002 and 2009 were identified. Standard demographic and radiographic data, needed for further surgeries, and radiographic evidence of healing were collected. Of 49 patients with 90 total pars defects (41 bilateral, 8 unilateral), 7 required reoperation. No serious complications were seen. None of the risk factors analyzed in our study were predictive of reoperation. The strongest preoperative predictor of Oswestry Disability Index score was Fujii chronicity (P = .041). Motion segment sparing repair of the pars is a safe and effective procedure for refractory cases of spondylolysis. PMID:23431550

Clegg, Travis; Carreon, Leah; Mutchnick, Ian; Puno, Rolando

2013-02-01

212

Résolution par Analogie de Problèmes Géométriques dans une Perspective Tutorielle  

Microsoft Academic Search

L'apprentissage humain est basé sur des expériences progressives. Dans ce but nous proposons un modèle de Raisonnement par Analogie qui retient l'expérience passée pour l'utiliser dans la résolution des nouveaux problèmes qui sont analogues à ceux déjà mémorisés. Nous définissons ce qu'on appelle deux problèmes analogues et comment évolue par Apprentissage Symbolique la Mémoire à Long Terme. Cette approche confère

Eugène Chouraqui; C. Inghilterra

1992-01-01

213

A New Family of the PARS Translation Systems  

Microsoft Academic Search

This paper presents a description of the well-known family of machine translation systems, PARS. PARS was developed in the\\u000a USSR as long ago as in 1989, and, since then, it has passed a difficult way from a mainframe-based, somewhat bulky system\\u000a to a modern PC-oriented product. At the same time, we understand but well that, as any machine translation software,

Michael Blekhman; Andrei Kursin; Alla Rakova

2002-01-01

214

Par reduction in ofdm via active constellation extension  

Microsoft Academic Search

The high peak-to-average power ratio (PAR) in orthogonal frequency division multiplexing (OFDM) modulation systems can significantly reduce power efficiency and performance. Methods exist which alter or introduce new signal constellations to combat large signal peaks. We present a new PAR-reduction method that dynamically extends outer constellation points in active (data-carrying) channels, within margin-preserving constraints, in order to minimize the peak

Brian Scott Krongold; Douglas L. Jones

2003-01-01

215

StePar: an automatic code for stellar parameter determination  

NASA Astrophysics Data System (ADS)

We introduce a new automatic code (StePar) for determinig stellar atmospheric parameters (T_{eff}, log{g}, ? and [Fe/H]) in an automated way. StePar employs the 2002 version of the MOOG code (Sneden 1973) and a grid of Kurucz ATLAS9 plane-paralell model atmospheres (Kurucz 1993). The atmospheric parameters are obtained from the EWs of 263 Fe I and 36 Fe II lines (obtained from Sousa et al. 2008, A&A, 487, 373) iterating until the excitation and ionization equilibrium are fullfilled. StePar uses a Downhill Simplex method that minimizes a quadratic form composed by the excitation and ionization equilibrium conditions. Atmospheric parameters determined by StePar are independent of the stellar parameters initial-guess for the problem star, therefore we employ the canonical solar values as initial input. StePar can only deal with FGK stars from F6 to K4, also it can not work with fast rotators, veiled spectra, very metal poor stars or Signal to noise ratio below 30. Optionally StePar can operate with MARCS models (Gustafson et al. 2008, A&A, 486, 951) instead of Kurucz ATLAS9 models, additionally Turbospectrum (Alvarez & Plez 1998, A&A, 330, 1109) can replace the MOOG code and play its role during the parameter determination. StePar has been used to determine stellar parameters for some studies (Tabernero et al. 2012, A&A, 547, A13; Wisniewski et al. 2012, AJ, 143, 107). In addition StePar is being used to obtain parameters for FGK stars from the GAIA-ESO Survey.

Tabernero, H. M.; González Hernández, J. I.; Montes, D.

2013-05-01

216

Quality and storage life of par-baked frozen breads  

Microsoft Academic Search

During storage of frozen par-baked breads for a prolonged period of time, bread quality may undergo changes such as increased firmness, moisture and flavour losses resulting in product deterioration. Four categories of par-baked breads namely—variety, white, multi-grain and rye were stored at ?18°C for 9 months to evaluate the effects of storage period on product quality, and to develop prediction

I. R Vulicevic; E. S. M Abdel-Aal; G. S Mittal; X Lu

2004-01-01

217

Le financement de la croissance par endettement extérieur  

Microsoft Academic Search

[fre] Le financement de la croissance par endettement extérieur. . Nous illustrons, à l'aide d'un modèle théorique simple avec générations imbriquées, les risques que peut présenter le financement de l'accumulation de capital par recours à l'investissement étranger ou à l'endettement extérieur. Nous examinons les effets du risque, des possibilités de retrait des investisseurs étrangers, de variations des taux d'intérêt, sur

Patrick Artus

1998-01-01

218

Secondary pupillary membranes treated by the pars plana\\/pars plicata approach: long-term results of 108 cases  

Microsoft Academic Search

One hundred and eight pupillary membranes treated with the vitrophage through a pars plicata or pars plana approach were evaluated for long-term results. The average follow-up was 3.86 years, with a range of 1 to 7 years. No major operative complications were encountered. Anatomical success was achieved in all cases. Vision improved in 67.5% of eyes. In 4 cases (3.7%)

C P Juarez; G A Peyman; M Raichand; M F Goldberg

1981-01-01

219

The Role of Neurosecretory Neurons in the Pars Intercerebralis and Pars Lateralis in Reproductive Diapause of the Blowfly, Protophormia terraenovae  

Microsoft Academic Search

Microlesions of the brain were made to examine the role of neurosecretory neurons in the pars intercerebralis (PI) and pars\\u000a lateralis (PL) in the induction of reproductive diapause of the female blowfly Protophormia terraenovae. Under both diapause-inducing (LD 12?:?12, 20???C) and diapause-averting conditions (LD 18?:?6, 25???C), the ovaries invariably\\u000a failed to develop when the PI was removed. When the PL

S. Shiga; H. Numata

2000-01-01

220

PAR1 and PAR2 Couple to Overlapping and Distinct Sets of G Proteins and Linked Signaling Pathways to Differentially Regulate Cell PhysiologyS?  

PubMed Central

The protease-activated receptors (PAR1 and PAR2) are unusual G protein-coupled receptors that are activated by distinct serine proteases and are coexpressed in many different cell types. Limited recent evidence suggests these closely related receptors regulate different physiological outputs in the same cell, although little is known about the comparative signaling pathways used by these receptors. Here we report that PAR1 and PAR2 couple to overlapping and distinct sets of G proteins to regulate receptor-specific signaling pathways involved in cell migration. In functionally PAR-null COS-7 cells, ectopically expressed PAR1 and PAR2 both form stable complexes with G?q, G?11, G?14, G?12, and G?13. It is surprising that PAR1 but not PAR2 coupled to G?o, G?i1, and G?i2. Consistent with these observations, PAR1 and PAR2 stimulation of inositol phosphate production and RhoA activation was blocked by specific inhibitors of Gq/11 and G12/13 signaling, respectively. Both receptors stimulated extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, but only PAR1 inhibited adenylyl cyclase activity, and pertussis toxin blocked PAR1 effects on both adenylyl cyclase and ERK1/2 signaling. Neu7 astrocytes express native PAR1 and PAR2 receptors that activate inositol phosphate, RhoA, and ERK1/2 signaling. However, only PAR1 inhibited adenylyl cyclase activity. PAR1 and PAR2 also stimulate Neu7 cell migration. PAR1 effects on ERK1/2 phosphorylation and cell migration were blocked both by pertussis toxin and by the mitogen-activated protein kinase kinase/ERK inhibitor [1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126)], whereas PAR2 effects were only blocked by U0126. These studies demonstrate that PAR1 and PAR2 physically and functionally link to overlapping and distinct profiles of G proteins to differentially regulate downstream signaling pathways and cell physiology.

McCoy, Kelly L.; Traynelis, Stephen F.

2010-01-01

221

Drosophila PAR1 and 14-3-3 Inhibit Bazooka\\/PAR3 to Establish Complementary Cortical Domains in Polarized Cells  

Microsoft Academic Search

PAR-1 kinases are required for polarity in diverse cell types, such as epithelial cells, where they localize laterally. PAR-1 activity is believed to be transduced by binding of 14-3-3 proteins to its phosphorylated substrates, but the relevant targets are unknown. We show that PAR-1 phosphorylates Bazooka\\/PAR-3 on two conserved serines to generate 14-3-3 binding sites. This inhibits formation of the

Richard Benton; Daniel St Johnston

2003-01-01

222

Platelet protease-activated receptor (PAR)4, but not PAR1, associated with neutral sphingomyelinase responsible for thrombin-stimulated ceramide-NF-?B signaling in human platelets  

PubMed Central

Thrombin activates platelets mainly through protease-activated receptor (PAR)1 and PAR4. However, downstream platelet signaling between PAR1 and PAR4 is not yet well understood. This study investigated the relationship between nSMase/ceramide and the NF-?B signaling pathway in PARs-mediated human platelet activation. The LC-MS/MS, aggregometry, flow cytometry, immunoprecipitation, and mesenteric microvessels of mice were used in this study. Human platelets stimulated by thrombin, 3-OMS (a neutral sphingomyelinase [nSMase] inhibitor) and Bay11-7082 (an NF-?B inhibitor) significantly inhibited platelet activation such as P-selectin expression. Thrombin also activated I?B kinase (IKK)? and I?B? phosphorylation; such phosphorylation was inhibited by 3-OMS and SB203580 (a p38 MAPK inhibitor). Moreover, 3-OMS abolished platelet aggregation, IKK?, and p38 MAPK phosphorylation stimulated by PAR4-AP (a PAR4 agonist) but not by PAR1-AP (a PAR1 agonist). Immunoprecipitation revealed that nSMase was directly associated with PAR4 but not PAR1 in resting platelets. In human platelets, C24:0-ceramide is the predominant form of ceramides in the LC/MS-MS assay; C24:0-ceramide increases after stimulation by thrombin or PAR4-AP, but not after stimulation by PAR1-AP. We also found that C2-ceramide (a cell-permeable ceramide analog) activated p38 MAPK and IKK? phosphorylation in platelets and markedly shortened the occlusion time of platelet plug formation in vivo. This study demonstrated that thrombin activated nSMase by binding to PAR4, but not to PAR1, to increase the C24:0-ceramide level, followed by the activation of p38 MAPK-NF-?B signaling. Our results showed a novel physiological significance of PAR4-nSMase/ceramide-p38 MAPK-NF-?B cascade in platelet activation.

Chen, Wei-Fan; Lee, Jie-Jen; Chang, Chao-Chien; Lin, Kuan-Hong; Wang, Shwu-Huey; Sheu, Joen-Rong

2013-01-01

223

Platelet protease-activated receptor (PAR)4, but not PAR1, associated with neutral sphingomyelinase responsible for thrombin-stimulated ceramide-NF-?B signaling in human platelets.  

PubMed

Thrombin activates platelets mainly through protease-activated receptor (PAR)1 and PAR4. However, downstream platelet signaling between PAR1 and PAR4 is not yet well understood. This study investigated the relationship between nSMase/ceramide and the NF-?B signaling pathway in PARs-mediated human platelet activation. The LC-MS/MS, aggregometry, flow cytometry, immunoprecipitation, and mesenteric microvessels of mice were used in this study. Human platelets stimulated by thrombin, 3-OMS (a neutral sphingomyelinase [nSMase] inhibitor) and Bay11-7082 (an NF-?B inhibitor) significantly inhibited platelet activation such as P-selectin expression. Thrombin also activated I?B kinase (IKK)? and I?B? phosphorylation; such phosphorylation was inhibited by 3-OMS and SB203580 (a p38 MAPK inhibitor). Moreover, 3-OMS abolished platelet aggregation, IKK?, and p38 MAPK phosphorylation stimulated by PAR4-AP (a PAR4 agonist) but not by PAR1-AP (a PAR1 agonist). Immunoprecipitation revealed that nSMase was directly associated with PAR4 but not PAR1 in resting platelets. In human platelets, C24:0-ceramide is the predominant form of ceramides in the LC/MS-MS assay; C24:0-ceramide increases after stimulation by thrombin or PAR4-AP, but not after stimulation by PAR1-AP. We also found that C2-ceramide (a cell-permeable ceramide analog) activated p38 MAPK and IKK? phosphorylation in platelets and markedly shortened the occlusion time of platelet plug formation in vivo. This study demonstrated that thrombin activated nSMase by binding to PAR4, but not to PAR1, to increase the C24:0-ceramide level, followed by the activation of p38 MAPK-NF-?B signaling. Our results showed a novel physiological significance of PAR4-nSMase/ceramide-p38 MAPK-NF-?B cascade in platelet activation. PMID:23065519

Chen, Wei-Fan; Lee, Jie-Jen; Chang, Chao-Chien; Lin, Kuan-Hong; Wang, Shwu-Huey; Sheu, Joen-Rong

2012-10-12

224

Par Pond vegetation status Summer 1995 -- June survey descriptive summary  

SciTech Connect

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments have been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned.

Mackey, H.E. Jr.; Riley, R.S.

1995-06-01

225

Ovarian function in ewes made hypogonadal with GnRH antagonist and stimulated with FSH in the presence or absence of low amplitude LH pulses  

Microsoft Academic Search

This study examined the eVect of LH pulses, of similar amplitude and frequency to those found in the luteal phase, on the pattern of hormone secretion and follicle develop- ment in GnRH antagonist-suppressed ewes stimulated with exogenous FSH. This experiment was conducted on ewes with ovarian autotransplants in a continuous study. Follicle development was suppressed in 18 ewes by 3

B K Campbell; H Dobson; R J Scaramuzzi

1998-01-01

226

Serum anti-M?llerian hormone is a better predictor of ovarian response than FSH and age in IVF patients with endometriosis  

PubMed Central

Objective To evaluate the ability of serum anti-Müllerian hormone (AMH), FSH, and age to clinically predict ovarian response to controlled ovarian hyperstimulation (COH) in IVF patients with endometriosis. Methods We evaluated 91 COH cycles, including 43 cycles with endometriosis (group I) and 48 cycles with male factor infertility (group II) from January to December, 2010. Patients were classified into study groups based on their surgical history of endometriosis-group Ia (without surgical history, n=16), group Ib (with a surgical history, n=27). Results The mean age was not significantly different between group I and group II. However, AMH and FSH were significantly different between group I and group II (1.9±1.9 ng/mL vs. 4.1±2.9 ng/mL, p<0.01; 13.1±7.2 mIU/mL vs. 8.6±3.3 mIU/mL, p<0.01). Furthermore, the number of retrieved oocytes and the number of matured oocytes were significantly lower in group I than in group II. In group II, AMH and FSH as well as age were significant predictors of retrieved oocytes on univariate analysis. Only the serum AMH level was a significant predictor of poor ovarian response in women with endometriosis. Conclusion Serum AMH may be a better predictor of the ovarian response of COH in patients with endometriosis than basal FSH or age. AMH level can be considered a useful clinical predictor of poor ovarian response in endometriosis patients.

Yoo, Ji Hee; Cha, Sun Hwa; Park, Chan Woo; Kim, Jin Young; Yang, Kwang Moon; Song, In Ok; Koong, Mi Kyoung; Kang, Inn Soo

2011-01-01

227

The Adapter Protein APPL1 Links FSH Receptor to Inositol 1,4,5-Trisphosphate Production and Is Implicated in Intracellular Ca2+ Mobilization  

PubMed Central

FSH binds to its receptor (FSHR) on target cells in the ovary and testis, to regulate oogenesis and spermatogenesis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and inositol 1,4,5-trisphosphate–mediated calcium signaling pathways. The adapter protein APPL1 (Adapter protein containing Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif), which has been linked to an assortment of other signaling proteins, was previously identified as an interacting protein with FSHR. Thus, alanine substitution mutations in the first intracellular loop of FSHR were generated to determine which residues are essential for FSHR-APPL1 interaction. Three amino acids were essential; when any one of them was altered, APPL1 association with FSHR mutants was abrogated. Two of the mutants (L377A and F382A) that displayed poor cell-surface expression were not studied further. Substitution of FSHR-K376A did not affect FSH binding or agonist-stimulated cAMP production in either transiently transfected human embryonic kidney cells or virally transduced human granulosa cells (KGN). In the KGN line, as well as primary cultures of rat granulosa cells transduced with wild type or mutant receptor, FSH-mediated progesterone or estradiol production was not affected by the mutation. However, in human embryonic kidney cells inositol 1,4,5-trisphosphate production was curtailed and KGN cells transduced with FSHR-K376A evidenced reduced Ca2+ mobilization from intracellular stores after FSH treatment.

Thomas, Richard M.; Nechamen, Cheryl A.; Mazurkiewicz, Joseph E.; Ulloa-Aguirre, Alfredo

2011-01-01

228

The adapter protein APPL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellular Ca(2+) mobilization.  

PubMed

FSH binds to its receptor (FSHR) on target cells in the ovary and testis, to regulate oogenesis and spermatogenesis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and inositol 1,4,5-trisphosphate-mediated calcium signaling pathways. The adapter protein APPL1 (Adapter protein containing Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif), which has been linked to an assortment of other signaling proteins, was previously identified as an interacting protein with FSHR. Thus, alanine substitution mutations in the first intracellular loop of FSHR were generated to determine which residues are essential for FSHR-APPL1 interaction. Three amino acids were essential; when any one of them was altered, APPL1 association with FSHR mutants was abrogated. Two of the mutants (L377A and F382A) that displayed poor cell-surface expression were not studied further. Substitution of FSHR-K376A did not affect FSH binding or agonist-stimulated cAMP production in either transiently transfected human embryonic kidney cells or virally transduced human granulosa cells (KGN). In the KGN line, as well as primary cultures of rat granulosa cells transduced with wild type or mutant receptor, FSH-mediated progesterone or estradiol production was not affected by the mutation. However, in human embryonic kidney cells inositol 1,4,5-trisphosphate production was curtailed and KGN cells transduced with FSHR-K376A evidenced reduced Ca(2+) mobilization from intracellular stores after FSH treatment. PMID:21285318

Thomas, Richard M; Nechamen, Cheryl A; Mazurkiewicz, Joseph E; Ulloa-Aguirre, Alfredo; Dias, James A

2011-02-01

229

An association study between the genetic polymorphisms within GnRHI, LH? and FSH? genes and central precocious puberty in Chinese girls  

Microsoft Academic Search

Objectives: Gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are three hypothalamic–pituitary–gonadal axis expressing hormones. They play critical roles in the onset of puberty. Here we report the relationship between the three hormones and Central Precocious Puberty (CPP) in Chinese Han girls. Methods: We analyzed the single nucleotide polymorphisms (SNPs) of 5?-flanking regions of these genes by DNA

Ying Zhao; Ting Chen; Yuxun Zhou; Kai Li; Junhua Xiao

2010-01-01

230

Plasma concentrations of ir-inhibin, inhibin A, inhibin pro-?C, FSH, and estradiol-17? during estrous cycle in mares and their relationship with follicular growth  

Microsoft Academic Search

The relationship among plasma levels of immunoreactive (ir)-inhibin, inhibin A, inhibin pro-?C, FSH, estradiol-17? and follicular\\u000a growth were investigated during the normal estrous cycle in mares. Seven mares were used for two successive normal estrous\\u000a cycles. Follicular diameters and ovulation were obtained by transrectal ultrasonography, and blood samples were collected\\u000a daily by jugular venipuncture for hormonal assay. The results showed

Mohamed S. Medan; Yasuo Nambo; Natsuko Nagamine; Hiromi Shinbo; Gen Watanabe; Nigel Groome; Kazuyoshi Taya

2004-01-01

231

Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu  

PubMed Central

BACKGROUND In humans, as well as in other higher primates, the infantile testis is exposed to an adult-like hormonal milieu, but spermatogenesis is not initiated at this stage of primate development. In the present study, we examined the molecular basis of this intriguing infertile state of the primate testis. METHODS The integrity of androgen receptor (AR) and FSH receptor (FSHR) signaling pathways in primary cultures of Sertoli cells (Scs) harvested from azoospermic infant and spermatogenic pubertal monkey testes were investigated under identical in vitro hormonal conditions. In order to synchronously harvest Scs from early pubertal testis, the activation of testicular puberty was timed experimentally by prematurely initiating gonadotrophin secretion in juvenile animals with an intermittent infusion of gonadotrophin-releasing hormone. RESULTS While qRT–PCR demonstrated that AR and FSHR mRNA expression in Scs from infant and pubertal testes were comparable, androgen-binding and FSH-mediated cAMP production by infant Scs was extremely low. Compromised AR and FSHR signaling in infant Scs was further supported by the finding that testosterone (T) and FSH failed to augment the expression of the T responsive gene, claudin 11, and the FSH responsive genes, inhibin-?B, stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF) in Scs harvested at this stage of development. CONCLUSION These results indicate that compromised AR and FSHR signaling pathways in Scs underlie the inability of the infant primate testis to respond to an endogenous hormonal milieu that later in development, at the time puberty, stimulates the initiation of spermatogenesis. This finding may have relevance to some forms of idiopathic infertility in men.

Majumdar, Subeer S.; Sarda, Kanchan; Bhattacharya, Indrashis; Plant, Tony M.

2012-01-01

232

Simultaneous evaluation of basal FSH and oestradiol response to GnRH analogue (F-G-test) allows effective drug regimen selection for IVF  

Microsoft Academic Search

To determine whether preliminary assessment of ovarian reserve by simultaneous evaluation of basal follicle- stimulating hormone (FSH) and oestradiol response to gonadotrophin releasing hormone (GnRH) analogue (F-G- test) can be used to tailor individually the drug regimen for ovarian stimulation, the in-vitro fertilization (IVF) results of 238 patients were retrospectively analysed. Sixty-two women with abnormal response to the test (?E2

D. M. Ranieri; P. Phophong; I. Khadum; F. Meo; C. Davis; P. Serhal

2001-01-01

233

Expression of Bone Morphogenetic Protein Receptor (BMPR) during Perinatal Ovary Development and Primordial Follicle Formation in the Hamster: Possible Regulation by FSH  

PubMed Central

To understand whether bone morphogenetic protein plays any role in the formation of primordial follicles in the hamster, we examined the temporal and spatial expression of bone morphogenetic protein receptor (BMPR) mRNA and protein in embryonic (E) 13 through postnatal day (P) 15 ovarian cells and a possible regulation by FSH during the formation of primordial follicles on P8. BMPRIA and BMPRII mRNA levels were significantly higher than that of BMPR1B throughout ovary development. BMPRIA and BMPRII mRNA levels increased significantly on E14 and declined by P5 through P6. Whereas BMPRII mRNA increased again by P7, BMPRIA mRNA levels increased through P8 concurrent with primordial follicle formation. In contrast, BMPRIB mRNA levels increased greater than 10-fold on P7-9, with a further 3-fold increase by P10. BMPR proteins were low in the somatic cells and oocytes on E13 but increased progressively during postnatal development. BMPR expression in somatic cells increased markedly on P8. Whereas BMPRII expression declined by P10 and remained steady thereafter, BMPRIA protein expression fluctuated until P15 when it became low and steady. Overall, BMPRIB immunoreactivity also declined by P10 and then remained low in the interstitial cells through P15. FSH antiserum treatment on E12 significantly attenuated receptor mRNA and protein levels by P8, but equine chorionic gonadotropin replacement on P1 reversed the inhibition. Furthermore, FSH in vitro up-regulated BMPR levels in P4 ovaries. This unique pattern of BMPR expression in the oocytes and somatic cells during perinatal ovary development suggests that BMP may play a regulatory role in primordial follicle formation. Furthermore, FSH may regulate BMP action by modulating the expression of its receptors.

Wang, Cheng; Roy, Shyamal K.

2009-01-01

234

Luteal-phase inhibin A and follicular-phase inhibin B levels are not characteristic of patients with an elevated LH-to-FSH ratio  

Microsoft Academic Search

Purpose: To test whether serum inhibin levels are related to differences in gonadotropin concentrations between patients with an elevated LH-to-FSH ratio (ELF patients) and controls.\\u000a Methods: 32 ELF patients were matched with controls by age, body mass index (BMI), and cycle length.\\u000a Results: No statistically significant difference was found in follicular-phase inhibin B levels or midluteal inhibin A levels between

Erik E. Hauzman; Péter Fancsovits; Ákos Murber; Thomas Rabe; Thomas Strowitzki; Zoltán Papp; János Urbancsek

2006-01-01

235

Co-existence of gonadotrophins (FSH, LH) and thyrotrophin (TSH) in single anterior pituitary cells of the musk shrew, Suncus murinus  

Microsoft Academic Search

According to recent immunocytochemical studies of anterior pituitary cells, it is obvious that the “one cell-one hormone” theory must be modified. Many pituitary morphologists have demonstrated that there are some cells that contain two hormones. In this study, we demonstrate by means of immuno-electronmicroscopy the co-existence of gonadotrophins (FSH and LH) and thyrotrophin (TSH) in the same anterior pituitary cells

Naomi Hirano; Masataka Shiino

1993-01-01

236

Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial  

Microsoft Academic Search

BACKGROUND: This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients with normal glucose tolerance. METHODS AND RESULTS: Thirty-two patients were randomized to metformin (n 16) and placebo (n 16) groups. Hormonal assessment, a 75 g oral glucose tolerance test

Hakan Yaralõ; Aygul Demirol; Hulusi B. Zeynelog; Nuray Yig; Orhan Bukulmez; Zehra Koray

2002-01-01

237

A truncated, activin-induced Smad3 isoform acts as a transcriptional repressor of FSH? expression in mouse pituitary  

PubMed Central

The receptor-regulated protein Smad3 is key player in the signaling cascade stimulated by the binding of activin to its cell surface receptor. Upon phosphorylation, Smad3 forms a heterocomplex with Smad2 and Smad4, translocates to the nucleus and acts as a transcriptional co-activator. We have identified a unique isoform of Smad3 that is expressed in mature pituitary gonadotropes. 5' RACE revealed that this truncated Smad3 isoform is transcribed from an ATG site within exon 4 and consists of 7 exons encoding half of the linker region and the MH2 region. In pituitary cells, the truncated Smad3 isoform was phosphorylated upon activin treatment, in a manner that was temporally distinct from the phosphorylation of full-length Smad3. Activin-induced phosphorylation of Smad3 and the truncated Smad3 isoform was blocked by both follistatin and siRNA-mediated knockdown of Smad3. The truncated Smad3 isoform antagonized Smad3-mediated, activin-responsive promoter activity. We propose that the pituitary gonadotrope contains an ultra-short, activin-responsive feedback loop utilizing two different isoforms of Smad3, one which acts as an agonist (Smad3) and another that acts as an intracrine antagonist (truncated Smad3 isoform) to regulate FSH? production.

Kim, So-Youn; Zhu, Jie; Woodruff, Teresa K.

2011-01-01

238

FSH modulates the expression of inhibin-alpha and the secretion of inhibins via orphan nuclear receptor NUR77 in ovarian granulosa cells.  

PubMed

It has been previously reported that follicle-stimulating hormone (FSH) regulates the expression of inhibin-alpha in human granulosa cells, but the precise molecular pathway remains unknown. In the present study, we investigated the role of the orphan nuclear receptor, NUR77, in both the transcriptional regulation of the inhibin ?-subunit gene and the secretion of inhibins. Our results showed that in a human granulosa cell tumor-derived cell line (KGN) and in human granulosa-lutein cells (hGL), FSH induced the expression of NUR77 and inhibin-alpha, although inhibin-alpha expression did not increased following FSH treatment if NUR77 was knocked down. Furthermore, simply overexpressing or reducing NUR77 levels affected inhibin-alpha expression, while NUR77 overexpression improved the secretion of inhibin A and B from human granulosa cells. In addition, chromatin immunoprecipitation-PCR, avidin-biotin-conjugated DNA precipitation, and luciferase reporter assays confirmed that NUR77 directly regulated the transcription of the inhibin-alpha gene through the specific NGFI-B response element located within its promoter. In the ovarian granulosa cells of the Nur77 knockout mice, the mRNA levels of inhibin-alpha were decreased relative to wild-type mice. These data indicate a role of NUR77 in the regulation of inhibin-alpha in ovarian granulosa cells. Mol. Reprod. Dev. 80: 734-743, 2013. © 2013 Wiley Periodicals, Inc. PMID:23836374

He, Qin-Yuan; Ding, Li-Jun; Sun, Hai-Xiang; Yu, Bin; Dai, An-Yi; Zhang, Ning-Yuan; Wang, Bin; Yan, Gui-Jun; Xu, Pei-Zhen; Hu, Ya-Li

2013-07-19

239

Par Pond vegetation status Summer 1995 -- October survey descriptive summary  

SciTech Connect

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

Mackey, H.E. Jr.; Riley, R.S.

1995-11-01

240

Par Pond vegetation status Summer 1995 -- September survey descriptive summary  

SciTech Connect

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

Mackey, H.E. Jr.; Riley, R.S.

1995-09-01

241

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.  

PubMed

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells. PMID:20826780

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-09-08

242

suPAR as a prognostic biomarker in sepsis  

PubMed Central

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis.

2012-01-01

243

Pars plana incisions of four patients: histopathology and electron microscopy.  

PubMed Central

The pathology of pars plana incisions of four patients is described: three with light microscopy and one with light and electron microscopy. Two eyes were removed because of choroidal melanoma, immediately and 8 days after vitrectomy and transvitreous retinal biopsy. Considerable disruption of tissues surrounding the pars plana incisions was observed. Vitreous was incarcerated in the wounds, which healed with granulation tissue. One eye was examined 4 months after vitrectomy for diabetic retinopathy and a failed pars plana filtering operation. It contained fibrovascular ingrowth from all the incisions, infiltrating the vitreous base with granulation tissue and causing vitreous haemorrhage and retinal detachment. One eye was removed 1 year after vitrectomy for anterior hyaloidal fibrovascular proliferation and early phthisis. The wound had fibrous ingrowth histologically and evidence of active fibroplasia. Images

Koch, F H; Kreiger, A E; Spitznas, M; Glasgow, B; Foos, R Y; Yoshizumi, M O

1995-01-01

244

Functional and ultrastructural characteristics of two types of rat granulosa cell cultured in the presence of FSH or transforming growth factor alpha (TGF-alpha).  

PubMed

Granulosa cells were isolated from 15-day-old, 25-day-old or PMSG-primed rats and were separated by Percoll gradient (20 to 60%) into five fractions. The cells in fraction 2 were mostly small cells (6.96-9.57 microns) and fractions 3 and 4 had a relatively high population of large cells (10.96-13.05 microns) which were sorted to collect a pure population of large cells. Aliquots of small or large cells were cultured separately in serum-free defined DMEM/F-12 medium containing 50 ng FSH ml-1, or 10 ng transforming growth factor alpha (TGF-alpha) ml-1 for 3 days. In PMSG-primed rats, the large cells produced 3.2-fold more progesterone than did small cells (with FSH/TGF alpha: 255 +/- 35.0 versus 77.32 +/- 14.5 x 10(-6) ng, day 1). Large and small cells from 25-day-old rats produced similar amounts of progesterone (FSH/TGF alpha: 65.68 +/- 9.6 versus 78.25 +/- 12.3 x 10(-6) ng, day 1). In 15-day-old rats, large and small cells produced very low concentrations of progesterone (FSH/TGF alpha: 4.69 +/- 1.2 versus 2.66 +/- 1.0 x 10(-6) ng, day 1). Large cells from PMSG-primed rats had characteristics of steroidogenic cells, i.e. smooth endoplasmic reticulum and well-developed mitochondria with tubular cristae compared with small cells, whereas small and large cells from 25- and 15-day-old rats contained the regularly occurring organelles without the endoplasmic reticulum of the smooth variety and mitochondria with lamellar cristae. This study shows that the heterogeneity of granulosa cells is related to size, metabolic response to FSH, TGF-alpha or to both factors and morphological features, all of which may be associated with the transition from preantral to preovulatory stages of follicle differentiation. PMID:8410800

Sanbuissho, A; Lee, G Y; Anderson, E

1993-07-01

245

Posterior high-frequency capsulotomy via pars plana  

Microsoft Academic Search

Summary  \\u000a In special forms of complicated secondary cataract, especially after a cataract operation in eyes with proliferative disease\\u000a and after a cataract operation associated with pars plana vitrectomy and silicone oil instillation, surgical capsulotomy must\\u000a be performed.\\u000a \\u000a \\u000a \\u000a \\u000a Methods: We developed a new surgical technique for posterior capsulorhexis via pars plana by using the high-frequency capsulotomy\\u000a method developed by Klti. We

Petra Meier; K. Pittasch

1998-01-01

246

Subcellular localization and characterization of the ParAB system from Corynebacterium glutamicum.  

PubMed

Faithful segregation of chromosomes and plasmids is a vital prerequisite to produce viable and genetically identical progeny. Bacteria use a specialized segregation system composed of the partitioning proteins ParA and ParB to segregate certain plasmids. Strikingly, homologues of ParA and ParB are found to be encoded in many chromosomes. Although mutations in the chromosomal Par system have effects on segregation efficiency, the exact mechanism by which the chromosomes are segregated into the daughter cells is not fully understood. We describe the polar localization of the ParB origin nucleoprotein complex in the actinomycete Corynebacterium glutamicum. ParB and the origin of replication were found to be stably localized to the cell poles. After replication, the origins move toward the opposite pole. Purified ParB was able to bind to the parS consensus sequence in vitro. C. glutamicum possesses two ParA-like partitioning ATPase proteins. Both proteins interact with ParB but show a slightly different subcellular localization and phenotype. While ParA might be part of a conventional partitioning system, PldP seems to play a role in division site selection. PMID:20435732

Donovan, Catriona; Schwaiger, Astrid; Krämer, Reinhard; Bramkamp, Marc

2010-04-30

247

Subcellular Localization and Characterization of the ParAB System from Corynebacterium glutamicum?  

PubMed Central

Faithful segregation of chromosomes and plasmids is a vital prerequisite to produce viable and genetically identical progeny. Bacteria use a specialized segregation system composed of the partitioning proteins ParA and ParB to segregate certain plasmids. Strikingly, homologues of ParA and ParB are found to be encoded in many chromosomes. Although mutations in the chromosomal Par system have effects on segregation efficiency, the exact mechanism by which the chromosomes are segregated into the daughter cells is not fully understood. We describe the polar localization of the ParB origin nucleoprotein complex in the actinomycete Corynebacterium glutamicum. ParB and the origin of replication were found to be stably localized to the cell poles. After replication, the origins move toward the opposite pole. Purified ParB was able to bind to the parS consensus sequence in vitro. C. glutamicum possesses two ParA-like partitioning ATPase proteins. Both proteins interact with ParB but show a slightly different subcellular localization and phenotype. While ParA might be part of a conventional partitioning system, PldP seems to play a role in division site selection.

Donovan, Catriona; Schwaiger, Astrid; Kramer, Reinhard; Bramkamp, Marc

2010-01-01

248

Microtubules induce self-organization of polarized PAR domains in C. elegans zygotes  

PubMed Central

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1, 2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1, 2, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3/aPKC complex to leave the cortex. Our findings illustrate how microtubules, independent of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.

Motegi, Fumio; Zonies, Seth; Hao, Yingsong; Cuenca, Adrian A.; Griffin, Erik; Seydoux, Geraldine

2011-01-01

249

Secondary pupillary membranes treated by the pars plana/pars plicata approach: long-term results of 108 cases.  

PubMed Central

One hundred and eight pupillary membranes treated with the vitrophage through a pars plicata or pars plana approach were evaluated for long-term results. The average follow-up was 3.86 years, with a range of 1 to 7 years. No major operative complications were encountered. Anatomical success was achieved in all cases. Vision improved in 67.5% of eyes. In 4 cases (3.7%) postoperative visual acuity was worse, because of glaucoma secondary to previous blunt ocular trauma. Six cases showed delay rhegmatogenous retinal detachment postoperatively. These could not be attributed to the surgical procedure per se.

Juarez, C P; Peyman, G A; Raichand, M; Goldberg, M F

1981-01-01

250

Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.  

PubMed

Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in patients with breast cancer, and Par-4 is downregulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence. PMID:23770012

Alvarez, James V; Pan, Tien-Chi; Ruth, Jason; Feng, Yi; Zhou, Alice; Pant, Dhruv; Grimley, Joshua S; Wandless, Thomas J; Demichele, Angela; Chodosh, Lewis A

2013-06-13

251

RevPAR determinants of individual hotels : Evidences from Milan  

Microsoft Academic Search

Purpose – This paper aims to identify revenue per available room (RevPAR) determinants of individual firms located in a destination. Independent variables are to be sought along “what” and “where” dimensions. Design\\/methodology\\/approach – The sample is composed of 72 individual firms, operating in the 3-5 star range and data have been collected from financial statements and questionnaires. Findings – The

Ruggero Sainaghi

2011-01-01

252

Pars plana vitrectomy in the management of ghost cell glaucoma  

Microsoft Academic Search

In this report we describe, herewith, 5 cases of ghost cell glaucoma that followed spontaneous vitreous hemorrhage complicating branch retinal vein occlusion in a phakic eye (one case), and traumatic vitreous hemorrhage (4 cases). Because intraocular pressure was uncontrolled, pars plana vitrectomy was performed to remove the reservoir of ghost cells. Vitrectomy resulted in successful control of intraocular pressure without

Ahmed M. Abu

1995-01-01

253

Management of persistent hyperplastic primary vitreous by pars plana vitrectomy  

Microsoft Academic Search

Two children with persistent hyperplastic primary vitreous (PHPV) underwent vitrectomy and lensectomy via the pars plana to remove the fibrovascular stalk. Postoperatively the eyes were quiet, only a slight vitreous haze obscured the fundus view in the immediate postoperative period, and the stumps of the stalks retracted. Early surgical treatment of PHPV may prevent later serious complications.

G A Peyman; D R Sanders; K C Nagpal

1976-01-01

254

The development of pars plana vitrectomy: a personal account  

Microsoft Academic Search

Vitreous surgery, after 25 years, has become routine. Many have been involved in its development. The early problems are mostly forgotten, the excitement of having overcome another barrier has become rare. Nevertheless, pars plana vitreous surgery has kept a very special appeal. Surgeons are fascinated by the challenge and variation of each single operation, in contrast to the routine of

Robert Macherner; R. Machemer

1995-01-01

255

Results of pars plana vitrectomy in penetrating ocular trauma  

Microsoft Academic Search

Thirty-four severely injured eyes were operated with pars plana vitrectomy. The nine cases with involvement exclusively of the anterior segment alone were operated with success in all cases. However, the injuries of the posterior segment still reflect significant problems in that only 50 percent obtained successful visual results. This reflects, in great part, the degree of severity of the initial

Stephen J. Ryan

1978-01-01

256

PARS PLANA VITRECTOMY WITHOUT SCLERAL BUCKLE FOR RHEGMATOGENOUS RETINAL DETACHMENT  

Microsoft Academic Search

Purpose To report the anatomical and visual results of pars plana vitrectomy (PPV) with- out scleral buckling which repairs rhegmatogenous retinal detachment (RRD). Methods The authors retrospectively reviewed 41 patients with primary RRD who under- went PPV without scleral buckling repair it between December 1997 and November 2001. Thirty-four patients (34 eyes) followed at least 4 months treatment and were

Direk Patikulsila; Nimitr Ittipunkul; Anchalee Patikulsila

2003-01-01

257

The Pars Triangularis in Dyslexia and ADHD: A Comprehensive Approach  

ERIC Educational Resources Information Center

|Limited research has been conducted on the structure of the pars triangularis (PT) in dyslexia despite functional neuroimaging research finding it may play a role in phonological processing. Furthermore, research to date has not examined PT size in ADHD even though the right inferior frontal region has been implicated in the disorder. Hence, one…

Kibby, Michelle Y.; Kroese, Judith M.; Krebbs, Hillery; Hill, Crystal E.; Hynd, George W.

2009-01-01

258

[Prevention of malignant glaucoma: pars-plana vitrectomy? (author's transl)].  

PubMed

Prevention of malignant glaucoma: in first case report lens extraction and trabeculectomy was followed by a malignant glaucoma; in the second case report pars-plana vitrectomy and trabeculectomy was successful. The role of a vitreous posterior blockage is discussed. PMID:153358

Offret, H; Saraux, H; Limon, S; Langlois, J L

1978-10-01

259

Photoémission de Csl induite par une impulsion laser intense femtoseconde  

NASA Astrophysics Data System (ADS)

Nous avons mesuré pour la première fois les spectres de photoélectrons émis par un cristal isolant à large bande interdite, Csl, avec une dynamique de 10^6 coups/s, excité par la source laser haute cadence du C.E.L.I.A (800 nm, 40 fs, 1 kHz, 1 TW). L'émission d'électrons jusqu'à des énergies de quelques dizaines d'électrons-volts a été observée pour des impulsions d'éclairement compris entre 0.5 et 3 TW/cm^2, relativement faible donc par comparaison aux éclairements utilisés pour accélérer les électrons d'un atome aux mêmes énergies. Ces spectres contiennent tous, en particulier, deux bandes dans le domaine des basses énergies d'électrons (<5 eV), également observées lors d'études précédentes. Les électrons les plus énergétiques forment un plateau intense légèrement structuré et limité par une coupure exponentielle. Pour des impulsions de 3 TW/cm^2 cette coupure est située à 27 eV. L'insuffisance du mécanisme électron-photon-phonon, considéré jusqu'à présent comme le principal processus d'échauffement des électrons dans les solides en interaction non destructrice avec un champ laser, nous a poussé à proposer un mécanisme alternatif. Ce modèle met en évidence les transitions directes multiphotoniques dans la bande de conduction du solide qui sont incontournables du fait de sa structure électronique multi-branches

Belsky, A.; Vasil'Ev, A.; Yatsenko, B.; Bachau, H.; Martin, P.; Geoffroy, G.; Guizard, S.

2003-06-01

260

Estimating PAR absorbed by vegetation from bidirectional reflectance measurements  

Microsoft Academic Search

Satellite remote sensing allows estimation, at a global scale, of the photosynthetically active radiation absorbed (APAR) by the vegetation. Current estimates are based on retrieving the fraction (fAPAR) of PAR absorbed by the canopy from spectral vegetation indices (SVI) derived from combinations of spectral reflectance measurements. We show that currently used SVI are strongly affected by the soil reflectance as

Jean-Louis Roujean; François-Marie Breon

1995-01-01

261

Par for the palette : INSECTS AND ARACHNIDS AS ART MEDIA  

Microsoft Academic Search

Par for the palette : Insects and Arachnids as Art Media The ubiquitous insects have been a cultural inspiration internationally, frequently used as symbols and meta- phors for human existence and experience. Their boundless forms and behaviors make them logical candidates for artistic expression, providing artists with novel media to translate the mood, message and effect of a work. I

Barrett Anthony KLEIN

262

Early pars plana vitrectomy in chronic endophthalmitis of toxocariasis  

Microsoft Academic Search

Pars plana vitrectomy was performed in 12 eyes affected with chronic endophthalmitis in patients 4–38 years of age. In 3 cases the indication was severe vitreitis and the surgical response was excellent. The other 9 eyes were operated upon during the cicatricial and sequelae stages, and the results were better the earlier surgery was performed. Lensectomy was associated in 5

Alvaro Rodríguez

1986-01-01

263

Tumeur du canal anal révélée par une fistule rectovaginale  

Microsoft Academic Search

\\u000a Résumé  La fistule rectovaginale (FRV) est une pathologie rare, une cause néoplasique en est exceptionnellement responsable. Nous\\u000a rapportons un cas de tumeur avancée du canal anal, révélée par une grosse FRV associée à de multiples fistules périnéales\\u000a externes.

M. Tamzaourte; I. Errabih; M. Fadlouallah; S. Tahri; H. Elkoundi; M. Lahmiri; H. Krami; H. Ouazzani

2010-01-01

264

Tissue Factor and PAR2 Signaling in the Tumor Microenvironment  

PubMed Central

Diverse oncogenic transformations result in the constitutive expression of tissue factor (TF) in cancer cells. The local and systemic activation of the coagulation cascade has long been a recognized hallmark for aggressive cancer, but genetic mouse models and new experimental therapeutics have only recently demonstrated crucial roles for TF initiated cell signaling in the pathogenesis of cancer. On tumor cells, the TF-VIIa binary complex mediates activation of protease activated receptor (PAR) 2 and thereby shapes the tumor microenvironment by inducing an array of pro-angiogenic and immune modulating cytokines, chemokines and growth factors. PAR2 also uniquely triggers tumor cell migration by G protein-independent pathways through ?-arrestin scaffolding. Metastatic tumor cells utilize additional signaling networks of the coagulation cascade by activating PAR1 through thrombin and/or the ternary TF-VIIa-Xa signaling complex in the vascular and potentially lymphatic system. Selective antagonists of TF-VIIa-PAR2 signaling may be used as anti-angiogenic therapy without increasing the risk of bleeding, whereas coagulation and associated signaling pathways on platelets and other host cells may be targeted for therapeutic benefit in advanced cancer and metastatic disease.

Schaffner, Florence; Ruf, Wolfram

2009-01-01

265

Cell polarity: ParA-logs gather around the Hub.  

PubMed

The chromosomal origin, chemotaxis arrays and flagellum of Vibrio cholerae congregate at the same pole of the cell. How? A recent study identifies a new pole-organizing protein, HubP, that recruits members of the ParA family of spatial regulators of subcellular structures to the pole. PMID:23257194

Kirkpatrick, Clare L; Viollier, Patrick H

2012-12-18

266

Ultrasound biomicroscopy of conventional and sutureless pars plana sclerotomies: a comparative and longitudinal study  

Microsoft Academic Search

PURPOSE: To report the rate of ultrasonically visible vitreous incarceration and longitudinal changes of incarcerated vitreous in pars plana sclerotomies after conventional suturing or sutureless technique using ultrasound biomicroscopy.METHODS: Twenty-five consecutive eyes (25 patients) undergoing primary three-port pars plana vitrectomy participated. The first 16 pars plana vitrectomies were performed with standard conventional sutured sclerotomies, and the following nine pars plana

Alvin K. H Kwok; Clement C. Y Tham; Angela V. P Loo; Dorothy S. P Fan; Dennis S. C Lam

2001-01-01

267

Par1 regulates stability of the posterior determinant Oskar by phosphorylation  

Microsoft Academic Search

Par-1 kinase is critical for polarization of the Drosophila melanogaster oocyte and the one-cell Caenorhabditis elegans embryo. Although Par-1 localizes specifically to the posterior pole in both cells, neither its targets nor its function at the posterior pole have been elucidated. Here we show that Drosophila Par-1 phosphorylates the posterior determinant Oskar (Osk) and demonstrate genetically that Par-1 is required

Veit Riechmann; Gustavo J. Gutierrez; Paolo Filardo; Angel R. Nebreda; Anne Ephrussi

2002-01-01

268

L'offre d'information volontaire par Internet et le gouvernement des entreprises françaises  

Microsoft Academic Search

(VF)Cette recherche analyse le phénomène de la diffusion d’information par Internet en France. En prolongeant les études antérieures sur l’offre volontaire d’information, nous cherchons à savoir comment les facteurs du gouvernement d’entreprise influent sur la communication par voie électronique. Nous examinons également l’impact des caractéristiques des entreprises sur la publication volontaire par Internet. Les résultats montrent que l’offre d’information par

Li LI

2010-01-01

269

Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development  

PubMed Central

Constitutive expression of tissue factor (TF) by cancer cells triggers local activation of the coagulation cascade and promotes breast cancer progression through cell signaling involving protease activated receptor (PAR)2. In human breast cancer, TF and PAR2 are up-regulated and TF cytoplasmic domain phosphorylation is correlated with relapse. Here we show that cancer cell PAR2 signaling promotes angiogenesis independent of PAR2 phosphorylation at the recognized ?-arrestin recruitment site. Similar to PAR2?/? mice, TF cytoplasmic domain–deleted (TF?CT) mice have delayed spontaneous breast cancer development in the polyoma middle T model. Simultaneous deletion of PAR2 in TF?CT mice did not further delay tumor appearance, consistent with overlapping roles of TF and PAR2 in promoting the angiogenic switch in early stages of breast cancer. In advanced carcinomas, tumor-associated macrophages were reduced in TF?CT and TF?CT/PAR2?/? mice, and increased tumor vessel diameters of TF?CT mice were partially reversed by PAR2-deficiency, indicating that the TF cytoplasmic domain has additional roles that are interdependent with PAR2 signaling in regulating host angiogenic responses. These experiments demonstrate a crosstalk of tumor cell TF cytoplasmic domain and PAR2 signaling and provide a possible mechanism for the close correlation between TF phosphorylation and cancer recurrence of TF and PAR2-positive clinical breast cancer.

Schaffner, Florence; Versteeg, Henri H.; Schillert, Anja; Yokota, Naho; Petersen, Lars C.; Mueller, Barbara M.

2010-01-01

270

Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development.  

PubMed

Constitutive expression of tissue factor (TF) by cancer cells triggers local activation of the coagulation cascade and promotes breast cancer progression through cell signaling involving protease activated receptor (PAR)2. In human breast cancer, TF and PAR2 are up-regulated and TF cytoplasmic domain phosphorylation is correlated with relapse. Here we show that cancer cell PAR2 signaling promotes angiogenesis independent of PAR2 phosphorylation at the recognized ?-arrestin recruitment site. Similar to PAR2(-/-) mice, TF cytoplasmic domain-deleted (TF(?CT)) mice have delayed spontaneous breast cancer development in the polyoma middle T model. Simultaneous deletion of PAR2 in TF(?CT) mice did not further delay tumor appearance, consistent with overlapping roles of TF and PAR2 in promoting the angiogenic switch in early stages of breast cancer. In advanced carcinomas, tumor-associated macrophages were reduced in TF(?CT) and TF(?CT)/PAR2(-/-) mice, and increased tumor vessel diameters of TF(?CT) mice were partially reversed by PAR2-deficiency, indicating that the TF cytoplasmic domain has additional roles that are interdependent with PAR2 signaling in regulating host angiogenic responses. These experiments demonstrate a crosstalk of tumor cell TF cytoplasmic domain and PAR2 signaling and provide a possible mechanism for the close correlation between TF phosphorylation and cancer recurrence of TF and PAR2-positive clinical breast cancer. PMID:20861457

Schaffner, Florence; Versteeg, Henri H; Schillert, Anja; Yokota, Naho; Petersen, Lars C; Mueller, Barbara M; Ruf, Wolfram

2010-09-22

271

Clinical outcomes of pars plana capsulotomy with anterior vitrectomy in pediatric cataract surgery  

Microsoft Academic Search

Purpose: The management of the posterior capsule in pediatric cataract surgery remains challenging. The purpose of our study was to evaluate the role and clinical outcomes of primary pars plana capsulotomy and pars plana anterior vitrectomy during pediatric cataract surgery with intraocular lens (IOL) implantation. Methods: Consecutive cases of pars plana capsulotomy and anterior vitrectomy during pediatric cataract surgery were

George Alexandrakis; M. Millicent Peterseim; M. Edward Wilson

2002-01-01

272

par genes in Mycobacterium bovis and Mycobacterium smegmatis are arranged in an operon transcribed from "SigGC" promoters  

PubMed Central

Background The ParA/Soj and ParB/Spo0J proteins, and the cis-acting parS site, participate actively in chromosome segregation and cell cycle progression. Genes homologous to parA and parB, and two putative parS copies, have been identified in the Mycobacterium bovis BCG and Mycobacterium smegmatis chromosomes. As in Mycobacterium tuberculosis, the parA and parB genes in these two non-pathogenic mycobacteria are located near the chromosomal origin of replication. The present work focused on the determination of the transcriptional organisation of the ~6 Kb orf60K-parB region of M. bovis BCG and M. smegmatis by primer extension, transcriptional fusions to the green fluorescence protein (GFP) and quantitative RT-PCR. Results The parAB genes were arranged in an operon. However, we also found promoters upstream of each one of these genes. Seven putative promoter sequences were identified in the orf60K-parB region of M. bovis BCG, whilst four were identified in the homologous region of M. smegmatis, one upstream of each open reading frame (ORF). Real-time PCR assays showed that in M. smegmatis, mRNA-parA and mRNA-parB levels decreased between the exponential and stationary phases. In M. bovis BCG, mRNA-parA levels also decreased between the exponential and stationary phases. However, parB expression was higher than parA expression and remained almost unchanged along the growth curve. Conclusion The majority of the proposed promoter regions had features characteristic of Mycobacterium promoters previously denoted as Group D. The -10 hexamer of a strong E. coli ?70-like promoter, located upstream of gidB of M. bovis BCG, overlapped with a putative parS sequence, suggesting that the transcription from this promoter might be regulated by the binding of ParB to parS.

Casart, Yveth; Gamero, Elida; Rivera-Gutierrez, Sandra; Gonzalez-y-Merchand, Jorge A; Salazar, Leiria

2008-01-01

273

Precise determination of TSH receptor antibody activity in serum containing bovine TSH (bTSH) binding antibody by absorption using denatured bTSH or sheep FSH.  

PubMed

A previous report demonstrated that sera with bovine TSH (bTSH) binding antibody showed abnormally negative TSH receptor antibody (TRAb) activity in the standard TRAb assay method. The corrected TRAb activity calculated by the determination of the nonspecific binding of the labeled bTSH for each test serum [NSB(T)] resulted in positive TRAb activity. However, the precise calculation was difficult because NSB(T) level was significantly higher than the nonspecific binding in normal pool serum [NSB(N)] level. In the present experiment the determination of the TRAb activity was performed after absorption of bTSH binding antibodies by the heat-denatured bTSH to obtain more precise TRAb activity. In addition, absorption by sheep FSH (sFSH) was performed because almost all bTSH binding antibodies showed specific binding to the alpha-subunit of mammalian pituitary glycoprotein hormones in our previous study. Three days absorption of test serum using 1 mU of the heat-denatured bTSH (100 degrees C for 1 h) or 5 mU of sFSH was chosen as optimal because NSB(T) decreased remarkably to NSB(N) levels. The corrected TRAb determined after these absorptions decreased significantly compared to the corrected TRAb activity without the absorption. When the complete absorption of bTSH binding antibody was performed by the decrease of the NSB(T) level to the NSB(N) level, the TRAb activity determined by these two different absorptions was almost similar (difference was less than 10%). However, it was difficult to obtain the precise TRAb activity in the cases with extremely high bTSH binding antibody, because the NSB(T) level was higher than the NSB(N) level by the incomplete absorption of bTSH binding antibody. PMID:8875749

Inui, T; Kouki, T; Okabe, H; Ochi, Y; Hachiya, T; Kajita, Y

1996-08-01

274

A mammalian PAR3–PAR6 complex implicated in Cdc42\\/Rac1 and aPKC signalling and cell polarity  

Microsoft Academic Search

Cellular asymmetry is critical for the development of multicellular organisms. Here we show that homologues of proteins necessary for asymmetric cell division in Caenorhabditis elegans associate with each other in mammalian cells and tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular distributions in the CNS and associate through their PDZ (PSD-95\\/Dlg\\/ZO-1) domains. mPAR-6 binds to Cdc42\\/Rac1 GTPases, and

Dan Lin; Amelia S. Edwards; James P. Fawcett; Geraldine Mbamalu; John D. Scott; Tony Pawson

2000-01-01

275

A critical role of follicle-stimulating hormone (Fsh) in mediating the effect of clotrimazole on testicular steroidogenesis in adult zebrafish.  

PubMed

Clotrimazole is a pharmaceutical fungicide known to inhibit several cytochrome P450 enzyme activities, including several steroidogenic enzymes. This study aimed to assess short-term in vivo effects of clotrimazole exposure on blood 11-ketotestosterone (11-KT) levels and on the transcriptional activity of genes in pituitary and testis tissue that are functionally relevant for androgen production with the view to further characterize the mode of action of clotrimazole on the hypothalamus-pituitary-gonad axis in zebrafish, a model vertebrate in toxicology. Adult male zebrafish were exposed to measured concentrations in water of 71, 159 and 258?g/L of clotrimazole for 7 days. Expression of pituitary gonadotropins ? subunit (lhb, fshb), testicular gonadotropins receptors (lhcgr, fshr) and testicular steroidogenesis-related genes (e.g., star, cyp17a1, cyp11c1) were assessed. Blood concentrations of 11-KT were measured. Short-term exposure to clotrimazole induced a concentration-dependent increase of star, cyp17a1, and cyp11c1 gene expression and Cyp17a1 and Cy11c1 protein synthesis in Leydig cells, but androgen levels in blood remained unchanged. fshb, but not lhb mRNA levels in the pituitary tended to increase in clotrimazole-exposed zebrafish. Testicular expression of the Fsh receptor gene was significantly up-regulated following exposure, when expression of this receptor was significantly correlated to the expression of steroidogenesis-related genes. Moreover, the Fsh-regulated insulin-like growth factor 3 (igf3) gene, a fish-specific Igf peptide expressed in Sertoli cells, was induced in testes. By using a network of genes functioning in pituitary and testis tissue, our study demonstrated that clotrimazole induced a cascade of molecular and cellular events which are in agreement with a role for Fsh (1) in stimulating Leydig cell steroidogenesis to compensate the inhibitory action of clotrimazole on 11-KT synthesis and (2) in inducing the expression of Fsh-regulated igf3 in Sertoli cells. PMID:22564764

Baudiffier, Damien; Hinfray, Nathalie; Vosges, Mélanie; Creusot, Nicolas; Chadili, Edith; Porcher, Jean-Marc; Schulz, Rüdiger W; Brion, François

2012-04-28

276

Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells.  

PubMed

PAR-1 kinases are required for polarity in diverse cell types, such as epithelial cells, where they localize laterally. PAR-1 activity is believed to be transduced by binding of 14-3-3 proteins to its phosphorylated substrates, but the relevant targets are unknown. We show that PAR-1 phosphorylates Bazooka/PAR-3 on two conserved serines to generate 14-3-3 binding sites. This inhibits formation of the Bazooka/PAR-6/aPKC complex by blocking Bazooka oligomerization and binding to aPKC. In epithelia, this complex localizes apically and defines the apical membrane, whereas Bazooka lacking PAR-1 phosphorylation/14-3-3 binding sites forms ectopic lateral complexes. Lateral exclusion by PAR-1/14-3-3 cooperates with apical anchoring by Crumbs/Stardust to restrict Bazooka localization, and loss of both pathways disrupts epithelial polarity. PAR-1 also excludes Bazooka from the posterior of the oocyte, and disruption of this regulation causes anterior-posterior polarity defects. Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells. PMID:14675534

Benton, Richard; St Johnston, Daniel

2003-12-12

277

Genetic Polymorphisms Influence the Ovarian Response to rFSH Stimulation in Patients Undergoing In Vitro Fertilization Programs with ICSI  

PubMed Central

Introduction Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI). Results Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01). Discussion We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed. Materials and Methods A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(?397T>C), BMP15(?9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(?725C>G), VEGF(+405G>C), TNF?(?308A>G), AMHR(?482 A>G), PAI-1 (4 G/5 G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the overall study population (n=427) and a subgroup with homogeneous characteristics (n=112).

Boudjenah, Radia; Molina-Gomes, Denise; Torre, Antoine; Bergere, Marianne; Bailly, Marc; Boitrelle, Florence; Taieb, Stephane; Wainer, Robert; Benahmed, Mohamed; de Mazancourt, Philippe; Selva, Jacqueline; Vialard, Francois

2012-01-01

278

Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas  

PubMed Central

Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident.

Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.

2010-01-01

279

Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma  

PubMed Central

Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC.

Jan, Yee-Jee; Ko, Bor-Sheng; Liu, Tzu-An; Wu, Yao-Ming; Liang, Shu-Man; Chen, Shyh-Chang; Wang, John; Liou, Jun-Yang

2013-01-01

280

Structure of the ParM filament at 8.5 ? resolution  

PubMed Central

The actin-like protein ParM forms the cytomotive filament of the ParMRC system, a type II plasmid segregation system encoded by Escherichia coli R1 plasmid. We report an 8.5 Å resolution reconstruction of the ParM filament, obtained using cryo-electron microscopy. Fitting of the 3D density reconstruction with monomeric crystal structures of ParM provides insights into dynamic instability of ParM filaments. The structural analysis suggests that a ParM conformation, corresponding to a metastable state, is held within the filament by intrafilament contacts. This filament conformation of ParM can be attained only from the ATP-bound state, and induces a change in conformation of the bound nucleotide. The structural analysis also provides a rationale for the observed stimulation of hydrolysis upon polymerisation into the filament.

Gayathri, Pananghat; Fujii, Takashi; Namba, Keiichi; Lowe, Jan

2013-01-01

281

A Bipolar Spindle Of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation  

PubMed Central

To ensure their stable inheritance by daughter cells during cell division, bacterial low copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of Escherichia coli R1 plasmid, ParM, an actin-like protein, forms the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters towards the poles.

Gayathri, P.; Fujii, T.; M?ller-Jensen, J.; van den Ent, F.; Namba, K.; Lowe, J.

2013-01-01

282

A bipolar spindle of antiparallel ParM filaments drives bacterial plasmid segregation.  

PubMed

To ensure their stable inheritance by daughter cells during cell division, bacterial low-copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of the Escherichia coli R1 plasmid, ParM, an actinlike protein, forms the spindle between ParRC complexes on sister plasmids. By using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles. PMID:23112295

Gayathri, P; Fujii, T; Møller-Jensen, J; van den Ent, F; Namba, K; Löwe, J

2012-10-25

283

Investigation of thrombin activity with PAR 1-based fluorogenic peptides.  

PubMed

Thrombin, a highly specific protease of blood coagulation, has two exosites that modulate its specificity. We designed two sets of synthetic substrate FRET peptides with 25- or 11- amino acids (aa) each, based on the PAR 1 sequence, to characterize the effect of exosite 1 engagement on substrate catalysis and preference. The 25-aa set encompassed a sequence binding to exosite 1, and structural modeling showed that binding to thrombin did not differ significantly from that of PAR 1 peptide. Modification at the P3´position of the 25 or 11-aa peptides resulted in small effect on kinetic parameters. Ionic strength higher than physiologic depressed thrombin action on the 25-aa peptides. Addition of ligands of the exosite 1 negatively modulated the catalysis of 25-aa substrates. In conclusion, we succeeded to mimic and study in real time, using these synthetic peptides, the influence of ligand binding to exosite 1 on thrombin activity. PMID:23688151

Vieira, Saulo Martins; dos Reis, Flávia Garcia; Geraldo, Reinaldo; Dutra, Denis Luis da Silva; Juliano, Luiz; Julianod, Maria Aparecida; Mignaco, Julio Alberto; Zingali, Russolina Benedeta

2013-10-01

284

Metabolism of (/sup 3/H) 5 alpha-androstane-3 alpha, 17 beta-diol by cultures of isolated rat sertoli cells and the effect of LH and FSH  

SciTech Connect

Sertoli cells from immature rats metabolized (/sup 3/H) 5 alpha-androstane-3 alpha, 17 beta-diol to (/sup 3/H) 5 alpha-androstane-3 alpha, 16 alpha, 17 beta-triol and (/sup 3/H) 3 alpha-hydroxy-5 alpha-androstan-17-one. This is the first report of 16 alpha-hydroxylation of 5 alpha-reduced androgens in the testis. FSH significantly stimulated 16 alpha-hydroxylation while LH significantly decreased this activity. 3 alpha-Hydroxy-5 alpha-androstan-17-one was the major metabolite formed and its production was significantly increased in the presence of both LH and FSH, although FSH stimulation was significantly more than LH. The possible role of 16 alpha-hydroxylase in androgen metabolism by immature rat Sertoli cells is discussed.

Tcholakian, R.K.; Berkowitz, A.S.; Newaz, S.N.

1984-04-01

285

Regulation of anterior pituitary gonadotropin subunit mRNA levels during the preovulatory gonadotropin surge: a physiological role of progesterone in regulating LH-beta and FSH-beta mRNA levels.  

PubMed

In a previous study we demonstrated that in the ovariectomized estrogen-primed immature rat, progesterone induced a gonadotropin surge while the gonadotropin mRNA subunit levels were either suppressed or unaltered. This observation has now been confirmed using more frequent time points. Progesterone administered at 0900 h was found to suppress LH-beta mRNA levels at 1300, 1400, and 0800 h the next day, with no subsequent effects at 1000, 1200 or 1600 h. FSH-beta mRNA levels were unaffected by progesterone except for a slight elevation at 1400 h and a suppression at 0800 h. Progesterone was either suppressive or had no effect on alpha mRNA levels. Since elevations in LH-beta and FSH-beta mRNA levels were observed in the cycling rat, the observed differences in the ovariectomized estrogen-primed rat could be due to a higher basal synthesis occurring due to ovariectomy. This was indeed the case because LH-beta and FSH-beta mRNA levels were 3.7- and 42.7-fold higher in such animals as compared to intact estrogen-primed rats. In contrast to the ovariectomized estrogen-primed rats, in intact estrogen-primed rats LH-beta mRNA levels were increased at 1000 h and FSH-beta mRNA levels were increased at 1000, 1200 and 1300 h after the administration of progesterone. In pregnant mare's serum gonadotropin-primed immature rats, LH-beta, FSH-beta and alpha-subunit mRNA levels were significantly elevated at 1800 and 2000 h, paralleling the serum LH and FSH surge. The progesterone antagonist RU486 (0.2 and 1.0 mg) significantly reduced serum LH and FSH levels at 2000 h. The lower dose reduced LH-beta and alpha-subunit mRNA levels at 2000 h and FSH-beta mRNA levels at 1800 h. The higher dose caused an increase in LH-beta mRNA levels at 1200 and 1800 h and a decrease in FSH-beta mRNA levels at 1800 and 2000 h. In conclusion, the present study provides evidence that preovulatory progesterone plays an important role in the increase in FSH-beta mRNA levels as well as the release of LH and FSH during the normal preovulatory gonadotropin surge. This relationship appears to be dependent on the ongoing rate of synthesis because this does not occur in the ovariectomized estrogen-primed rat in which synthesis is at a high basal level. Furthermore, the correlation with FSH appears to be tighter as compared to LH. PMID:8217874

Brann, D W; O'Conner, J L; Wade, M F; Zamorano, P L; Mahesh, V B

1993-10-01

286

Developmental Control of a parAB Promoter Leads to Formation of Sporulation-Associated ParB Complexes in Streptomyces coelicolor  

PubMed Central

The Streptomyces coelicolor partitioning protein ParB binds to numerous parS sites in the oriC-proximal part of the linear chromosome. ParB binding results in the formation of large complexes, which behave differentially during the complex life cycle (D. Jakimowicz, B. Gust, J. Zakrzewska-Czerwinska, and K. F. Chater, J. Bacteriol. 187:3572-3580, 2005). Here we have analyzed the transcriptional regulation that underpins this developmentally specific behavior. Analysis of promoter mutations showed that the irregularly spaced complexes present in vegetative hyphae are dependent on the constitutive parABp1 promoter, while sporulation-specific induction of the promoter parABp2 is required for the assembly of arrays of ParB complexes in aerial hyphae and thus is necessary for efficient chromosome segregation. Expression from parABp2 depended absolutely on two sporulation regulatory genes, whiA and whiB, and partially on two others, whiH and whiI, all four of which are needed for sporulation septation. Because of this pattern of dependence, we investigated the transcription of these four whi genes in whiA and whiB mutants, revealing significant regulatory interplay between whiA and whiB. A strain in which sporulation septation (but not vegetative septation) was blocked by mutation of a sporulation-specific promoter of ftsZ showed close to wild-type induction of parABp2 and formed fairly regular ParB-enhanced green fluorescent protein foci in aerial hyphae, ruling out strong morphological coupling or checkpoint regulation between septation and DNA partitioning during sporulation. A model for developmental regulation of parABp2 expression is presented.

Jakimowicz, Dagmara; Mouz, Sebastien; Zakrzewska-Czerwinska, Jolanta; Chater, Keith F.

2006-01-01

287

Pars plana vitrectomy for epiretinal membrane associated with sarcoidosis  

Microsoft Academic Search

Purpose: To examine retrospectively the visual outcomes in patients undergoing vitrectomy for epiretinal membranes secondary to sarcoid uveitis.Methods: Eleven consecutive patients (11 eyes) with epiretinal membrane and uveitis associated with sarcoidosis underwent pars plana vitrectomy.Results: Nine eyes (82%) gained two or more lines of Snellen visual acuity at 1–12 months after surgery. However, 4 of these 9 eyes lost two

Junichi Kiryu; Mihori Kita; Teruyo Tanabe; Kenji Yamashiro; Yoshiaki Ieki; Shinji Miura; Shinsuke Miyahara; Hiroshi Tamura; Yoshihito Honda

2003-01-01

288

Results of Preliminary Tests of PAR Bunch Cleaning  

Microsoft Academic Search

A particle accumulator ring (PAR) is used at the Advanced Photon Source (APS) to collect multiple linac bunches and compress them into a 0.3-ns single bunch for booster injection. A 9.77-MHz fundamental and a 117.3-MHz harmonic rf system (RF12) are employed for initial beam capture and bunch-length compression, respectively. Satellite bunches with very low charge form when the phase or

C. Y. Yao; N. S. Sereno; M. Borland; A. E. Grelick; A. H. Lumpkin

2005-01-01

289

PAR Measurements: Calculating The Solar Constant Using A TI-8  

NSDL National Science Digital Library

In this activity students measure photosynthetically available radiation (PAR). Students determine the solar input by calculating the amount of heat absorbed by a known mass of water exposed to a known cross-sectional area of sunlight. Students discuss the variables influencing their measurements, the reasons why solar input might vary, measure and calculate solar input at their watershed testing site, and compare and discuss data differences with that of the McMurdo Dry Valleys.

Schulz, Barbara; Wygoda, Linda

290

Tonic pupil following pars plana vitrectomy and endolaser.  

PubMed

Tonic pupil was observed in a 67 year-old patient following a retinal detachment repair with pars plana vitrectomy, endolaser and silicone oil tamponade performed under retrobulbar anesthesia. The probable location of disturbance is the postganglionic parasympathetic fibers in the short ciliary nerves along their course to the pupil in the suprachoroidal space. A likely explanation for this phenomenon is injury to short ciliary nerves by endolaser treatment. PMID:19721706

Ebrahim, Benyamin; Frohman, Larry; Zarbin, Marco; Bhagat, Neelakshi

2009-07-08

291

Tonic Pupil Following Pars Plana Vitrectomy and Endolaser  

PubMed Central

Tonic pupil was observed in a 67 year-old patient following a retinal detachment repair with pars plana vitrectomy, endolaser and silicone oil tamponade performed under retrobulbar anesthesia. The probable location of disturbance is the postganglionic parasympathetic fibers in the short ciliary nerves along their course to the pupil in the suprachoroidal space. A likely explanation for this phenomenon is injury to short ciliary nerves by endolaser treatment.

Ebrahim, Benyamin; Frohman, Larry; Zarbin, Marco; Bhagat, Neelakshi

2009-01-01

292

Goat oocyte production by standard or one-shot FSH treatments and quantitative analysis of transcripts for EGF ligands and its receptor after in vitro maturation.  

PubMed

Hormonal ovarian stimulation may affect the success of embryo production by regulating transcripts in recovered cumulus-oocyte complexes (COCs). Here, in parallel to morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of epidermal growth factor (EGF) and its receptor (EGFR) in oocytes and cumulus cells from goat COCs recovered by laparoscopy after standard [multi-dose follicle-stimulating hormone (FSH)] or one-shot (single dose FSH plus eCG) treatments. No differences were observed among the number of recovered and morphologically graded COCs or the IVM rates for both gonadotropic treatments. However, the standard protocol produced COCs with higher EGFR expression in the cumulus cells than the one-shot treatment. Additionally, EGF mRNA levels were less than EGFR mRNA levels, and they did not differ among COCs from both treatments. However, during maturation, the EGF transcripts increased in oocytes derived only from the standard protocol. Interestingly, IVM strikingly increased EGFR expression in oocytes and cumulus cells but not in oocytes that fail in first polar body extrusion, irrespective of hormonal treatment. These results appear to be related to the resumption of meiosis and suggest that EGF may act through the cumulus cells or directly on the oocyte receptor. PMID:21923881

Pereira, A F; Alcântara Neto, A S; Albuquerque, E S; Luciano, M C S; Teixeira, D I A; Freitas, V J F; Melo, L M

2011-09-16

293

Anterior PAR Proteins Function During Cytokinesis and Maintain DYN-1 at the Cleavage Furrow in Caenorhabditis elegans  

PubMed Central

PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time.

Pittman, Kelly J.; Skop, Ahna R.

2013-01-01

294

Ultrasound biomicroscopy of hyperpressurized eyes following pars plana vitrectomy  

PubMed Central

Early elevated intraocular pressure (IOP) following pars plana vitrectomy is a common complication of vitreoretinal surgery and severe pressure elevation may result in visual loss. To investigate the mechanism of IOP elevation following pars plana vitrectomy, a retrospective review of 119 patients (132 eyes) who had undergone vitreoretinal surgery was performed. Ultrasound biomicroscopy (UBM) was used to observe the changes in the structure of the anterior segment following vitrectomy and to compare various parameters pre- and postsurgery. The UBM examination revealed inflammation within the anterior chamber and hyphema with increased IOP. In certain patients, the iris had adhered to the trabecular meshwork and the anterior chamber angle was closed. Cyclodialysis involving the pars plicata and iris was also observed. Furthermore, silicone oil emulsification in the anterior chamber angle and posterior chamber presurgery were noted in certain cases. Edema and forward rotation of the ciliary body resulted in the closure of the anterior chamber angle. The measured parameters indicated that the anterior chamber became shallower and that the anterior chamber angle was narrowed in phakic eyes with elevated IOP. Eyes with elevated IOP and intraocular lenses were not observed to be different from phakic eyes with elevated IOP. This may be due to the fact that an eye with an intraocular lens is thinner than a phakic eye. This study suggests that UBM examination is useful for investigating the pathogenesis of elevated IOP following vitrectomy, and provides a theoretical basis.

WU, NA; ZHANG, HONG

2013-01-01

295

Crystallization of Soluble Urokinase Receptor (suPAR) in Complex with Urokinase Amino-Terminal Fragment (1-431)  

SciTech Connect

Urokinase-type plasminogen activator (urokinase, uPA) and its receptor, uPAR, have been implicated in cell adhesion, migration, tissue remodeling and tumor-cell invasion. uPAR has three domains and is anchored to membranes by a glycosyl-phosphatidylinositol (GPI) anchor. Recombinant uPAR without its GPI anchor, soluble uPAR (suPAR), tends to oligomerize, making it difficult to crystallize. The amino-terminal fragment (ATF) of uPA is the major receptor-binding determinant in suPAR and binds to suPAR with nanomolar affinity, indistinguishable from membrane-bound uPAR. It is shown that uPA is capable of dissociating the oligomerization of suPAR and the crystallization of the suPAR-ATF complex is reported here. The resulting crystals diffract to 3.1 Angstroms using a synchrotron X-ray source.

Huang,M.

2005-01-01

296

The Role of Neurosecretory Neurons in the Pars Intercerebralis and Pars Lateralis in Reproductive Diapause of the Blowfly, Protophormia terraenovae  

NASA Astrophysics Data System (ADS)

Microlesions of the brain were made to examine the role of neurosecretory neurons in the pars intercerebralis (PI) and pars lateralis (PL) in the induction of reproductive diapause of the female blowfly Protophormia terraenovae. Under both diapause-inducing (LD 12 : 12, 20° C) and diapause-averting conditions (LD 18 : 6, 25° C), the ovaries invariably failed to develop when the PI was removed. When the PL was removed bilaterally, the ovaries developed in most of the females, irrespective of the rearing conditions. Removal of the PL prevented females from entering reproductive diapause. These results show that certain neurosecretory neurons in the PI are necessary for vitellogenesis, and that the PL contains inhibitory neurons which suppress vitellogenesis during reproductive diapause.

Shiga, S.; Numata, H.

297

The role of neurosecretory neurons in the pars intercerebralis and pars lateralis in reproductive diapause of the blowfly, Protophormia terraenovae.  

PubMed

Microlesions of the brain were made to examine the role of neurosecretory neurons in the pars intercerebralis (PI) and pars lateralis (PL) in the induction of reproductive diapause of the female blowfly Protophormia terraenovae. Under both diapause-inducing (LD 12:12, 20 degrees C) and diapause-averting conditions (LD 18:6, 25 degrees C), the ovaries invariably failed to develop when the PI was removed. When the PL was removed bilaterally, the ovaries developed in most of the females, irrespective of the rearing conditions. Removal of the PL prevented females from entering reproductive diapause. These results show that certain neurosecretory neurons in the PI are necessary for vitellogenesis, and that the PL contains inhibitory neurons which suppress vitellogenesis during reproductive diapause. PMID:10798197

Shiga, S; Numata, H

2000-03-01

298

Horizontal portion of arcuate fasciculus fibers track to pars opercularis, not pars triangularis, in right and left hemispheres: A DTI study  

Microsoft Academic Search

The arcuate fasciculus (AF) is a white matter pathway traditionally considered to connect left Broca's area with posterior language zones. We utilized diffusion tensor imaging (DTI) in eight healthy subjects (5 M) to track pathways in the horizontal mid-portion of the AF (hAF) to subregions of Broca's area — pars triangularis (PTr) and pars opercularis (POp); and to ventral premotor

Elina Kaplan; Margaret A. Naeser; Paula I. Martin; Michael Ho; Yunyan Wang; Errol Baker; Alvaro Pascual-Leone

2010-01-01

299

Comparison and influence of two newly produced Iranian oil dispersants (Pars1 &Pars2) with the Gamlen OD4000 on rainbow trout  

Microsoft Academic Search

Dispersants are the group of chemicals, designed to be sprayed on to the oil slicks to accelerate the process of natural dispersion. In this study, the acute toxicity of two newly produced Iranian oil dispersants (Pars1 &Pars2) was evaluated and compared to the Gamlen OD 4000 in different concentrations on 28–32 g of rainbow trout (Oncorhynchus mykiss). The 50% of

Leila Bordbar; Mozhgan Emtyazjoo; Daroush Farkhani

2008-01-01

300

The PAR complex regulates pulsed actomyosin contractions during amnioserosa apical constriction in Drosophila.  

PubMed

Apical constriction is a major mechanism underlying tissue internalization during development. This cell constriction typically requires actomyosin contractility. Thus, understanding apical constriction requires characterization of the mechanics and regulation of actomyosin assemblies. We have analyzed the relationship between myosin and the polarity regulators Par-6, aPKC and Bazooka (Par-3) (the PAR complex) during amnioserosa apical constriction at Drosophila dorsal closure. The PAR complex and myosin accumulate at the apical surface domain of amnioserosa cells at dorsal closure, the PAR complex forming a patch of puncta and myosin forming an associated network. Genetic interactions indicate that the PAR complex supports myosin activity during dorsal closure, as well as during other steps of embryogenesis. We find that actomyosin contractility in amnioserosa cells is based on the repeated assembly and disassembly of apical actomyosin networks, with each assembly event driving constriction of the apical domain. As the networks assemble they translocate across the apical patch of PAR proteins, which persist at the apical domain. Through loss- and gain-of-function studies, we find that different PAR complex components regulate distinct phases of the actomyosin assembly/disassembly cycle: Bazooka promotes the duration of actomyosin pulses and Par-6/aPKC promotes the lull time between pulses. These results identify the mechanics of actomyosin contractility that drive amnioserosa apical constriction and how specific steps of the contractile mechanism are regulated by the PAR complex. PMID:20392741

David, Daryl J V; Tishkina, Alisa; Harris, Tony J C

2010-04-14

301

A model for the condensation of the bacterial chromosome by the partitioning protein ParB  

NASA Astrophysics Data System (ADS)

The molecular machinery responsible for faithful segregation of the chromosome in bacteria such as Caulobacter crescentus and Bacillus subtilis includes the ParABS a.k.a. Spo0J/Soj partitioning system. In Caulobacter, prior to division, hundreds of ParB proteins bind to the DNA near the origin of replication, and localize to one pole of the cell. Subsequently, the ParB-DNA complex is translocated to the far pole by the binding and retraction of the ParA spindle-like apparatus. Remarkably, the localization of ParB proteins to specific regions of the chromosome appears to be controlled by only a few centromeric parS binding sites. Although lateral interactions between DNA-bound ParB are likely to be important for their localization, the long-range order of ParB domains on the chromosome appears to be inconsistent with a picture in which protein-protein interactions are limited to neighboring DNA-bound proteins. We developed a coarse-grained Brownian dynamics model that allows for lateral and 3D protein-protein interactions among bound ParB proteins. Our model shows how such interactions can condense and organize the DNA spatially, and can control the localization and the long-range order of the DNA-bound proteins.

Broedersz, Chase; Wingreen, Ned

2013-03-01

302

MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo  

PubMed Central

PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell divisions, the asymmetric distribution of cell fate specification markers, and the distribution of PAR-1 protein in par-1 mutant embryos, indicating that this genetic interaction is functionally relevant for embryonic development. Furthermore, disrupting the function of other components of the MAPK signaling pathway resulted in suppression of par-1 embryonic lethality. Our data therefore indicates that MAP kinase signaling antagonizes PAR-1 signaling during early C. elegans embryonic polarization.

Spilker, Annina C.; Rabilotta, Alexia; Zbinden, Caroline; Labbe, Jean-Claude; Gotta, Monica

2009-01-01

303

Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis  

SciTech Connect

Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm and is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis.

Boosen, Meike [Institute of Genetics, University of Bonn, Roemerstr. 164, D-53117 Bonn (Germany); Vetterkind, Susanne [Institute of Genetics, University of Bonn, Roemerstr. 164, D-53117 Bonn (Germany); Koplin, Ansgar [Institute of Genetics, University of Bonn, Roemerstr. 164, D-53117 Bonn (Germany); Illenberger, Susanne [Cell Biology, Zoological Institute, Technical University of Braunschweig, D-38092 Braunschweig (Germany); Preuss, Ute [Institute of Genetics, University of Bonn, Roemerstr. 164, D-53117 Bonn (Germany)]. E-mail: u.preuss@uni-bonn.de

2005-12-10

304

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study  

PubMed Central

Background The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality. Methods In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor. Results Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009). Conclusion Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.

Hernandez, Norma A; Correa, Elma; Avila, Esther P; Vela, Teresa A; Perez, Victor M

2009-01-01

305

Dissection of the ATPase active site of P1 ParA reveals multiple active forms essential for plasmid partition.  

PubMed

The segregation, or partition, of bacterial plasmids is driven by the action of plasmid-encoded partition ATPases, which work to position plasmids inside the cell. The most common type of partition ATPase, generally called ParA, is represented by the P1 plasmid ParA protein. ParA interacts with P1 ParB (the site-specific DNA binding protein that recognizes the parS partition site), and interacts with the bacterial chromosome via an ATP-dependent nonspecific DNA binding activity. ParA also regulates expression of the par genes by acting as a transcriptional repressor. ParA requires ATP for multiple steps and in different ways during the partition process. Here, we analyze the properties of mutations in P1 ParA that are altered in a key lysine in the Walker A motif of the ATP binding site. Four different residues at this position (Lys, Glu, Gln, Arg) result in four different phenotypes in vivo. We focus particularly on the arginine substitution (K122R) because it results in a worse-than-null and dominant-negative phenotype called ParPD. We show that ParAK122R binds and hydrolyzes ATP, although the latter activity is reduced compared with wild-type. ParAK122R interacts with ParB, but the consequences of the interaction are damaged. The ability of ParB to stimulate the ATPase activity of ParA in vitro and its repressor activity in vivo is defective. The K122R mutation specifically damages the disassembly of ParA-ParB-DNA partition complexes, which we believe explains the ParPD phenotype in vivo. PMID:23632076

Vecchiarelli, Anthony G; Havey, James C; Ing, Lori L; Wong, Erin O Y; Waples, William G; Funnell, Barbara E

2013-04-30

306

uPAR regulates pericellular proteolysis through a mechanism involving integrins and fMLF-receptors.  

PubMed

The expression of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) can be regulated by several hormones, cytokines, and tumour promoters. uPAR is a glycosyl-phosphatidyl inositol (GPI)-linked cell-surface protein; however, it is capable to transduce signals inside the cell by interacting with other cell-surface proteins, such as integrins and G-protein coupled (GPC) receptors. We previously reported that uPAR cell-surface expression can be positively regulated by its ligand, uPA, independently of its proteolytic activity. We now demonstrate that uPAR overexpression induces or increases uPA secretion both in uPAR-negative and in uPAR-expressing cells. Accordingly, uPAR depletion impairs uPA expression in cells which constitutively express both uPA and its receptor. uPAR exerts its regulatory effect through the activation of the ERK mitogen-activated protein kinases (MAPKs), whereas the p-38 MAPK is not involved. Overexpression of truncated forms of uPAR, lacking the N-terminal domain (DI) and not able to interact with membrane co-receptors, failed to increase uPA expression. Inhibition of uPAR-integrin interaction by the specific P-25 peptide, as well as Gi-protein inhibition by cholera pertussin toxin or depletion of the GPC receptors for fMLF (fMLF-Rs) also impaired uPAR capability to regulate uPA expression. These findings demonstrate that uPAR, whose expression is regulated by uPA, can, in turn, regulate uPA expression through a mechanism involving its functional interaction with integrins and fMLF-Rs. PMID:23238745

Montuori, Nunzia; Cosimato, Vincenzo; Rinaldi, Loredana; Rea, Vincenza Elena Anna; Alfano, Daniela; Ragno, Pia

2012-12-13

307

Influences of Baking and Thawing Conditions on Quality of Par-Baked French Bread  

Microsoft Academic Search

Cereal Chem. 84(1):38-43 We examined the effects of baking time and temperature for the preparation of par-baked French bread, and of thawing and second baking conditions on the characteristics of bread prepared from par-baked bread. Par-baked French bread with loaf volume and crumb structure com- parable to fully baked bread (control) was obtained with ?6 min baking at 218°C, which

Chul Soo Park; Byung-Kee Baik

2007-01-01

308

Asymptotic Performance Analysis and Successive Selected Mapping for PAR Reduction in OFDM  

Microsoft Academic Search

One major drawback of orthogonal frequency-division multiplexing (OFDM) systems is the high peak-to-average power ratio (PAR) of the transmit signal. In order to overcome this problem, selected mapping (SLM) is a well known method for PAR reduction. In this paper, asymptotic performance analysis of SLM is carried out and a bound on the maximum tolerable PAR values is derived. Starting

Christian Siegl; Robert F. H. Fischer

2009-01-01

309

Suppression of Par4 Protects Human Renal Proximal Tubule Cells from Apoptosis Induced by Oxidative Stress  

Microsoft Academic Search

Background: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury

Bin Sun; Chao Lu; Guo-Ping Zhou; Chang-Ying Xing

2011-01-01

310

ScalParC: A New Scalable and Efficient Parallel Classification Algorithm for Mining Large Datasets  

Microsoft Academic Search

In this paper, we present ScalParC ( Scalable Parallel Classifier), a new parallel formulation of a decision tree based classification process. Like other state-of-the-art de- cision tree classifiers such as SPRINT, ScalParC is suited for handling large datasets. We show that existing parallel formulation of SPRINT is unscalable, whereas ScalParC is shown to be scalable in both runtime and memory

Mahesh V. Joshi; George Karypis; Vipin Kumar

1998-01-01

311

Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis  

PubMed Central

Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed.

Melnikova, Vladislava O.; Villares, Gabriel J.

2008-01-01

312

Environmental assessment of par pond sluice gate test. Revision 0  

SciTech Connect

FERC mandates that spillway gates be opened to full height once every 5 years to ensure safe operation in emergency. The Savannah River Site is proposing to conduct a test in which the sluice gate near the base of the Par Pond Dam is opened high enough to produce a nominal flow of 200,000 gpm and then reclosed. This report discusses 3 environmental impact concerns: high flows will resuspend sediments containing Cesium-137 and carry them downstream to the Savannah River; water chemistry will be adversely affected resulting in deleterious effects on the biota; high flow velocities and scouring of the stream bed will disturb biota.

Paller, M.H.; Bowers, J.A.

1996-12-31

313

Diffraction d’ondes électromagnétiques impulsionnelles par des obstacles métalliques  

Microsoft Academic Search

\\u000a Analyse  \\u000a La diffraction en régime transitoire est traitée directement dans le domaine temporel par une méthode originale utilisant\\u000a la théorie des distributions. Pour les obstacles métalliques parfaitement conducteurs, cette approche généralise les solutions\\u000a existantes dans la littérature, mais permet aussi d’établir de nouvelles équations intégrales donnant la solution des problèmes\\u000a de diffraction à deux dimensions (l’onde et l’obstacle présentent une

Bernard Jecko

1983-01-01

314

Comparisons of mRNA expression for aromatase, FSH receptor, and IGF-I in the granulosa of small ovarian follicles between cattle selected and unselected for twin ovulations  

Technology Transfer Automated Retrieval System (TEKTRAN)

Long-term selection of cattle for the production of twin ovulations and births has enhanced the development of preantral and antral ovarian follicles and increased the frequency of twin or triplet ovulations to greater than 60%. However, these differences have not been linked to differences in FSH s...

315

Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA Expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying.  

PubMed

It has been proposed that gonadotropins and/or gonadotropin releasing hormone (GnRH) could be involved in the pathophysiology of the side effects after spaying in bitches, such as urinary incontinence and an increased production of a woolly undercoat. In order to provide tools to investigate the role of these hormones in dogs we developed immunohistochemical techniques and real-time RT-PCR to study whether GnRH-, LH-, and FSH-receptors exist in canine skin and urinary bladder. Tissue samples from the skin of the flank region and the ventral midline of the urinary bladder from euthanised dogs were examined. We were able to quantify mRNA expression of GnRH-, FSH-, and LH-receptors in canine skin and bladder biopsies with a high primer efficacy. Immunohistochemical studies showed that GnRH-, FSH-, and LH-receptors are expressed in vessel walls, the epidermis, the hair follicle and in sebaceous and sweat glands in canine skin and in transitional epithelium, and smooth muscle tissue in the urinary bladder. Our data provide the fundamentals to examine the distribution of FSH-, LH-, and GnRH-receptors in canine skin and urinary bladder and to assess gene activity at the transcriptional level by real-time RT-PCR. PMID:16715322

Welle, Monika M; Reichler, Iris M; Barth, Andrea; Forster, Ursula; Sattler, Ursula; Arnold, Susi

2006-05-20

316

PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs.  

PubMed

The evolutionarily conserved partitioning defective (PAR) protein PAR-3 is pivotal for establishing and maintaining cell polarity. During mammalian oocyte maturation, the radially symmetric oocyte is transformed into a highly polarized metaphase II (MII)-arrested egg. We therefore examined several aspects of PAR-3 expression during oocyte maturation. We cloned two novel PAR-3 transcripts from an oocyte library that likely encode proteins of Mr = 73 K and 133 K that are phosphorylated during maturation. PAR-3, which is found throughout the GV-intact oocyte, becomes asymmetrically localized during meiosis. Following germinal vesicle breakdown, PAR-3 surrounds the condensing chromosomes and associates with the meiotic spindles. Prior to emission of the first and second polar bodies, PAR-3 is located within a central subdomain of the polarized actin cap, which overlies the spindle. This cortical PAR-3 localization depends on intact microfilaments. These results suggest a role for PAR-3 in establishing asymmetry in the egg and in defining the future site of polar body emission. PMID:15766746

Duncan, Francesca E; Moss, Stuart B; Schultz, Richard M; Williams, Carmen J

2005-04-01

317

Aberrations in Pseudoautosomal Regions (PARs) Found in Infertile Men with Y-Chromosome Microdeletions  

PubMed Central

Context: The pseudoautosomal regions (PARs) of the Y-chromosome undergo meiotic recombination with the X-chromosome. PAR mutations are associated with infertility and mental and stature disorders. Objective: The aim of the study was to determine whether men with Y-chromosome microdeletions have structural defects in PARs. Design and Participants: Eighty-seven infertile men with Y-chromosome microdeletions and 35 controls were evaluated for chromosomal rearrangements using commercial or custom (X- and Y-chromosome) array comparative genomic hybridization or by quantitative PCR of selected PAR genes. Multisoftware-defined chromosomal gains or losses were validated by quantitative PCR and FISH. Results: Array comparative genomic hybridization confirmed the AZF deletions identified by multiplex PCR. All men with Y-chromosome microdeletions and an abnormal karyotype displayed PAR abnormalities, as did 10% of men with Y-chromosome microdeletions and a normal karyotype. None of the control subjects or infertile men without Y-chromosome microdeletions had PAR duplications or deletions. SHOX aberrations occurred in 14 men (nine gains and five losses); four were short in stature (<10th percentile), and one was tall (>95th percentile). In contrast, the height of 23 men with Y-chromosome microdeletions and normal PARs was average at 176.8 cm (50th percentile). Conclusions: Y-chromosome microdeletions can include PAR defects causing genomic disorders such as SHOX, which may be transmitted to offspring. Previously unrecognized PAR gains and losses in men with Y-chromosome microdeletions may have consequences for offspring.

Weedin, John W.; Sahin, Aysegul; Tannour-Louet, Mounia; Han, Shuo; Bournat, Juan C.; Mielnik, Anna; Cheung, Sau Wai; Nangia, Ajay K.; Schlegel, Peter N.; Lipshultz, Larry I.

2011-01-01

318

[Multifactorial analysis of the blood levels of LH, FSH and estradiol in relation to ovular harvesting rates, fertilization and segmentation in patients undergoing assisted reproduction (GIFT-FIVTE)].  

PubMed

This study shows that there is certain tendency to asssign more value to the observation of follicular growth by ultrasound than to hormonal levels "per se". However, the appreciation of growth is only part of the phenomenon of development and ovarian maturity, for that, surveillance with hormonal monitor of ovarian response keeps with a most important role in Assisted Reproduction Clinica. The basal levels, mainly of FSH and in a less degree LH, inversely correlate with the amount of retrieved ovocytes. Estradiol values should be interpreted with a fixed point of reference, as the day of HCG administration, and a direct relation is seen between estradiol levels and captured ovocytes; however, is of highest usefulness to value the conduct of estradiol level, with the knowledge that the prognosis for good capture rates improves with ascending values and above 700 pg in the day of HCG administration. PMID:1601316

Di Castro Stringher, P; Espinosa de los Monteros Mena, A; Hernández Vazquez, J; Parra Covarrubias, A; Kably Ambe, A; Alvarado Duran, A

1992-04-01

319

A method for estimating the incident PAR on inclined surfaces  

NASA Astrophysics Data System (ADS)

A new simple model has been developed that incorporates Digital Elevation Model (DEM) and Moderate Resolution Imaging Spectroradiometer (MODIS) products to produce incident photosynthetically active radiation (PAR) for tilted surface. The method is based on a simplification of the general radiative transfer equation, which considers five major processes of attenuation of solar radiation: 1) Rayleigh scattering, 2) absorption by ozone and water vapor, 3) aerosol scattering, 4) multiple reflectance between surface and atmosphere, and 5) three terrain factors: slope and aspect, isotropic sky view factor, and additional radiation by neighbor reflectance. A comparison of the model results with observational data from the Yucheng and Changbai Mountain sites of the Chinese Ecosystem Research Network (CERN) shows the correlation coefficient as 0.929 and 0.904, respectively. A comparison of the model results with the 2006 filed measured PAR in the Yucheng and Changbai sites shows the correlation coefficient as 0.929 and 0.904, respectively, and the average percent error as 10% and 15%, respectively.

Xie, Xiaoping; Gao, Wei; Gao, Zhiqiang

2008-08-01

320

Hoechstintegration in der Mikroelektronik: Entwicklungen von Digitalen Asics fuer PARS3-LR (Highest Integration in Microelectronics: Development of Digital Asics for PARS3-LR).  

National Technical Information Service (NTIS)

Essential electronic system components by PARS3-LR, show high requirements in calculation power, power consumption and reliability, by immediately increasing integration thicknesses. These problems are solved by using integrated circuits, developed by LSI...

P. Scholler R. Vonlutz

1989-01-01

321

Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development.  

PubMed

Thrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two protease-activated thrombin receptors on human platelets are denoted PAR1 and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PAR1 activation alone. In the present study we have investigated the role of PARs in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PAR1 activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PAR1 is more important for fibrinolysis; inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR1 inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum. PMID:17334509

Vretenbrant, Karin; Ramström, Sofia; Bjerke, Maria; Lindahl, Tomas L

2007-03-01

322

Modulation of expression of innate immunity markers CXCL5/ENA-78 and CCL20/MIP3? by protease-activated receptors (PARs) in human gingival epithelial cells  

PubMed Central

Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in host defense. The two most highly expressed members of the PAR family in gingival epithelial cells (GECs) are PAR1 and PAR2. The major virulence factors of periodontal pathogen Porphyromonas gingivalis are its proteases which can activate PAR2. However, little is known about the function of PARs in GECs when they are activated by their endogenous agonist enzymes. The purpose of this study was to characterize how the expression of innate immune markers is modulated when PAR1 and PAR2 are activated by their agonist enzymes, thrombin and trypsin, respectively. Here, we report that activation of PAR1 and PAR2 induces cell proliferation at low concentration. Activation of PAR via proteolytic activity of thrombin and trypsin induces expression of CXCL5/ENA-78 and CCL20/MIP3? in a concentration-dependent manner. Induction of CXCL5 via PAR1 was inhibited in the presence of PAR1 cleavage blocking antibodies and by PAR1 siRNA. The induction of CXCL5 and CCL20 via PAR2 was inhibited by PAR2 siRNA. These findings indicate an active role in innate immune responses by PAR1 and PAR2 in GECs. Modulation of innate immunity by PARs may contribute to co-ordinated and balanced immunosurveillance in GECs.

Rohani, Maryam G.; Beyer, Richard P.; Hacker, Beth M.; Dommisch, Henrik; Dale, Beverly A.; Chung, Whasun O.

2010-01-01

323

Results of Anterior Chamber Clearance via the Pars plana in Pseudophakic Endophthalmitis  

Microsoft Academic Search

Purpose: Patients with endophthalmitis have extensive fibrinous exudates in the anterior chamber. Clearance of these exudates in pseudophakic patients during vitrectomy is difficult. We evaluated the results of the pars plana approach for clearing these exudates. Material and Methods: Eighteen patients with pseudophakic endophthalmitis underwent clearance of anterior chamber exudates through the pars plana approach after initial creation of a

Rajashekhar Patil; Dinesh Talwar; Lalit K. Verma; Yog Raj Sharma; Sanjeev Nainiwal; Raj Vardhan Azad; Hem K. Tewari

2003-01-01

324

Immediate Pars Plana Vitrectomy Improves Outcome in Retained Intravitreal Lens Fragments after Phacoemulsification  

Microsoft Academic Search

Purpose: To investigate the clinical features, visual acuity outcomes and the most appropriate intervention time in patients with retained lens fragments managed by pars plana vitrectomy. Methods: This was a retrospective review of the records of 78 patients who underwent pars plana vitrectomy for retained lens fragments at the Tri-Service General Hospital from January 1, 2000, to December 31, 2006.

Ching-Long Chen; Teng-Yi Wang; Jen-Hao Cheng; Ming-Cheng Tai; Da-Wen Lu; Jiann-Torng Chen

2008-01-01

325

Visual Results and Complications after Trans Pars Plana Vitrectomy and Lensectomy for Lens Dislocation  

Microsoft Academic Search

Background: The aim of this study is to determine the relationship between the cause of lens dislocation and visual outcomes with complications in patients undergo- ing trans pars plana vitrectomy (TPPV) and trans pars plana lensectomy (TPPL) for lens dislocation. Methods: This retrospective study was carried out from July 1995 through November 2003. After excluding patients with previous retinal detachment

Hsiu-Mei Huang; Min-Lun Kao; Shih-Hao Tsai; Yung-Jen Chen; Chi-Chang Liu

326

Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association.  

PubMed

The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network. PMID:23940457

Huang, Hong-Ling; Wang, Shimin; Yin, Meng-Xin; Dong, Liang; Wang, Chao; Wu, Wei; Lu, Yi; Feng, Miao; Dai, Chuanyang; Guo, Xiaocan; Li, Li; Zhao, Bin; Zhou, Zhaocai; Ji, Hongbin; Jiang, Jin; Zhao, Yun; Liu, Xin-Yuan; Zhang, Lei

2013-08-06

327

Enhanced PAR Irradiance Under Broken Cloud Fields and its Significance for Tropical Forest Photosynthesis  

NASA Astrophysics Data System (ADS)

Field measurements of total and diffuse photosynthetically active radiation (PAR, 400-700 nm) were combined with modeling to investigate the effects of atmospheric scattering by clouds on the surface PAR regime, forest canopy PAR absorption, and simulated photosynthetic rates for a moist tropical site at Putussibau, West Kalimantan Province, Indonesia (0.84N, 112.93E). Time-series PAR data collected in 2007 are characterized by large diffuse PAR fractions and frequent occurrence of enhanced global PAR irradiance (often exceeding the extraterrestrial flux) associated with reflectance and scattering by broken cloud fields. Simulations of canopy-absorbed PAR and gross photosynthesis with the Forest Light Environmental Simulator (FLiES) demonstrate the role of clouds in controlling forest canopy light-use efficiency and rates of photosynthesis and vegetation-atmosphere carbon exchange in this moist tropical environment. Application of a high dynamic range sky imaging system (HDR-SIS) to analysis of the sky radiance distribution of PAR under various atmospheric conditions is described.

Dye, D. G.; Kobayashi, H.; Wu, P.; Sulistyowati, R.; Sarodja, D.; Syamsudin, F.

2008-12-01

328

Diffraction de rayons X sur les plaquettes de fer durcies par cyanuration  

NASA Astrophysics Data System (ADS)

Une méthode de cyanuration a été developpée pour les surfaces des plaquettes de fer, basée sur une réaction thermochimique qui conduit à la formation des couches dures sur le métal. Les échantillons ont été analysés, pour de temps différents de traitement, par diffraction de rayons X et par mesures de dureté.

Popescu, M.; Hoyer, W.; Stegarescu, M.; Cornet, A.; Broll, N.

2004-11-01

329

Effect of frozen storage time on the bread crumb and aging of par-baked bread  

Microsoft Academic Search

The effect of frozen storage time of par-baked bread on the bread crumb and staling of bread obtained after thawing and full baking is described. The moisture content, hardness and retrogradation enthalpy of the amylopectin were determined in the par-baked bread and in the full baked bread after 7, 14, 28 and 42 days of frozen storage at ?25 °C.

María Eugenia Bárcenas; Cristina M. Rosell

2006-01-01

330

Identification and characterization of yeasts causing chalk mould defects on par-baked bread  

Microsoft Academic Search

Pichia anomala, Hyphopichia burtonii and Saccharomycopsis fibuligera are spoilage yeasts causing chalk mould defects on par-baked breads packaged under modified atmosphere. The first objective of this study was to identify yeasts isolated from spoiled par-baked breads by means of a RAPD protocol and to determine the dominant spoilers amongst identified strains. The second objective was to determine the effects of

N. Deschuyffeleer; K. Audenaert; S. Samapundo; S. Ameye; M. Eeckhout; F. Devlieghere

2011-01-01

331

Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.  

PubMed

Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin. PMID:12003791

Ubl, Joachim J; Grishina, Zoryana V; Sukhomlin, Tatiana K; Welte, Tobias; Sedehizade, Fariba; Reiser, Georg

2002-06-01

332

OFDM transmitter power amplifier and PAR reduction performance: measurement and simulation  

Microsoft Academic Search

Orthogonal frequency division multiplexing (OFDM) is known to exhibit high peak-to-average power ratio (PAR), which may limit the average transmitted power output from a nonlinear power amplifier (PA). We evaluate spectral regrowth and bit-error-rate (BER) performance characteristics when applying OFDM PAR reduction techniques, while integrated to a fixed output level \\

Steve Gifford; John E. Kleider; Scott Chuprun

2002-01-01

333

Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association  

PubMed Central

The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network.

Yin, Meng-Xin; Dong, Liang; Wang, Chao; Wu, Wei; Lu, Yi; Feng, Miao; Dai, Chuanyang; Guo, Xiaocan; Li, Li; Zhao, Bin; Zhou, Zhaocai; Ji, Hongbin; Jiang, Jin; Zhao, Yun; Liu, Xin-Yuan; Zhang, Lei

2013-01-01

334

Small Family with Key Contacts: Par14 and Par17 Parvulin Proteins, Relatives of Pin1, Now Emerge in Biomedical Research  

PubMed Central

The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer’s and Parkinson’s disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding two protein species—Par14 and Par17. Much less is known about these enzymes although their sequences are highly conserved in all metazoans. Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling. Pharmaceutical modulation of Par14 might therefore have benefits for certain types of cancer. Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development. This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.

Mueller, Jonathan W; Bayer, Peter

2008-01-01

335

Reproductive performance of donor mares subsequent to eFSH treatment in early vernal transition: Comparison between the first, second, and mid-season estrous cycles of the breeding season.  

PubMed

The objective was to compare the reproductive performances associated with the first (Cycle-1), second (Cycle-2), and mid-season (MS-Cycle) ovulations of the breeding season in donor mares that were treated with equine-FSH (eFSH) in the early vernal transition. Mares (n=15) kept under ambient light were examined ultrasonographically per-rectum starting January 30. When an ovarian follicle > or =25mm in diameter was detected, twice daily eFSH treatments were initiated. The eFSH treatments ceased when a follicle > or =35mm was detected, and 36h later hCG was administered. Thereafter, mares were artificially inseminated every 48h until ovulation (Day 0). Trans-cervical embryo recovery attempts were performed on Day 8, and subsequently PGF2alpha was administered. Equine FSH was not administered in the subsequent estrous cycles. In Cycle-2 and in the MS-Cycle, hCG was administered when a follicle > or =35mm was detected; breeding, embryo recovery, and PGF2alpha administration, were similar to Cycle-1. Mares had an untreated estrous cycle (no treatment or breeding) between Cycle-2 and the MS-Cycle. All mares developed follicle(s) > or =35mm after 4.9+/-0.6 days of eFSH treatment, and subsequently ovulations occurred; mean (95% CI) interval from treatment initiation to ovulation was 7.9 (6.5-9.3) days. The number of preovulatory follicles (> or =30mm) at the time of hCG administration (Cycle-1: 2.2+/-0.3 compared with Cycle-2: 1.0+/-0 compared with MS-Cycle: 1.1+/-0.1 follicles), and the number of ovulations (2.5+/-0.4 compared with 1.0+/-0 compared with 1.1+/-0.1 ovulations) were greater (p<0.05) in Cycle-1. Nevertheless, mean embryo numbers did not differ among cycles (0.8+/-0.2 compared with 0.5+/-0.1 compared with 0.5+/-0.1 embryo/mare). On average, embryo morphology grade was less (p<0.05) in Cycle-1 as compared to non-eFSH cycles (combined Cycle-2 and MS-Cycle). This impaired embryo quality could be due to a seasonal effect, or negative effect of the eFSH treatment, which was possibly related to alterations in the hormonal environment (estradiol-17beta and progesterone). A prolonged IOI (>21 days) was recorded in 7 of 15 mares following the Cycle-1 ovulation, but not subsequently. In conclusion, eFSH treatment of vernal transitional donor mares stimulated ovulation within only few days of treatment, and the following embryo recovery rate was at least as good as in the subsequent estrous cycles; however, on average, embryos were morphologically impaired. In subsequent estrous cycles in the breeding season, ovulations, embryo recovery rates, and embryo variables did not appear to be negatively affected; however, the first inter-ovulatory interval of the breeding season was prolonged in approximately half of the mares. PMID:19171444

Raz, Tal; Hunter, Barbara; Carley, Sylvia; Card, Claire

2008-12-24

336

ParA-like protein uses nonspecific chromosomal DNA binding to partition protein complexes  

PubMed Central

Recent data have shown that plasmid partitioning Par-like systems are used by some bacterial cells to control localization of protein complexes. Here we demonstrate that one of these homologs, PpfA, uses nonspecific chromosome binding to separate cytoplasmic clusters of chemotaxis proteins upon division. Using fluorescent microscopy and point mutations, we show dynamic chromosome binding and Walker-type ATPase activity are essential for cluster segregation. The N-terminal domain of a cytoplasmic chemoreceptor encoded next to ppfA is also required for segregation, probably functioning as a ParB analog to control PpfA ATPase activity. An orphan ParA involved in segregating protein clusters therefore uses a similar mechanism to plasmid-segregating ParA/B systems and requires a partner protein for function. Given the large number of genomes that encode orphan ParAs, this may be a common mechanism regulating segregation of proteins and protein complexes.

Roberts, Mark A. J.; Wadhams, George H.; Hadfield, Katie A.; Tickner, Susan; Armitage, Judith P.

2012-01-01

337

The ParA/MinD family puts things in their place  

PubMed Central

Bacteria must segregate their DNA and position a septum to grow and divide. In many bacteria MinD is involved in spatial regulation of the cytokinetic Z ring and ParAs are involved in chromosome and plasmid segregation. The use of the MinD/ParA family to provide positional information for spatial organization continues to expand with the recognition that orphan ParAs are required for segregating cytoplasmic protein clusters and the polar localization of chemotaxis proteins, conjugative transfer machinery, type IV pili and cellulose synthesis. Also, some bacteria lacking MinD use orphan ParAs to regulate cell division. Positioning of MinD/ParA proteins is either due to self-organization on a surface or reliance on a landmark protein which functions as a molecular beacon.

Lutkenhaus, Joe

2012-01-01

338

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions  

PubMed Central

The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion.

Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

2003-01-01

339

Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner.  

PubMed

Thrombin is a multifunctional coagulation protease with pro- and anti-inflammatory vascular effects. We questioned whether thrombin may have segmentally differentiated effects on pulmonary endothelium. In cultured rat endothelial cells, rat thrombin (10 U/ml) recapitulated the previously reported decrease in transmonolayer electrical resistance (TER), F-actin stress fiber formation, paracellular gap formation, and increased permeability. In contrast, in rat pulmonary microvascular endothelial cells (PMVEC), isolated on the basis of Griffonia simplicifolia lectin recognition, thrombin increased TER, induced fewer stress fibers, and decreased permeability. To assess for differential proteinase-activated receptor (PAR) expression as a basis for the different responses, PAR family expression was analyzed. Both pulmonary artery endothelial cells and PMVEC expressed PAR-1 and PAR-2; however, only PMVEC expressed PAR-3, as shown by both RT-PCR and Western analysis. PAR-1 activating peptides (PAR-APs: SFLLRN-NH(2) and TFLLRN-NH(2)) were used to confirm a role for the PAR-1 receptor. PAR-APs (25-250 muM) also increased TER, formed fewer stress fibers, and did not induce paracellular gaps in PMVEC in contrast to that shown in pulmonary artery endothelial cells. These results were confirmed in isolated perfused rat lung preparations. PAR-APs (100 mug/ml) induced a 60% increase in the filtration coefficient over baseline. However, by transmission electron microscopy, perivascular fluid cuffs were seen only along conduit veins and arteries without evidence of intra-alveolar edema. We conclude that thrombin exerts a segmentally differentiated effect on endothelial barrier function in vitro, which corresponds to a pattern of predominant perivascular fluid cuff formation in situ. This may indicate a distinct role for thrombin in the microcirculation. PMID:18083763

Troyanovsky, B; Alvarez, D F; King, J A; Schaphorst, K L

2007-12-14

340

La structure des verres étudiée par diffraction des neutrons  

NASA Astrophysics Data System (ADS)

La diffraction des neutrons est une méthode largement utilisée pour déterminer la structure des matériaux amorphes et en particulier des verres. L'utilisation de la méthode de substitution isotopique permet d'extraire les fonctions de distribution de paires partielles centrées autour d'un élément choisi. Nous présentons quelques exemples récents d'études par diffraction des neutrons sur des verres qui ont permis de mieux comprendre à la fois le réseau polymérique de la matrice vitreuse et l'environnement local et à moyenne distance autour des cations. Ces études ont révélées un ordre structural s'étendant au delà des premiers voisins, jusque vers de distances d'environ 10Å. Le couplage avec d'autres méthodes expérimentales (diffraction anormale des rayons X) et des techniques de simulations (dynamique moléculaire, Monte Carlo Inverse ou RMC) sont indispensables pour affiner nos connaissances de la structure des verres.

Cormier, L.

2003-09-01

341

Pars plana vitrectomy and endoresection of a retinal vasoproliferative tumor.  

PubMed

A healthy 31-year-old woman developed decreased vision due to vitreous hemorrhage from 2 retinal vascular lesions. Because of the patient's desire for visual rehabilitation and the concern for von Hippel-Lindau (VHL) disease-associated retinal hemangioblastomas, pars plana vitrectomy and endoresection of both lesions were performed. Surgical techniques included the use of chandelier illumination to enable bimanual manipulation of tissue, endolaser around the tumor prior to resection, endodiathermy to cauterize the tumor's feeder vessels, and long-acting gas tamponade following the retinectomy. Histopathology showed a vascular anomaly within the retina that consisted of multiple large vessels with multiple lumens and no evidence of VHL-associated retinal hemangioblastoma. Long-term follow-up revealed no evidence of recurrent disease. This surgical technique may be valuable in select patients to differentiate between retinal vasoproliferative tumors and VHL disease-associated retinal hemangioblastomas for diagnostic, therapeutic, and counseling purposes. PMID:20837805

Yeh, Steven; Wilson, David J

2010-09-01

342

Fixed-time AI protocols replacing eCG with a single dose of FSH were less effective in stimulating follicular growth, ovulation, and fertility in suckled-anestrus Nelore beef cows.  

PubMed

The aim of the present study was to evaluate the effects of a single treatment with FSH on diameter of the largest follicle and on conception rates of suckled Bos indicus beef cows submitted to timed artificial insemination (TAI). Four hundred fifty-six suckled anestrous Nelore beef cows at 30-60 days postpartum were assigned to treatments. At the first day of the estrous synchronization protocol (Day 0), all cows received a progesterone-releasing intravaginal device plus 2mg of estradiol benzoate. On Day 8, cows were assigned to blocks according to the diameter of the largest follicle and then allocated to one of three treatment groups (Control, FSH, or eCG) within each block. Simultaneously to progesterone device withdrawal on Day 8, cows in the eCG treatment group (n=150) received 300 IU of eCG and cows in FSH treatment group (n=153) received 10mg of FSH, and Control cows (n=153) did not receive any additional treatment. Additional treatments with 150 ?g of cloprostenol and 1mg of estradiol cypionate (EC) were also administered concurrently to progesterone device removal in all cows on Day 8. Two days later (D10), TAI and ovarian ultrasonic examinations to evaluate follicle size were performed in all cows. On Day 12, a subset of cows (n=389) were submitted a second ultrasonic exam to confirm ovulation. Final follicular growth (mm/day) was less (P=0.006) in both Control (0.95±0.11) and in FSH-treated cows (0.90±0.10) than in eCG-treated cows (1.40±0.13). Interestingly, there was a treatment-by-BCS interaction in ovulation results (P=0.03), in which, eCG treatment increased percentage of cows having ovulations with a lesser BCS. Similarly, there was a treatment-by-BCS interaction for conception (P=0.04), where the eCG treatment increased fertility in cows with a lesser BCS. In conclusion, FSH failed to stimulate final follicular growth, ovulation, and conception rate in sucked-anestrous beef cows submitted to TAI as effectively as eCG. However, physiological effects of eCG seem to be more evident in cows with a lesser BCS. PMID:21376482

Sales, J N S; Crepaldi, G A; Girotto, R W; Souza, A H; Baruselli, P S

2011-02-13

343

A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl  

Microsoft Academic Search

The evolutionarily conserved proteins Par-6, atypical protein kinase C (aPKC), Cdc42 and Par-3 associate to regulate cell polarity and asymmetric cell division, but the downstream targets of this complex are largely unknown. Here we identify direct physiological interactions between mammalian aPKC, murine Par-6C (mPar-6C) and Mlgl, the mammalian orthologue of the Drosophila melanogaster tumour suppressor Lethal (2) giant larvae. In

Pamela J. Plant; James P. Fawcett; Dan C. C. Lin; Amy D. Holdorf; Kathleen Binns; Sarang Kulkarni; Tony Pawson

2003-01-01

344

Étude comparative des techniques d'analyse par fluorescence X à dispersion d'énergie (ED-XRF) et à dispersion de longueur d'onde (WD-XRF), et par spectrométrie d'émission atomique à source plasma couplée par induction (ICP-AES)  

Microsoft Academic Search

Dans ce travail, nous présentons une étude comparative des techniques d'analyse par fluorescence X à dispersion d'énergie (ED-XRF) et à dispersion de longueur d'onde (WD-XRF), et par spectrométrie d'émission atomique à source plasma couplée par induction (ICP-AES). Les résultats de la calibration des spectromètres à dispersion d'énergie, à excitation par sources radioactives (55Fe, 109Cd et 241Am) et à excitation secondaire

A. Rahmani; F. Benyaïch; M. Bounakhla; E. Bilal; J. Moutte; J. J. Gruffat; F. Zahry

2004-01-01

345

An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway  

PubMed Central

Activated protein C (APC) is a protease with anticoagulant and cell-signaling activities. In the central nervous system, APC and its analogs with reduced anticoagulant activity but preserved cell signaling activities, such as 3K3A-APC, exert neuroprotective, vasculoprotective and anti-inflammatory effects. Murine APC promotes subependymal neurogenesis in rodents in vivo after ischemic and traumatic brain injury. Whether human APC can influence neuronal production from resident progenitor cells in humans is unknown. Here we show that 3K3A-APC, but not S360A-APC (an enzymatically inactive analog of APC), stimulated neuronal mitogenesis and differentiation from fetal human neural stem and progenitor cells (NPCs). 3K3A-APC’s effects on proliferation and differentiation were comparable to those respectively obtained with fibroblast growth factor and brain-derived growth factor. Its promoting effect on neuronal differentiation was accompanied by inhibition of astroglial differentiation. In addition, 3K3A-APC exerted modest anti-apoptotic effects during neuronal production. These effects appeared mediated through specific protease activated (PAR) and sphingosine-1-phosphate (S1PR) receptors, in that siRNA-mediated inhibition of PARs 1–4 and S1PRs 1–5 revealed that PAR1, PAR3 and S1PR1 are required for the neurogenic effects of 3K3A-APC. 3K3A-APC activated Akt, a downstream target of S1PR1, which was inhibited by S1PR1, PAR1 and PAR3 silencing. Adenoviral transduction of NPCs with a kinase-defective Akt mutant abolished the effects of 3K3A-APC on NPCs, confirming a key role of Akt activation in 3K3A-APC-mediated neurogenesis. Thus, APC and its pharmacological analogues, by influencing PAR and S1PR signals in resident neural progenitor cells, may be potent modulators of both development and repair in the human CNS.

Guo, Huang; Zhao, Zhen; Yang, Qi; Wang, Min; Bell, Robert D.; Wang, Su; Chow, Nienwen; Davis, Thomas P.; Griffin, John H.; Goldman, Steven A.; Zlokovic, Berislav V.

2013-01-01

346

DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila.  

PubMed

The Drosophila protein Bazooka is required for both apical-basal polarity in epithelial cells and directing asymmetric cell division in neuroblasts. Here we show that the PDZ-domain protein DmPAR-6 cooperates with Bazooka for both of these functions. DmPAR-6 colocalizes with Bazooka at the apical cell cortex of epithelial cells and neuroblasts, and binds to Bazooka in vitro. DmPAR-6 localization requires Bazooka, and mislocalization of Bazooka through overexpression redirects DmPAR-6 to ectopic sites of the cell cortex. In the absence of DmPAR-6, Bazooka fails to localize apically in neuroblasts and epithelial cells, and is distributed in the cytoplasm instead. Epithelial cells lose their apical-basal polarity in DmPAR-6 mutants, asymmetric cell divisions in neuroblasts are misorientated, and the proteins Numb and Miranda do not segregate correctly into the basal daughter cell. Bazooka and DmPAR-6 are Drosophila homologues of proteins that direct asymmetric cell division in early Caenorhabditis elegans embryos, and our results indicate that homologous protein machineries may direct this process in worms and flies. PMID:11146625

Petronczki, M; Knoblich, J A

2001-01-01

347

Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer.  

PubMed

Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and (111)In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard (18)F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope (177)Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology. PMID:23400595

LeBeau, Aaron M; Duriseti, Sai; Murphy, Stephanie T; Pepin, Francois; Hann, Byron; Gray, Joe W; VanBrocklin, Henry F; Craik, Charles S

2013-02-11

348

The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.  

PubMed

The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system. PMID:19461880

Hovius, Joppe W R; Bijlsma, Maarten F; van der Windt, Gerritje J W; Wiersinga, W Joost; Boukens, Bastiaan J D; Coumou, Jeroen; Oei, Anneke; de Beer, Regina; de Vos, Alex F; van 't Veer, Cornelis; van Dam, Alje P; Wang, Penghua; Fikrig, Erol; Levi, Marcel M; Roelofs, Joris J T H; van der Poll, Tom

2009-05-22

349

The activin receptor-like kinase 6 Booroola mutation enhances suppressive effects of bone morphogenetic protein 2 (BMP2), BMP4, BMP6 and growth and differentiation factor-9 on FSH release from ovine primary pituitary cell cultures  

Microsoft Academic Search

Bone morphogenetic proteins (BMPs) have been shown to influence the regulation of FSH synthesis and secretion at the level of the pituitary. Primary pituitary cells were harvested and cultured from Booroola ewes homozygous for a mutation in activin receptor-like kinase 6 (ALK6) also known as BMP receptor IB (BMPRIB), and from wild-type (WT) ewes to determine if the mutation caused

Julia M Young; Jennifer L Juengel; Kenneth G Dodds; Mhairi Laird; Peter K Dearden; Alan S McNeilly; Kenneth P McNatty; Theresa Wilson

2008-01-01

350

Thrombin induces rapid PAR1-mediated non-classical FGF1 release  

SciTech Connect

Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis.

Duarte, Maria [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kolev, Vihren [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Soldi, Raffaella [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kirov, Alexander [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Graziani, Irene [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Oliveira, Silvia Marta [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Kacer, Doreen [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Friesel, Robert [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Maciag, Thomas [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States); Prudovsky, Igor [Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 (United States)]. E-mail: prudoi@mmc.org

2006-11-24

351

A functioning FSH-secreting pituitary macroadenoma causing an ovarian hyperstimulation syndrome with multiple cysts resected and relapsed after leuprolide in a reproductive-aged woman.  

PubMed

Bioactive gonadotropin-secreting pituitary adenomas are very rare in fertile women and can cause an ovarian hyperstimulation syndrome (OHSS). A 31-year-old woman with oligo-amenorrhea, severe ovarian cystic swelling and high serum estradiol was submitted to the resection of ovarian cysts and then treated with long-acting leuprolide 11.25 mg. Two months later, the ovarian multicystic hyperplasia relapsed, thus a pituitary MRI was performed and a pituitary macroadenoma was detected. In January 2010, she was referred to our Endocrinology Department where her hormonal evaluation showed high serum estradiol, FSH, ?-subunit and inhibin with low LH. In April 2010, she underwent a trans-sphenoidal pituitary adenomectomy, which rapidly regularized the hormonal profile, the ovary and pituitary morphology and the menses. The case presented confirms that gonadotrophinomas occurring in reproductive-aged women frequently produce symptoms of ovarian hyperstimulation and proves that the use of GnRH analogs is not indicated in this condition. PMID:21770827

Macchia, Enrico; Simoncini, Tommaso; Raffaelli, Valentina; Lombardi, Martina; Iannelli, Aldo; Martino, Enio

2011-07-20

352

Differentiation of chicken gonad as an endocrine organ: expression of LH receptor, FSH receptor, cytochrome P450c17 and aromatase genes.  

PubMed

The gonad is an endocrine organ secreting sex hormones and also a target of pituitary gonadotrophins. The expression of mRNAs encoding LH receptor (LHR), FSH receptor (FSHR), P450c17 and P450aromatase in the developing gonads of embryos between day 4 and day 6 of incubation was determined using a RT-PCR to elucidate the chicken gonad as a target organ of gonadotrophins. Although expression of mRNAs encoding LHR, FSHR and P450c17 was detected at day 4 of incubation in both sexes, mRNA encoding P450aromatase appeared at day 6 in female embryos only, indicating that mRNAs encoding gonadotrophin receptors can be identified before sexual differentiation. Quantitative PCR analysis revealed that expression of mRNA encoding LHR and FSHR remained low in male gonads from day 4 to day 6 of incubation, whereas they increased on day 6 in female gonads. The sexual dimorphism in the expression of mRNAs encoding LHR and FSHR was confirmed in the sexually differentiated gonads of embryos at day 12 of incubation (LHR in ovary ratio LHR in testis = 7 ratio 1; FSHR in ovary ratio FSHR in testis = 9 ratio 1). PMID:12006100

Akazome, Y; Abe, T; Mori, T

2002-05-01

353

Cloud-Induced Variability of Photosynthetically Active Radiation, Tropical Forest PAR Absorption and Photosynthesis in Central Borneo  

NASA Astrophysics Data System (ADS)

Ground-based measurements of total and diffuse photosynthetically active radiation (PAR, 400-700 nm) were combined with process modeling to investigate the effects of atmospheric scattering by clouds on the surface PAR regime, simulated forest canopy PAR absorption and photosynthetic rates for a moist tropical site at Putussibau, West Kalimantan Province, Indonesia (0.84N, 112.93E). Time-series PAR data collected in 2007 are characterized by large diffuse PAR fractions and frequent occurrence of enhanced global PAR irradiance (relative to cloudless sky conditions) associated with 3-D scattering by the broken cloud fields that typify this region. Model estimates of canopy-absorbed PAR and gross photosynthesis from the Forest Light Environmental Simulator (FLiES) demonstrate the role of clouds in controlling forest canopy light-use efficiency and rates of photosynthesis and vegetation-atmosphere carbon exchange in this moist tropical environment.

Dye, D. G.; Kobayashi, H.; Wu, P.; Syamsudin, F.; Sulistyowati, R.; Sarodja, D.

2008-05-01

354

Four cases of endophthalmitis after 25-gauge pars plana vitrectomy  

PubMed Central

We report our recent experience with four cases of endophthalmitis (one male, three females) after 25-gauge pars plana vitrectomy (PPV). One was a case of persistent cystoid macular edema caused by branch retinal vein occlusion, whereas the remaining three were cases of epiretinal membrane. Preoperative antibiotics before the first PPV procedure were not administered in three of the four cases. Endophthalmitis occurred 2–4 days after the first procedure in all cases, for which ceftazidime 2.0 mg/0.1 mL and vancomycin 1.0 mg/0.1 mL were injected into the vitreous cavity. This was followed by emergent 20-gauge PPV and intraocular lens removal using an infusion fluid containing ceftazidime and vancomycin. After the second PPV procedure, progress was good in three cases while retinal detachment occurred in the remaining case one month after surgery; this case required a third PPV procedure. Final best-corrected visual acuity ranged from 20/100 to 20/25 for the four cases. Bacterial cultures were negative after the second PPV procedure in all cases. In conclusion, postoperative endophthalmitis occurred in four of 502 cases (0.80%) that underwent 25-gauge PPV at our hospital. It is important to minimize the incidence of endophthalmitis after 25-gauge PPV.

Mutoh, Tetsuya; Kadoya, Koji; Chikuda, Makoto

2012-01-01

355

Photometric monitoring of the young star Par 1724 in Orion  

NASA Astrophysics Data System (ADS)

We report new photometric observations of the ˜ 200 000 year old naked weak-line run-away T Tauri star Par 1724, located north of the Trapezium cluster in Orion. We observed in the broad band filters B, V, R, and I using the 90 cm Dutch telescope on La Silla, the 80 cm Wendelstein telescope, and a 25 cm telescope of the University Observatory Jena in Großschwabhausen near Jena. The photometric data in V and R are consistent with a ˜ 5.7 day rotation period due to spots, as observed before between 1960ies and 2000. Also, for the first time, we present evidence for a long-term 9 or 17.5 year cycle in photometric data (V band) of such a young star, a cycle similar to that to of the Sun and other active stars. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University; a telescope of the University Observatory Munich on Mount Wendelstein, the 0.9m ESO-Dutch telescope on La Silla, Chile, and with the All Sky Automated Survey (ASAS) project (www.astrouw.edu.pl/asas).

Neuhäuser, R.; Koeltzsch, A.; Raetz, St.; Schmidt, T. O. B.; Mugrauer, M.; Young, N.; Bertoldi, F.; Roell, T.; Eisenbeiss, T.; Hohle, M. M.; Va?ko, M.; Ginski, C.; Rammo, W.; Moualla, M.; Broeg, C.

2009-05-01

356

Intravitreous granulation tissue and retinal detachment following pars plana injection for cytomegalovirus retinopathy  

Microsoft Academic Search

Recently, the pars plana route of injection has been used to administer drugs for the treatment of severe intraocular infections. We observed a complication of this method in a patient with AIDS and cytomegalovirus (CMV) retinopathy.

Allan E. Kreiger; Robert Y. Foos; Marc O. Yoshizumi

1992-01-01

357

NASA Signs Agreement with PaR Systems for Use of Unique Facility  

NASA Website

NASA's Kennedy Space Center in Florida has signed a new partnership agreement with PaR Systems Inc. of Shoreview, Minn., for use of the Hangar N facility and its unique nondestructive testing (NDT) equipment.

358

78 FR 42584 - Additional Designation of Aluminat, Pars Amayesh Sanaat Kish, Parviz Khaki, Pishro Systems...  

Federal Register 2010, 2011, 2012, 2013

...Arak Road, Parcham Street, Arak, Iran PARS Amayesh Sanaat Kish AKA: PASK AKA: Vacuumkaran AKA: Vacuum Karan AKA: Vacuum Karan Co. Address: 3rd Floor, No. 6, East 2nd, North Kheradmand, Karimkhan Street, Tehran, Iran Parviz...

2013-07-16

359

Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex.  

PubMed

PDZ protein interaction domains are typically selective for C-terminal ligands, but non-C-terminal, 'internal' ligands have also been identified. The PDZ domain from the cell polarity protein Par-6 binds C-terminal ligands and an internal sequence from the protein Pals1/Stardust. The structure of the Pals1-Par-6 PDZ complex reveals that the PDZ ligand-binding site is deformed to allow for internal binding. Whereas binding of the Rho GTPase Cdc42 to a CRIB domain adjacent to the Par-6 PDZ regulates binding of C-terminal ligands, the conformational change that occurs upon binding of Pals1 renders its binding independent of Cdc42. These results suggest a mechanism by which the requirement for a C terminus can be readily bypassed by PDZ ligands and reveal a complex set of cooperative and competitive interactions in Par-6 that are likely to be important for cell polarity regulation. PMID:15475968

Penkert, Rhiannon R; DiVittorio, Heather M; Prehoda, Kenneth E

2004-10-10

360

Model parameterization to simulate and compare the PAR absorption potential of two competing plant species.  

PubMed

Mountain pastures dominated by the pasture grass Setaria sphacelata in the Andes of southern Ecuador are heavily infested by southern bracken (Pteridium arachnoideum), a major problem for pasture management. Field observations suggest that bracken might outcompete the grass due to its competitive strength with regard to the absorption of photosynthetically active radiation (PAR). To understand the PAR absorption potential of both species, the aims of the current paper are to (1) parameterize a radiation scheme of a two-big-leaf model by deriving structural (LAI, leaf angle parameter) and optical (leaf albedo, transmittance) plant traits for average individuals from field surveys, (2) to initialize the properly parameterized radiation scheme with realistic global irradiation conditions of the Rio San Francisco Valley in the Andes of southern Ecuador, and (3) to compare the PAR absorption capabilities of both species under typical local weather conditions. Field data show that bracken reveals a slightly higher average leaf area index (LAI) and more horizontally oriented leaves in comparison to Setaria. Spectrometer measurements reveal that bracken and Setaria are characterized by a similar average leaf absorptance. Simulations with the average diurnal course of incoming solar radiation (1998-2005) and the mean leaf-sun geometry reveal that PAR absorption is fairly equal for both species. However, the comparison of typical clear and overcast days show that two parameters, (1) the relation of incoming diffuse and direct irradiance, and (2) the leaf-sun geometry play a major role for PAR absorption in the two-big-leaf approach: Under cloudy sky conditions (mainly diffuse irradiance), PAR absorption is slightly higher for Setaria while under clear sky conditions (mainly direct irradiance), the average bracken individual is characterized by a higher PAR absorption potential. (approximately 74 MJ m(-2) year(-1)). The latter situation which occurs if the maximum daily irradiance exceeds 615 W m(-2) is mainly due to the nearly orthogonal incidence of the direct solar beam onto the horizontally oriented frond area which implies a high amount of direct PAR absorption during the noon maximum of direct irradiance. Such situations of solar irradiance favoring a higher PAR absorptance of bracken occur in approximately 36% of the observation period (1998-2005). By considering the annual course of PAR irradiance in the San Francisco Valley, the clear advantage of bracken on clear days (36% of all days) is completely compensated by the slight but more frequent advantage of Setaria under overcast conditions (64% of all days). This means that neither bracken nor Setaria show a distinct advantage in PAR absorption capability under the current climatic conditions of the study area. PMID:19937454

Bendix, Jörg; Silva, Brenner; Roos, Kristin; Göttlicher, Dietrich Otto; Rollenbeck, Rütger; Nauss, Thomas; Beck, Erwin

2009-11-25

361

PAR2-induced inflammatory responses in human kidney tubular epithelial cells.  

PubMed

Protease-activated receptor-2 (PAR2) is a G protein-coupled receptor abundantly expressed in the kidney. The aim of this study was to profile inflammatory gene and protein expression induced by PAR2 activation in human kidney tubular epithelial cells (HTEC). A novel PAR2 antagonist, GB88, was used to confirm agonist specificity. Intracellular Ca(2+) (iCa(2+)) mobilization, confocal microscopy, gene expression profiling, qRTPCR, and protein expression were used to characterize PAR2 activation. PAR2 induced a pronounced increase in iCa(2+) concentration that was blocked by the PAR2 antagonist. Treatment with SLIGKV-NH2 at the apical or basolateral cell surface for 5 h induced expression of a range of inflammatory genes by greater than fourfold, including IL-1?, TRAF1, IL-6, and MMP-1, as assessed by cDNA microarray and qRTPCR analysis. Using antibody arrays, GM-CSF, ICAM-1, TNF-?, MMP-1, and MMP-10 were among the induced proteins secreted. Cytokine-specific ELISAs identified three- to sixfold increases in GM-CSF, IL-6, IL-8, and TNF-?, which were blocked by GB88 and protein kinase C inhibitors. Treatment of cells at the basolateral surface induced more potent inflammatory responses, with release of MCP-1 and fibronectin to the apical and basolateral compartments; apical treatment only increased secretion of these factors to the apical compartment. PAR2 activation at the basolateral surface dramatically reduced transepithelial electrical resistance (TEER) whereas apical treatment had no effect. There was very little leakage (<5%) of peptides across the cell monolayer (liquid chromatography-mass spectrometry). In summary, SLIGKV-NH2 induced robust proinflammatory responses in HTEC that were antagonized by GB88. These results suggest that PAR2 antagonists could be useful disease-modifying, anti-inflammatory agents in kidney disease. PMID:23283995

Vesey, David A; Suen, Jacky Y; Seow, Vernon; Lohman, Rink-Jan; Liu, Ligong; Gobe, Glenda C; Johnson, David W; Fairlie, David P

2013-01-02

362

Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells  

PubMed Central

Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37 and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150 and Arg-154) and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R.

2012-01-01

363

UV-B and PAR in a grass (Lolium perenne L.) canopy  

Microsoft Academic Search

The penetration of natural and artificial UV-BBE (Biologically Effective UV-B, Caldwell 1971) and PAR (400–700 nm) in a grass canopy with increasing LAI was followed during 2 months. Overall, the transmission of UV-BBE sunlight is significantly higher than of PAR sunlight. This is mainly due to the higher proportion of diffuse light in the UV-B. Under cloudy conditions no difference

Gaby Deckmyn; Ivan Impens

1998-01-01

364

Combined pars plana vitrectomy and glaucoma drainage implant placement for refractory glaucoma  

Microsoft Academic Search

PURPOSE:To report visual acuity and intraocular pressure outcomes among patients who have undergone combined pars plana vitrectomy and placement of a glaucoma drainage implant.METHODS:The medical records of all patients who underwent combined pars plana vitrectomy and placement of a glaucoma drainage implant at the Bascom Palmer Eye Institute by one of the authors between January 1, 1990, and February 28,

Ingrid U Scott; George Alexandrakis; Harry W Flynn; William E Smiddy; Timothy G Murray; Joyce Schiffman; Steven J Gedde; Donald L Budenz; Francisco Fantes; Richard K Parrish

2000-01-01

365

Nd:YAG vitreolysis and pars plana vitrectomy: surgical treatment for vitreous floaters  

Microsoft Academic Search

Purpose of study To determine the efficacy of Nd:YAG vitreolysis and pars plana vitrectomy in the treatment of vitreous floaters.Methods This is a single centre retrospective study of 31 patients (42 eyes) who underwent 54 procedures, Nd:YAG vitreolysis or pars plana vitrectomy, for the treatment of vitreous floaters between January 1992 and December 2000. Main outcome measures were percentage symptomatic

Y M Delaney; A Oyinloye; L Benjamin

2002-01-01

366

‘Mini-Gauge’ Pars Plana Vitrectomy: ‘Inside-Out View’ with the GRIN Solid Rod Endoscope  

Microsoft Academic Search

Purpose: To stimulate the discussion about ‘mini-gauge’ pars plana vitrectomy. Methods: Gradient index high-resolution endoscopy to analyze the 23- or 25-gauge access into the vitreous cavity. A total number of 66 pars plana interventions (almost 200 cannulas) were performed and recorded with the gradient index solid rod endoscope as well as through the microscope. Results: Five main ‘inside-out’ observations were

Frank H. J. Koch; K. Peter Luloh; Pankaj Singh; Stephan Scholtz; Michael Koss

2007-01-01

367

Immediate pars plana vitrectomy for dislocated intravitreal lens fragments during cataract surgery  

Microsoft Academic Search

PurposeTo assess the outcome of patients who underwent instantaneous pars plana vitrectomy for dislocated lens fragments during cataract surgery.MethodsThe medical records of 29 patients who underwent immediate pars plana vitrectomy for dislocated lens fragments at the same sitting of phacoemulsification surgery were reviewed. Data including patients' demographics, preoperative and postoperative vision, risk factors for lens fragment dislocation, and intraoperative and

T Y Y Lai; A K H Kwok; Y-S Yeung; K Y W Kwan; D C F Woo; K S C Yuen; A V P Loo; AKH Kwok

2005-01-01

368

Une justification par les comptes de surplus des subventions à l'agriculture  

Microsoft Academic Search

[fre] Face à revenus qui agriculteurs revendiquent réajustements en renâclant à passer pour des assistés. L'aide qu'ils sollicitent auprès de l'Etat ne représente en fait qu'une contre-partie d'un trop perçu par les agents implantés aussi bien en amont qu'en aval de la filière agroalimentaire. Les subventions accordées, loin d'être des largesses, ne sont qu'une restitution de gains grandement mérités par

Michel Bourdon

1982-01-01

369

Elements Optiques Holographiques Generes Par Ordinateur a Fonction de Phase Semi-Continue et Distribuee  

Microsoft Academic Search

Occupant une place grandissante dans la conception optique, les elements optiques holographiques (EOH) peuvent accomplir des taches qui seraient difficilement rendues par un groupe d'elements optiques conventionnels. Dans plusieurs systemes optiques utilisant une source laser, ces elements holographiques permettent d'imaginer des systemes optiques jusqu'ici impossibles a construire. Par consequent, ce type d'hologramme permet aux concepteurs la fabrication d'elements optiques speciaux.

Guylain Lemelin

1995-01-01

370

Étude par simulation numérique de l'annihilation en surface d'une dislocation coin  

Microsoft Academic Search

Nous avons étudié par simulation numérique à l'échelle atomique la stabilité d'une dislocation coin, de plan de glissement proche et parallèle à une surface libre. La même étude à été conduite pour le débris idéalisé d'annihilation d'une telle dislocation : une cavité de longueur infinie, de section rectangulaire et de profondeur variable, créée par élimination partielle d'atomes appartenant à deux

P. Geysermans; V. Pontikis

2003-01-01

371

Pars plana vitrectomy for diabetic fibrovascular proliferation with and without internal limiting membrane peeling  

Microsoft Academic Search

ObjectiveTo evaluate the anatomical and functional results of internal limiting membrane (ILM) peeling during pars plana vitrectomy for fibrovascular proliferation (FVP) in diabetic retinopathy.MethodsThe study was a prospective comparative case series in design. Patients undergoing pars plana vitrectomy for mild to moderate diabetic FVP were divided into either Group 1: vitrectomy only, or Group 2: further ILM peeling in the

P-Y Chang; C-M Yang; C-H Yang; M-S Chen; J-Y Wang

2009-01-01

372

Identification of uPAR-positive Chemoresistant Cells in Small Cell Lung Cancer  

Microsoft Academic Search

BackgroundThe urokinase plasminogen activator (uPA) and its receptor (uPAR\\/CD87) are major regulators of extracellular matrix degradation and are involved in cell migration and invasion under physiological and pathological conditions. The uPA\\/uPAR system has been of great interest in cancer research because it is involved in the development of most invasive cancer phenotypes and is a strong predictor of poor patient

Margarita Gutova; Joseph Najbauer; Anna Gevorgyan; Marianne Z. Metz; Yehua Weng; Chu-Chih Shih; Karen S. Aboody; Christopher Arendt

2007-01-01

373

Recruitment of the ParG Segregation Protein to Different Affinity DNA Sites? §  

PubMed Central

The segrosome is the nucleoprotein complex that mediates accurate plasmid segregation. In addition to its multifunctional role in segrosome assembly, the ParG protein of multiresistance plasmid TP228 is a transcriptional repressor of the parFG partition genes. ParG is a homodimeric DNA binding protein, with C-terminal regions that interlock into a ribbon-helix-helix fold. Antiparallel ?-strands in this fold are presumed to insert into the OF operator major groove to exert transcriptional control as established for other ribbon-helix-helix factors. The OF locus comprises eight degenerate tetramer boxes arranged in a combination of direct and inverted orientation. Each tetramer motif likely recruits one ParG dimer, implying that the fully bound operator is cooperatively coated by up to eight dimers. OF was subdivided experimentally into four overlapping 20-bp sites (A to D), each of which comprises two tetramer boxes separated by AT-rich spacers. Extensive interaction studies demonstrated that sites A to D individually are bound with different affinities by ParG (C > A ? B ? D). Moreover, comprehensive scanning mutagenesis revealed the contribution of each position in the site core and flanking sequences to ParG binding. Natural variations in the tetramer box motifs and in the interbox spacers, as well as in flanking sequences, each influence ParG binding. The OF operator apparently has evolved with sites that bind ParG dissimilarly to produce a nucleoprotein complex fine-tuned for optimal interaction with the transcription machinery. The association of other ribbon-helix-helix proteins with complex recognition sites similarly may be modulated by natural sequence variations between subsites.

Zampini, Massimiliano; Derome, Andrew; Bailey, Simon E. S.; Barilla, Daniela; Hayes, Finbarr

2009-01-01

374

Embryonic development of the pars intercerebralis\\/central complex of the grasshopper  

Microsoft Academic Search

We have studied the embryonic development of the pars intercerebralis\\/central complex in the brain of the grasshopper using\\u000a immunocytochemical and histochemical techniques. Expression of the cell-surface antigen lachesin reveals that the neuroblasts\\u000a of the pars intercerebralis first differentiate from the neuroectoderm at around 26% of embryogenesis. Differentiation of\\u000a medial and lateral neuroblasts occurs first. By the 28% stage a more

G. S. Boyan; J. L. D. Williams

1997-01-01

375

Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation in migrating cells  

PubMed Central

Summary Background Centrosome orientation toward the leading edge of migrating cells depends on dynein and microtubules (MTs) and as well on a number of signaling factors at the leading edge. However, centrosomes are maintained at the cell center during orientation in fibroblasts suggesting that factors working at sites other than the leading edge may also be involved. Results In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of the centrosome at the cell center, the same phenotype as that observed with dynein inhibition. Par3 associated with dynein through its N-terminal dimerization and PDZ1 domains, and interacted specifically with dynein light intermediate chain 2 (LIC2). siRNA knockdown of LIC2, but not LIC1, or overexpression of LIC2 or the N-terminal domain of Par3, also inhibited centrosome orientation by disrupting centrosome position. Par3 specifically localized to cell-cell contacts in wound-edge fibroblasts where it overlapped with MT ends and dynein puncta in a LIC2 dependent fashion. Live imaging showed that MTs exhibited increased pausing at cell-cell contacts compared to the leading edge and that this elevated pausing was dependent on Par3 and LIC2. Conclusion Par3 associates with dynein and contributes to the local regulation of MT dynamics at cell-cell contacts and proper positioning of the centrosome at the cell center. We propose that Par3 acts as a cortical factor that tethers MTs through its association with LIC2-dynein.

Schmoranzer, J.; Fawcett, J. P.; Segura, M.; Tan, S.; Vallee, R. B.; Pawson, T.; Gundersen, G. G.

2009-01-01

376

Evolution Des Recherches Sur Les Plants Mycorhizes Par la Truffe et Perspectives de Developpement  

Microsoft Academic Search

La mise au point d'une méthode de production de plants mycorhizés par la truffe, en France, date du début des années 70. Depuis, les grands principes de la méthode utilisée n'ont pas subi d'évolution importante. La majorité des plants sont obtenus par semis et inoculés avec des préparations à base de spores de truffe. Cette pratique entraïne une hétérogénéité du

G. Chevalier

1994-01-01

377

Pseudopodial and ?-arrestin-interacting proteomes from migrating breast cancer cells upon PAR2 activation.  

PubMed

Metastatic cancer cells form pseudopodia (PD) to facilitate their migration. The proteinase-activated receptor-2 (PAR-2) transduces migratory signals from proteases, and it forms protein complexes with ?-arrestin and other signalling molecules that are enriched in pseudopodia. More generally, however, pseudopodial regulation is poorly understood. Here, we purified the pseudopodial proteomes of breast cancer cells after activation of the endogenous PAR-2 and we combined gel-based approaches with label-free high-resolution mass spectrometry to identify proteins that accumulate at the pseudopodia upon PAR-2-mediated migration. We identified >410 proteins in the cell body and >380 in the pseudopodia upon PAR2 activation, of which 93 were enriched in the pseudopodia. One of the pathways strongly enriched in the PD was the clathrin-mediated endocytosis signalling pathway, highlighting the importance of the scaffolding function of ?-arrestin in PAR-2 signalling via its endocytosis. We therefore immunoprecipitated ?-arrestins, and with mass spectrometry we identified 418 novel putative interactors. These data revealed novel ?-arrestin functions that specifically control PAR-2-regulated signalling in migrating breast cancer cells but also showed that some ?-arrestin functions are universal between GPCRs and cell types. In conclusion, this study reveals novel proteins and signalling pathways potentially important for migration of breast cancer cells. PMID:23313222

Parisis, Nikolaos; Metodieva, Gergana; Metodiev, Metodi V

2013-01-01

378

Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4.  

PubMed

The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo. Today, investigations in worms, flies and mammals have established PAR proteins as conserved and fundamental regulators of animal cell polarization in a broad range of biological phenomena requiring cellular asymmetries. The human homologue of invertebrate PAR-4, a serine-threonine kinase LKB1/STK11, has caught attention as a gene behind Peutz-Jeghers polyposis syndrome and as a bona fide tumour suppressor gene commonly mutated in sporadic cancer. LKB1 functions as a master regulator of AMP-activated protein kinase (AMPK) and 12 other kinases referred to as the AMPK-related kinases, including four human homologues of PAR-1. The role of LKB1 as part of the energy sensing LKB1-AMPK module has been intensively studied, whereas the polarity function of LKB1, in the context of homoeostasis or cancer, has gained less attention. Here, we focus on the PAR-4 identity of LKB1, discussing the weight of evidence indicating a role for LKB1 in regulation of cell polarity and epithelial integrity across species and highlight recent investigations providing new insight into the old question: does the PAR-4 identity of LKB1 matter in cancer? PMID:24062587

Partanen, Johanna I; Tervonen, Topi A; Klefström, Juha

2013-09-23

379

PAR-4 as a Possible New Target for Pancreatic Cancer Therapy  

PubMed Central

Importance of the field Pancreatic cancer (PC) is a deadly disease that is so far intractable to currently available treatment regimens. Although well described in different tumors types, the importance of apoptosis inducer Par-4 in PC has not been appreciated. PC is a oncogenic kras driven disease which is known to down-regulate Par-4. Therefore, this review highlights its significance and builds a strong case supporting the role of Par-4 as a possible therapeutic target in PC. Areas covered in this review This article covers literature based evidence spanning the last 15 years on Par-4 and its significance in PC. What the reader will gain This review provides comprehensive knowledge of the significance of Par-4 and its association with kras status in PC, along with the crosstalk with crucial resistance and survival molecules NF-kB and Bcl-2 that ultimately are responsible for the overall poor outcome of different therapeutic approaches in this disease. Take home message Par-4 holds promise as a potential therapeutic target that can be induced by chemopreventive agents and small molecule inhibitors either alone or in combination with standard chemotherapeutics leading to selective apoptosis in PC cells. It also acts as a chemosensitizer and therefore warrants further clinical investigations in this deadly disease.

Azmi, Asfar S; Philip, Philip A.; Zafar, Syed F.; Sarkar, Fazlul H.; Mohammad, Ramzi M.

2010-01-01

380

Interaction of Par-6 and Crumbs complexes is essential for photoreceptor morphogenesis in Drosophila.  

PubMed

Apicobasal cell polarity is crucial for morphogenesis of photoreceptor rhabdomeres and adherens junctions (AJs) in the Drosophila eye. Crumbs (Crb) is specifically localized to the apical membrane of photoreceptors, providing a positional cue for the organization of rhabdomeres and AJs. We show that the Crb complex consisting of Crb, Stardust (Sdt) and Discs-lost (Dlt) colocalizes with another protein complex containing Par-6 and atypical protein kinase C (aPKC) in the rhabdomere stalk of photoreceptors. Loss of each component of the Crb complex causes age-dependent mislocalization of Par-6 complex proteins, and ectopic expression of Crb intracellular domain is sufficient to recruit the Par-6 complex. We also show that the absence of Par-6 complex proteins results in severe mislocalization and loss of Crb complex. We further demonstrate that Dlt directly binds to Par-6, providing a molecular basis for the mutual dependence of the two complexes. These results suggest that the interaction of Crb and Par-6 complexes is required for the organization and maintenance of apical membranes and AJs of photoreceptors. PMID:12900452

Nam, Sang-Chul; Choi, Kwang-Wook

2003-09-01

381

uPAR-induced cell adhesion and migration: vitronectin provides the key  

PubMed Central

Expression of the membrane receptor uPAR induces profound changes in cell morphology and migration, and its expression correlates with the malignant phenotype of cancers. To identify the molecular interactions essential for uPAR function in these processes, we carried out a complete functional alanine scan of uPAR in HEK293 cells. Of the 255 mutant receptors characterized, 34 failed to induce changes in cell morphology. Remarkably, the molecular defect of all of these mutants was a specific reduction in integrin-independent cell binding to vitronectin. A membrane-tethered plasminogen activator inhibitor-1, which has the same binding site in vitronectin as uPAR, replicated uPAR-induced changes. A direct uPAR–vitronectin interaction is thus both required and sufficient to initiate downstream changes in cell morphology, migration, and signal transduction. Collectively these data demonstrate a novel mechanism by which a cell adhesion molecule lacking inherent signaling capability evokes complex cellular responses by modulating the contact between the cell and the matrix without the requirement for direct lateral protein–protein interactions.

Madsen, Chris D.; Ferraris, Gian Maria Sarra; Andolfo, Annapaola; Cunningham, Orla; Sidenius, Nicolai

2007-01-01

382

ParA2, a Vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on DNA  

PubMed Central

Most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. These loci encode ATPases called ParA that are thought to contribute to the mechanical force required for chromosome and plasmid segregation. In Vibrio cholerae, the chromosome II (chrII) par locus is essential for chrII segregation. Here, we found that purified ParA2 had ATPase activities comparable to other ParA homologs, but, unlike many other ParA homologs, did not form high molecular weight complexes in the presence of ATP alone. Instead, formation of high molecular weight ParA2 polymers required DNA. Electron microscopy and three-dimensional reconstruction revealed that ParA2 formed bipolar helical filaments on double-stranded DNA in a sequence-independent manner. These filaments had a distinct change in pitch when ParA2 was polymerized in the presence of ATP versus in the absence of a nucleotide cofactor. Fitting a crystal structure of a ParA protein into our filament reconstruction showed how a dimer of ParA2 binds the DNA. The filaments formed with ATP are left-handed, but surprisingly these filaments exert no topological changes on the right-handed B-DNA to which they are bound. The stoichiometry of binding is one dimer for every eight base pairs, and this determines the geometry of the ParA2 filaments with 4.4 dimers per 120 ? pitch left-handed turn. Our findings will be critical for understanding how ParA proteins function in plasmid and chromosome segregation.

Hui, Monica P.; Galkin, Vitold E.; Yu, Xiong; Stasiak, Alicja Z.; Stasiak, Andrzej; Waldor, Matthew K.; Egelman, Edward H.

2010-01-01

383

A Novel Function for the PAR Complex in Subcellular Morphogenesis of Tracheal Terminal Cells in Drosophila melanogaster  

PubMed Central

The processes that generate cellular morphology are not well understood. To investigate this problem, we use Drosophila melanogaster tracheal terminal cells, which undergo two distinct morphogenetic processes: subcellular branching morphogenesis and subcellular apical lumen formation. Here we show these processes are regulated by components of the PAR-polarity complex. This complex, composed of the proteins Par-6, Bazooka (Par-3), aPKC, and Cdc42, is best known for roles in asymmetric cell division and apical/basal polarity. We find Par-6, Bazooka, and aPKC, as well as known interactions between them, are required for subcellular branch initiation, but not for branch outgrowth. By analysis of single and double mutants, and isolation of two novel alleles of Par-6, one of which specifically truncates the Par-6 PDZ domain, we conclude that dynamic interactions between apical PAR-complex members control the branching pattern of terminal cells. These data suggest that canonical apical PAR-complex activity is required for subcellular branching morphogenesis. In addition, we find the PAR proteins are downstream of the FGF pathway that controls terminal cell branching. In contrast, we find that while Par-6 and aPKC are both required for subcellular lumen formation, neither Bazooka nor a direct interaction between Par-6 and aPKC is needed for this process. Thus a novel, noncanonical role for the polarity proteins Par-6 and aPKC is used in formation of this subcellular apical compartment. Our results demonstrate that proteins from the PAR complex can be deployed independently within a single cell to control two different morphogenetic processes.

Jones, Tiffani A.; Metzstein, Mark M.

2011-01-01

384

Co-culture of spermatogonial stem cells with sertoli cells in the presence of testosterone and FSH improved differentiation via up-regulation of post meiotic genes.  

PubMed

Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout life in the male. Maintenance of SSCs and induction of spermiogenesis in vitro may provide a therapeutic strategy to treat male infertility. This study investigated in vitro differentiation of mouse SSCs in presence or absence of Sertoli cells, hormones and vitamins. Spermatogonial populations were enriched from testes of 4-6 week old males by magnetic activated cell sorting and anti-Thy-1 antibody. Sertoli cells isolated from 6-8 week old testes were enriched using lectin-DSA-coated plates. Isolated SSCs were cultured in the presence of Leukemia inhibitory factor (LIF) for 7 days in gelatin-coated dishes, then dissociated and cultured for 7 days in media lacking LIF in the presence or absence of Sertoli cells, with or without FSH, testosterone and vitamins. After one week, the effects of Sertoli cells ± supplementary media on SSC differentiation was evaluated by microscopy and expression of meiotic and postmeiotic transcripts using RT-PCR. SSC colonies had limited development after LIF removal alone, exhibiting low expression of meiotic (Scp3, Th2b) but not postmeiotic transcript, and loss of Stra8 and Dazl expression. SSCs co-cultured with Sertoli cells, hormones and vitamins developed spermatid-like cells expressing postmeiotic markers (TP1, TP2, Prm1) at levels over 2-fold higher than Sertoli cells or hormone/vitamins alone. Our present SSC-Sertoli co-culture provides conditions that may allow efficient in vitro differentiation of SSCs for the treatment of male infertility. PMID:23456578

Minaee Zanganeh, Bagher; Rastegar, Tayebeh; Habibi Roudkenar, Mehryar; Ragerdi Kashani, Iraj; Amidi, Fardin; Abolhasani, Farid; Barbarestani, Mohammad

2013-01-01

385

The Geoland2 BioPar burned area product  

NASA Astrophysics Data System (ADS)

The European Commission Geoland2 project intends to constitute a major step forward to the implementation of the GMES Land Monitoring Core Service (LMCS). The Bio-geophysical Parameters (BioPar) Core Monitoring Service aims at setting-up pre-operational infrastructures for providing regional, European, and global bio-geophysical variables, both in near real time and off-line mode, for describing the vegetation state, the radiation budget at the surface, and the water cycle. The burned area product is part of the BioPar portfolio. The burned area product further builds on the experience of the Global Burned Area (GBA2000) and L3JRC projects. In the GBA2000 project, several algorithms were developed for different geographical regions of the world, and applied to a 1-year time series (the year 2000) of SPOT-VEGETATION data. In the L3JRC project, a single algorithm was improved and applied to a 7-year global dataset of SPOT-VEGETATION data. Since the conception of the Geoland2 project, work has been undertaken to improve the L3JRC algorithm, mainly based on user comments and feedback. Furthermore, the Geoland2 burned area product specification has been developed to meet the requirements of the Core Information Service, specifically LandCarbon and Natural Resource Monitoring in Africa (Narma). The Geoland2 burned area product has the following improvements over the L3JRC product: • It resolves issues with users extracting statistics and burned area estimates for time periods considered to be outside the main seasons for burning. Specifically, this deals with issues in northern latitude winters. • The number of pre-processing steps has been shortened, reducing processing time. • An improved land-water mask has been used. This resolves a problem around the coastlines of land masses which were frequently being detected as being burned. • A season metric calculation is performed over a 1x1 degree grid. For each grid cell, a date is logged against the start of the fire season, peak of the fire season and then the end of the fire season. Once a fire season has been confirmed as being finished, the region effectively resets itself, which means that the land surface can burn again when the next fire season starts. This automated season reset feature enables multiple fire seasons to be analysed. • Provides easy to interpret seasonality tables every 10 days (the reporting period for the product). It is intended that the product will be validated using CEOS-approved protocols and data sets currently being developed through the European Space Agency Fire-CCI project. In this paper, initial results being produced operationally and will be presented along with examples highlighting the performance of the seasonality metric.

Tansey, K.; Bradley, A.; Smets, B.; van Best, C.; Lacaze, R.

2012-04-01

386

Differential effects of quercetin, apigenin and genistein on signalling pathways of protease-activated receptors PAR1 and PAR4 in platelets  

PubMed Central

Background and purpose: The modulation by flavonoids of platelet responses induced by thrombin has been little investigated, and the antiplatelet activity, as well as possible inhibitory mechanisms of these compounds on thrombin signalling, has not yet been elucidated. We explored whether flavonoids affect platelet signalling pathways triggered by thrombin and by the selective activation of its protease-activated receptors (PARs) 1 and 4, and analysed the antagonism of these polyphenols at thrombin receptors. Experimental approach: We investigated the effect of a range of polyphenolic compounds on platelet aggregation, 5-HT secretion, intracellular calcium mobilization, protein kinase activity and tyrosine phosphorylation, triggered by thrombin and PAR agonist peptides (PAR-APs). The ability of these flavonoids to bind to thrombin receptors was investigated by competitive radioligand binding assays using 125I-thrombin. Key results: Quercetin, apigenin and genistein impaired platelet aggregation, as well as 5-HT release and calcium mobilization, induced by thrombin and PAR-APs. Quercetin and apigenin were inhibitors of protein kinases, but genistein exhibited a minimal ability to suppress platelet phosphorylation. Binding assays did not establish any kind of interaction between thrombin receptors and any of the flavonoids tested. Conclusions and implications: Quercetin, apigenin and genistein did not inhibit thrombin responses by interacting with thrombin receptors, but by interfering with intracellular signalling. While inhibition by genistein may be a consequence of affecting calcium mobilization, subsequent platelet secretion and aggregation, for quercetin and apigenin, inhibition of kinase activation may also be involved in the impairment of platelet responses.

Navarro-Nunez, L; Rivera, J; Guerrero, JA; Martinez, C; Vicente, V; Lozano, ML

2009-01-01

387

CDC42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans  

Microsoft Academic Search

Background: The polarization of the anterior–posterior axis (A-P) of the Caenorhabditis elegans zygote depends on the activity of the par genes and the presence of intact microfilaments. Functional links between the PAR proteins and the cytoskeleton, however, have not been fully explored. It has recently been shown that in mammalian cells, some PAR homologs form a complex with activated Cdc42,

Amanda J. Kay; Craig P. Hunter

2001-01-01

388

Intrinsic and integrative properties of substantia nigra pars reticulata neurons.  

PubMed

The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active type 3 transient receptor potential (TRPC3) channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches -60 mV, a voltage-gated persistent sodium current (I(NaP)) starts to activate, further depolarizing the membrane potential. At or slightly below -50 mV, the large transient voltage-activated sodium current (I(NaT)) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of I(NaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. I(NaT) also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators including dopamine, serotonin, endocannabinoids, and H?O?. PMID:21839148

Zhou, F-M; Lee, C R

2011-08-02

389

Effects of protease-activated receptors (PARs) on intracellular calcium dynamics of acinar cells in rat lacrimal glands.  

PubMed

Protease-activated receptors (PARs) represent a novel class of seven transmembrane domain G-protein coupled receptors, which are activated by proteolytic cleavage. PARs are present in a variety of cells and have been prominently implicated in the regulation of a number of vital functions. Here, lacrimal gland acinar cell responses to PAR activation were examined, with special reference to intracellular Ca(2+) concentration ([Ca(2+)]i) dynamics. In the present study, detection of acinar cell mRNA specific to known PAR subtypes was determined by reverse transcriptase polymerase chain reaction. Only PAR2 mRNA was detected in acinar cells of lacrimal glands. Both trypsin and a PAR2-activating peptide (PAR2-AP), SLIGRL-NH2, induced an increase in [Ca(2+)]i in acinar cells. The removal of extracellular Ca(2+) and the use of Ca(2+) channel blockers did not inhibit PAR2-AP-induced [Ca(2+)]i increases. Furthermore, U73122 and xestospongin C failed to inhibit PAR2-induced increases in [Ca(2+)]i. The origin of the calcium influx observed after activated PAR2-induced Ca(2+) release from intracellular Ca(2+) stores was also evaluated. The NO donor, GEA 3162, mimicked the effects of PAR2 in activating non-capacitative calcium entry (NCCE). However, both calyculin A (100 nM) and a low concentration of Gd(3+) (5 ?M) did not completely block the PAR2-AP-induced increase in [Ca(2+)]i. These findings indicated that PAR2 activation resulted primarily in Ca(2+) mobilization from intracellular Ca(2+) stores and that PAR2-mediated [Ca(2+)]i changes were mainly independent of IP3. RT-PCR indicated that TRPC 1, 3 and 6, which play a role in CCE and NCCE, are expressed in acinar cells. We suggest that PAR2-AP differentially regulates both NCCE and CCE, predominantly NCCE. Finally, our results suggested that PAR2 may function as a key receptor in calcium-related cell homeostasis under pathophysiological conditions such as tissue injury or inflammation. PMID:23463389

Oikawa, Makoto; Saino, Tomoyuki; Kimura, Katsura; Kamada, Yuki; Tamagawa, Yasunori; Kurosaka, Daijiro; Satoh, Yoh-Ichi

2013-03-06

390

Effects of oestradiol-17 beta, progesterone or bovine follicular fluid on the plasma concentrations of FSH and LH in ovariectomized Booroola ewes which were homozygous carriers or non-carriers of a fecundity gene.  

PubMed

The plasma concentrations of FSH and LH were measured in ovariectomized Booroola FF and ++ ewes before and after treatment with subcutaneous implants of oestradiol-17 beta (0, 2 or 8 cm Silastic capsules; 5 ewes/genotype per dose) or progesterone (0, 1 or 3 Silastic envelopes; 5 ewes/genotype per dose) or subcutaneous injections of steroid-free bovine follicular fluid (bFF; 0, 0.5, 1.0, 2.5 or 5 ml; 4 ewes/genotype per dose). During the first 50 h after implantation of oestradiol or progesterone, or the first 24 h after bFF treatment, the FSH and LH concentrations in plasma were not different between the genotypes although there were significant effects of the steriods and bFF with respect to dose (P less than 0.05). At 6 days after steroid implantation, no gene-specific effects were noted for the plasma concentrations of FSH although significant effects of dose of oestradiol (P less than 0.01) but not progesterone were noted. Also at 6 days after steroid implantation, no gene-specific differences in the pulsatile patterns (i.e. peak frequency or amplitude) of plasma LH concentrations were noted although there were significant effects of steriod dose (P less than 0.05) on frequency and/or amplitude. It is concluded that the higher ovulation-rate in FF than ++ Booroola ewes is unlikely to be due to gene-specific differences in the sensitivity of the hypothalamic-pituitary axis to ovarian hormones. PMID:2513391

McNatty, K P; Hudson, N L; Collins, F; Fisher, M; Health, D A; Henderson, K M

1989-11-01

391

Valproate Alters Dopamine Signaling in Association with Induction of Par-4 Protein Expression  

PubMed Central

Chromatin remodeling through histone modifications has emerged as a key mechanism in the pathophysiology of psychiatric disorders. Valproate (VPA), a first-line medication for bipolar disorder, is known to have histone deacetylase (HDAC) inhibitor activity, but the relationship between its efficacy as a mood stabilizer and HDAC inhibitory activity is unclear. Here we provide evidence that prostate apoptosis response-4 (Par-4), an intracellular binding partner of dopamine D2 receptors (DRD2), plays a role in mediating the effectiveness of VPA. We found that chronic VPA treatment enhanced the expression of Par-4 in cultured neurons and adult mouse brains. This Par-4 induction phenomenon occurred at the transcriptional level and was correlated with an increase in histone H3 and H4 acetylation of the Par-4 promoter regions. Furthermore, chronic VPA treatment potentiated the suppression of the cAMP signaling cascade upon dopamine stimulation, which was blocked by sulpiride treatment. These results indicate that VPA potentiates DRD2 activity by enhancing Par-4 expression via a chromatin remodeling mechanism.

Lee, Saebom; Jeong, Jaehoon; Park, Young-Un; Kwak, Yongdo; Lee, Seol Ae; Lee, Haeryun; Son, Hyeon; Park, Sang Ki

2012-01-01

392

A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis  

PubMed Central

Sepsis is a deadly disease characterized by the inability to regulate the inflammatory–coagulation response in which the endothelium plays a key role. The cause of this perturbation remains poorly understood and has hampered the development of effective therapeutics. Matrix metalloproteases (MMPs) are involved in the host response to pathogens, but can also cause uncontrolled tissue damage and contribute to mortality. We found that human sepsis patients had markedly elevated plasma proMMP-1 and active MMP-1 levels, which correlated with death at 7 and 28 days after diagnosis. Likewise, septic mice had increased plasma levels of the MMP-1 ortholog, MMP-1a. We identified mouse MMP-1a as an agonist of protease-activated receptor-1 (PAR1) on endothelial cells. MMP-1a was released from endothelial cells in septic mice. Blockade of MMP-1 activity suppressed endothelial barrier disruption, disseminated intravascular coagulation (DIC), lung vascular permeability as well as the cytokine storm and improved survival, which was lost in PAR1-deficient mice. Infusion of human MMP-1 increased lung vascular permeability in normal wild-type mice but not in PAR1-deficient mice. These findings implicate MMP-1 as an important activator of PAR1 in sepsis and suggest that therapeutics that target MMP1-PAR1 may prove beneficial in the treatment of sepsis.

Tressel, Sarah L; Kaneider, Nicole C; Kasuda, Shogo; Foley, Caitlin; Koukos, Georgios; Austin, Karyn; Agarwal, Anika; Covic, Lidija; Opal, Steven M; Kuliopulos, Athan

2011-01-01

393

A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis.  

PubMed

Sepsis is a deadly disease characterized by the inability to regulate the inflammatory-coagulation response in which the endothelium plays a key role. The cause of this perturbation remains poorly understood and has hampered the development of effective therapeutics. Matrix metalloproteases (MMPs) are involved in the host response to pathogens, but can also cause uncontrolled tissue damage and contribute to mortality. We found that human sepsis patients had markedly elevated plasma proMMP-1 and active MMP-1 levels, which correlated with death at 7 and 28 days after diagnosis. Likewise, septic mice had increased plasma levels of the MMP-1 ortholog, MMP-1a. We identified mouse MMP-1a as an agonist of protease-activated receptor-1 (PAR1) on endothelial cells. MMP-1a was released from endothelial cells in septic mice. Blockade of MMP-1 activity suppressed endothelial barrier disruption, disseminated intravascular coagulation (DIC), lung vascular permeability as well as the cytokine storm and improved survival, which was lost in PAR1-deficient mice. Infusion of human MMP-1 increased lung vascular permeability in normal wild-type mice but not in PAR1-deficient mice. These findings implicate MMP-1 as an important activator of PAR1 in sepsis and suggest that therapeutics that target MMP1-PAR1 may prove beneficial in the treatment of sepsis. PMID:21591259

Tressel, Sarah L; Kaneider, Nicole C; Kasuda, Shogo; Foley, Caitlin; Koukos, Georgios; Austin, Karyn; Agarwal, Anika; Covic, Lidija; Opal, Steven M; Kuliopulos, Athan

2011-05-18

394

Participatory Action Research (PAR) in Middle School: Opportunities, Constraints, and Key Processes  

PubMed Central

Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth’s sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools.

Ritterman, Miranda L.; Wanis, Maggie G.

2010-01-01

395

Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology.  

PubMed

In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform. PMID:24113286

Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

2013-10-10

396

Operative repair of symptomatic spondylolysis following a positive response to diagnostic pars injection.  

PubMed

From 1989 to 1996, 275 patients (245 male and 20 female) with back pain symptoms and spondylolysis of the lumbar spine were reviewed. All patients were evaluated by a protocol that included nonoperative treatment, bone scan, and pars injection. Only those whose symptoms failed nonoperative measures, showing negative bone scan and positive pars injection, were regarded as candidates for surgical management. Pars injection with Marcaine was done, and there were 93 cases with a positive response of reproducing symptoms and symptom relief. Patients then received autogenous bone grafting and internal fixation of the pars interarticularis defect. The internal fixation devices used included translaminar screws (AO 3.5 cancellous screw) for the most frequent level of L5, hook screws for levels above L4, and augmentation with wire for cases with concomitant spinal bifida occulta. The average age of the surgical group (85 male and 8 female) was 23 years (range: 19-35 years). After a follow-up averaging 30.4 months (range: 24-48 months), fusion results were 87%. Clinical results of 85 cases (91.3%) were excellent to good; 8 cases were fair; there were no poor cases. Direct repair of the pars defect by internal fixation and bone grafting was done to preserve involved motion segment and to prevent abnormal stresses at adjacent levels. These procedures seemed to be clinically effective. PMID:10078944

Wu, S S; Lee, C H; Chen, P Q

1999-02-01

397

12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity.  

PubMed

Following initial platelet activation, arachidonic acid is metabolised by cyclooxygenase-1 and 12-lipoxygenase (12-LOX). While the role of 12-LOX in the platelet is not well defined, recent evidence suggests that it may be important for regulation of platelet activity and is agonist-specific in the manner in which it regulates platelet function. Using small molecule inhibitors selective for 12-LOX and 12-LOX-deficient mice, the role of 12-LOX in regulation of human platelet activation and thrombosis was investigated. Pharmacologically inhibiting 12-LOX resulted in attenuation of platelet aggregation, selective inhibition of dense versus alpha granule secretion, and inhibition of platelet adhesion under flow for PAR4 and collagen. Additionally, 12-LOX-deficient mice showed attenuated integrin activity to PAR4-AP and convulxin compared to wild-type mice. Finally, platelet activation by PARs was shown to be differentially dependent on COX-1 and 12-LOX with PAR1 relying on COX-1 oxidation of arachidonic acid while PAR4 being more dependent on 12-LOX for normal platelet function. These studies demonstrate an important role for 12-LOX in regulating platelet activation and thrombosis. Furthermore, the data presented here provide a basis for potentially targeting 12-LOX as a means to attenuate unwanted platelet activation and clot formation. PMID:23784669

Yeung, J; Apopa, P L; Vesci, J; Stolla, M; Rai, G; Simeonov, A; Jadhav, A; Fernandez-Perez, P; Maloney, D J; Boutaud, O; Holman, T R; Holinstat, M

2013-06-20

398

Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology  

NASA Astrophysics Data System (ADS)

In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody–antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

Bache, Michael; Bosco, Filippo G.; Brøgger, Anna L.; Frøhling, Kasper B.; Sonne Alstrøm, Tommy; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

2013-11-01

399

Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2.  

PubMed

Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease by restoring a normal immunity against allergens. The preparation of allergen-solid lipid nanoparticles as delivery vehicles for therapeutic proteins, P. judaica major allergen Par j 2, was investigated. The Par j 2 allergen was expressed in a large amount in Escherichia coli and purified to homogeneity. Its immunological properties were studied by western blotting and enzyme-linked immunosorbent assay inhibition. Solid lipid nanoparticles were obtained by water-in-oil-in-water multiple emulsion method and characterized in terms of mean size and surface charge. These systems (approximately 250 nm diameter and negative surface charge) incorporated recombinant Par j 2 with 40% or greater efficiency. Moreover, the endotoxin level and anaphylactic activity of the empty solid lipid nanoparticles and recombinant Par j 2-loaded solid lipid nanoparticles were evaluated by looking at the overexpression of CD203c marker on human basophils. These results demonstrate that recombinant Par j 2-nanoparticles could be proposed as safe compositions for the development of new therapeutic dosage forms to cure allergic reactions. PMID:22162654

Bondì, Maria Luisa; Montana, Giovanna; Craparo, Emanuela Fabiola; Di Gesù, Roberto; Giammona, Gaetano; Bonura, Angela; Colombo, Paolo

2011-11-21

400

Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage  

PubMed Central

Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures.

Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

2011-01-01

401

Effect of hot-rolling and heat-treatment conditions on the structure and mechanical and technological properties of nitrogen-bearing austenitic steel 05Kh22AG15N8M2FSh  

Microsoft Academic Search

The effect of hot-rolling conditions on the structure, strength, ductility, fracture toughness, and technological properties\\u000a of the nonmagnetic steel 05Kh22AG15N8M2F-Sh containing 0.55% N has been studied. A homogeneous and fine-grained austenitic\\u000a structure forms in the steel upon rolling at 1000–1050C and a reduction of more than 60–70%. This structure provides the\\u000a following properties: ?0.2 = 1044 N\\/mm2, ?u = 1172

O. A. Bannykh; V. M. Blinov; M. V. Kostina; E. V. Blinov; G. Yu. Kalinin

2006-01-01