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Sample records for alternating cg oligodeoxynucleotides

  1. Intronic non-CG DNA hydroxymethylation and alternative mRNA splicing in honey bees.

    Science.gov (United States)

    Cingolani, Pablo; Cao, Xiaoyi; Khetani, Radhika S; Chen, Chieh-Chun; Coon, Melissa; Sammak, Alya'a; Bollig-Fischer, Aliccia; Land, Susan; Huang, Yun; Hudson, Matthew E; Garfinkel, Mark D; Zhong, Sheng; Robinson, Gene E; Ruden, Douglas M

    2013-09-30

    Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole genome analyses of DNA modifications at non-CG sites in honey bees and correlated the effects of these DNA modifications on gene expression and alternative mRNA splicing. We confirmed, using unbiased analyses of whole-genome shotgun bisulfite sequencing (BS-seq) data, with both new data and published data, the previous finding that CG DNA methylation is enriched in exons in honey bees. However, we also found evidence that cytosine methylation and hydroxymethylation at non-CG sites is enriched in introns. Using antibodies against 5-hydroxmethylcytosine, we confirmed that DNA hydroxymethylation at non-CG sites is enriched in introns. Additionally, using a new technique, Pvu-seq (which employs the enzyme PvuRts1l to digest DNA at 5-hydroxymethylcytosine sites followed by next-generation DNA sequencing), we further confirmed that hydroxymethylation is enriched in introns at non-CG sites. Cytosine hydroxymethylation at non-CG sites might have more functional significance than previously appreciated, and in honey bees these modifications might be related to the regulation of alternative mRNA splicing by defining the locations of the introns.

  2. The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

    Science.gov (United States)

    Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

    2012-01-01

    Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the

  3. DW_CG-832

    Data.gov (United States)

    Department of Homeland Security — Flat file data from the Office of Resource Management - Financial Analysis Division, CG-832 used for reporting cost allocation models within the Coast Guard Business...

  4. DETECTION OF COMPLEXES OLIGODEOXYNUCLEOTIDES WITH POLYMERIC CARRIERS

    Directory of Open Access Journals (Sweden)

    V. V. Vlizlo

    2013-10-01

    Full Text Available The new method for detection of cationic oligoelectrolytes conjugates with oligodeoxyonucleotides, based on free diffusion of these substances in 0.8% agarose gels is developed. It enables to simplify and reduce the cost of visual identification of the best carrier among various polymer compounds and to uncover the fact of complex formation between the interacting agents resulting in formation of a ring precipitation. The universality of the proposed methodological approach is confirmed by interaction of coligodeoxynucleotides with other cationic polymer of natural origin, namely chitosan. Comparative analysis of our approach applicationto turbidimetry data concerning coligodeoxynucleotides complexes and their electrophoresis showed some advantages, among them are the ability to screen simultaneously a large number of polymeric carriers and no need for using of more expensive equipment and materials. To conclude the complexing occurrence it is enough nanomol amounts of oligodeoxynucleotide.

  5. Short hairpin-looped oligodeoxynucleotides reduce hepatitis C virus replication

    Directory of Open Access Journals (Sweden)

    Broecker Felix

    2012-07-01

    Full Text Available Abstract Background Persistent infection with hepatitis C virus (HCV is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Standard therapy consists of a combination of interferon-alpha and ribavirin, but many patients respond poorly, especially those infected with HCV genotypes 1 and 4. Furthermore, standard therapy is associated with severe side-effects. Thus, alternative therapeutic approaches against HCV are needed. Findings Here, we studied the effect of a new class of antiviral agents against HCV, short, partially double-stranded oligodeoxynucleotides (ODNs, on viral replication. We targeted the 5’ nontranslated region (5’ NTR of the HCV genome that has previously been shown as effective target for small interfering RNAs (siRNAs in vitro. One of the investigated ODNs, ODN 320, significantly and efficiently reduced replication of HCV replicons in a sequence-, time- and dose-dependent manner. ODN 320 targets a genomic region highly conserved among different HCV genotypes and might thus be able to inhibit a broad range of genotypes and subtypes. Conclusions ODNs provide an additional approach for inhibition of HCV, might be superior to siRNAs in terms of stability and cellular delivery, and suitable against HCV resistant to standard therapy. This study underlines the potential of partially double-stranded ODNs as antiviral agents.

  6. Kathon CG: a review.

    Science.gov (United States)

    de Groot, A C; Weyland, J W

    1988-02-01

    Kathon CG, a cosmetics preservative containing, as active ingredients, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, appears to be a frequent cause of contact dermatitis in Europe. In the United States, where Kathon CG was introduced some 5 years later, the use of this preservative system for cosmetics and toiletries is rapidly increasing. Undoubtedly cases of contact sensitization will soon emerge in this country. Most cases of contact allergy are caused by the use of moisturizing creams on (slightly) damaged skin. Sensitization by the use of cosmetic products on previously healthy skin, especially the face, does occur but appears to be less frequent. Rinse-off products do not seem to have a substantial potential for the induction and elicitation of contact allergic reactions to Kathon CG because of dilution of the product and the allergen with water as well as a short contact time with the skin. This review provides a synopsis of current knowledge on the preservative system Kathon CG, with emphasis on the risk of sensitization and diagnostic procedures.

  7. Kathon CG and cosmetic products.

    Science.gov (United States)

    Rastogi, S C

    1990-03-01

    Kathon CG was determined in 156 of the most commonly used cosmetic products in Denmark. 42% of the cosmetic products were found to contain Kathon CG. Kathon CG was present in 48% of "rinse off" and 31% of "leave on" cosmetic products. The 3:1 ratio of chloromethyl isothiazolinone (CMI): methyl isothiazolinone (MI) in Kathon CG was found to be disturbed in 41% of Kathon CG preserved cosmetic products. The disturbed CMI/MI ratio was shown in 29% "rinse off" and 73% "leave on" cosmetic products. It is suggested that the chemical reaction of the ketone group of the isothizaolinones with other ingredients in cosmetic products may disturb the CMI/MI ratio of Kathon CG. The results of the study have been discussed in relation to the use of Kathon CG in cosmetic products as well as test material for allergic reaction.

  8. [Contact allergy to Kathon CG].

    Science.gov (United States)

    Frosch, P J; Schulze-Dirks, A

    1987-07-01

    Among 671 consecutive patients who underwent the patch test with Kathon CG (100 ppm active ingredient), 23 (3.43%) showed a positive reaction (87% females). In 52.2% of these cases the clinical relevance of these reactions was considered to be proven. Most of the patients were suffering from contact dermatitis of the face or hands. Cosmetics were found to be the major cause of sensitization. In view of the widespread use of this preservative, testing with Kathon CG is recommended in all cases of contact dermatitis.

  9. (beta-HC CG) in

    African Journals Online (AJOL)

    raoul

    urothelial cancer is more commonly associated with tumours of high grade and high category and that the expression .... 2 bladder cancers, Crawford et al [6] suggested that such expression may indicate chemosensitivity. .... population size is a balance of mitosis and mortality, Butler and associates [15] proposed that hCG.

  10. (beta-HC CG) in

    African Journals Online (AJOL)

    raoul

    hormones human chorionic gonadotropin (hCG) and its derivatives hCGalpha, hCGbeta, hCGbetacf, luteinizing hormone ... protein hormones placental lactogen (hPL) and growth hormone ((hGH-V/N). Dirnhofer and ... bladder tumours is therefore likely to be the result of altered gene regulation and not a rearrangement or ...

  11. Biotinylation of Deoxyguanosine at the Abasic Site in Double-Stranded Oligodeoxynucleotides

    Directory of Open Access Journals (Sweden)

    Chun Wu

    2016-01-01

    Full Text Available Biotinylation of deoxyguanosine at an abasic site in double-stranded oligodeoxynucleotides was studied. The biotinylation of deoxyguanosine is achieved by copper-catalyzed click reaction after the conjugation of the oligodeoxynucleotide with 2-oxohex-5-ynal. The biotinylation enables visualization of the biotinylated oligodeoxynucleotides by chemiluminescence on a nylon membrane. In order to investigate the biotinylated site, the biotinylated oligodeoxynucleotides were amplified by the DNA polymerase chain reaction. Replacement of guanine opposing the abasic site with adenine generated by the activity of the terminal deoxynucleotidyl transferase of DNA polymerase was detected by DNA sequencing analysis and restriction endonuclease digestion. This study suggests that 2-oxohex-5-ynal may be useful for the detection of the unpaired deoxyguanosine endogenously generated at abasic sites in genomic DNA.

  12. Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication

    Directory of Open Access Journals (Sweden)

    Heinrich Jochen

    2009-04-01

    Full Text Available Abstract The Herpes simplex virus (HSV is known as an infectious agent and widespread in the human population. The symptoms of HSV infections can range from mild to life threatening, especially in immune-compromised individuals. HSV infections are commonly treated with the guanosine analogue Aciclovir, but reports of resistance are increasing. Efforts are made to establish single-stranded antisense oligodeoxynucleotides (as and small interfering ribonucleic acids (siRNAs for antiviral treatment. Recently, another class of short interfering nucleic acids, partially double-stranded hairpin loop-structured 54 mer oligodeoxynucleotides (ODNs, was shown to allow hydrolysis of HIV RNA by binding to the viral RNA. This leads to a substrate for the viral RNase H. To assess the potential of such ODNs for inhibition of HSV-1 replication, five partially double-stranded ODNs were designed based on the sequences of known siRNAs against HSV-1 with antiviral activity. Three of them are directed against early and two against leaky late genes. Primary human lung fibroblasts, MRC-5, and African green monkey kidney cells, Vero, were transfected with ODNs and subsequently infected. The effect on HSV-1 replication was determined by analyzing the virus titer in cell culture supernatants by quantitative PCR and plaque assays. An inhibitory effect was observed with all five selected ODNs, with two cases showing statistical significance in both cell types. The observed effect was sequence-specific and dose dependent. In one case the ODN was more efficient than a previously described siRNA directed against the same target site in the mRNA of UL5, a component of the helicase/primase complex. HSV-1 virions and ODNs can be applied simultaneously without transfection reagent, but at a 50-fold higher concentration to Vero cells with similar efficiencies. The results underline the potential of partially double-stranded hairpin loop-structured ODNs as antiviral agents.

  13. Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: comparison of immune responses in intranasal versus intramuscular administrations.

    Science.gov (United States)

    EL-Malky, Mohamed A; Al-Harthi, Saeed A; Mohamed, Raafat T; EL Bali, Mohamed A; Saudy, Niveen S

    2014-06-01

    Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.

  14. Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

    Science.gov (United States)

    Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

    2016-10-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

  15. Determination of hCG in choriocarcinoma using RIA kits for hCG and hCG-beta

    International Nuclear Information System (INIS)

    Vlachova, J.; Ruzkova, M.; Jakoubkova, J.; Skrivan, J.; Zavadil, M.

    1981-01-01

    The difference between the clinical finding and hCG levels in the serum is shown in two choriocarcinoma patients with widely progressing metastatic processes in the lungs. In the patient showing low hCG levels and poor chemotherapeutic response the presence is presumed of a free hCG-alpha subunit. The opinion is backed that negativity or relapse of a trophoblastic disease in the sensitive and specific hCG*-anti hCG-beta system should be watched because intact hCG is a dominant form of the hormone secerning due to the disease. It is admitted, however, that possible determination of the alpha and beta subunits of the hormone would greatly contribute to assessing the progress of the disease. (author)

  16. Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis.

    Science.gov (United States)

    Sparwasser, T; Hültner, L; Koch, E S; Luz, A; Lipford, G B; Wagner, H

    1999-02-15

    Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequence-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis. Challenging mice with immunostimulatory CpG-ODN sequences led to transient splenomegaly, with a maximum increase of spleen weight at day 6. The induction of splenomegaly by CpG-ODNs was sequence-specific, dose-dependent, and associated with an increase in splenic cell count, in numbers of granulocyte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-forming units-erythroid). The transfer of spleen cells from CpG-ODN-pretreated animals into lethally irradiated syngeneic mice yielded an increase of spleen CFUs. Furthermore, the challenge of sublethally irradiated mice with CpG-ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytotoxic T cell function was enhanced. The increase in GM-CFU and CTL function correlated with an enhanced resistance to Listeria infection in irradiated mice. We conclude from these data that CpG-ODNs trigger extramedullary hemopoiesis, and that this finding could be of therapeutic relevance in myelosuppression.

  17. Patch test sensitivity to Kathon CG.

    Science.gov (United States)

    Hjorth, N; Roed-Petersen, J

    1986-03-01

    Among 1511 consecutive patients patch tested with Kathon CG at 100 ppm active ingredient, 13 (0.8%) gave a positive reaction. Use test with a lotion containing Kathon CG (8.6 ppm) revealed no reaction in 11 patients with a positive patch test. It is concluded that a positive patch test reaction to 100 ppm does not initiate eczema after use of products preserved with Kathon CG in the low concentrations (3-15 ppm) used in final products.

  18. Parallel preconditioning techniques for sparse CG solvers

    Energy Technology Data Exchange (ETDEWEB)

    Basermann, A.; Reichel, B.; Schelthoff, C. [Central Institute for Applied Mathematics, Juelich (Germany)

    1996-12-31

    Conjugate gradient (CG) methods to solve sparse systems of linear equations play an important role in numerical methods for solving discretized partial differential equations. The large size and the condition of many technical or physical applications in this area result in the need for efficient parallelization and preconditioning techniques of the CG method. In particular for very ill-conditioned matrices, sophisticated preconditioner are necessary to obtain both acceptable convergence and accuracy of CG. Here, we investigate variants of polynomial and incomplete Cholesky preconditioners that markedly reduce the iterations of the simply diagonally scaled CG and are shown to be well suited for massively parallel machines.

  19. Micro-dose hCG as luteal phase support without exogenous progesterone administration

    DEFF Research Database (Denmark)

    Andersen, C Yding; Fischer, R; Giorgione, V

    2016-01-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the Gn......RHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple...... advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently...

  20. Contact allergy to the preservative Kathon CG.

    Science.gov (United States)

    Björkner, B; Bruze, M; Dahlquist, I; Fregert, S; Gruvberger, B; Persson, K

    1986-02-01

    Of 976 patients routinely patch tested with Kathon CG (Rohm & Haas), 300 ppm, 43 (4.4%) gave a positive reaction. Of 170 patients routinely tested with Kathon CG 250 ppm, 10 (5.9%) gave a positive reaction. Out of 34 patients tested with serial dilutions of Kathon CG, 17 (50%) reacted to 100 ppm, 8 to 30 ppm and 2 to 10 ppm. The concentration of 1000 ppm of Kathon CG was irritant in some cases, but 300 ppm was not irritant. Of the 976 patients tested with Kathon CG 300 ppm, 8 (0.8%) showed a "flare-up" reaction, indicating patch test sensitization. Of the 170 tested with Kathon CG 250 ppm, 2 (1.2%) were sensitized. When the patch-test-sensitized patients were retested with serial dilutions, they showed the same pattern as the other patients. 13 sensitized patients were use tested and 7 (54%) gave responses. In the literature, Kathon CG 100 ppm is recommended as the routine patch test concentration. However, 50% of the sensitive persons may then be overlooked. In our clinics, Kathon CG has become the second most common contact sensitizer, but the sensitivity cannot be traced in all patients with clinically relevant allergy without an unacceptable risk of patch test sensitization.

  1. Transcription factor CgMTF-1 regulates CgZnT1 and CgMT expression in Pacific oyster (Crassostrea gigas) under zinc stress

    International Nuclear Information System (INIS)

    Meng, Jie; Zhang, Linlin; Li, Li; Li, Chunyan; Wang, Ting; Zhang, Guofan

    2015-01-01

    Highlights: • CgMTF-1 and CgZnT1 were first identified in oysters. • CgMTF-1 localized in cell nucleus under unstressed conditions. • CgMTF-1 proteins could bind with the typical MRE motif. • CgMTF-1 activated CgZnT1, CgMT1 and CgMT4 promoters and regulated their expressions under zinc exposure. - Abstract: Oysters accumulate zinc at high tissue concentrations, and the metal response element (MRE)-binding transcription factor (MTF) functions as the cellular zinc sensor that coordinates the expression of genes involved in zinc efflux and storage, as well as those that protect against metal toxicity. In this study, we cloned MTF-1 in oysters and examined its regulation mechanism for its classic target genes, including MTs and ZnT1 under zinc exposure conditions. We cloned CgMTF-1 and determined the subcellular locations of its protein product in HEK293 cells. CgMTF-1 has a 2826 bp open reading frame that encodes a predicted polypeptide with 707 amino acid residues, showing six well-conserved zinc finger domains that are required for metal binding. In HEK293 cell lines, CgMTF-1 primarily localizes in the cell nucleus under unstressed conditions and nuclear translocation was not critical for the activation of this gene. We searched for CgMTF-1-regulated genes in oysters using RNA interference. Decreased expression levels of CgMT1, CgMT4, and CgZnT1 were observed after CgMTF-1 interference (>70% inhibition) under zinc exposure, indicating the critical role of CgMTF-1 in the regulation of these genes. We searched for a direct regulation mechanism involving CgMTF-1 for CgMT1, CgMT4, and CgZnT1 in vitro. EMSA experiments indicated that CgMTF-1 can bind with the MREs found in the CgZnT1, CgMT1 and CgMT4 promoter regions. Additionally, luciferase reporter gene experiments indicated that CgMTF-1 could activate the CgMT1, CgMT4, and CgZnT1 promoters. Overall, our results suggest that CgMTF-1 directly coordinates the regulation of CgMTs and CgZnT1 expression and plays

  2. Decreased levels of genuine large free hCG alpha in men presenting with abnormal semen analysis

    Directory of Open Access Journals (Sweden)

    Plas Eugen

    2011-08-01

    alternative glycosylation pattern on the free large hCG alpha in seminal plasma might reflect a modified function of this subunit in the male reproductive tract.

  3. Inhibition of leukemia cell proliferation by receptor-mediated uptake of c-myb antisense oligodeoxynucleotides.

    Science.gov (United States)

    Citro, G; Perrotti, D; Cucco, C; D'Agnano, I; Sacchi, A; Zupi, G; Calabretta, B

    1992-01-01

    Exposure of human leukemia HL-60 cells to an oligodeoxynucleotide complementary to an 18-base sequence (codons 2-7) of c-myb-encoded mRNA has previously been shown to result in inhibition of cell proliferation. Because HL-60 cells express high levels of transferrin receptor we adapted a DNA delivery system based on receptor-mediated endocytosis to introduce myb oligomers complexed with a transferrin-polylysine conjugate into those cells. A DNA.RNA duplex resistant to S1 nuclease digestion was detected as early as 12 hr after culture of HL-60 cells in the presence of the myb antisense/transferrin-polylysine complex. Exposure of HL-60 cells to the myb antisense/transferrin-polylysine complex resulted in rapid and profound inhibition of proliferation and loss of cell viability much more pronounced than that occurring in cells exposed to free myb antisense oligodeoxynucleotides. The transferrin-polylysine/myb sense complex or the transferrin-polylysine conjugate alone had no effect on HL-60 cell proliferation and viability. These findings indicate that myb synthetic oligodeoxynucleotides enter efficiently into HL-60 by transferrin receptor-mediated endocytosis and exert a profound biological effect. Such a delivery system could exploit other ligand-receptor interactions for the selective delivery of oncogene-targeted antisense oligodeoxynucleotides. Images PMID:1495997

  4. hCG Test (Pregnancy Test)

    Science.gov (United States)

    ... test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges ... to detecting the presence of hCG with different brands of home pregnancy kits. Home tests are sometimes ...

  5. Biological functions of hCG and hCG-related molecules

    Science.gov (United States)

    2010-01-01

    Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

  6. Biological functions of hCG and hCG-related molecules

    Directory of Open Access Journals (Sweden)

    Cole Laurence A

    2010-08-01

    Full Text Available Abstract Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

  7. Target organ of hCG

    International Nuclear Information System (INIS)

    Yanaginuma, Tsutomu; Kobayashi, Takuro

    1974-01-01

    The author and his associated gave intravenous infusions of hCG labeled with 125 I to female rats and investigated its distribution in their brains. The results showed a significantly higher radioactivity in the median eminence than in the other parts of the brain. This indicated that there were receptors of hCG in the median eminence of the hypothalamus of a female rat. The mechanism of gonadotropin action was also discussed in this report. By giving 125 I and 125 I-BSA to the same rats which had been used in the study of hCG distribution in the brain, and by investigating the radioactivity of their ovaries, the author explained the receptor of gonadotropin in corpora lutea. (Serizawa, K.)

  8. Diagnostic patch test concentration for Kathon CG.

    Science.gov (United States)

    Maibach, H I

    1985-10-01

    Patch test studies, 21-day cumulative irritancy assays and Draize repeat insult patch tests with Kathon CG, were used to ascertain an appropriate diagnostic patch test concentration. A dilution of 100 ppm a.i. (aq. or pet.) appears to have low irritancy potential. Further observations are required to verify if this concentration is high enough to detect most cases of sensitization.

  9. Prolog+CG: A Maintainer's Perspective

    DEFF Research Database (Denmark)

    Petersen, Ulrik

    2006-01-01

    Prolog+CG is an implementation of Prolog with Conceptual Graphs as first-class datastructures, on a par with terms. As such, it lends itself well to applications in which reasoning with Conceptual Graphs and/or ontologies plays a role. It  as originally developed by Prof. Dr. Adil Kabbaj, who in ...

  10. hCG - related molecules and their measurement.

    Science.gov (United States)

    Szczerba, Anna; Białas, Piotr; Pięta, Paweł Piotr; Jankowska, Anna

    2016-01-01

    Measurements of human chorionic gonadotropin (hCG) synthesized by trophoblast cells is a powerful tool of pregnancy monitoring. It was showed that similarly to pregnancy also trophoblastic and nontrophoblastic malignancies produce variety of hCG molecules. In urine and serum of both pregnant women and tumors patients a fifteen various forms of hCG, such as: regular hCG, hyperglycosylated hCG and predominant hyperglycosylated hCG free β, were identified. These forms might be useful in order to recognize between physiological and pathological pregnancies as well as cancers. Even the presence of these different hormone variants is well documented the commercially available biochemical tests detecting hCG failed to identified and distinguish among these forms. Especially hard is to identify glycan chains linked to heterodimer. Thus, a detailed analysis of hCG-related molecules produced during physiological and pathological condition, together with a new tests development are needed.

  11. PROVISIONAL ADVISORY LEVELS (PALs) FOR PHOSGENE (CG)

    Energy Technology Data Exchange (ETDEWEB)

    Glass-Mattie, Dana F [ORNL; McClanahan, Mark [Centers for Disease Control and Prevention; Koller, Loren [Environmental Health and Toxicology, Corvallis, Oregon; Adeshina, Femi [U.S. Environmental Protection Agency; Ross, Robert Hord [ORNL

    2009-01-01

    The PAL protocol was applied to estimate inhalation exposure limits for phosgene (CG). Data on humans are limited to occupational exposures or accounts from the use of phosgene as a chemical warfare agent in WWI. Animal studies with phosgene show a steep dose-response curve for pulmonary edema and mortality with little species variability in effects. Although immediately upon exposure lacrimation and upper respiratory irritation can occur, the main effect in the target organ, a progressive pulmonary edema, occurs after a latency period of 1-24 hours. PAL estimates were approved by the Expert Consultation Panel for Provisional Advisory Levels in May 2007. Exposure limits for oral exposure to CG are not developed due to insufficient data. PAL estimates for inhalation exposure to CG are presented: The 24-hour PAL values for severity levels 1, 2, and 3 are 0.0017, 0.0033 and 0.022 ppm, respectively. The 30-day PAL values are 0.0006 and 0.0012 ppm for the PAL 1 and 2 values, respectively. These 30-day inhalation values were also accepted as the 90-day and 2-year PAL 1 and 2 values. Data were not available for deriving 30-day, 90-day and 2-year PAL 3 values.

  12. oprM as a new target for reversion of multidrug resistance in Pseudomonas aeruginosa by antisense phosphorothioate oligodeoxynucleotides.

    Science.gov (United States)

    Wang, Hui; Meng, Jingru; Jia, Min; Ma, Xue; He, Gonghao; Yu, Jichen; Wang, Rutao; Bai, Hui; Hou, Zheng; Luo, Xiaoxing

    2010-12-01

    Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is one of the leading Gram-negative organisms associated with nosocomial infections. The increasing frequency of MDR-PA has represented a huge challenge in conventional antibacterial therapy. The loss of effectiveness of commonly used antibiotics calls for the immediate need to develop an alternative strategy for combating MDR-PA infections. The multiantibiotic resistance of MDR-PA is largely attributable to the production of multidrug efflux pumps, MexAB-OprM. OprM forms the antibiotic-ejecting duct and plays a crucial role in exporting incoming chemotherapeutic agents across the membranes. Disruption of the OprM expression may inhibit the function of multidrug efflux pumps and lead to restoration of MDR-PA susceptibility to antibiotics. In this study, we developed a novel anion liposome for encapsulating and delivering specific anti-oprM phosphorothioate oligodeoxynucleotide (PS-ODN617) and polycation polyethylenimine (PEI) complexes. The additions of the encapsulated anti-oprM PS-ODN617/PEI to MDR-PA isolates caused a significant reduction of oprM expression and inhibition of MDR-PA growth in the presence of piperacillin in a concentration-dependent manner. The encapsulated PS-ODN617 treatment also reduced minimal inhibitory concentrations of five most commonly used antibiotics to the sensitive margin values on MDR-PA clinical isolates, respectively. The results of present study firstly indicate that PS-ODN targeted to oprM can significantly restore the susceptibility of MDR-PA to existing antibiotics, which appears to be a novel strategy for treating MDR-PA infections. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. Study of the interaction of Kathon(R) CG-Germall(R) II in hydrophilic creams.

    Science.gov (United States)

    Favet, J; Griffiths, W; Holzner, G; Amacker, P A; Schorer, E

    1987-04-01

    Summary The authors studied the combination of Kathon(R) CG and Germall(R) II (0.1%-0.1%) in hydrophilic creams. Their objective was to find an alternative to the use of parabens. Kathon(R) CG was chosen due to its antimicrobial effectiveness and its broad spectrum of activity. It must be indicated, however, that it has only a weak action against Staphylococcus aureus. In order to reinforce its microbicidal action it was combined with Germall(R) II. The Kathon(R) CG-Germall(R) II combination showed addition, indeed even synergy, with respect to Escherichia coli (Gram negative rod) and Aspergillus niger (fungus). In the case of Candida albicans (yeast) the antifungal effect of Kathon(R) CG dominates. Finally, the combination can have effects from addition to antagonism in the case of the three strains of Staphylococcus aureus tested (Gram positive coccus). The time required to eliminate 10(6) UFC of these bacteria per g of cream can often exceed 48 h. If the concentration of Germall(R) II is increased to 0.3% then the effectiveness of the mixture is markedly reinforced. Caution must be observed, however, due to recent apprehensions expressed by certain dermatologists concerning possible allergic reactions due to Kathon(R) CG. A multi-centre patch test study is currently being carried out with this preservative in the dermatological clinics of the five Swiss university hospitals.

  14. Direct production of mouse disease models by embryo microinjection of TALENs and oligodeoxynucleotides.

    Science.gov (United States)

    Wefers, Benedikt; Meyer, Melanie; Ortiz, Oskar; Hrabé de Angelis, Martin; Hansen, Jens; Wurst, Wolfgang; Kühn, Ralf

    2013-03-05

    The study of genetic disease mechanisms relies mostly on targeted mouse mutants that are derived from engineered embryonic stem (ES) cells. Nevertheless, the establishment of mutant ES cells is laborious and time-consuming, restricting the study of the increasing number of human disease mutations discovered by high-throughput genomic analysis. Here, we present an advanced approach for the production of mouse disease models by microinjection of transcription activator-like effector nucleases (TALENs) and synthetic oligodeoxynucleotides into one-cell embryos. Within 2 d of embryo injection, we created and corrected chocolate missense mutations in the small GTPase RAB38; a regulator of intracellular vesicle trafficking and phenotypic model of Hermansky-Pudlak syndrome. Because ES cell cultures and targeting vectors are not required, this technology enables instant germline modifications, making heterozygous mutants available within 18 wk. The key features of direct mutagenesis by TALENs and oligodeoxynucleotides, minimal effort and high speed, catalyze the generation of future in vivo models for the study of human disease mechanisms and interventions.

  15. Pregnancy testing with hCG--future prospects.

    Science.gov (United States)

    Berger, Peter; Sturgeon, Catharine

    2014-12-01

    Pregnancy tests for human chorionic gonadotrophin (hCG) are used widely in hospital and home settings. Assays measuring hCG also have uses in prenatal screening and oncology. The output from three recent international workshops provides a framework for reliable measurement of hCG. Requirements for future hCG assays include use of clear descriptive nomenclature, informed selection of antibodies of well-defined epitope specificities, and design of robust methods. Tests will be precisely characterized and calibrated in SI units using six International Reference Reagents (IRR) for hCG and variants, and the Fifth International Standard for hCG 07/364, making it possible to report clinical results in molar units. These measures will help to increase patient safety by reducing the risk of erroneous or misleading hCG results. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Determination of hCG-alpha subunit in threatened pregnancy

    International Nuclear Information System (INIS)

    Talas, M.; Pohanka, J.; Fingerova, H.; Janouskova, M.; Krikal, Z.; Prasilova, J.; Zupkova, H.

    1987-01-01

    Radioimmunoassay of the hCG-alpha subunit was made using an antibody anti hCG-alpha serum, highly purified hCG-alpha for 125 I-labelling and the standard hCG-alpha. Sera of healthy pregnant women sampled throughout the whole pregnancies were used to determine x-bar±S.D. of hCG-alpha for 14-day intervals. Included in the study were groups of women with high risk of premature labor, late toxemia of pregnancy, twins and fetal hypotrophy. It was shown that increased hCG-alpha is found in pregnant women in whom signs of late toxemia of pregnancy are combined with high risk of premature labor, or with twin pregnancies, while in those with fetal hypotrophy hCG-alpha is within normal limits. (author). 3 figs., 7 refs

  17. Analysis list: CG8478 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available CG8478 Cell line,Embryo,Pupae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/CG8478.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/CG8478.5.tsv http://dbarchive.bios...ciencedbc.jp/kyushu-u/dm3/target/CG8478.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/CG8478.Cell_line.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/CG8478.Embryo.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/CG8478.Pupae.tsv http://dbarchive.biosciencedbc.jp/kyus

  18. Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

    Science.gov (United States)

    Bellavia, Marina; de Geyter, Christian; Streuli, Isabelle; Ibecheole, Victoria; Birkhäuser, Martin H; Cometti, Barbara P S; de Ziegler, Dominique

    2013-02-01

    A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

  19. Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I-deficient and -proficient HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Šímová, Jana; Bubeník, Jan

    2006-01-01

    Roč. 118, č. 7 (2006), s. 1836-1842 ISSN 0020-7136 R&D Projects: GA ČR(CZ) GA301/04/0492 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * immunotherapy * CpG oligodeoxynucleotides Subject RIV: EC - Immunology Impact factor: 4.693, year: 2006

  20. hCG, the wonder of today's science

    Science.gov (United States)

    2012-01-01

    Background hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. Content These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. Conclusions The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. PMID:22455390

  1. Measurement and charactereistics of hCG β-subunit

    International Nuclear Information System (INIS)

    Isojima, Shinzo; Koyama, Koji; Naga, Osamu.

    1975-01-01

    The authors studied an hCG-radioimmunoassay method in which the anti-hCG β-subunit antibody- 125 I-hCG β-subunit system was used, and they determined that in this method the antibody reacted much more specifically against hCG than in the usual radioimmunoassay method in which the anti-hCG antibody- 125 I-hCG has been used. In addition, they explained that a specific method for hCG-radioimmunoassay can be established in which the reaction system does not depend on the amount of physiological LH secretion. The significance of the clinical application of this method was considered and it was proved that the method was necessary, especially for studies of the hCG secretion pattern in patients with villous tumors having a low level of LH. Furthermore, the phenomenon of the cellular effect, namely a temporary increase of the hCG value which was thought to be caused by the administration of anticancerous agents, was proved to be due to hCG hypersecretion, not merely to LH variation. (Ichikawa, K.)

  2. CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Neal, Robert; Hunter, Nancy; Ariga, Hisanori; Ang, Kian; Milas, Luka

    2006-01-01

    Background and purpose: Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9) and stimulate both innate and adaptive immune reactions and possess anti-tumor activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non-immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present study explored whether CpG ODN 1826 also improves the response of murine tumors to the chemotherapeutic agent docetaxel (DOC). Materials and methods: CpG ODN 1826 (100 μg) was given sc three times: when leg tumors were 6 mm, when they grew to 8 mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation (10 Gy) were given when tumors were 8 mm. Effects of the treatments were assayed by tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in diameter. Results: Treatment with CpG ODN 1826 resulted in strongly enhanced response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic agent DOC. Enhancement of tumor treatment response was demonstrated by a strong prolongation in the primary tumor treatment endpoint, tumor growth delay. Coincidentally, this treatment also resulted in a higher rate of tumor cure than that observed after tumor radiotherapy or chemotherapy alone. When all three agents were combined the effect was comparable to that of the combination of CpG ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826 with DOC in the case of MCa-K. Conclusion: Overall results show that CpG ODN 1826 can markedly improve tumor response

  3. Immunoradiometric assay and radioimmunodetection using monoclonal human chorionic gonadotropin (hCG) antibodies recognizing only native hCG

    International Nuclear Information System (INIS)

    Miyachi, Y.; Mizuchi, A.; Iio, M.

    1985-01-01

    Monoclonal antibodies to human chorionic gonadotropin (hCG), which recognize conformational determinants of native hCG molecules, were used for two-site immunoradiometric assay (IRMA) and radioimmunodetection (RID) of hCG-producing tumours in nude mice. Several monoclonal hCG antibodies were produced against hCG, one of which (21-D-6) reacted with only native hCG with a high Ksub(a) value of 8.8x10 9 L/mol; another antibody (3-D-1) had a specificity for the epitopes located on the β-subunit of hCG. The antibodies 3-A-3, 12-A-5 and 24-B-6 cross-reacted substantially with LH. The antibodies 21-D-6 and 3-D-1, reacting with different antigenic sites, were used in a two-site IRMA in which 3-D-1 was immobilized and 21-D-6 was labelled with 125 I. This two-site IRMA was highly specific for hCG and there was no cross-reaction with hCG-α and hCG-β; the sensitivity of this IRMA was comparable with that of hCG radioiummunoassay (RIA) using polyclonal hCG antibodies. The hCG values in amniotic fluids were determined by IRMA and routine RIA, using SB-6 as hCG antiserum. Both values were significantly correlated (r=0.85, p 2 fractions prepared from 21-D-6 were iodinated by the lactoperoxidase method and used to detect hCG-containing tumours in nude mice by whole-body photoscans with a gamma scintillation camera. Positive RID results were obtained for all three tumour sites, at 144 h and 240 h after 131 I-IgG injection with a slightly higher background activity, and at 48 h after 131 I-F(ab prime) 2 administration with essentially no background activity. These results indicate that monoclonal anti-hCG and its radiolabelled fragment, which recognizes the conformation of the native hCG but not that of the subunit, are preferable for two-site IRMA and for RID of hCG-producing tumours. (author)

  4. Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

    Science.gov (United States)

    Nome, Ragnhild V; Bjøro, Trine; Paus, Elisabeth; Bjerner, Johan; Fosså, Sophie D; Steen, Rita; Nustad, Kjell; Bolstad, Nils

    2018-02-01

    Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. We found low hCG levels for all men and women hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice. Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.

  5. Elevated β-hCG associated with aggressive Osteoblastoma.

    Science.gov (United States)

    Morris, Carol D; Hameed, Meera R; Agaram, Narasimhan P; Hwang, Sinchun

    2017-09-01

    We present a unique case of an aggressive scapular osteoblastoma that produced β-hCG as a paraneoplastic manifestation in a 20-year-old woman. Serum β-hCG was found to be elevated during presurgical workup and consequently delayed surgical resection of the increasingly painful tumor because of suspected pregnancy. The paraneoplastic production of β-hCG was later proven by positive immunohistochemical stain of β-hCG in a curettage specimen and normalization of β-hCG levels after surgical resection of the aggressive osteoblastoma. Production of beta-human chorionic gonadotropin (β-hCG) has been reported in several carcinomas and sarcomas but, to our knowledge, it has not been reported in osteoblastoma in the English-language literature.

  6. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotide

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Verthelyi, D.; Klinman, D.M.

    2001-01-01

    -6, IL-12 and TNF-alpha. By screening a large panel (>100) of ODNs, the palindromic hexamer 'ATCGAT' was identified as being optimally active in all animals examined (N = 10). These findings are the first to establish the immunostimulatory activity of CpG ODN in pigs, and suggest that the therapeutic......Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found...... in bacterial but not vertebrate DNA. Different motifs are optimally stimulatory in different species. This work examines whether oligodeoxynucleotides (ODNs) containing CpG motifs stimulate peripheral blood mononuclear cells from pigs. Results show that pigs respond to CpG ODN by proliferating and secreting IL...

  7. Demonstration of Kathon CG in some commercial products.

    Science.gov (United States)

    Gruvberger, B; Persson, K; Björkner, B; Bruze, M; Dahlquist, I; Fregert, S

    1986-07-01

    The preservative Kathon CG has become one of the most common sensitizers. It has, however, been difficult to explain the sensitization and to assess the clinical relevance of the contact allergy, partly due to lack of specification of the preservative in products. A high-performance liquid chromatography method was used to demonstrate Kathon CG in 123 commercial products of both "leave on" and "rinse off" types. 38 of these contained Kathon CG in the range of 1-15 ppm of active ingredients. There were no differences between "leave on" and "rinse off" products concerning the relative number of products containing Kathon CG and the concentrations of the preservative.

  8. Cervical Ectopic Pregnancy: Persistence Despite a Serologically Negative β-hCG. A Case Report.

    Science.gov (United States)

    Tien, Shelly H; Yamamura, Yasuko

    2015-01-01

    Cervical pregnancy is a rare type of ectopic pregnancy that can be associated with significant hemorrhage and loss of fertility. Given its rarity, most effective treatment protocols are not well established. A 33-year-old primigravid woman at 11 weeks' gestation presented to our institution with a cervical ectopic pregnancy with an initial β-hCG of 114,080 IU/L. She received 2 doses of systemic multidose methotrexate (1 mg/kg) with oral leucovorin on alternating days. Fetal intracardiac potassium chloride injection was also performed. Despite an appropriate decline to undetectable levels of serum β-hCG, as well as resumption of menses, there was persistent sonographic demonstration of the cervical ectopic pregnancy. Surgery was ultimately required to remove the ectopic products of conception. Despite seemingly successful medical treatment of the cervical ectopic pregnancy with resultant undetectable serum β-hCG levels, surgery was necessary for complete resolution of the cervical pregnancy. This report supports the need to integrate both serum β-hCG levels and ultrasound to ensure complete resolution of these rare pregnancies.

  9. Radioimmunoasay of hCG in urine and serum by use of anti-beta-subunit hCG serum

    International Nuclear Information System (INIS)

    Tomoda, Yutaka; Asai, Yasumasa; Miwa, Tadahito; Saeki, Akihiko; Ishizuka, Naotaka.

    1976-01-01

    Using anti-β-subunit hCG sera, radioimmunoassay (RIA) for hCG in urine and serum was developed, and its problems were examined. In the two measuring systems, the cross reaction between hCG and LH, and the non-specific inhibition of urine and serum were observed. For actual measurement, therefore, when a standard curve is prepared using urine or serum, and the measuring sensitivity is adjusted to 16 mIU/ml for urine hCG and to 8 mIU/ml for serum hCG, the effect of LH can be eliminated relatively, and the RIA obtained can be quite specific for hCG. When this method was applied clinically, the results were in agreement with the results from cases of trophoblastic tumors under treatment, those in remission, and menopausal females with high LH. Hardly any LH was detected in the cases in remission, menopausal females, or normal females. This method enables us to judge whether or not hCG-like substances are excreted from malignant tumors. In addition, it gives clearer information on the behavior of low level hCG in patients with trophoblastic tumors than does the pre-existing RIA for hCG. This method can be applied extensively to clinical practice. (Chiba, N.)

  10. Hazards summary report: Projects CG-558 and CG-600 reactor plant modifications. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Trumble, R.E.

    1956-12-21

    It is believed that the overall safety of reactor operation will be improved upon completion of projects CG-558, 600, even at the higher power levels anticipated. Installation of sub-critical monitoring instruments concurrent with these projects is a factor in this conclusion. Higher power levels will not of themselves increase the probability of a disaster initiating event; however, higher power levels will reduce the time available for remedial action and will increase the severity of the consequences of a disaster. Loss of process cooling water will precede or accompany a reactor disaster. A reactor containing a normal inventory of fission products will surely be destroyed, with release of some fission products, if cooling water is lost at operational power levels or within hours after shutting down the reactor from operational levels. A power excursion along with the water loss, unless causing a puff release of fission product, will only hasten the destruction. A power excursion not caused by loss of cooling water is possible, but appears to be of almost negligibly small probability. Such an excursion will not become disastrous unless a significant fraction of the cooling water is boiled out of the reactor. The scope of projects CG-558 and CG-600, a discussion of reactor hazards, a technical summary of pertinent aspects of reactor control and reactor cooling, and a discussion of development programs designed to increase efficiency of operation and further decrease the hazards are included in Volume 1.

  11. Clotrimazole Drug Resistance in Candida glabrata Clinical Isolates Correlates with Increased Expression of the Drug:H(+) Antiporters CgAqr1, CgTpo1_1, CgTpo3, and CgQdr2.

    Science.gov (United States)

    Costa, Catarina; Ribeiro, Jonathan; Miranda, Isabel M; Silva-Dias, Ana; Cavalheiro, Mafalda; Costa-de-Oliveira, Sofia; Rodrigues, Acácio G; Teixeira, Miguel C

    2016-01-01

    For years, antifungal drug resistance in Candida species has been associated to the expression of ATP-Binding Cassette (ABC) multidrug transporters. More recently, a few drug efflux pumps from the Drug:H(+) Antiporter (DHA) family have also been shown to play a role in this process, although to date only the Candida albicans Mdr1 transporter has been demonstrated to be relevant in the clinical acquisition of antifungal drug resistance. This work provides evidence to suggest the involvement of the C. glabrata DHA transporters CgAqr1, CgQdr2, CgTpo1_1, and CgTpo3 in the clinical acquisition of clotrimazole drug resistance. A screening for azole drug resistance in 138 C. glabrata clinical isolates, from patients attending two major Hospitals in Portugal, was performed. Based on this screening, 10 clotrimazole susceptible and 10 clotrimazole resistant isolates were selected for further analysis. The transcript levels of CgAQR1, CgQDR2, CgTPO1_1, and CgTPO3 were found to be significantly up-regulated in resistant isolates when compared to the susceptible ones, with a level of correlation that was found to be similar to that of CgCDR2, an ABC gene known to be involved in the clinical acquisition of resistance. As a proof-of-concept experiment, the CgTPO3 gene was deleted in an azole resistant C. glabrata isolate, exhibiting high levels of expression of this gene. The deletion of CgTPO3 in this isolate was found to lead to decreased resistance to clotrimazole and fluconazole, and increased accumulation of azole drugs, thus suggesting the involvement of this transporter in the manifestation of azole resistance.

  12. Declarative Programming with Temporal Constraints, in the Language CG

    Science.gov (United States)

    2015-01-01

    Specifying and interpreting temporal constraints are key elements of knowledge representation and reasoning, with applications in temporal databases, agent programming, and ambient intelligence. We present and formally characterize the language CG, which tackles this issue. In CG, users are able to develop time-dependent programs, in a flexible and straightforward manner. Such programs can, in turn, be coupled with evolving environments, thus empowering users to control the environment's evolution. CG relies on a structure for storing temporal information, together with a dedicated query mechanism. Hence, we explore the computational complexity of our query satisfaction problem. We discuss previous implementation attempts of CG and introduce a novel prototype which relies on logic programming. Finally, we address the issue of consistency and correctness of CG program execution, using the Event-B modeling approach. PMID:25893212

  13. Declarative Programming with Temporal Constraints, in the Language CG.

    Science.gov (United States)

    Negreanu, Lorina

    2015-01-01

    Specifying and interpreting temporal constraints are key elements of knowledge representation and reasoning, with applications in temporal databases, agent programming, and ambient intelligence. We present and formally characterize the language CG, which tackles this issue. In CG, users are able to develop time-dependent programs, in a flexible and straightforward manner. Such programs can, in turn, be coupled with evolving environments, thus empowering users to control the environment's evolution. CG relies on a structure for storing temporal information, together with a dedicated query mechanism. Hence, we explore the computational complexity of our query satisfaction problem. We discuss previous implementation attempts of CG and introduce a novel prototype which relies on logic programming. Finally, we address the issue of consistency and correctness of CG program execution, using the Event-B modeling approach.

  14. The cg Package for Comparison of Groups

    Directory of Open Access Journals (Sweden)

    Bill Pikounis

    2013-01-01

    Full Text Available In research of medicines, the comparison of treatments, test articles, conditions, administrations, etc., is very common. Studies are completed, and the data are then most often analyzed with a default mixture of equal variance t tests, analysis of variance, and multiple comparison procedures. But even for an implicit, presumed one-factor linear model to compare groups, more often than not there is the added need to accommodate data which is better suited for expression of multiplicative effects, potential outliers, and limits of detection. Base R and contributed packages provide all the pieces to develop a comprehensive strategy to account for these needs. Such an approach includes exploration of the data, fitting models, formal analysis to gauge the magnitude of effects, and checking of assumptions. The cg package is developed with those goals in mind, using a flow of wrapper functions to guide the full analysis and interpretation of the data. Examples from our non-clinical world of research will be used to illustrate the package and strategy.

  15. Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

  16. Systematic evaluation of oligodeoxynucleotide binding and hybridization to modified multi-walled carbon nanotubes.

    Science.gov (United States)

    Kaufmann, Anika; Hampel, Silke; Rieger, Christiane; Kunhardt, David; Schendel, Darja; Füssel, Susanne; Schwenzer, Bernd; Erdmann, Kati

    2017-07-17

    In addition to conventional chemotherapeutics, nucleic acid-based therapeutics like antisense oligodeoxynucleotides (AS-ODN) represent a novel approach for the treatment of bladder cancer (BCa). An efficient delivery of AS-ODN to the urothelium and then into cancer cells might be achieved by the local application of multi-walled carbon nanotubes (MWCNT). In the present study, pristine MWCNT and MWCNT functionalized with hydrophilic moieties were synthesized and then investigated regarding their physicochemical characteristics, dispersibility, biocompatibility, cellular uptake and mucoadhesive properties. Finally, their binding capacity for AS-ODN via hybridization to carrier strand oligodeoxynucleotides (CS-ODN), which were either non-covalently adsorbed or covalently bound to the different MWCNT types, was evaluated. Pristine MWCNT were successfully functionalized with hydrophilic moieties (MWCNT-OH, -COOH, -NH 2 , -SH), which led to an improved dispersibility and an enhanced dispersion stability. A viability assay revealed that MWCNT-OH, MWCNT-NH 2 and MWCNT-SH were most biocompatible. All MWCNT were internalized by BCa cells, whereupon the highest uptake was observed for MWCNT-OH with 40% of the cells showing an engulfment. Furthermore, all types of MWCNT could adhere to the urothelium of explanted mouse bladders, but the amount of the covered urothelial area was with 2-7% rather low. As indicated by fluorescence measurements, it was possible to attach CS-ODN by adsorption and covalent binding to functionalized MWCNT. Adsorption of CS-ODN to pristine MWCNT, MWCNT-COOH and MWCNT-NH 2 as well as covalent coupling to MWCNT-NH 2 and MWCNT-SH resulted in the best binding capacity and stability. Subsequently, therapeutic AS-ODN could be hybridized to and reversibly released from the CS-ODN coupled via both strategies to the functionalized MWCNT. The release of AS-ODN at experimental conditions (80 °C, buffer) was most effective from CS-ODN adsorbed to MWCNT-OH and

  17. Hyperglycosylated hCG and Placenta Accreta Spectrum.

    Science.gov (United States)

    Einerson, Brett D; Straubhar, Alli; Soisson, Sean; Szczotka, Kathryn; Dodson, Mark K; Silver, Robert M; Soisson, Andrew P

    2018-02-28

     We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy.  This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H.  Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p  = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively.  Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Kathon CG: cosmetic allergy and patch test sensitization.

    Science.gov (United States)

    de Groot, A C; Liem, D H; Weyland, J W

    1985-02-01

    Three cases of contact allergy to Kathon CG, a preservative for cosmetics and toiletries containing, as active ingredients, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one are presented. In two patients, Kathon CG was contained in a moisturizing cream, and the third was sensitized by a diagnostic patch test. Although it has been used extensively in cosmetics and toiletries for 9 years in Europe and 4 years in the USA, these appear to be the first case reports of non-occupational sensitization to Kathon CG.

  19. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Xiao [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Gang, Yi [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province (China); Wang, Honghong [No. 518 Hospital of Chinese People’s Liberation Army, Xi’an 710043, Shaanxi Province (China); Wang, Jiayin [The Genome Institute, Washington University in St. Louis, St. Louis, MO 63108 (United States); Zhao, Lina [Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Xu, Li, E-mail: lxuhelen@163.com [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Liu, Zhiguo, E-mail: liuzhiguo@fmmu.edu.cn [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China)

    2015-02-06

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.

  20. Employment of Oligodeoxynucleotide plus Interleukin-2 Improves Cytogenetic Analysis in Splenic Marginal Zone Lymphoma

    Directory of Open Access Journals (Sweden)

    Antonella Bardi

    2011-01-01

    Full Text Available To compare the efficiency of novel mitogenic agents and traditional mitosis inductors, 18 patients with splenic marginal zone lymphoma (SMZL were studied. Three cultures using oligodeoxynucleotide (ODN plus interleukin-2 (IL-2, or TPA, or LPS were setup in each patient. Seventeen/18 cases with ODN+IL2 had moderate/good proliferation (94,4% as compared with 10/18 cases with TPA and LPS (55% (P=.015; 14/18 (77,7% cases with ODN+IL2 had sufficient good quality of banding as compared with 8/18 cases (44,4% with TPA and LPS. The karyotype could be defined from ODN+IL2-stimulated cultures in all 18 patients, 14 of whom (77,7% had a cytogenetic aberration, whereas clonal aberrations could be documented in 9 and in 3 cases by stimulation with LPS and TPA, respectively. Recurrent chromosome aberrations in our series were represented by aberrations of chromosome 14q in 5 patients, by trisomy 12 and 7q deletion in 4 cases each, and by abnormalities involving 11q and 13q in two cases each. These findings show that stimulation with ODN+IL2 offers more mitotic figures of better quality and results in an increased rate of clonal aberrations in SMZL, making this method ideal for prospective studies aiming at the definition of the prognostic impact of cytogenetic aberrations in this disorder.

  1. Use of oligodeoxynucleotide signature probes for identification of physiological groups of methylotrophic bacteria

    International Nuclear Information System (INIS)

    Tsien, H.C.; Bratina, B.J.; Tsuji, K.; Hanson, R.S.

    1990-01-01

    Oligodeoxynucleotide sequences that uniquely complemented 16S rRNAs of each group of methylotrophs were synthesized and used as hybridization probes for the identification of methylotrophic bacteria possessing the serine and ribulose monophosphate (RuMP) pathways for formaldehyde fixation. The specificity of the probes was determined by hybridizing radiolabeled probes with slot-blotted RNAs of methylotrophs and other eubacteria followed by autoradiography. The washing temperature was determined experimentally to be 50 and 52 degrees C for 9-α (serine pathway) and 10-γ (RuMP pathway) probes, respectively. RNAs isolated from serine pathway methylotrophs bound to probe 9-α, and RNAs from RuMP pathway methylotrophs bound to probe 10-γ. Nonmethylotrophic eubacterial RNAs did not bind to either probe. The probes were also labeled with fluorescent dyes. Cells fixed to microscope slides were hybridized with these probes, washed, and examined in a fluorescence microscope equipped with appropriate filter sets. Cells of methylotrophic bacteria possessing the serine or RuMP pathway specifically bind probes designed for each group. Samples with a mixture of cells of type I and II methanotrophs were detected and differentiated with single probes or mixed probes labeled with different fluorescent dyes, which enabled the detection of both types of cells in the same microscopic field

  2. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotide

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Verthelyi, D.; Klinman, D.M.

    2001-01-01

    Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found in bacter......Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found...... in bacterial but not vertebrate DNA. Different motifs are optimally stimulatory in different species. This work examines whether oligodeoxynucleotides (ODNs) containing CpG motifs stimulate peripheral blood mononuclear cells from pigs. Results show that pigs respond to CpG ODN by proliferating and secreting IL......-6, IL-12 and TNF-alpha. By screening a large panel (>100) of ODNs, the palindromic hexamer 'ATCGAT' was identified as being optimally active in all animals examined (N = 10). These findings are the first to establish the immunostimulatory activity of CpG ODN in pigs, and suggest that the therapeutic...

  3. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    International Nuclear Information System (INIS)

    Chen, Alex M; Santhakumaran, Latha M; Nair, Sandhya K; Amenta, Peter S; Thomas, Thresia; He, Huixin; Thomas, T J

    2006-01-01

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN

  4. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.

    Science.gov (United States)

    Hanagata, Nobutaka

    2017-01-01

    Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

  5. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    International Nuclear Information System (INIS)

    Xiao, Xiao; Gang, Yi; Wang, Honghong; Wang, Jiayin; Zhao, Lina; Xu, Li; Liu, Zhiguo

    2015-01-01

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity

  6. CpG oligodeoxynucleotides as TLR9 agonists: therapeutic applications in cancer.

    Science.gov (United States)

    Murad, Yanal M; Clay, Timothy M

    2009-01-01

    Toll-like receptors (TLRs) are part of the innate immune system, and they belong to the pattern recognition receptors (PRR) family. The PRR family is designed to recognize and bind conserved pathogen-associated molecular patterns, which are not generated by the host and are restricted and essential to micro-organisms. TLR9, which recognizes unmethylated CpG (cytosine guanosine dinucleotide), is a very promising target for therapeutic activation. Stimulation of TLR9 activates human plasmacytoid dendritic cells and B cells, and results in potent T helper-1 (T(h)1)-type immune responses and antitumor responses in mouse tumor models and in patients. Several pharmaceutical companies, such as Pfizer, Idera, and Dynavax, are developing CpG oligodeoxynucleotides (ODNs) for the treatment of cancer, along with other conditions, such as infections and allergy. CpG ODNs have shown promising results as vaccine adjuvants and in combination with cancer immunotherapy. Several TLR9 agonists are being developed and have entered clinical trials to evaluate their safety and efficacy for the treatment of several hematopoietic and solid tumors. In this review, we discuss the use of CpG ODNs in several phase I and II clinical trials for the treatment of NHL, renal cell carcinoma, melanoma, and non-small cell lung cancer, either alone or in combination with other agents.

  7. Coast Guard Enterprise Project Management (CG-EPM)

    Data.gov (United States)

    Department of Homeland Security — CG-EPM provides the following capabilities: A Project Center, Portfolio Analysis Tools, Project Planning Tool, Web-based Project Plan Updater, Project Collaboration...

  8. Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

    Science.gov (United States)

    Cole, Laurence A

    2014-11-01

    Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

  9. [Effect of AP-1 decoy oligodeoxynucleotides on neonatal rat cardiac fibroblast proliferation and collagen synthesis].

    Science.gov (United States)

    Xie, Shuang-lun; Wang, Jing-feng; Nie, Ru-qiong; Yuan, Wo-liang; Li, Fei; Lin, Mao-huan

    2008-05-01

    To investigate the inhibitory effects of AP-1 decoy oligodeoxynucleotides (ODNs) on angiotensin II (AngII)-induced proliferation and collagen synthesis in neonatal rat cardiac fibroblasts (CFs). The CFs of neonatal SD rats were cultured in serum-free medium for 24 h and stimulated with 10(-7) mol/L AngII in the presence of AP-1 decoy ODNs or mutational AP-1 decoy ODNs at varied concentrations. MTT assay was employed for quantitative evaluation of the CF proliferation. Collagen synthesis in the CFs was assessed with hydroxyproline, and the cell cycle distribution determined with flow cytometry (FCM). With the increase of the concentration of AP-1 decoy ODNs, the absorbance at 490 nm (OD490) of the CFs decreased gradually as shown by MTT assay. Treatment with 100 or 200 nmol/L AP-1 decoy ODNs resulted in significantly lowered OD490 of the CFs as compared with that of AngII group. The concentration of hydroxyproline increased significantly after treatment with 10(-7) mol/L AngII in comparison with the control group (P<0.05). Hydroxyproline concentration in cells treated with 100 or 200 nmol/L AP-1 decoy ODNs was significantly lower than that in the 10(-7) mol/L AngII-treated cells. AP-1 decoy ODNs decreased the cell percentage in S phase and increased hydroxyproline concentration, but increased the percentage of cells in G0/G1 phase. AP-1 decoy ODNs at 100 and 200 nmol/L did not obviously affect AngII-induced CF proliferation and collagen synthesis (P<0.01). AP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.

  10. 5'-Phosphate oligodeoxynucleotides enhance the phosphodiester-CpG DNA-induced inflammatory response in macrophages.

    Science.gov (United States)

    Yoshida, Hiroyuki; Nishikawa, Makiya; Kiyota, Tsuyoshi; Uno, Shota; Toyota, Hiroyasu; Takahashi, Rei; Narita, Miwako; Takakura, Yoshinobu

    2011-02-01

    Dying cells release genomic DNA into the surroundings where the DNA is first degraded to oligodeoxynucleotides, then to nucleotides, nucleosides and so on. Given that the unmethylated CpG dinucleotide (CpG motif), which is characteristic of bacterial DNA, is also contained in mammalian DNA and has been reported to be involved in the exacerbation of DNA-associated autoimmune diseases, we investigated whether nucleotides and nucleosides affect immune responses to phosphodiester (PO)-CpG DNA. Addition of non-CpG DNA to RAW264.7, murine macrophage-like cells, induced no significant TNF-α production irrespective of treatment with DNase I; however, DNase I-treated, but not untreated, non-CpG DNA increased the PO-CpG DNA-mediated TNF-α production. This increase was not observed with phosphorothioate-CpG DNA or ligands for TLR3, TLR4 or TLR7. Deoxynucleotides with a 5'-phosphate showed similar effects to those of DNase I-treated non-CpG DNA, but DNase II-treated DNA or deoxynucleosides did not. Subcutaneous injection of PO-CpG DNA into the mouse footpad induced little swelling of the paw; however, significant swelling was observed when DNase I-treated DNA was co-injected with PO-CpG DNA. These results imply that PO-CpG DNA-dependent inflammatory responses are increased by DNA molecules with a 5'-phosphate; such molecules could therefore be considered as exacerbating factors for CpG motif-related inflammation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome.

    Science.gov (United States)

    Arif, Rawa; Zaradzki, Marcin; Remes, Anca; Seppelt, Philipp; Kunze, Reiner; Schröder, Hannes; Schwill, Simon; Ensminger, Stephan M; Robinson, Peter N; Karck, Matthias; Müller, Oliver J; Hecker, Markus; Wagner, Andreas H; Kallenbach, Klaus

    2017-12-15

    Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. hCG: Biological Functions and Clinical Applications.

    Science.gov (United States)

    Nwabuobi, Chinedu; Arlier, Sefa; Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-09-22

    Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80-85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications.

  13. Human safety study of body lotion containing Kathon CG.

    Science.gov (United States)

    Schwartz, S R; Weiss, S; Stern, E; Morici, I J; Moss, J N; Goodman, J J; Scarborough, N L

    1987-04-01

    The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

  14. Effect of additional human chorionic gonadotrophin (hCG) on follicular growth and ovulation in gonadotrophin-treated gilts

    Science.gov (United States)

    Manjarín, Rodrigo; Cassar, Glen; Friendship, Robert M.; Garcia, José C.; Dominguez, J. Carlos; Kirkwood, Roy N.

    2015-01-01

    The objective of this study was to determine the effect of additional human chorionic gonadotrophin (hCG) on the ovarian response of gilts previously treated with 200 IU hCG combined with 400 IU equine chorionic gonadotrophin (eCG) (eCG/hCG). Seventy-one prepuberal gilts (105 ± 7.5 kg) were assigned to groups: i) eCG/hCG (hCG-0; n = 25); ii) eCG/hCG followed by 100 IU of hCG at 24 h (hCG-100; n = 24); iii) eCG/hCG followed by 200 IU hCG at 24 h (hCG-200; n = 10); and iv) controls (CON; n = 12). Ovulation response was assessed by ovarian dissection or real-time ultrasonography. Additional hCG did not significantly improve numbers of gilts ovulating. Numbers of corpora lutea increased with hCG, and was higher in hCG-200 (P hCG-0, the frequency of cysts in gilts was higher in hCG-100 (P hCG-200 (P hCG. We conclude that supplemental hCG will increase the number of corpora lutea but will be associated with follicular cyst development in a dose dependent manner. PMID:26130853

  15. Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities

    NARCIS (Netherlands)

    Butler, SA; Mantingh, A; Cole, LA

    2000-01-01

    Hyperglycosylated human chorionic gonadotrophin (H-hCG), also known as Invasive Trophoblast Antigen or ITA, is a unique metabolic variant of hCG with more complex oligosaccharide side chains. Concentrations are independent of regular hCG. Urine H-hCG has recently proved to be a highly sensitive

  16. Patch test sensitivity to the preservative Kathon CG in Spain.

    Science.gov (United States)

    Hasson, A; Guimaraens, D; Condé-Salazar, L

    1990-05-01

    Kathon CG is a very well studied preservative used in cosmetics and toiletries. It is effective in low concentrations (3 to 15 ppm active ingredients) and exhibits outstanding antimicrobial activity against gram-negative and gram-positive bacteria, yeasts and fungi. Although this biocide is not considered to pose a toxicological hazard at recommended use levels, the sensitizing potential of Kathon CG has been established. From November 1988 to June 1989, we patch tested 626 unselected contact dermatitis patients with Kathon CG solution containing 200 ppm active ingredients and obtained 22 (3.5%) positive reactions. Relevance was established in 7 of the 22 patients. Women were predominantly sensitized, the principal source of sensitization being cosmetics.

  17. Sensitization to Kathon CG in Geneva and Switzerland.

    Science.gov (United States)

    Pasche, F; Hunziker, N

    1989-02-01

    Between October 1986 and June 1987 we patch tested 420 patients with Kathon CG at 100 ppm and obtained 23 positive reactions (5.5%). The other 5 Swiss university clinics joined our study between January and June 1987 and obtained sensitization rates ranging from 0.7 to 7.5%. The total mean value including Geneva was 3.6%. We did threshold patch testing in 12 patients with the following Kathon CG dilutions: 100, 50, 25, 15 and 7 ppm. We observed progressively diminishing skin reactions, especially below 25 ppm, but we still obtained slight positive reactions in 2 patients with Kathon CG at 7 ppm. Those reactions were relevant because the dermatitis disappeared when the use of Kathon-containing creams was discontinued.

  18. Rapid increase in contact allergy to Kathon CG in Finland.

    Science.gov (United States)

    Hannuksela, M

    1986-10-01

    In unselected eczema patients subjected to routine patch testing, the number with positive reactions to Kathon CG 100 ppm increased from none in 1983 to 0.7% in January-August 1985, and to 4.6% in September 1985 to March 1986. Repeated open application tests (ROAT) with creams containing 7-15 ppm of the isothiazolinones were positive in 12 of 24 patients tested. 2 of the ROAT-positive cases had negative patch tests to 100 ppm Kathon CG, but 1 was positive with 200 ppm. Atopic dermatitis, chronic hand dermatitis and lower leg dermatitis were the most common disorders in the positive patients. The cause of the rapid increase of Kathon CG allergy in Finland during the winter of 1985-1986 was the use of a popular moisturizing cream containing first 19 ppm, then 7 ppm of a mixture of 2 isothiazolinones (Euxyl K 100).

  19. AHRR (cg05575921) hypomethylation marks smoking behaviour, morbidity and mortality

    DEFF Research Database (Denmark)

    Bojesen, Stig E; Timpson, Nicholas; Relton, Caroline

    2017-01-01

    RATIONALE AND OBJECTIVES: Self-reported smoking underestimates disease risk. Smoking affects DNA methylation, in particular the cg05575921 site in the aryl hydrocarbon receptor repressor (AHRR) gene. We tested the hypothesis that AHRR cg05575921 hypomethylation is associated with risk of smoking......-related morbidity and mortality. METHODS: From the Copenhagen City Heart Study representing the Danish general population, we studied 9234 individuals. Using bisulphite treated leucocyte DNA, AHRR (cg05575921) methylation was measured. Rs1051730 (CHRN3A) genotype was used to evaluate smoking heaviness. Participants...... was associated with former and current smoking status, high daily and cumulative smoking, short time since smoking cessation (all p values smoking-related CHRN3A genotype (-0.48% per T-allele, p=0.002). The multifactorially adjusted HRs for the lowest versus highest methylation quintiles were...

  20. Extending the QUDA Library with the eigCG Solver

    Energy Technology Data Exchange (ETDEWEB)

    Strelchenko, Alexei [Fermilab; Stathopoulos, Andreas [William-Mary Coll.

    2014-12-12

    While the incremental eigCG algorithm [ 1 ] is included in many LQCD software packages, its realization on GPU micro-architectures was still missing. In this session we report our experi- ence of the eigCG implementation in the QUDA library. In particular, we will focus on how to employ the mixed precision technique to accelerate solutions of large sparse linear systems with multiple right-hand sides on GPUs. Although application of mixed precision techniques is a well-known optimization approach for linear solvers, its utilization for the eigenvector com- puting within eigCG requires special consideration. We will discuss implementation aspects of the mixed precision deflation and illustrate its numerical behavior on the example of the Wilson twisted mass fermion matrix inversions

  1. Contact allergy to the active ingredients of Kathon CG.

    Science.gov (United States)

    Bruze, M; Dahlquist, I; Fregert, S; Gruvberger, B; Persson, K

    1987-04-01

    The preservative Kathon CG is a commercial preparation, consisting of 2 active ingredients and other components. 28 patients with contact allergy to Kathon CG participated in a study in which patch testing was performed with serial dilutions, and with 5 chromatographically separated fractions. All reacted to fraction IV, and 2 patients also to fraction II. Mass spectrometry and nuclear magnetic resonance spectrometry identified fraction II and IV to be the active ingredients; 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one.

  2. Hybrid DFP-CG method for solving unconstrained optimization problems

    Science.gov (United States)

    Osman, Wan Farah Hanan Wan; Asrul Hery Ibrahim, Mohd; Mamat, Mustafa

    2017-09-01

    The conjugate gradient (CG) method and quasi-Newton method are both well known method for solving unconstrained optimization method. In this paper, we proposed a new method by combining the search direction between conjugate gradient method and quasi-Newton method based on BFGS-CG method developed by Ibrahim et al. The Davidon-Fletcher-Powell (DFP) update formula is used as an approximation of Hessian for this new hybrid algorithm. Numerical result showed that the new algorithm perform well than the ordinary DFP method and proven to posses both sufficient descent and global convergence properties.

  3. Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells.

    Science.gov (United States)

    Park, Jong-Ju; Seong, Hun-Ki; Kim, Jeong-Soo; Munkhzaya, Byambaragchaa; Kang, Myung-Hwa; Min, Kwan-Sik

    2017-06-01

    Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn 56 of the α-subunit. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

  4. Selection of effective antisense oligodeoxynucleotides with a green fluorescent protein-based assay. Discovery of selective and potent inhibitors of glutathione S-transferase Mu expression

    NARCIS (Netherlands)

    Hoen, P.A.; Rosema, B.S.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Manoharan, M.; van Berkel, T.J.; Biessen, E.A.; Bijsterbosch, M.K.

    2002-01-01

    Antisense oligodeoxynucleotides (AS-ODNs) are frequently used for the down-regulation of protein expression. Because the majority of potential antisense sequences lacks effectiveness, fast screening methods for the selection of effective AS-ODNs are needed. We describe a new cellular screening assay

  5. Selection of effective antisense oligodeoxynucleotides with a green fluorescent protein-based assay. Discovery of selective and potent inhibitors of glutathione S-transferase Mu expression.

    NARCIS (Netherlands)

    Hoen, P.A.; Rosema, B.S.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Manoharan, M.; van Berkel, T.J.; Biessen, E.A.; Bijsterbosch, M.K.

    2002-01-01

    Antisense oligodeoxynucleotides (AS-ODNs) are frequently used for the down-regulation of protein expression. Because the majority of potential antisense sequences lacks effectiveness, fast screening methods for the selection of effective AS-ODNs are needed. We describe a new cellular screening assay

  6. Selection of effective antisense oligodeoxynucleotides with a green fluorescent protein-based assay. Discovery of selective and potent inhibitors of glutathione S-transferase Mu expression

    NARCIS (Netherlands)

    ’t Hoen, Peter a.C; Rosema, Bram-Sieben; Commandeur, Jan N M; Vermeulen, Nico P E; Manoharan, Muthiah; van Berkel, Theo J C; Biessen, Eric A L; Bijsterbosch, Martin K

    Antisense oligodeoxynucleotides (AS-ODNs) are frequently used for the down-regulation of protein expression. Because the majority of potential antisense sequences lacks effectiveness, fast screening methods for the selection of effective AS-ODNs are needed. We describe a new cellular screening assay

  7. Dynamic GnRH and hCG testing

    DEFF Research Database (Denmark)

    Bang, A Kirstine; Nordkap, Loa; Almstrup, Kristian

    2017-01-01

    OBJECTIVE: Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after Gn......RH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses. DESIGN: GnRH and hCG stimulation tests were performed on 77 healthy men, 18-40 years (reference group) at a specialized andrology referral center at a university hospital. The potential......: For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7-67.6 nmol/L) during hCG testing. None of the polymorphisms had any major...

  8. Effects of equine chorionic gonadotropin (eCG) administration and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... with eCG or increasing doses of royal jelly. Anim. Reprod. Sci. 92(1-2): 75-85. Landau DJ, Molle G (1997). Nutrition effects on fertility in small ruminants with an emphasis on Mediterranean sheep breeding systems. In: Recent advances in small ruminant nutrition proc. CIHEAM-IAMZ meeting. Zaragoza ...

  9. Using a decline in serum hCG between days 0–4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Skubisz Monika

    2013-02-01

    Full Text Available Abstract Background The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4–7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0–4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications. Methods We conducted a retrospective study of women (n=206 treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L at Scottish hospitals between 2006–2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0–4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4–7 of treatment and an alternate early measure ( Results In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94% (121/136. A falling serum hCG between days 0–4 predicted treatment success in 85% (95% CI 79-92% of cases (94/110 and a Conclusions We have verified that a decline in serum hCG between days 0–4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.

  10. Characterization of CgHIFα-Like, a Novel bHLH-PAS Transcription Factor Family Member, and Its Role under Hypoxia Stress in the Pacific Oyster Crassostrea gigas.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Hypoxia-inducible factor (HIF, a critical member of the basic-helix-loop-helix (bHLH-containing Per-Arnt-Sim (PAS protein family, is a master transcription factor involved in maintaining oxygen homeostasis. In the present study, we isolated and characterized a novel bHLH-PAS family member, CgHIFα-like gene, from the Pacific oyster Crassostrea gigas, and determined its importance during hypoxia stress. The 3020-bp CgHIFα-like cDNA encoded a protein of 888 amino acids. The predicted CgHIFα-like amino acid sequence was conserved in the N-terminal bHLH, PAS, and PAC domains (but not in the C-terminal domain and was most closely related to the HIF family in the bHLH-PAS protein phylogenic tree. Similar to the mammalian HIF-1α, CgHIFα-like could be expressed as four mRNA isoforms containing alternative 5'-untranslated regions and different translation initiation codons. At the mRNA level, these isoforms were expressed in a tissue-specific manner and showed increased transcription to varying degrees under hypoxic conditions. Additionally, the western blot analysis demonstrated that CgHIFα-like was induced by hypoxia. Electrophoretic mobility shift assay indicated that CgHIFα-like could bind to the hypoxia responsive element (HRE, whereas dual-luciferase reporter analysis demonstrated that CgHIFα-like could transactivate the reporter gene containing the HREs. In addition to CgHIFα-like, we identified CgARNT from the C. gigas, analyzed its expression pattern, and confirmed its interaction with CgHIFα-like using a yeast two-hybrid assay. In conclusion, this is the first report on the cloning and characterization of a novel hypoxia transcription factor in mollusks, which could accumulate under hypoxia and regulate hypoxia related gene expression by binding to HRE and dimerizing with CgARNT. As only one member of HIF has been identified in invertebrates to date, our results provide new insights into the unique mechanisms of hypoxia tolerance in

  11. Kathon CG y Dermatología Laboral: Actualización Kathon CG and Occupational Dermatology: An update

    Directory of Open Access Journals (Sweden)

    Ana Rita Rodrigues Barata

    2012-09-01

    Full Text Available El Kathon CG constituye el nombre comercial de una mezcla de isotiazolinas: Metilcloroisotiazolinona y Metilisotiazolinona. Es un conservante muy utilizado, sobre todo en la industria cosmética, aunque en los últimos años también se ha impuesto su presencia en productos de limpieza de uso doméstico y actualmente a concentraciones más altas en preparados de uso industrial como aceites de corte, emulsiones de látex, pinturas al temple, aceites para motores Diesel, etc. Por su alto poder sensibilizante y amplia utilización, constituye actualmente una de las causas más frecuentes de alergia de contacto por preservativos, tanto en nuestra vida privada, como en el ámbito profesional. Objetivos: Estudiar la capacidad sensibilizante del Kathon CG y su relación con el desarrollo de eczema de contacto alérgico de origen profesional. Métodos: Estudio observacional descriptivo, a través de la revisión de las historias clínicas de los pacientes vistos en el Servicio de Dermatología Laboral del Instituto Nacional de Medicina y Seguridad en el Trabajo durante los años 2008-2012; 1520 pacientes fueron evaluados y estudiados mediante pruebas epicutáneas para descartar una posible dermatosis profesional. Se registraron los casos de sensibilización al Kathon CG y se analizaron las siguientes variables: genero, edad, grupo profesional, localización de las lesiones cutáneas, relevancia y relación profesional. El análisis estadístico se realizó con el programa SPSS 15.0. Resultados: Se observó sensibilización al Kathon CG en 88 pacientes (5,8%, correspondiendo un 42% a sensibilizaciones de origen profesional. Conclusiones: La alergia de contacto profesional por Kathon CG constituye actualmente es un problema de alta prevalencia. Ante un paciente con positividad a este alérgeno hay que interrogar siempre por su profesión.Kathon CG is the tradename for a mixture of isothiazolines: methylchloroisothiazolinone and methylisothiazolinone. It

  12. Urine reference intervals for human chorionic gonadotropin (hCG) isoforms by immunoextraction-tandem mass spectrometry to detect hCG use.

    Science.gov (United States)

    Butch, Anthony W; Ahrens, Brian D; Avliyakulov, Nuraly K

    2017-11-03

    Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles and can normalize suppressed testosterone concentrations in males following prolonged anabolic steroid use. Because of the potential for abuse by males, hCG is on the World Anti-Doping Agency (WADA) list of prohibited substances. The majority of WADA-accredited laboratories measure urinary hCG using an automated immunoassay. Only immunoassays that recognize the intact alpha and beta heterodimer of hCG (intact hCG) should be used to measure urinary hCG for doping control purposes since intact hCG is the only biologically active molecule. WADA further requires that confirmation testing is performed using an intact hCG immunoassay that is different from the one used in the initial testing procedure or by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study we measured the concentration of intact hCG, free β-subunit (hCGβ) and β-subunit core fragment (hCGβcf) in 570, 275, and 256 male urine samples, respectively, by an immunoextraction LC-MS/MS method. Mean concentrations of intact hCG, hCGβ and hCGβcf were 0.04 IU/L, 0.47 pmol/L and 0.16 pmol/L, respectively. The upper reference limits (97.5 th percentile) for intact hCG, hCGβ and hCGβcf were 0.21 IU/L, 0.40 pmol/L, and 1.86 pmol/L, respectively. Based on these data, we recommend a threshold of 1.0 IU/L for intact hCG (false positive rate of hCG. Copyright © 2017 John Wiley & Sons, Ltd.

  13. [Research on Kathon CG in cosmetic and personal hygiene products].

    Science.gov (United States)

    Vezia, V; Renacco, E; Castelain, P Y; Caperan, A; Lanza, M; Pastor, J

    1990-09-01

    Kathon is an anti-microbial agent that is used as a preservative in cosmetics and bodily hygiene products. At the recommended levels of usage Kathon is innocuous and has a recognised efficacy. Nevertheless, following reappearance of contact allergic eczemas due to cosmetics and bodily hygiene products different authors have reported increase in sensitisation to it. We have met the same problems in the Service de Dermatology++ of the Hospital Sainte Marguerite at Marseille and we wished to make a deeper examination of the question and to ascertain whether the current cosmetics contained Kathon CG. For this we have developed a technique of liquid chromatography and tested 44 creams. Eight contained Kathon CG, of which 2 were responsible for contact eczema in patients.

  14. Sensitivity to Kathon CG: findings in 365 consecutive patients.

    Science.gov (United States)

    Fransway, A F

    1988-11-01

    In the period from 1983 through 1986, 365 consecutive patients suspected as having allergic contact dermatitis were tested for reaction to Kathon CG. This test was positive in 20 of these patients: irritant responses in 7 and allergic sensitivity in 13. Provocative use testing was positive in 1 of the 3 allergic patients tested. The characteristics of this group of patients include having a mean age older than that of the general population or of our population of dermatologic patients, having histories of long-standing dermatitis, and reporting exposure to various leave-on formulations. Our rate of positive tests, 3.6%, is similar to that reported by other investigators, although sensitivity testing results differ from center to center. It is recommended that, in certain clinical situations, caution be exercised in the unsupervised use of leave-on products containing Kathon CG.

  15. Effects of equine chorionic gonadotropin (eCG) administration and ...

    African Journals Online (AJOL)

    Pregnancy rate in group F was more than the control group (p < 0.05). Twinning rates and kid crops in groups E+F and F were significantly higher than control group (p < 0.05). Time of onset of estrus decreased in groups with eCG administration (E and E+F). Therefore, it is concluded that the flushing especially coupled with ...

  16. MD Simulations of Viruslike Particles with Supra CG Solvation Affordable to Desktop Computers.

    Science.gov (United States)

    Machado, Matı As R; González, Humberto C; Pantano, Sergio

    2017-10-10

    Viruses are tremendously efficient molecular devices that optimize the packing of genetic material using a minimalistic number of proteins to form a capsid or envelope that protects them from external threats, being also part of cell recognition, fusion, and budding machineries. Progress in experimental techniques has provided a large number of high-resolution structures of viruses and viruslike particles (VLP), while molecular dynamics simulations may furnish lively and complementary insights on the fundamental forces ruling viral assembly, stability, and dynamics. However, the large size and complexity of these macromolecular assemblies pose significant computational challenges. Alternatively, Coarse-Grained (CG) methods, which resign atomistic resolution privileging computational efficiency, can be used to characterize the dynamics of VLPs. Still, the massive amount of solvent present in empty capsids or envelopes suggests that hybrid schemes keeping a higher resolution on regions of interest (i.e., the viral proteins and their surroundings) and a progressively coarser description on the bulk may further improve efficiency. Here we introduce a mesoscale explicit water model to be used in double- or triple-scale simulations in combination with popular atomistic parameters and the CG water used by the SIRAH force field. Simulations performed on VLPs of different sizes, along with a comprehensive analysis of the PDB, indicate that most of the VLPs so far reported are amenable to be handled on a GPU-accelerated desktop computer using this simulation scheme.

  17. Design and simulation of the CG1 beamline at HFIR

    CERN Document Server

    Nagler, S E; Moon, R M

    2002-01-01

    In the near future a super-critical hydrogen cold source will be installed in the HB4 beam tube of the High Flux Isotope Reactor (HFIR), Oak Ridge National Laboratory. The cold source will illuminate four neutron guides. Here we discuss the design and simulation of the guide CG1, dedicated to a new triple axis spectrometer. The conceptual design for the HFIR guides, including CG1, was aided by numerical calculations of neutron trajectories and acceptance diagrams. The CG1 guide consists of a partially trumpeting two-channel bender and a straight guide section. The design was subsequently modeled in detail from source to specimen, utilizing the McStas program. The lessons learned from the McStas simulations resulted in some minor but important changes in the design, and these were also verified using the original method of calculation. The resulting combination of guide and vertically focusing monochromator should deliver a beam with excellent spatial and angular distributions in and out of the scattering plan...

  18. Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

    Science.gov (United States)

    Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

    2015-04-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

  19. Oligodeoxynucleotides Can Transiently Up- and Downregulate CHS Gene Expression in Flax by Changing DNA Methylation in a Sequence-Specific Manner

    Directory of Open Access Journals (Sweden)

    Magdalena Dzialo

    2017-05-01

    Full Text Available Chalcone synthase (CHS has been recognized as an essential enzyme in the phenylpropanoid biosynthesis pathway. Apart from the leading role in the production of phenolic compounds with many valuable biological activities beneficial to biomedicine, CHS is well appreciated in science. Genetic engineering greatly facilitates expanding knowledge on the function and genetics of CHS in plants. The CHS gene is one of the most intensively studied genes in flax. In our study, we investigated engineering of the CHS gene through genetic and epigenetic approaches. Considering the numerous restrictions concerning the application of genetically modified (GM crops, the main purpose of this research was optimization of the plant's modulation via epigenetics. In our study, plants modified through two methods were compared: a widely popular agrotransformation and a relatively recent oligodeoxynucleotide (ODN strategy. It was recently highlighted that the ODN technique can be a rapid and time-serving antecedent in quick analysis of gene function before taking vector-mediated transformation. In order to understand the molecular background of epigenetic variation in more detail and evaluate the use of ODNs as a tool for predictable and stable gene engineering, we concentrated on the integration of gene expression and gene-body methylation. The treatment of flax with a series of short oligonucleotides homologous to a different part of CHS gene isoforms revealed that those directed to regulatory gene regions (5′- and 3′-UTR activated gene expression, directed to non-coding region (introns caused gen activity reduction, while those homologous to a coding region may have a variable influence on its activity. Gene expression changes were accompanied by changes in its methylation status. However, only certain (CCGG motifs along the gene sequence were affected. The analyzed DNA motifs of the CHS flax gene are more accessible for methylation when located within a Cp

  20. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    Antisense oligodeoxynucleotide (ODN) inhibition emerges as an effective means for probing gene function in plant cells. Employing this method we have established the importance of the SUSIBA2 transcription factor for regulation of starch synthesis in barley endosperm, and arrived at a model for the role of the SUSIBAs in sugar signaling and source-sink commutation during cereal endosperm development. In this addendum we provide additional data demonstrating the suitability of the antisense ODN technology in studies on starch branching enzyme activities in barley leaves. We also comment on the mechanism for ODN uptake in plant cells. Antisense ODNs are short (12-25 nt-long) stretches of single-stranded ODNs that hybridize to the cognate mRNA in a sequence-specific manner, thereby inhibiting gene expression. They are naturally occurring in both prokaryotes and eukaryotes where they partake in gene regulation and defense against viral infection. The mechanisms for antisense ODN inhibition are not fully understood but it is generally considered that the ODN either sterically interferes with translation or promotes transcript degradation by RNase H activation. The earliest indication of the usefulness of antisense ODN technology for the purposes of molecular biology and medical therapy was the demonstration in 1978 that synthetic ODNs complementary to Raos sarcoma virus could inhibit virus replication in tissue cultures of chick embryo fibroblasts. Since then the antisense ODN technology has been widely used in animal sciences and as an important emerging therapeutic approach in clinical medicine. However, antisense ODN inhibition has been an under-exploited strategy for plant tissues, although the prospects for plant cells in suspension cultures to take up single-stranded ODNs was reported over a decade ago. In 2001, two reports from Malho and coworker demonstrated the use of cationic-complexed antisense ODNs to suppress expression of genes encoding pollen

  1. Selective reversible deuteriation of oligodeoxynucleotides: simplification of two-dimensional nuclear Overhauser effect NMR spectra assignment of a non-self-complementary dodecamer duplex

    International Nuclear Information System (INIS)

    Brush, C.K.; Stone, M.P.; Harris, T.M.

    1988-01-01

    Oligodeoxynucleotides are reversibly deuteriated at the purine C8 and cytosine C5 positions with deuterioammonium bisulfite at pD 7.8. The exchange reaction is complete after 48 h at 65 0 C. When an oligomer deuteriated under these conditions is analyzed by 1 H nuclear magnetic resonance (NMR) spectroscopy, the purine H8 and cytosine H5 proton signals are selectively removed from the spectrum. A non-self-complementary oligodeoxynucleotide that has been deuteriated in this manner may be annealed with its complement and the resulting heteroduplex analyzed by two-dimensional nuclear Overhauser enhancement (NOESY) spectroscopy. The intense cytosine H5-H6 cross-peaks are also removed from the spectrum of the deuteriated strand, which further simplifies interpretation since these strong cross-peaks often interfere with less intense NOE cross-peaks arising from dipolar coupling between purine H8 or pyrimidine H6 and deoxyribose anomeric protons. The resulting spectral simplification allows unambiguous assignments to be made on NOEs that otherwise may be difficult to distinguish. The deuteriation procedure is demonstrated with the sequence d(CGTTATAATGCG)-d(CGCATTATAACG), which has previously been assigned by traditional NOESY methods. Although the assignment of this dodecadeoxynucleotide may be completed without deuteriation, several NOEs must be assigned indirectly because of degeneracies in the chemical shift of the purine H8 protons. This methodology should have wide applicability to NMR spectral interpretation of oligodeoxynucleotides, particularly to oligonucleotides of 12 bases or longer

  2. A 43-year-old woman with unexplained elevation of hCG.

    Science.gov (United States)

    Johnson, Lisa M; Gniadek, Thomas J; Cohn, Claudia S; Bachowski, Gary; Karger, Amy B

    2018-03-26

    This case report investigates an unusual hCG result in a woman who is not pregnant. A 43-year-old woman was admitted for recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma exchange (TPE) was initiated. Prior to transitioning the patient from TPE to immunosuppressive therapy, a serum qualitative hCG test was performed and was positive. Several etiologies for elevated hCG were considered and investigated, including heterophile antibody interference, endogenous hCG from pituitary or malignancy, and exogenous hCG. Retrospective measurement of hCG levels in remnant samples, including a sample obtained prior to TPE initiation, demonstrated that the hCG elevation occurred with plasma administration for TPE. Further investigation with the American Red Cross confirmed that a plasma donor was unknowingly pregnant and in the latter half of the first trimester at the time of donation, when hCG levels peak. In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source. Copyright © 2018. Published by Elsevier Inc.

  3. Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations.

    Science.gov (United States)

    Koistinen, Hannu; Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

    2015-12-01

    Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.

  4. Serum hCG Levels following the Ovulatory Injection: Associations with Patient Weight and Implantation Time

    Science.gov (United States)

    Noorhasan, Dorette J.; McGovern, Peter G.; Cho, Michael; Seungdamrong, Aimee; Ahmad, Khaliq; McCulloh, David H.

    2015-01-01

    Objective. To test if serum hCG levels the morning after the ovulatory hCG injection correlate with (1) retrieval efficiency, (2) oocyte maturity, (3) embryo quality, (4) pregnancy, and/or (5) time to implantation in patients undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Design. Retrospective cohort analysis. Setting. University-based IVF clinic. Patient(s). All IVF/ICSI cycles from April 2005 to February 2008 whose hCG administration was confirmed (n = 472 patients). Intervention(s). Serum hCG was measured the morning following the ovulatory injection, on the 16th day following retrieval, and repeated on day 18 for those with positive results. Main Outcome Measure(s). Number of follicles on the day of hCG injection, number of oocytes retrieved, maturity of oocytes, embryo quality, pregnancy outcome, and time to implantation. Result(s). hCG levels did not correlate with retrieval efficiency, oocyte maturity, embryo quality, or pregnancy. Postinjection hCG levels were inversely associated with patient weight and time to implantation. Conclusion(s). No correlation was found between hCG level and any parameter of embryo quality. Patient weight affected hCG levels following hCG injection and during the early period of pregnancy following implantation. No association between postinjection hCG level and time of implantation (adjusted for patient weight) was apparent. PMID:26587025

  5. Clinical effects of CG (Hythiol) tablets on leukopenia resulting from radiotherapy

    International Nuclear Information System (INIS)

    Fukui, Hideki; Sakaguchi, Kokichi; Sekiba, Kaoru

    1984-01-01

    A double-blind comparative study of CG(L-cysteine) tablets and approved drugs (CG capsules) was made to assess clinical effects of CG tablets on leukopenia. The subjects were 75 patients with cancer of the uterine cervix in whom the number of WBC was 4,500-7,500/mm before irradiation. The ratios of patients who kept WBC as 3,500/mm or more were 64.7% in the group with CG tablets and 50% in the group with CG capsules with no statistical significance. The ratios of patients who kept WBC as 3,000/mm or more were 82.4% in the group with CG tablets and 79.4% in the group with CG capsules with no statistical significance. The ratios to prevent leukopenia were 70.6% in the group with CG tablets and 58.8% in the group with CG capsules with no significant difference. Other hematological findings, subjective symptoms and the performance of radiotherapeutic protocol were not different between the groups. No marked side effects were observed. These results suggest that CG tablets, as well as CG capsules, are effective for preventing leukopenia resulting from radiotherapy. (Namekawa, K.)

  6. Determination of serum hCG levels by radioreactor assay in the clinical laboratory

    International Nuclear Information System (INIS)

    Boyko, W.L.

    1979-01-01

    The radioreceptorassay (RRA) has been used for measuring human chorionic gonadotropin (hCG) in sera from 751 individuals. The RRA is shown to be sensitive (98%) and specific (99.8%) in detecting hCG in a wide variety of conditions, including normal pregnancy and threatened or missed abortions. As a rapid qualitative or semiquantitative assay for hCG, the RRA is a valuable adjunct in the laboratory to less sensitive tests for hCG. Variation among different quantitative assays for hCG is examined, and it is concluded that the same assay system should be used for monitoring hCG levels in a single individual over a period of time in order to avoid inconsistent results. Application of the quantitative RRA for hCG in detecting the midcycle luteinizing hormone surge in infertillity is also presented

  7. [Influence of hCG glycosylation on its functions in female reproduction].

    Science.gov (United States)

    Oborná, I; Fingerová, H

    To review contemporary knowledge of the hCG molecule, its isoforms and the importance of glycosylation. Biologic variants and glycoforms of hCG have different biological activities and functions related to the control of menstrual cycle, conception, gestation as well as gynaecologic and non-gynaecologic malignancies. A review. Department of Obstetrics and Gynaecology, University Hospital Olomouc. To present own experience and an overview of recent literature in molecular biology, clinical biochemistry and clinical practice. Recent knowledge of the role of hCG glycosylation in physiologic and pathologic events in female organism will provide a better understanding of regulation of processes like ovulation (co-operation of pituitary hCG with LH), implantation and hemochorial placentation (invasivity of hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important for the prediction of certain pathologies of pregnancy, prenatal screening of inborn errors (free beta hCG) as well as in the treatment of infertility.

  8. Contact allergy to a contaminant in Kathon CG in the guinea pig.

    Science.gov (United States)

    Bruze, M; Gruvberger, B; Persson, K

    1987-01-01

    Kathon CG is a commercial preservative, consisting of the two active ingredients, 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one (5243-K-CG) and other components. 4,5-dichloro-2-methyl-4-isothiazolin-3-one (45243-K-CG) is a contaminant in Kathon CG. The chemically related active ingredients are known to be contact sensitizers in humans and guinea pigs. Aims of this study were to determine the sensitizing capacity of this contaminant and also to investigate the cross-reaction pattern by guinea pig sensitization tests. 45243-K-CG was demonstrated to be a strong sensitizer; all animals reacting to 45243-K-CG also reacted to 5243-K-CG when rechallenged.

  9. Frequency of sensitisation to the preservative Kathon CG.

    Science.gov (United States)

    Cronin, E; Hannuksela, M; Lachapelle, J M; Maibach, H I; Malten, K; Meneghini, C L

    1988-05-01

    The incidences of sensitisation to Kathon CG are reported for patients routinely tested from 1984 to 1986 in Bari, London, Louvain, Nijmegen, Oulu and San Francisco. For these 3 years, the overall frequency of sensitisation varied for women from 3.3% in Oulu to 0.6% in London and San Francisco and for men from 1.4% in Oulu to 0% in San Francisco. Women were predominantly sensitised, probably by cosmetics, toiletries and domestic cleaners. Occupational sensitisation was much less frequent.

  10. Routine patch testing with the preservative system Kathon CG.

    Science.gov (United States)

    Groot, A C; Bruynzeel, D P; Schroeff, J G; Bos, J D

    1988-04-01

    Synopsis Of 1620 patients routinely patch tested with Kathon CG 100 p.p.m. aqua for suspected allergic contact dermatitis, 81 (5.0%) had a positive reaction. Sixty-two reactions (3.8%) were relevant for the dermatitis for which the patient consulted the dermatologist. Most patients were females who presented with dermatitis of the hands and/or face. Forty-six per cent of the patients had become sensitized by using cosmetic products on healthy skin. The other 54% had pre-existing dermatitis, especially atopic dermatitis and irritant dermatitis. Most reactions were caused by moisturizing creams.

  11. Analytical sensitivity of four commonly used hCG point of care devices.

    Science.gov (United States)

    Kamer, Sandy M; Foley, Kevin F; Schmidt, Robert L; Greene, Dina N

    2015-04-01

    Point of care (POC) hCG assays are often used to rule-out pregnancy and therefore diagnostic sensitivity, especially at low concentrations of hCG, is important. There are very few studies in the literature that seek to verify the claimed analytical sensitivity of hCG POC devices. The analytical sensitivity of four commonly used hCG POC devices (Alere hCG Combo Cassette, ICON 20 hCG, OSOM hCG Combo Test, and Sure-Vue Serum/Urine hCG-STAT) was challenged using urine samples (n=50) selected based on quantitative hCG concentrations. The majority of these specimens (n=40) had an hCG concentration between 20 and 200 U/L. Each specimen/device combination was reviewed by three individuals. Statistical calculations were performed using Stata 12. The analytical sensitivity of the OSOM was significantly lower inferior than that of the other POC devices. There was no significant difference in the sensitivity of the Alere, ICON 20 and Sure-Vue devices. There was no significant difference in the individual interpretation of the hCG POC results. All hCG POC devices evaluated in this study were susceptible to false negative results at low concentrations of urine hCG. Laboratorians and clinicians should be aware that there are limitations when using urine hCG POC devices to rule out early pregnancy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Polyethyleneimine-functionalized boron nitride nanospheres as efficient carriers for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides

    Directory of Open Access Journals (Sweden)

    Zhang HJ

    2015-08-01

    Full Text Available Huijie Zhang,1 Shini Feng,1 Ting Yan,1 Chunyi Zhi,2 Xiao-Dong Gao,1 Nobutaka Hanagata3,41The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Physics and Materials Science, City University of Hong Kong, Kowlong, Hong Kong SAR, People’s Republic of China; 3Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Ibaraki, Japan; 4Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, JapanAbstract: CpG oligodeoxynucleotides (ODNs stimulate innate and adaptive immune responses. Thus, these molecules are promising therapeutic agents and vaccine adjuvants against various diseases. In this study, we developed a novel CpG ODNs delivery system based on polyethyleneimine (PEI-functionalized boron nitride nanospheres (BNNS. PEI was coated on the surface of BNNS via electrostatic interactions. The prepared BNNS–PEI complexes had positive zeta potential and exhibited enhanced dispersity and stability in aqueous solution. In vitro cytotoxicity assays revealed that the BNNS–PEI complexes with concentrations up to 100 µg/mL exhibited no obvious cytotoxicity. Furthermore, the positively charged surface of the BNNS–PEI complexes greatly improved the loading capacity and cellular uptake efficiency of CpG ODNs. Class B CpG ODNs loaded on the BNNS–PEI complexes enhanced the production of interleukin-6 and tumor necrosis factor-α from peripheral blood mononuclear cells compared with CpG ODNs directly loaded on BNNS. Contrary to the free CpG ODNs or CpG ODNs directly loaded on BNNS, class B CpG ODNs loaded on the BNNS–PEI complexes induced interferon-α simultaneously. PEI coating may have changed the physical form of class B CpG ODNs on BNNS, which further affected their interaction with Toll-like receptor 9 and induced interferon

  13. Use of reduced doses of eCG applied by different routes in the TAI program in Santa Ines sheep

    Directory of Open Access Journals (Sweden)

    Karla Dias Antunes-Melo

    2015-06-01

    Full Text Available The aims of this study were to improve the cost-benefit ratio of the application of artificial insemination in fixed time (TAI by the transcervical route in sheep, to test the dosage reduction and the use of the vulvar submucosa (VSM route as an alternative for the application of equine chorionic gonadotropin (eCG on the efficiency of the synchronization protocol and fertility to artificial insemination (AI and to measure the level of cortisol in ewes as a result the application of this biotechnique. Blood samples were collected before AI, immediately after AI and seven days after AI. Six groups of twenty animals were used, and each group received doses of 200, 300 and 400 IU of eCG by the intramuscular route (IM and VSM. Estrus was detected, and 48 hours later, the inseminations were performed by the transcervical route. Among the 120 treated ewes, 87.5% came in estrus. The percentage of the intrauterine deposition of semen was 88.3%. The pregnancy rate ranged from 20 to 70% between treatments, with an average of 46.66%. The VSM route was viable for the application of eCG in doses of 300 and 400 IU. The reduction in the eCG dose to 200 IU by the IM route reduces costs while maintaining the efficiency of estrus synchronization protocols and TAI with frozen semen in Santa Ines ewes. The average levels of cortisol were significant, at 1.15, 2.86 and 0.52 ?g/dL according to the three collections, being higher after the animal was off the easel at the end of AI. The procedures for performing the transcervical AI technique indicate that stress in the animals produces satisfactory fertility results and a low cost in multiparous ewes of the Santa Ines breed.

  14. [Kathon CG--a new contact sensitizing preservative].

    Science.gov (United States)

    Knudsen, B B; Menné, T

    1990-03-05

    Kathon CG is a preservative, widely used in skin care products and cosmetics. Prior to introduction to the market, extensive studies on the sensitizing potential of this product were performed. The conclusion drawn from these studies was, that the risk of sensitization was extremely small, when used in concentrations below 15 ppm. Now, ten years later, the frequency of allergy to Kathon CG is 1-2% in the Danish population, which is in the same range as the frequencies for the other preservatives. It is concluded, that the preliminary studies were insufficient and monitoring of the prevalence rates of sensitization is important, when new potential sensitizers are introduced. A total ban on the isothiazolinone derivates from the cosmetics, will only transfer the problem to the other preservatives already known as sensitizers. It might be technically acceptable to lower the concentrations further. Since the cosmetic products are not declared, a correct diagnose may be delayed or missed in patients with eczema. Ingredient labelling should be required by the authorities.

  15. Kathon CG y Dermatología Laboral: Actualización Kathon CG and Occupational Dermatology: An update

    OpenAIRE

    Ana Rita Rodrigues Barata; Jesús Rodríguez Espinosa; Felipe Heras Mendaza; Luis Conde-Salazar Gomèz

    2012-01-01

    El Kathon CG constituye el nombre comercial de una mezcla de isotiazolinas: Metilcloroisotiazolinona y Metilisotiazolinona. Es un conservante muy utilizado, sobre todo en la industria cosmética, aunque en los últimos años también se ha impuesto su presencia en productos de limpieza de uso doméstico y actualmente a concentraciones más altas en preparados de uso industrial como aceites de corte, emulsiones de látex, pinturas al temple, aceites para motores Diesel, etc. Por su alto poder sensibi...

  16. Status of a Unique Vaccine against hCG for Contraception and Advanced Stage Cancers expressing ectopically hCG

    OpenAIRE

    Talwar GP; Singh P; Gupta JC

    2015-01-01

    Dear Egon!br God bless you on your 95th Birthday! May you complete 100 years.br Being submitted in your honor is a brief article on my continuing work to make available a unique vaccine preventing pregnancy in women without blocking ovulation, her normal production of sex steroid hormones and retaining her regular menstrual cycles and bleeding profiles.br The vaccine is directed at the Human chorionic gonadotropin (hCG), which emerges following fertilization of the egg [1]. Healthy, non-p...

  17. hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

    Science.gov (United States)

    Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

    2015-08-01

    Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Studies on scintillation proximity assay for the measurement of alpha-hCG

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tae Hyun; Choi, Chang Woon; Lim, Sang Moo; Woo, Kwang Sun; Chung, Wee Sup; Lim, Soo Jeong; Lee, Su Jin; Lee, Tae Sup [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Awh, Ok Doo [College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

    2002-04-01

    Scintillation Proximity Assay (SPA) does not require the physical separation of receptor bound form from free form. SPA was applied to the study of interaction of human chorionic gonadotropin (hCG) and anti-{alpha} hCG in serum. Anti-{alpha} hCG was biotinylated for the binding to streptavidin. The assay was based on the simple competitive binding method between [{sup 125}I]hCG and the hCG in sample serum, with anti -{alpha} hCG-coated beads. Aliquots of biotinylated anti- {alpha} hCG were dispensed into scintillation vials containing 100 {mu}l [{sup 125}I]hCG and 200 {mu}l of either a standard concentration of hCG for preparation of standard curve or unknown sample, and incubated for 20 min. at room temperature. Then 20 {mu}l streptavidin-coated beads were added to vials, and finally incubated for 10 min at room temperature. Values for unknown samples were then calculated from the standard curve. Optimal background counts were cerificated using varied radioactivity of radionuclides. Appropriate standard curve was obtained from SPA method successively, and the concentration of hCG from unknown serum was determined by standard curve. The result from SPA assay was similar to that of RIA. This observation confirms that SPA method could be useful for clinical diagnosis.

  19. [Replacement of Kathon CG by Euxyl K 400 in cosmetics; from the frying pan into the fire?].

    Science.gov (United States)

    Hulsmans, R F; van der Kley, A M; Weyland, J W; de Groot, A C

    1992-03-21

    The recent negative publicity on the cosmetics preservative Kathon CG has made many cosmetic manufacturers look for safer alternatives. The most popular substitute appears to be Euxyl K 400, containing phenoxyethanol and methyldibromoglutaronitrile. Unfortunately, this preservative also induces allergic reactions to cosmetics and (at least in the Netherlands) to 'moist toilet paper'. Therefore, in cases of apparent reactions to cosmetics and of eczema ani, allergy to methyldibromoglutaronitrile should be suspected. Testing the finished products often results in false-negative reactions, and consequently the allergen (suggested concentration 0.05% in petrolatum) should preferably be tested separately.

  20. The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV-2.

    Science.gov (United States)

    Gil, Lázaro; Marcos, Ernesto; Izquierdo, Alienys; Lazo, Laura; Valdés, Iris; Ambala, Peris; Ochola, Lucy; Hitler, Rikoi; Suzarte, Edith; Álvarez, Mayling; Kimiti, Prisilla; Ndung'u, James; Kariuki, Thomas; Guzmán, María Guadalupe; Guillén, Gerardo; Hermida, Lisset

    2015-01-01

    Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice. Consequently, the ODN 39M was selected to perform further experiments in mice and nonhuman primates. Mice receiving the preparation 39M-DIIIC-2 were solidly protected against dengue virus (DENV) challenge. Moreover, monkeys immunized with the same preparation developed neutralizing antibodies, as measured by four different neutralization tests varying the virus strains and the cell lines used. Two of the immunized monkeys were completely protected against challenge, whereas the third animal had a single day of low-titer viremia. This is the first work describing the induction of short-term protection in monkeys by a formulation that is suitable for human use combining a recombinant protein from DENV with alum.

  1. Discrepant serum and urine β-hCG results due to production of β-hCG by a cribriform-morular variant of thyroid papillary carcinoma.

    Science.gov (United States)

    Alikhan, Mir; Koshy, Anoopa; Hyjek, Elizabeth; Stenson, Kerstin; Cohen, Ronald N; Yeo, Kiang-Teck J

    2015-01-01

    Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer. We present a patient with the cribriform morular variant of papillary thyroid cancer in association with familial adenomatous polyposis who developed a positive pregnancy test in the absence of known pregnancy. The patient had developed vaginal bleeding, and her laboratory testing was characterized by elevated serum human chorionic gonadotropin (β-hCG) concentrations, but negative qualitative urine results. After a thorough gynecological evaluation to exclude unexpected normal, ectopic, or molar pregnancy, we pursued an evaluation for other sources of β-hCG production. We showed that the elevated serum β-hCG concentrations were not the result of heterophile antibody interferences, and ultimately we proved that her recurrent tumor produced the ectopic β-hCG. This is the first report of β-hCG production by papillary thyroid cancer. Thus, the possibility of ectopic production of β-hCG by papillary thyroid cancer needs to be included in the differential diagnosis of elevated hCG concentration in the absence of pregnancy. This study of an unusual paraneoplastic syndrome highlights the importance of investigating discrepancies in the clinical laboratory. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

    Science.gov (United States)

    Korevaar, Tim I M; Steegers, Eric A P; de Rijke, Yolanda B; Schalekamp-Timmermans, Sarah; Visser, W Edward; Hofman, Albert; Jaddoe, Vincent W V; Tiemeier, Henning; Visser, Theo J; Medici, Marco; Peeters, Robin P

    2015-09-01

    Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

  3. Using a decline in serum hCG between days 0-4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study.

    Science.gov (United States)

    Skubisz, Monika; Dutton, Philip; Duncan, William Colin; Horne, Andrew W; Tong, Stephen

    2013-02-01

    The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4-7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0-4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications. We conducted a retrospective study of women (n=206) treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L) at Scottish hospitals between 2006-2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0-4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4-7 of treatment) and an alternate early measure (treatment), and all three measures were compared for their ability to predict medical treatment success. In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94%) (121/136). A falling serum hCG between days 0-4 predicted treatment success in 85% (95% CI 79-92%) of cases (94/110) and a treatment success in 94% (95% CI 88-100%) of cases (59/63). There was no significant difference in the ability of these tests to predict medical treatment success. We have verified that a decline in serum hCG between days 0-4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.

  4. 5-Methylation of Cytosine in CG:CG Base-Pair Steps: A Physicochemical Mechanism for the Epigenetic Control of DNA Nanomechanics

    Science.gov (United States)

    Yusufaly, Tahir; Olson, Wilma; Li, Yun

    2014-03-01

    Van der Waals density functional theory is integrated with analysis of a non-redundant set of protein-DNA crystal structures from the Nucleic Acid Database to study the stacking energetics of CG:CG base-pair steps, specifically the role of cytosine 5-methylation. Principal component analysis of the steps reveals the dominant collective motions to correspond to a tensile ``opening'' mode and two shear ``sliding'' and ``tearing'' modes in the orthogonal plane. The stacking interactions of the methyl groups are observed to globally inhibit CG:CG step overtwisting while simultaneously softening the modes locally via potential energy modulations that create metastable states. The results have implications for the epigenetic control of DNA mechanics.

  5. Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

    Science.gov (United States)

    Evans, Jemma

    2016-03-01

    Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. CpG oligodeoxynucleotide-loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells.

    Science.gov (United States)

    Taghavi Pourianazar, Negar; Gunduz, Ufuk

    2016-03-01

    One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe3O4 magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV-spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA-MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40±10nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG-ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Nanostructure of polyplexes formed between cationic diblock copolymer and antisense oligodeoxynucleotide and its influence on cell transfection efficiency.

    Science.gov (United States)

    Zhao, Xiubo; Pan, Fang; Zhang, ZhuoQi; Grant, Colin; Ma, YingHua; Armes, Steven P; Tang, YiQing; Lewis, Andrew L; Waigh, Thomas; Lu, Jian R

    2007-11-01

    Although various cationic polymers have been used to condense anionically charged DNA to improve their transfection efficiency, there is still a lack of fundamental understanding about how to control the nanostructure and charge of the polyplexes formed and how to relate such information to cell transfection efficiency. In this work, we have synthesized a weak cationic and phosphorylcholine-containing diblock copolymer and used it as a model vector to deliver an antisense oligodeoxynucleotide (ODN) into HeLa cells. Small angle neutron scattering (SANS) was used to determine the copolymer/ODN polyplex structure. The SANS data revealed the formation of polyplex nanocylinders at high copolymer (N)/ODN (P) charge ratios, where N symbolizes the amine groups on the copolymer and P symbolizes the phosphate groups. However, the cylindrical lengths remained constant, indicating that the ODN binding over this region did not alter the cylindrical shape of the copolymer in solution. As the N/P ratio decreased and became close to unity the polyplex diameters remained constant, but their lengths increased substantially, suggesting the end-to-end bridging by ODN binding between copolymer cylinders. As the N/P ratios went below unity (with ODN in excess), the polyplex diameters increased substantially, indicating different ODN bridging to bundle the small polyplexes together. Transfection studies from HeLa cells indicated a steady increase in transfection efficiency with increasing cationic charge and decreasing polyplex size. Cell growth inhibition assay showed significant growth inhibition by the polyplexes coupled with weak cytotoxicity, indicating effective ODN delivery. While this study has confirmed the overall charge effect, it has also revealed progressive structural changes of the polyplexes against varying charge ratio, thereby providing useful insight into the mechanistic process behind the ODN delivery.

  8. CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs.

    Science.gov (United States)

    Hu, Jiaqing; Yang, Dandan; Wang, Hui; Li, Chuanhao; Zeng, Yongqing; Chen, Wei

    2016-01-01

    Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) mimic the immunostimulatory activity of microbial DNA by interacting with Toll-like receptor 9 (TLR9) to activate both the innate and adaptive immune responses in different species. However, few studies have been published to compare the effects of CpG ODN on different pig breeds. Therefore, in this study, whole blood gene expression profiles of DPL and Landrace pigs treated with CpG ODN were studied using RNA-seq technology. Five Hundred differentially expressed genes (DEGs) were identified between the two breeds. DPL pigs had significantly higher number of immune-relevant DEGs than the Landrace pigs after CpG ODN treatment. Pathway analysis showed that cytokine-cytokine receptor interaction and chemokine signaling pathway were the major enriched pathways of the immune-relevant DEGs. Further in vitro experiments showed that PBMCs of the DPL pigs had significantly higher levels of TLR9 mRNA than those of the Landrace pigs, both before and after CpG ODN stimulation. Cytokine and chemokine induction in the PBMCs of both breeds were also measured after CpG ODN stimulation. Our data showed that mRNA levels of cytokines (IFNα, IL8, IL12 p40) and chemokines (CXCL9, CXCL13) were significantly higher in the PBMCs of the DPL pigs than those of the Landrace pigs. Taken together, our data provide new information regarding the pig breed difference in response to CpG ODN stimulation and that higher levels of TLR9 mRNA in DPL pigs may be a major contributor for disease resistance.

  9. The Effect of TLR9 Agonist CpG Oligodeoxynucleotides on the Intestinal Immune Response of Cobia (Rachycentron canadum

    Directory of Open Access Journals (Sweden)

    Omkar Byadgi

    2014-01-01

    Full Text Available Cytosine-guanine oligodeoxynucleotide (CpG ODN motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9 and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1β. Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds and B (30 folds isoforms at 10 dpi (CpG ODN 1668 and MyD88 (21 folds at 6 dpv (CpG ODN 2395. Subsequently, IL-1β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

  10. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

    OpenAIRE

    Li, Yu-Tao; He, Bei; Wang, Yu-Zhu; Wang, Jing

    2009-01-01

    Abstract To determine if nuclear factor-κB (NF-κB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model syste...

  11. Analytical and Clinical Validation of the Immulite 1000 hCG Assay for Quantitative Analysis in Urine

    Science.gov (United States)

    Cate, Frances L.; Moffett, Courtney; Gronowski, Ann M.; Grenache, David G.; Hartmann, Katherine E.; Woodworth, Alison

    2013-01-01

    Background The Siemens Immulite hCG assay detects all major hCG variants in serum. Currently, this assay is only FDA approved for qualitative measurement of hCG in urine. Methods Complete validation of the hCG assay in urine was performed on the Siemens Immulite 1000 immunoassay platform. Reference intervals were established for females hCG assay was precise for measuring hCG in urine from pregnant patients with intra- and inter-assay imprecision of hCG and hCGβ respectively. The assay was non-linear for hCGβcf. No hook effect was observed at concentrations up to 1,200,000 pmol/l, for hCGβ or hCGβcf. The reference intervals were hCG assay can accurately quantify hCG in urine. PMID:23470427

  12. Increased N-terminal CgA in circulation associated with cardiac reperfusin in pigs

    DEFF Research Database (Denmark)

    Frydland, Martin; Kousholt, Birgitte S.; Larsen, Jens Rolighed

    2013-01-01

    Aim: Acute myocardial infarction causes neurohumoral activation characterized by increased sympathetic activity. CgA is a protein released during sympathoadrenal stress from neuroendocrine tissue. Recently, increased CgA concentrations in circulation have been reported and suggested to be an inde...

  13. Association between the ADRA2A 1291 C/G polymorphism and the metabolic syndrome

    NARCIS (Netherlands)

    Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar F.; Arends, Johan; Mulder, Hans

    Background: Studies have found an association between the ADRA2A 1291 C/G polymorphism and antipsychoticinduced weight gain. A possible association with the metabolic syndrome has not been studied. Objectives: To investigate the association between the ADRA2A 1291 C/G polymorphism and the metabolic

  14. Kinderen met hyperthyreoïdie door verhoogd hCG

    NARCIS (Netherlands)

    Jöbsis, Jasper J.; van Trotsenburg, A. S. Paul; Merks, Johannes H. M.; Kamp, Gerdine A.

    2014-01-01

    We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking

  15. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study

    NARCIS (Netherlands)

    T.I.M. Korevaar (Tim); E.A.P. Steegers (Eric); Y.B. de Rijke (Yolanda); S. Schalekamp-Timmermans (Sarah); W.E. Visser (Wil Edward); A. Hofman (Albert); V.W.V. Jaddoe (Vincent); H.W. Tiemeier (Henning); T.J. Visser (Theo); M. Medici (Marco); R.P. Peeters (Robin)

    2015-01-01

    textabstractHuman chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on

  16. Occupational dermatitis in a milk industry worker due to Kathon CG.

    Science.gov (United States)

    Fernandez-Redondo, Virginia; Beiras-Fernandez, Andres; Toribio, Jaime

    2004-06-01

    The allergenic properties of the preservative Kathon CG have been well known since 1980. Kathon CG is regularly used in many industrial processes because of its germicidal powers. The most common sources of exposure for people are cosmetics and toiletries. Occupational contact dermatitis is unusual among milk industry workers because of the high level of factory automation.

  17. Kathon CG reactivity in 1396 consecutively patch tested patients in the Copenhagen area.

    Science.gov (United States)

    Menné, T; Hjorth, N

    1988-10-01

    In 1396 consecutively patch tested patients 18 (1.3%) reacted to Kathon CG. Relevance was established in 4 of the 18 patients. The frequency of positive reactions to Kathon CG in eczema patients seems to have been stable in Denmark during the period 1983 to 1988.

  18. Contact allergy to the active ingredients of Kathon CG in the guinea pig.

    Science.gov (United States)

    Bruze, M; Fregert, S; Gruvberger, B; Persson, K

    1987-01-01

    Preservative Kathon CG (K-CG) is a commercial preparation, consisting of the two active ingredients (a.i.), 2-methyl-4-isothiazolin-3-one (243-K-CG) and 5-chloro-2-methyl-4-isothiazolin-3-one (5243-K-CG) and also of other components. Both a.i. are known contact sensitizers in humans. In this study guinea pig maximization tests were performed with the a.i. in order to assess and compare the degrees of the sensitizing capacities. The animals were also rechallenged with the sensitizer and 4 chemically related compounds, all being preservatives or known ingredients in preservatives, in order to study the cross-reaction patterns. 5243-K-CG was demonstrated to be a strong sensitizer and 243-K-CG a weak sensitizer. With 5243-K-CG as the sensitizer, 4.5-dichloro-2-methyl-4-isothiazolin-3-one was a possible cross-reacting compound. Possible cross-reactivity was indicated between the a.i. when 243-K-CG was the sensitizer.

  19. Myth vs. Fact: The Human Chorionic Gonadotropin (hCG) Diet

    Science.gov (United States)

    ... infertility • headaches • possible increased long- term risk of breast cancer for pre-menopausal women Prescription hCG Doctors worry that injectable hCG—which can affect sex hormones in both men and women—can cause harmful or unexpected effects. Doctors also worry that hCG might not be ...

  20. Analysis of exopolysaccharide production by Lactobacillus casei CG11, isolated from cheese.

    OpenAIRE

    Kojic, M; Vujcic, M; Banina, A; Cocconcelli, P; Cerning, J; Topisirovic, L

    1992-01-01

    Exopolysaccharide-producing Lactobacillus casei CG11 was isolated from soft, white, homemade cheese. In basal minimal medium, it produces a neutral heteropolysaccharide consisting predominantly of glucose (about 75%) and rhamnose (about 15%). Plasmid curing experiments revealed that exopolysaccharide production by strain CG11 is linked to a plasmid approximately 30 kb in size.

  1. Role of CgHOG1 in Stress Responses and Glycerol Overproduction of Candida glycerinogenes.

    Science.gov (United States)

    Ji, Hao; Zhuge, Bin; Zong, Hong; Lu, Xinyao; Fang, Huiying; Zhuge, Jian

    2016-12-01

    Candida glycerinogenes, the glycerol producer with excellent multi-stress tolerances, is considered to be a potential biotechnological host used in the production of glycerol and its derivatives under extreme fermentation conditions. In this study, to evaluate the multiple roles of mitogen-activated protein kinase CgHOG1, we constructed a gene disruption system in the diploid C. glycerinogenes to obtain CgHOG1 null mutant. Pseudohyphae generation of the CgHOG1 mutant under non-inducing condition indicated a repressor role in morphological transitions. Disruption of CgHOG1 resulted in increased sensitivities to osmotic, acetic acid, and oxidative stress but not involved in thermotolerance. In the CgHOG1 mutant, NaCl shock failed to stimulate the accumulation of intracellular glycerol and was fatal. In addition, the CgHOG1 mutant displayed a significant prolonged growth lag phase in YPD medium with no decrease in glycerol production, whereas the mutant cannot grow under hyperosmotic condition with no detectable glycerol in broth. These results suggested that CgHOG1 plays important roles in morphogenesis and multi-stress tolerance. The growth and glycerol overproduction under osmotic stress are heavily dependent on CgHOG1 kinase.

  2. Postmenopausal pregnancy? Evaluation of elevated hCG in a 59-year-old woman.

    Science.gov (United States)

    Basham, Mary Margaret; Bryan, Teresa

    2017-06-05

    Slightly elevated serum human chorionic gonadotropin (hCG) can be a normal finding in postmenopausal women. We report a case of a 59-year-old woman with a history of abnormal uterine bleeding who presented with a concern for pregnancy after developing nausea and vomiting a few weeks after unprotected intercourse. Although pregnancy was extremely unlikely, hCG was obtained in order to reassure the patient since she reported that her mother conceived at the age of 60. Serum hCG was positive, prompting concern for malignancy versus pregnancy. Stable serum hCG levels, elevated follicle-stimulating hormone and negative transvaginal ultrasound ruled out both malignancy and pregnancy. Positive serum pregnancy test and hCG elevation was attributed to normal postmenopausal state. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Sequential Versus Continual Purified Urinary FSH/hCG in Men With Idiopathic Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Zhang, Manna; Tong, Guoyu; Liu, Yanling; Mu, Yiming; Weng, Jianping; Xue, Yaoming; Luo, Zuojie; Xue, Yuanming; Shi, Lixin; Wu, Xueyan; Sun, Shouyue; Zhu, Yanhua; Cao, Ying; Zhang, Jie; Huang, Hong; Niu, Ben; Li, Hong; Guo, Qinghua; Gao, Yan; Li, Zhibin; Ning, Guang; Zhu, Dalong; Li, Xiaoying

    2015-06-01

    Gonadotropin therapy using a human chorionic gonadotropin (hCG) and FSH preparation is an effective regimen in inducing masculinization and spermatogenesis in men with idiopathic hypogonadotropic hypogonadism (IHH). However, the high cost of medication and frequent injections affect compliance. The aim of this study was to determine the efficacy of sequential use of highly purified urinary FSH (uFSH)/hCG in men with IHH. A randomized, open-label, prospective, controlled noninferiority trial with an 18-month follow-up was conducted in 9 tertiary hospitals. A total of 67 Chinese men with IHH were randomly allocated into group A receiving continual uFSH (75 U, 3 times a week) and hCG (2000 U, twice a week) injection and group B receiving sequential uFSH (75 U, 3 times a week every other 3 months) and hCG (2000 U, twice a week) injection. The primary outcome was the proportion of subjects with a sperm concentration of ≥ 1.0 × 10(6)/mL during the 18 months. The efficacy between groups A and B was compared for noninferiority. Of the patients, 17/33 (51.5%) receiving continual uFSH/hCG and 19/34 (55.9%) receiving sequential uFSH/hCG achieved sperm concentrations of ≥ 1.0 × 10(6)/mL. The efficacy in the sequential uFSH/hCG group was not inferior to that in the continual uFSH/hCG group (noninferiority, P = .008) by intention-to-treat analysis. The efficacy of the sequential uFSH/hCG regimen is not inferior to that of the continual uFSH/hCG regimen in inducing spermatogenesis and masculinization of patients with IHH.

  4. A study of the drift function and relative scale factors based on two juxtaposed CG5 relative gravimeters.

    Science.gov (United States)

    Nielsen, Jens Emil; Strykowski, Gabriel

    2014-05-01

    A time-wise drift of one standard relative gravimeter can be modelled by linking the measurements of a gravity survey to high accuracy gravity stations with known gravity values. Alternatively, the measurements can be performed in one station with not necessarily known, but a constant gravity value. In both cases, and prior to drift function estimation, the gravity measurements should be corrected for systematics caused by the tidal accelerations. Typically the time-wise drift is modelled by a linear function. For Scintrex CG5 this linear drift is particularly strong and significant. We have performed long time series measurements (weeks and months) using two juxtaposed CG5 instruments on our new absolute gravity station at the Technical University of Denmark. The instruments are only few decimetres apart, so it is reasonable to assume that the true tidal acceleration on both gravimeters is the same. However, the signature of the tidal components is in principle scaled by a scaling factor for each gravimeter relating the differences in the counter reading values to the gravity differences in mGals. For Scintrex CG5 this scaling factor is close to one. Knowing the position of our gravimeters the available tidal model yields a time-wise signature of the tidal accelerations on both gravimeters. The above setup can be used to decompose the gravity measurements into the following constituencies: • The tidal signal • The relative scale factor between the two gravimeters • The individual drift function for each gravimeter • The noise Concerning the individual drift function for each gravimeter it is only for short time windows that it can be regarded linear. For wider time windows there is a significant 2nd order component of the drift function. In our poster we will discuss the above decomposition and study the appropriate drift model for different widths of the time-window and its stability in time.

  5. βhCG monitoring after single-dose methotrexate treatment of tubal ectopic pregnancy: is the Day 4 βhCG necessary? A retrospective cohort study.

    Science.gov (United States)

    Atkinson, Monique; Gupta, Sarika; Mcgee, Therese

    2014-10-01

    In ectopic pregnancy (EP) management, failure of βhCG to fall more than 15% between Days 4 and 7 after methotrexate administration indicates the need for a second dose. Regimens preferring a 25% fall in βhCG between methotrexate administration and Day 7 have been proposed. Our study analysed these and other regimens' performance in predicting treatment success. Secondarily, we investigated how each regimen guided the prescription of additional methotrexate doses. Medical files of 88 women with ultrasound confirmed tubal EP and pretreatment βhCG Treatment success was defined if the EP resolved without surgical intervention. Statistical analysis was performed using McNemar's test. Overall, treatment success with methotrexate was 92% (n = 81/88). Predicting success of methotrexate (PPV 98-100%) and detecting those needing surgery (specificity 86-100%) were equivalent across all monitoring regimens. However, the 25% Day 0/1-7 fall (and the Day 0/1-4 regimens) over-selected women for a second dose of methotrexate (P treatment success. However, a regimen aiming for a 25% fall in βhCG Day 0/1-7 over-selects patients for a second methotrexate dose. In comparison, any drop in βhCG Day 0/1-7 does not over-select women and eliminates Day 4 testing. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  6. Differential processing of the two subunits of human choriogonadotropin (hCG) by granulosa cells. I. Preparation and characterization of selectively labeled hCG

    International Nuclear Information System (INIS)

    Landefeld, T.D.; Byrne, M.D.; Campbell, K.L.; Midgley, A.R. Jr.

    1981-01-01

    The alpha- and beta-subunits of hCG were radioiodinated and recombined with unlabeled complementary subunits. The resultant recombined hormones, selectively labeled in either the alpha- or beta-subunit, were separated from unrecombined subunit by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, extracted with Triton X-100, and characterized by binding analysis. The estimates of maximum binding (active fraction) of the two resultant selectively labeled, recombined hCG preparations, determined with excess receptor were 0.41 and 0.59. These values are similar to those obtained when hCG is labeled as an intact molecule. The specific activities of the recombined preparations were estimated by four different methods, and the resulting values were used in combination with the active fraction estimates to determine the concentrations of active free and bound hormone. Binding analyses were run using varying concentrations of both labeled and unlabeled hormone. Estimates of the equilibrium dissociation binding constant (Kd) and receptor capacity were calculated in three different ways. The mean estimates of capacity (52.6 and 52.7 fmol/mg tissue) and Kd (66.6 and 65.7 pM) for the two preparations were indistinguishable. Additionally, these values were similar to values reported previously for hCG radioiodinated as an intact molecule. The availability of well characterized, selectively labeled hCG preparations provides new tools for studying the mechanism of action and the target cell processing of the subunits of this hormone

  7. Emulsified nanoparticles containing inactivated influenza virus and CpG oligodeoxynucleotides critically influences the host immune responses in mice.

    Directory of Open Access Journals (Sweden)

    Ming-Hsi Huang

    2010-08-01

    Full Text Available Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1 formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span(R85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 microg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2.Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a

  8. Ultrasensitive immunoradiometric assay for chorionic gonadotropin which does not cross-react with luteinizing hormone nor free β chain of hCG and which detects hCG in blood of non-pregnant humans

    International Nuclear Information System (INIS)

    Griffin, J.; Odell, W.D.

    1987-01-01

    A sensitive, non-competitive, two-monoclonal antibody, sandwich-type or immunoradiometric assay has been developed for human chorionic gonadotropin (hCG) which shows no cross-reaction with the free β chain of hCG nor with human luteinizing hormone (LH). In the assay procedure, two, highly selected monoclonal antibodies reacted in solution with hCG to be quantified. One antibody was covalently conjugated to biotin. This antibody was specific for the β subunit of hCG, and showed no reaction with LH nor the α subunit. The second antibody was labelled with 125 I and was specific for intact hCG and LH, showing no cross-reaction with βhCG nor the α subunit. The separation system was a polystyrene ball conjugated with biotin. This ball bound via an avidin bridge the monoclonal 'sandwich' containing hCG. Counts per minute bound to the ball were directly proportional to the amount of hCG present. The assay was specific for whole hCG and showed no reaction with βhCG, βLH, intact LH nor the free α subunit. Sensitivity was adequate to detect 'hCG-like' material in all post menopausal women and, when single samples were obtained, in over 2/3 of normal men. When multiple samples were obtained, 'hCG-like' material was detectable in all eugonadal adults studied. 27 refs.; 4 figs.; 1 table

  9. Standardization of Epitopes for Human Chorionic Gonadotropin (hCG) Immunoassays.

    Science.gov (United States)

    Berger, Peter; Lapthorn, Adrian J

    2016-01-01

    hCG and its variants are markers for pregnancy tests, pregnancyrelated complications, trophoblastic diseases, pre-natal screening of Down's syndrome and doping controls. Strong demands are imposed on diagnostic methods by the dynamic changes in the absolute and relative levels of hCG protein backbone variants and glycosylation isoforms in serum and urine during development of pregnancy or the progression/remission of tumors. Observed differences in the results between commercial diagnostic immunoassays reflect the unequal molar recognition of the different metabolic hCG variants, in particular the hCG beta core fragment (hCGβcf), by the diagnostic antibodies (Abs), as their epitopes are not standardized, and the fact that suboptimal hCG standards are used. To rapidly characterize Abs by their epitope recognition and specificity to evaluate their suitability for diagnostic immunoassays a procedure of comparative epitope mapping has been developed using epitope-defined reference Abs. Comparative epitope mapping of diagnostic Abs will provide the basis for the standardization of diagnostic antigenic domains/epitopes and consequently for improved reliability of hCG measurements. Diagnostic first line assays likely consist of pairs of Abs that recognize specific epitopes at the top of the neighboring peptide loops 1 and 3 (Ł1+3) and the cystine knot (ck) of hCGβ, respectively. In future, significant improvements of reliability, robustness and comparability of the results of immunoassays for complex glycoproteins such as hCG will be achieved by the use (i) of standardized diagnostic Abs against welldefined epitopes and (ii) of the new International Standards for hCG and for five hCG variants established by WHO, that are calibrated in molar (SI) units.

  10. Potential role of hCG in apoptosis of human luteinized granulosa cells

    Science.gov (United States)

    HIRATA, Rei; HOJO, Takuo; SANO, Masahiro; HAYASHI, Nobuyoshi; OKUDA, Kiyoshi

    2014-01-01

    The corpus luteum (CL) forms after ovulation and acts as a temporary endocrine gland that produces progesterone (P4), a hormone that is essential for implantation and maintenance of pregnancy in mammals. In pregnant women, human chorionic gonadotropin (hCG) secreted by the conceptus prevents luteolysis. hCG also increases the survival of cultured human luteinized granulosa cells (hLGCs). To clarify the maintenance mechanism of the human CL, we investigated the effects of hCG and P4 receptor antagonists, onapristone (OP) and RU486, on the viability of hLGCs. With the patients’ consent, hLGCs were isolated from follicular aspirates for in vitro fertilization. The cells were cultured with hCG (0.1, 1, 10, 100 IU/ml), OP (10, 25, 50, 100 μM), RU486 (100 μM), P4 (1, 10, 25, 50 μM) or some combination of the four for 24 h. Cell viability was significantly increased by hCG (100 IU/ml) and significantly decreased by OP (100 μM) compared with the control. Cells treated with hCG and OP together were significantly less viable than the control and OP-treated cells. The combined treatment also significantly increased CASP3 activity and cleaved CASP3 protein expression. Furthermore, P4 addition reversed the reduction in cell viability caused by the combination of hCG and OP treatment. The overall findings suggest that hCG cooperates with P4 to increase survival of hLGCs and to induce apoptosis when P4 action supported by hCG is attenuated in the human CL. PMID:25451535

  11. Demonstration of Z-d(5BrCGAT5BrCG) and B-d(CGCGATCGCG) form crystal structures in DNA-cobalt hexammine complexes by Kr 647.1 nm excitation of Raman spectra.

    OpenAIRE

    Benevides, J M; Wang, A H; Thomas, G J

    1993-01-01

    Cobalt hexammine [Co(NH3)6(3+)] is an efficient DNA complexing agent which significantly perturbs nucleic acid secondary structure. We have employed red excitation (647.1 nm) from a krypton laser to obtain Raman spectra of the highly colored complexes formed between cobalt hexammine and crystals of the DNA oligomers, d(5BrCGAT5BrCG) and d(CGCGATCGCG), both of which incorporate out-of-alternation pyrimidine/purine sequences. The Co(NH3)6(3+) complex of d(5BrCGAT5BrCG) exhibits a typical Z-form...

  12. Silicon membrane interface for the direct analysis of Kathon CG in aqueous solutions and cosmetic emulsions.

    Science.gov (United States)

    Favretto, D; Traldi, P; Benassi, C A; Bettero, A

    1991-11-01

    An easy determination of Kathon CG, an antimicrobial agent widely used in cosmetic and toiletry products, has been achieved by means of silicone membrane interfaced mass spectrometry. Low levels of the above preservative (up to p.p.b.) could be easily detected in both aqueous solutions and cosmetic emulsions. Valuable information has been obtained on the stabilization and decomposition processes to which the organic components of Kathon CG are subject. The role of magnesium ions, which are present as a stabilizing agent in Kathon CG formulation, in these processes has been investigated, leading to the identification of some degradation products.

  13. 99mTc-Cysteine-Glucosamine (99mTc-CG) in the evaluation of patients with malignant tumors. Histopathological correlation

    International Nuclear Information System (INIS)

    Noguera, EC; Palazzo, E; Borello, A; Terlecki, A; Garcia, JJ; Mayoraz, M; Mondino, JC; Orozco, S

    2006-01-01

    18 F fluorodeoxyglucose with PET( 18 FDG-PET) imaging is used to image tumors. Due to the high cost and low availability, PET is not accessible to many patients. Labelled 99m Tc agents to be used with SPECT could be an alternative to 18 FDG-PET. Glucosamine (G), a six-carbon amino sugar, enters the cells by a glucose transporter system and by phosphate and glycolytic pathways forms glucosamine-6-phosphate. Reacting G with cysteine (C) labeled with 99m Tc ( 99m TcCG) could be used to show with SPECT hypermetabolic lesions similar to 18 FDG-PET imaging. The aim of this study was to evaluate the imaging with 99m Tc-CG in detecting tumors and correlate them with pathology. Material and Methods: Labelling of 99m Tc-CG was done by adding (C), (G), N-hydroxysuccinimide, carbodiimide, and stannous chloride to the 99m Tc. Patients: 35 patients (23 F, 12 M, range age 7-79 years, mean 52 ) with histopathology diagnosis were referred for scintigraphy with 99m Tc-CG. Imaging: Patients fasted for 12 hr, and 1-4 hours after the i.v. injection of 920-1088 MBq of 99m Tc-CG, underwent 1) whole body scan, 2) SPECT images (reconstructed with OSEM algorithm) on the field of view of the lesion. To eliminate the intravascular and interstitial activity of the 99m TcC-G imaging, patients were given 737 MBq of 99m Tc human serum albumin( 99m Tc-HSA) and other SPECT was done. We normalized both SPECT images and subsequently the 99m Tc-HSA image was subtracted from the 99m Tc-CG image. All images were visually analysed. Results: 32 lesions were malignant (breast (5), colon (8), lung (9), Hodgkin's disease(6), thyroid(1), bladder (1), melanoma (1), ependimoma (1), and 3 were benign (brain radiation necrosis, breast inflammations and inespecific granuloma). 99m Tc C-G show abnormal focal uptake in all malignant lesions (sensitivity=100%) as well as in two benign lesion (false positive). Accuracy of 99m TcC-G in patients with malign tumors was 94%. SPECT images defined the tumor uptake better

  14. Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

    Science.gov (United States)

    van Mello, N M; Mol, F; Verhoeve, H R; van Wely, M; Adriaanse, A H; Boss, E A; Dijkman, A B; Bayram, N; Emanuel, M H; Friederich, J; van der Leeuw-Harmsen, L; Lips, J P; Van Kessel, M A; Ankum, W M; van der Veen, F; Mol, B W; Hajenius, P J

    2013-01-01

    What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (treatment, side effects and serum hCG clearance time. From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant

  15. Early serum human chorionic gonadotropin (hCG) trends after medication abortion.

    Science.gov (United States)

    Pocius, Katherine D; Maurer, Rie; Fortin, Jennifer; Goldberg, Alisa B; Bartz, Deborah

    2015-06-01

    Despite increased reliance on human chorionic gonadotropin (hCG) for early pregnancy monitoring, there is limited information about hCG trends soon after medication abortion. The purpose of this study was to determine if there is a predictable decline in serum hCG values shortly after medication abortion. This is a retrospective study of women with early intrauterine pregnancies who underwent medication abortion with mifepristone and misoprostol and had a serum hCG level on Day 1 (day of mifepristone) and a repeat value on Day 2 to 6. The percent hCG decline was calculated from baseline to repeat measure, with repeat values from the same patient accounted for through repeated measure analysis of variance. Eighty-eight women with a mean gestational age of 5.5 weeks and median baseline hCG of 5220 IU met study criteria over a 3-year period. The mean decline (±SD) in hCG from the Day 1 baseline value was 56.9%±29.5% on Day 3, 73.5%±38.6% on Day 4, 86.1%±8.8% on Day 5, and 92.9%±3.4% on Day 6. Eighty-two women (93% of the cohort) had a complete abortion without further intervention. The least square means hCG decline among these women was 57.6% [95% confidence interval (CI): 50.3-64.9%] on Day 3, 78.9% (95% CI: 75.0-82.8%) on Day 4 and 86.2% (95% CI: 81.3-91.1%) on Day 5. There is a rapid decline in serum hCG within the first few days after early medication abortion. Further research is needed to delineate how soon after medication abortion this decline may be specific enough to confirm abortion completion. This study provides the largest cohort of patients followed with serial hCG values in the first few days after medication abortion. Our findings demonstrate the trend in hCG decline in this population, which may be predictable by Day 5. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The Nonhydrostatic Unified Model of the Atmosphere (NUMA): CG Dynamical Core

    Science.gov (United States)

    2011-03-01

    The Nonhydrostatic Unified Model of the Atmosphere ( NUMA ): CG Dynamical Core Frank Giraldo Department of Applied Mathematics Naval Postgraduate...School Monterey CA 93943 http://faculty.nps.edu/projects/ NUMA Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden...AND SUBTITLE The Nonhydrostatic Unified Model of the Atmosphere ( NUMA ): CG Dynamical Core 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  17. Induksi Superovulasi dengan Kombinasi CIDR, Hormon FSH dan hCG pada Induk Sapi Potong

    Directory of Open Access Journals (Sweden)

    E.M. Kaiin

    2006-12-01

    Full Text Available The aim of this study was to evaluate the effect of superovulation treatment using combination of CIDR, FSH and hCG in beef cattle as donor embryos using MOET programme. All animals had been palpated to evaluated the ovary status and normal cows were used as donor and synchronized with CIDR (Eazy BreedTM . At day 10 of oestrus cycle, cows were divided into two groups, first group: cows were injected intramuscularly with FSH (Antrin 40 IU per cow with decreasing doses (for 4 days and second group cows were treated the same way but at day 5 after FSH injection, they were injected intramuscularly with 1,500 IU hCG (Chorulon. Embryo collection was done at day 7 after Artificial Insemination (AI. Average number of corpora lutea (CL in animals that superovulated with CIDR, FSH and hCG was significantly higher (P<0.05 compared to animals treated with CIDR and FSH only (5.52. Average number of embryo collection and number of transferable embryos were also higher in group treated with hCG (6.00 vs 5.44 compared with those treated without hCG (4.33 vs 3.17. The conclusion is hCG superovulation injection with CIDR and FSH can increase the respon of superovulation

  18. Combined ovulation triggering with GnRH agonist and hCG in IVF patients.

    Science.gov (United States)

    Kasum, Miro; Kurdija, Kristijan; Orešković, Slavko; Čehić, Ermin; Pavičić-Baldani, Dinka; Škrgatić, Lana

    2016-11-01

    The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation.

  19. Heterophile antibody interference in qualitative urine/serum hCG devices: Case report.

    Science.gov (United States)

    Patel, Khushbu K; Gronowski, Ann M

    2016-06-01

    This case report investigates the origin of a false positive result on a serum qualitative human chorionic gonadotropin (hCG) device. A 46-year-old woman diagnosed with chronic myeloid leukemia presented with nausea and vomiting. A qualitative serum hCG test was interpreted as positive; however, a quantitative serum hCG test was negative (hCG devices composed of antibodies from different animal sources. Blocking reagent from an automated quantitative immunoassay was also tested for its ability to inhibit the heterophile antibody interference. The qualitative test result was negative after pretreatment with heterophilic blocking reagent. Other devices composed of antibodies from different animal sources also demonstrated mixed results with the patient's sample. Blocking reagent obtained from the automated quantitative assay inhibited the heterophile antibody interference in the patient's sample. This case demonstrates that positive serum point-of-care hCG results should be interpreted with caution and confirmed with a quantitative serum hCG immunoassay when clinical suspicion is raised. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. The CG1 instrument development test station at the high flux isotope reactor

    Science.gov (United States)

    Crow, Lowell; Robertson, Lee; Bilheux, Hassina; Fleenor, Mike; Iverson, Erik; Tong, Xin; Stoica, Ducu; Lee, W. T.

    2011-04-01

    The CG1 instrument development station at the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory began commissioning operation in 2009. When completed, the station will have four beams. CG1A is a 4.22 Å monochromatic beam intended for spin-echo resolved grazing incidence scattering (SERGIS) prototype development. Initial beam operation and characterization are in progress. CG1B will be a 2.35 Å monochromatic beam for a 2-axis utility diffractometer for sample alignment and monochromator development. CG1C will have a double-bounce monochromator system, which will produce a variable wavelength beam from about 1.8-6.4 Å, and will be used for imaging and optical development. The CG1D beam is a single chopper time-of-flight system, used for instrument prototype and component testing. The cold neutron spectrum, with an integrated flux of about 2.7×109 n/cm2 s, has a guide cutoff at 0.8 Å and useful wavelengths greater than 20 Å.Initial results from CG1 include spectral characterization, imaging tests, detector trials, and polarizer tests. An overview of recent tests will be presented, and upcoming instrument prototype efforts will be described.

  1. Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region.

    Science.gov (United States)

    Grzesik, Paul; Kreuchwig, Annika; Rutz, Claudia; Furkert, Jens; Wiesner, Burkhard; Schuelein, Ralf; Kleinau, Gunnar; Gromoll, Joerg; Krause, Gerd

    2015-01-01

    The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge

  2. Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor’s Extracellular Hinge Region

    Science.gov (United States)

    Grzesik, Paul; Kreuchwig, Annika; Rutz, Claudia; Furkert, Jens; Wiesner, Burkhard; Schuelein, Ralf; Kleinau, Gunnar; Gromoll, Joerg; Krause, Gerd

    2015-01-01

    The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) – secreted by the placenta, and lutropin (LH) – produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor’s leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the

  3. Classification of pregnancies of unknown location according to four different hCG-based protocols.

    Science.gov (United States)

    Fistouris, J; Bergh, C; Strandell, A

    2016-10-01

    How do four protocols based on serial human chorionic gonadotropin (hCG) measurements perform when classifying pregnancies of unknown location (PULs) as low or high risk of being an ectopic pregnancy (EP)? The use of cut-offs in hCG level changes published by NICE, and a logistic regression model, M4, correctly classify more PULs as high risk, compared with two other protocols. A logistic regression model, M4, based on the mean of two consecutive hCG values and the hCG ratio (hCG 48 h/hCG 0 h) that classify PULs into low- and high-risk groups for triage purposes, identifies more EPs than a protocol using the cut-offs between a 13% decline and a 66% rise in hCG levels over 48 h. A retrospective comparative study of four different hCG-based protocols classifying PULs as low or high risk of being an EP was performed at a gynaecological emergency unit over 3 years. We identified 915 women with a PUL. Initial transvaginal ultrasonography (TVS) findings categorised 187 of the PULs as probable intrauterine pregnancies (IUPs) and 16 as probable EPs. The rate of change in hCG levels over 48 h was calculated for each patient and subjected to three different hCG threshold intervals and a logistic regression model for outcome prediction. Each PUL was subsequently dichotomised to either low-risk (i.e. failed PUL/IUP) or high-risk (i.e. EP) classification, which allowed us to compare the diagnostic performance. In 'Protocol A', a PUL was classified as low risk if >13% hCG level decline or >66% hCG level rise was achieved; otherwise, the PUL was classified as high risk of being an EP. 'Protocol B' classified a PUL as low or high risk using cut-offs of 35-50% declining hCG levels and of 53% rising hCG levels. Similarly, 'Protocol C' used hCG level cut-offs published by NICE, 50% for declining hCG levels and 63% for rising hCG levels. Finally, if a logistic regression model 'Protocol M4' calculated a ≥5% risk of the PUL being an EP, it was classified as high risk, and otherwise

  4. Study on the changes of serum HA and CG levels in several diseases besides liver disorders

    International Nuclear Information System (INIS)

    Lu Zhiping; Ma Yunbao; Zhang Xiaoyi; Lv Weihua

    2005-01-01

    Objective: To study the changes of serum hyaluronic acid (HA) and cholyglycine (CG) in several diseases besides liver disorders. Methods: Serum HA and CG levels were measured with RIA in 78 patients with chronic liver diseases (with 70 controls), (84 patients with primary hepatic carcinoma ), 70 pediatric patients with various infections diseases (with 40 controls), 50 pediatric patients with recurrent respiratory infection (RRI, with 30 controls) and 428 pregnant women ( with 60 controls). In addition, RBC C 3 b receptor ratio (RBCC 3 bRR) and RBC immune-complex ratio (RBCICR) (both with yeast rosette method) as well as serum IgG,IgM,IgA,C 3 levels (with immunoturbidity test) were examined in the 50 RRI pediatric patients, ALT levels were examined in the 70 pediatric patients with infectious diseases and SF examined in the 78 patients with chronic liver diseases. Results: The serum CG, HA and SF levels in the three groups of patients with chronic liver diseases ( CPH, CAH, Cirrhosis) were significantly higher than those in the controls (all P 0.05). In patients with hepatic carcinoma, the CG and HA levels were positively correlated with the mortality at 4 months (P 0.05). For ALT, levels only increased in patients with hepatitis and typhoid fever with none in bacillary dysentery and mumps. In pediatric patients with RRI, RBCC 3 bRR (%), CG, C 3 , IgG levels were significantly higher than those in controls (P 0.05). Conclusion: Various infectious diseases in pediatric patients could induce mild liver damage, which was closely related to the depressed immune status. High CG and HA levels in liver cancer patients suggested high mortality at 4 months. Women in late pregnancy might harbour disturbances in CG metabolism and mild liver injury though without overt symptoms. (authors)

  5. Differences in signal activation by LH and hCG are mediated by the LH/CG receptor`s extracellular hinge region

    Directory of Open Access Journals (Sweden)

    Paul eGrzesik

    2015-09-01

    Full Text Available The human lutropin/choriogonadotropin receptor (LHCGR can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG - secreted by the placenta, and lutropin (LH - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich repeat domain (LRRD, as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting mutations. These helix preserving modifications showed no effect on hormone induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10 deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region s. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region

  6. Functional reconstitution into liposomes of purified human RhCG ammonia channel.

    Directory of Open Access Journals (Sweden)

    Isabelle Mouro-Chanteloup

    Full Text Available BACKGROUND: Rh glycoproteins (RhAG, RhBG, RhCG are members of the Amt/Mep/Rh family which facilitate movement of ammonium across plasma membranes. Changes in ammonium transport activity following expression of Rh glycoproteins have been described in different heterologous systems such as yeasts, oocytes and eukaryotic cell lines. However, in these complex systems, a potential contribution of endogenous proteins to this function cannot be excluded. To demonstrate that Rh glycoproteins by themselves transport NH(3, human RhCG was purified to homogeneity and reconstituted into liposomes, giving new insights into its channel functional properties. METHODOLOGY/PRINCIPAL FINDINGS: An HA-tag introduced in the second extracellular loop of RhCG was used to purify to homogeneity the HA-tagged RhCG glycoprotein from detergent-solubilized recombinant HEK293E cells. Electron microscopy analysis of negatively stained purified RhCG-HA revealed, after image processing, homogeneous particles of 9 nm diameter with a trimeric protein structure. Reconstitution was performed with sphingomyelin, phosphatidylcholine and phosphatidic acid lipids in the presence of the C(12E(8 detergent which was subsequently removed by Biobeads. Control of protein incorporation was carried out by freeze-fracture electron microscopy. Particle density in liposomes was a function of the Lipid/Protein ratio. When compared to empty liposomes, ammonium permeability was increased two and three fold in RhCG-proteoliposomes, depending on the Lipid/Protein ratio (1/300 and 1/150, respectively. This strong NH(3 transport was reversibly inhibited by mercuric and copper salts and exhibited a low Arrhenius activation energy. CONCLUSIONS/SIGNIFICANCE: This study allowed the determination of ammonia permeability per RhCG monomer, showing that the apparent Punit(NH3 (around 1x10(-3 microm(3xs(-1 is close to the permeability measured in HEK293E cells expressing a recombinant human RhCG (1.60x10

  7. Transgenerational maintenance of transgene body CG but not CHG and CHH methylation.

    Science.gov (United States)

    Dalakouras, Athanasios; Dadami, Elena; Zwiebel, Michele; Krczal, Gabi; Wassenegger, Michael

    2012-09-01

    In plants, RNA-directed DNA methylation (RdDM) can target both transgene promoters and coding regions/gene bodies. RdDM leads to methylation of cytosines in all sequence contexts: CG, CHG and CHH. Upon segregation of the RdDM trigger, at least CG methylation can be maintained at promoter regions in the progeny. So far, it is not clear whether coding region methylation can be also maintained. We showed that the body of Potato spindle tuber viroid (PSTVd) transgene constructs became densely de novo methylated at CG, CHG and CHH sites upon PSTVd infection. In this study, we demonstrate that in viroid-free progeny plants, asymmetric CHH and CHG methylation was completely lost. However, symmetric CG methylation was stably maintained for at least two generations. Importantly, the presence of transgene body methylation did not lead to an increase of dimethylation of histone H3 lysine 9 or a decrease of acetylation of H3. Our data supports the view that CG methylation can be maintained not only in promoters but also in the body of transgenes. They further suggest that maintenance of methylation may occur independently of tested chromatin modifications.

  8. Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

    Science.gov (United States)

    Sinitskiy, Anton V.; Voth, Gregory A.

    2018-01-01

    Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

  9. Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

    Science.gov (United States)

    Craciunas, Laurentiu; Tsampras, Nikolaos; Coomarasamy, Arri; Raine-Fenning, Nick

    2016-05-20

    Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction. To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction. We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator. We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin. Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of

  10. Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

    Science.gov (United States)

    Sinitskiy, Anton V; Voth, Gregory A

    2018-01-07

    Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

  11. Exciting Science being done on the CG-2 Small Angle Neutron Scattering beam line at HFIR

    Science.gov (United States)

    Debeer-Schmitt, Lisa; Bailey, Kathy; Melnichenko, Yuri; Wignall, George; Littrell, Ken

    2010-03-01

    The small-angle neutron scattering (SANS) beam line, CG-2, has been in operation since 2007. CG-2 has been optimized so that structures from 0.5 to 200 nm can be thoroughly investigated. HFIR's cold source places the flux at CG-2 among the best in the world. Along with high flux, many varied sample environments can easily be integrated into the beam line which gives the user a versatile temperature range from 1.5 K to 1000K. In addition there are two cryomagents (horizontal 4.5 T and vertical 7 T), pressure cells and load frames available to users allowing for the availability of multiple configurations of experimental setups. Due to all the above equipment and the flux at CG-2, there have been many diverse and intriguing scientific developments. One such outcome is the study of flux- line lattices found in Type-II superconductors including the highly touted iron pnictides. Besides superconductors, other science studied on CG2 ranges from molecular self-assembly and interactions in complex fluids to phase separation, grain growth and orientation in metallurgical alloys.

  12. Comparison of dual trigger with combination GnRH agonist and hCG versus hCG alone trigger of oocyte maturation for normal ovarian responders.

    Science.gov (United States)

    Zhou, Xingyu; Guo, Pingping; Chen, Xin; Ye, Desheng; Liu, Yudong; Chen, Shiling

    2018-02-01

    To investigate whether dual triggering of oocyte maturation with a gonadotropin-releasing hormone (GnRH) agonist and standard dose of human chorionic gonadotropin (hCG) can improve clinical outcomes for normal ovarian responders in GnRH antagonist cycles. The present retrospective cohort study included women aged up to 40 years with normal ovarian response who underwent in vitro fertilization and/or intracytoplasmic sperm injection under the GnRH antagonist protocol at Nanfang Hospital, China, between January 1 and December 31, 2015. Patients were grouped by whether oocyte maturation was triggered with GnRH agonist plus 5000-10 000 IU of hCG (dual trigger) or hCG alone. The primary outcome was live delivery rate. There were 325 women included; 224 in the dual trigger group and 101 in the hCG alone group. The live delivery rate did not differ significantly between the groups (P=0.083). The mean number of retrieved oocytes was similar in the two groups (P=0.719), but the mean number of two-pronuclear embryos (P=0.004), the mean number of embryos available (P=0.001), and the mean number of high-quality embryos (P=0.011) was higher in the dual trigger group. Dual trigger of oocyte maturation was not associated with any change in the live delivery rate but was associated with improvements in the quantity and quality of embryos; it could optimize pregnancy outcomes for normal ovarian responders. © 2018 International Federation of Gynecology and Obstetrics.

  13. Effect of oestrus synchronization with PGF2α/eCG/hCG on luteal P4 synthesis in early pregnant gilts.

    Science.gov (United States)

    Szymanska, M; Morawska-Pucinska, E; Krawczynski, K; Kiewisz, J; Ziecik, A J; Blitek, A

    2014-12-01

    Administration of hormones to synchronize oestrus is a useful tool in animal breeding. However, exogenous ovarian stimulation may be detrimental to reproductive function. This study was aimed to examine whether an oestrus synchronization with PGF2α/eCG/hCG could affect luteal P4 synthesis in early pregnant gilts. Corpora lutea (CLs) were collected on days 9, 12 and 16 of pregnancy from gilts with natural (n = 16) and synchronized (n = 18) oestrus and analysed for (i) the expre-ssion of steroidogenic acute regulatory protein (StAR), cytochrome P450 family 11 subfamily A polypeptide (CYP11A1), and 3β-hydroxysteroid dehydrogenase (3βHSD); (ii) the concentration of P4 in the luteal tissue and blood; and (iii) the expression of luteinizing hormone receptors (LHR) and oestrogen receptors (ERα and ERβ). Additionally, the effect of LH on P4 secretion from CL slices collected from synchronized and naturally ovulated animals has been studied in vitro. PGF2α /eCG/hCG administration increased mRNA expression of StAR, CYP11A1, 3βHSD, and LHR on day 9 and CYP11A1 and LHR on day 12 of pregnancy compared with the control group (p gilts with hormonally induced oestrus compared with control animals. Blood serum levels of P4 were lower in synchronized than control gilts (p gilts (p gilts did not impair the expression of luteal P4 synthesis system, although decreased P4 concentration in the blood. © 2014 Blackwell Verlag GmbH.

  14. Alternative security

    International Nuclear Information System (INIS)

    Weston, B.H.

    1990-01-01

    This book contains the following chapters: The Military and Alternative Security: New Missions for Stable Conventional Security; Technology and Alternative Security: A Cherished Myth Expires; Law and Alternative Security: Toward a Just World Peace; Politics and Alternative Security: Toward a More Democratic, Therefore More Peaceful, World; Economics and Alternative Security: Toward a Peacekeeping International Economy; Psychology and Alternative Security: Needs, Perceptions, and Misperceptions; Religion and Alternative Security: A Prophetic Vision; and Toward Post-Nuclear Global Security: An Overview

  15. Clinical significance of changes of serum TBA, CG, HA levels in neonate with parenteral nutrition

    International Nuclear Information System (INIS)

    Huang Weiliang; Zhou Jiongying; Zhang Xiaoyi; Lv Weihua; Ma Yunbao; He Qizhi

    2010-01-01

    Objective: To study the clinical significance of changes of serum levels of TBA, CG, HA in neonate with parenteral nutrition. Methods: Serum total bile acid (TBA, with biochemistry) and CG, HA (with RIA) contents were measured in 52 neonates (full-term 32, preterm 20) with parenteral nutrition and 28 neonates (full-term 16, preterm 12) without parenteral nutrition (as controls). Results: Before parenteral nutrition,the serum TBA, CG and HA levels in full-term neonates were not significantly different from those in the controls (P>0.05). After parenteral nutrition,serum levels were significantly higher than those before parenteral nutrition (P<0.01). The levels in pre-term neonates were significantly higher after parenteral nutrition than those in full-term neonates (P<0.05). Conclusion: Long term parenteral nutrition might be harmful to hepatic and gall bladder function in neonates especially in premature ones. (authors)

  16. Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

    Science.gov (United States)

    Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

    2017-09-01

    Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy. Copyright © 2017 Endocrine Society

  17. Penile Growth in Response to Human Chorionic Gonadotropin (hCG) Treatment in Patients with Idiopathic Hypogonadotrophic Hypogonadism

    OpenAIRE

    Kim, Sun-Ouck; Ryu, Kwang Ho; Hwang, In Sang; Jung, Seung Il; Oh, Kyung Jin; Park, Kwangsung

    2011-01-01

    Penile growth is under androgenic control. Human chorionic gonadotropin (hCG) has a stimulatory effect on testicular steroidogenesis and penile growth. The purpose of this study was to evaluate the effect of hCG treatment on the gonadal response and penile growth in male idiopathic hypogonadotrophic hypogonadism (IHH) presenting with micropenis. A total of 20 IHH patients who met the criteria for micropenis were included in this study. hCG (1,500-2,000 IU) was administrated intramuscularly, 3...

  18. Education System Using Interactive 3D Computer Graphics (3D-CG) Animation and Scenario Language for Teaching Materials

    Science.gov (United States)

    Matsuda, Hiroshi; Shindo, Yoshiaki

    2006-01-01

    The 3D computer graphics (3D-CG) animation using a virtual actor's speaking is very effective as an educational medium. But it takes a long time to produce a 3D-CG animation. To reduce the cost of producing 3D-CG educational contents and improve the capability of the education system, we have developed a new education system using Virtual Actor.…

  19. An antisense oligodeoxynucleotide targeted against the type IIβ regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects

    International Nuclear Information System (INIS)

    Tortora, G.; Clair, T.; Cho-Chung, Y.S.

    1990-01-01

    The type II β regulatory subunit of cAMP-dependent protein kinase (RII β ) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this tissue, HL-60 human promyelocytic leukemia cells were exposed to RII β antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII β antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII β protein. Exposure to RII β sense, RI α and RII α antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII β regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells

  20. Agonist trigger: what is the best approach? Agonist trigger and low dose hCG

    DEFF Research Database (Denmark)

    Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2012-01-01

    Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)......Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)...

  1. Empty follicle syndrome after GnRHa triggering versus hCG triggering in COS

    DEFF Research Database (Denmark)

    Castillo, Juan C; Garcia-Velasco, Juan; Humaidan, Peter

    2012-01-01

    This study aimed to explore the incidence of empty follicle syndrome (EFS) in oocyte donors who had final oocyte maturation triggered with GnRHa and to compare the incidence of EFS in this group of patients with IVF patients who had final oocyte maturation with hCG.......This study aimed to explore the incidence of empty follicle syndrome (EFS) in oocyte donors who had final oocyte maturation triggered with GnRHa and to compare the incidence of EFS in this group of patients with IVF patients who had final oocyte maturation with hCG....

  2. Hook effect in Abbott i-STAT β-human chorionic gonadotropin (β-hCG) point of care assay.

    Science.gov (United States)

    Wilgen, Urs; Pretorius, Carel J; Gous, Rehna S; Martin, Cameron; Hale, Vincent J; Ungerer, Jacobus P J

    2014-09-01

    Point-of-care testing for β-hCG has been widely advocated to allow rapid diagnosis/exclusion of pregnancy in the emergency department. A quantitative blood β-hCG assay has the additional benefit of being able to monitor the viability of pregnancy, using serial measurements, to determine the appropriate expected increase in β-hCG levels over time (e.g. ectopic pregnancy), and aiding in determining if an intrauterine gestational sac should be visible on sonographic imaging. Evaluation of the newly released Abbott i-STAT β-hCG point-of-care assay with the Beckman Coulter β-hCG laboratory assay in use. Whole blood, plasma and serum samples with a wide range of β-hCG concentrations were analysed by both methods. The Abbott I-STAT β-hCG compares favourably, can be performed on heparinised whole blood, plasma and serum, and shows acceptable accuracy and precision. However a hook effect at elevated β-hCG was shown in gestational trophoblastic disease as well as normal pregnancies. The i-STAT β-hCG performs acceptably in its intended use in the early detection of pregnancy, but results should always be interpreted within the clinical context, as a hook effect may occur. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  3. Alternative additives; Alternative additiver

    Energy Technology Data Exchange (ETDEWEB)

    2007-08-15

    In this project a number of industrial and agricultural waste products have been characterised and evaluated in terms of alkali-getter performance. The intended use is for biomass-fired power stations aiming at reducing corrosion or slagging related problems. The following products have been obtained, characterised and evaluated: 1) Brewery draff 2) Danish de-gassed manure 3) Paper sludge 4) Moulding sand 5) Spent bleaching earth 6) Anorthosite 7) Sand 8) Clay-sludge. Most of the above alternative additive candidates are deemed unsuitable due to insufficient chemical effect and/or expensive requirements for pre-treatment (such as drying and transportation). 3 products were selected for full-scale testing: de-gassed manure, spent bleaching earth and clay slugde. The full scale tests were undertaken at the biomass-fired power stations in Koege, Slagelse and Ensted. Spent bleaching earth (SBE) and clay sludge were the only tested additive candidates that had a proven ability to react with KCl, to thereby reduce Cl-concentrations in deposits, and reduce the deposit flux to superheater tubes. Their performance was shown to nearly as good as commercial additives. De-gassed manure, however, did not evaluate positively due to inhibiting effects of Ca in the manure. Furthermore, de-gassed manure has a high concentration of heavy metals, which imposes a financial burden with regard to proper disposal of the ash by-products. Clay-sludge is a wet clay slurring, and drying and transportation of this product entails substantial costs. Spent bleaching does not require much pre-treatment and is therefore the most promising alternative additive. On the other hand, bleaching earth contains residual plant oil which means that a range of legislation relating to waste combustion comes into play. Not least a waste combustion fee of 330 DKK/tonne. For all alternative (and commercial) additives disposal costs of the increase ash by-products represents a significant cost. This is

  4. Serum human chorionic gonadotropin (hCG) trend within the first few days after medical abortion: a prospective study.

    Science.gov (United States)

    Pocius, Katherine D; Bartz, Deborah; Maurer, Rie; Stenquist, Asha; Fortin, Jennifer; Goldberg, Alisa B

    2017-03-01

    To prospectively describe the decline in serum human chorionic gonadotropin (hCG) in the first 5 days after complete medical abortion and evaluate the influence of initial hCG and gestational duration. We conducted a prospective, physiologic study of women ≤63 days gestation who underwent medical abortion with 200 mg mifepristone and 800 mcg buccal misoprostol. We stratified enrollment into two gestational cohorts, hCG values on Day 1 (day of mifepristone), Day 3, Day 5 and a routine follow up hCG on Days 7-14. We calculated the percent hCG decline from Day 1 to each repeat measure and evaluated trends based on initial serum hCG level and gestation. We enrolled 66 women; 59 were protocol-adherent and included in our analysis. Mean gestation on Day 1 was 49 days and mean baseline hCG was 72,332 IU. Fifty-seven subjects (97%) had a complete medical abortion without further intervention. The mean serum hCG decline among subjects with complete medical abortion was 70.0±10.6% [range 36.9-98.6%] on Day 3 and 91.4±4.4% [range 68.4-97.7%] on Day 5. The mean serum hCG decline from Day 1 to routine follow-up on Days 7-9 was 97.1±1.7% [range 92.4-99.2%], from Day 1 to Day 10-11 was 98.5±1.4% [range 94.7-99.6%] and from Day 1 to Day 12-14 was 98.7±2.8% [range 86.7-99.9%]. There was no difference in percent hCG decline stratified by initial hCG or gestation. There is a rapid and predictable decline in serum hCG as early as Day 5 after complete medical abortion through 63 days gestation. Rate of hCG decline is not affected by initial hCG or gestational duration. For women who require confirmation of complete abortion sooner than 1 week after mifepristone, due to patient preference, logistical constraints or in the setting of pregnancy of unconfirmed location, a single repeat hCG on Day 5 may be clinically useful. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications.

    Science.gov (United States)

    Dogan, Askin; Gulhan, Ibrahim; Uyar, Ibrahim; Ekin, Atalay; Gezer, Cenk; Bilgin, Muzaffer; Taner, Cüneyt E; Ertas, Ibrahim E

    2016-06-01

    Our aim was to evaluate the relationship between the success of methotrexate treatment and β-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m(2) was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6%) responded to medical treatment, while the remaining 59 (15.36%) underwent surgery due to treatment failure. β-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116±3157 vs. 4178±3422, 2062±3551 vs. 4935±4103, and 1532±3007 vs. 3900±4783, respectively). The receiver operating characteristics curve for β-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively). Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial β-hCG levels were >1418 mIU/mL. Copyright © 2016. Published by Elsevier Taiwan.

  6. Pre-evacuation hCG glycoforms in uneventful complete hydatidiform mole and persistent trophoblastic disease.

    NARCIS (Netherlands)

    Thomas, C.M.G.; Kerkmeijer, L.G.W.; Ariaens, H.J.; Steen, R. van der; Massuger, L.F.A.G.; Sweep, F.C.

    2010-01-01

    OBJECTIVE: To investigate whether the glycoform distribution patterns of human chorionic gonadotropin (hCG) obtained by chromatofocusing in pre-evacuation serum are different for patients who will eventually develop into persistent trophoblastic disease in case of complete hydatidiform mole

  7. Negative βhCG and Molar Pregnancy: The Hook Effect

    Directory of Open Access Journals (Sweden)

    Isabel Lobo Antunes

    2017-09-01

    Full Text Available Molar pregnancy, included in gestational trophoblastic disease, is a benign pathology with ability to metastasize, usually occurring with excessively high βhCG levels. Clinical scenario is usually a woman in extremes of reproductive age presenting with amenorrhoea, pain and vaginal blood loss; signs derived from high βhCG levels may be present (hyperthyroidism, hyperemesis. Diagnosis is based on a positive pregnancy test – usually a qualitative urinary test. The limitation of this test results from its inability to become positive in presence of markedly high levels of βhCG, saturating the antigens used – known as the ‘hook effect’. With the widespread use of gynaecological ultrasound cases of molar pregnancy have been diagnosed in timely fashion. We describe a case referred as a degenerating fibroid, with a negative urinary pregnancy test. Transvaginal ultrasound was highly suggestive of molar pregnancy, which was confirmed with a quantitative βhCG test, allowing for timely treatment. The importance of a high index of suspicion for this pathology is tremendous to avoid the devastating consequences of a delayed diagnosis.

  8. Maternal urinary beta-core hCG in chromosomally abnormal pregnancies in the first trimester

    NARCIS (Netherlands)

    Kornman, LH; Morssink, LP; Wortelboer, MJM; Beekhuis, [No Value; DeWolf, BTHM; Pratt, JJ; Mantingh, A

    We evaluated urinary beta-core human chorionic gonadotropin (beta-core hCG) in the detection of fetal Down's syndrome (DS) in the first trimester of pregnancy. Urine was collected prior to performing chorionic villous sampling (CVS) between 10 and 12 completed weeks from the last menstrual period.

  9. hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

    Science.gov (United States)

    Paulesu, Luana; Rao, Ch.V.; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

    2018-01-01

    Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. PMID:29558393

  10. Effect of human chorionic gonadotropin (hCG) on in vitro oocyte ...

    African Journals Online (AJOL)

    In vitro exposure of Barilius vagra ovarian follicles to human chorionic gonadotropin (hCG) influenced the position of germinal vesicle and resulted in a maturation of oocyte, although the response was time dependent. There was slight but significant (P<0.05) increased in germinal vesicle breakdown (GVBD, 12.42 vs.

  11. Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications

    Directory of Open Access Journals (Sweden)

    Askin Dogan

    2016-06-01

    Full Text Available Our aim was to evaluate the relationship between the success of methotrexate treatment and β-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m2 was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6% responded to medical treatment, while the remaining 59 (15.36% underwent surgery due to treatment failure. β-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116±3157 vs. 4178±3422, 2062±3551 vs. 4935±4103, and 1532±3007 vs. 3900±4783, respectively. The receiver operating characteristics curve for β-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively. Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial β-hCG levels were >1418 mIU/mL.

  12. Two qubits for C.G. Jung’s theory of personality

    NARCIS (Netherlands)

    Blutner, R.; Hochnadel, E.

    2010-01-01

    We propose a formalization of C.G. Jung’s theory of personality using a four-dimensional Hilbert-space for the representation of two qubits. The first qubit relates to Jung’s four psychological functions: Thinking, Feeling, Sensing and iNtuition, which are represented by two groups of projection

  13. Effect of high doses of equine chorionic gonadotrophin (eCG ...

    African Journals Online (AJOL)

    The aim of this study was to determine the effects of the superovulatory technique using equine chorionic gonadothrophin (eCG) on follicle response, ovulation and pregnancy rate in Boer goats. Twenty nine (29) does were divided into three groups, G1 (n = 11), G2 (n = 8) and G3 (control, n = 10). All groups had their estrus ...

  14. Bridging CAGD knowledge into CAD/CG applications: Mathematical theories as stepping stones of innovations

    Science.gov (United States)

    Gobithaasan, R. U.; Miura, Kenjiro T.; Hassan, Mohamad Nor

    2014-07-01

    Computer Aided Geometric Design (CAGD) which surpasses the underlying theories of Computer Aided Design (CAD) and Computer Graphics (CG) has been taught in a number of Malaysian universities under the umbrella of Mathematical Sciences' faculty/department. On the other hand, CAD/CG is taught either under the Engineering or Computer Science Faculty. Even though CAGD researchers/educators/students (denoted as contributors) have been enriching this field of study by means of article/journal publication, many fail to convert the idea into constructive innovation due to the gap that occurs between CAGD contributors and practitioners (engineers/product/designers/architects/artists). This paper addresses this issue by advocating a number of technologies that can be used to transform CAGD contributors into innovators where immediate impact in terms of practical application can be experienced by the CAD/CG practitioners. The underlying principle of solving this issue is twofold. First would be to expose the CAGD contributors on ways to turn mathematical ideas into plug-ins and second is to impart relevant CAGD theories to CAD/CG to practitioners. Both cases are discussed in detail and the final section shows examples to illustrate the importance of turning mathematical knowledge into innovations.

  15. Vaginal Fluid hCG Levels for Detecting Premature Rupture of Membranes

    Directory of Open Access Journals (Sweden)

    T. Artimani

    2004-04-01

    Full Text Available The aim of this study was to determine whether there is any different in hCG levels of vaginal fluids from normal pregnant women, women with confirmed PROM and with suspected PROM. After irrigating the posterior vaginal fornix with 3 ml of sterile saline and procuring vaginal washing , we measured hCG levels. Samples were analyzed from 38 normal pregnant women , 31 women with confirmed PROM , 28 women with suspected PROM. The mean of vaginal fluid hCG levels of normal pregnant women were 11.2 (0.00-98.6 mIu/ml. That of women with PROM was 140.2 (0.5 , 390.1 and that of women with suspected PROM was 21.5 (0.0 , 143.9. Sensivity was 80%, specility 83% , positive predictive value 73.7% , negative predictive value 88.1% , using a cut-value 20. It was concluded that the hCG level in vaginal fluid is a marker of PROM during third trimester.

  16. Effect of high doses of equine chorionic gonadotrophin (eCG ...

    African Journals Online (AJOL)

    SAM

    2014-03-19

    Mar 19, 2014 ... in the highest ovulation rate. Different doses of eCG however did not influence the pregnancy rate in superovulated does. Key words: Equine chorionic gonadotrophin, follicular, ovulation, pregnancy, estrus synchronization, goat. INTRODUCTION. The optimization of reproductive performance is one of.

  17. hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

    Directory of Open Access Journals (Sweden)

    Luana Paulesu

    2018-03-01

    Full Text Available Human chorionic gonadotropin (hCG is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs. Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA and para-Nonylphenol (p-NP, indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

  18. "hCG priming" effect in controlled ovarian stimulation through a long protocol

    Directory of Open Access Journals (Sweden)

    Antsaklis Aris

    2009-08-01

    Full Text Available Abstract Background Recently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa, a short-term pre-treatment with recombinant LH (rLH, prior to recombinant FSH (rFSH administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of "hCG priming" in controlled ovarian hyperstimulation (COH through a long GnRH-a protocol, which binds the same receptor (LH/hCGR, though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate. Methods Patients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group or a long protocol with rFSH and pre-treatment with hCG (hCG group. In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed. Results The mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate. Conclusion All the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial "hCG priming" effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.

  19. Ectopic pregnancy: using the hCG ratio to select women for expectant or medical management.

    Science.gov (United States)

    Kirk, Emma; Van Calster, Ben; Condous, George; Papageorghiou, Aris T; Gevaert, Olivier; Van Huffel, Sabine; De Moor, Bart; Timmerman, Dirk; Bourne, Tom

    2011-03-01

    To identify variables that can be used to select women with an ectopic pregnancy for expectant or medical management with systemic methotrexate. Cohort study. Early Pregnancy Unit of a London teaching hospital. Women with a tubal ectopic pregnancy managed non-surgically. The diagnosis of tubal ectopic pregnancy was made using transvaginal sonography. Human chorionic gonadotrophin (hCG) levels had to be taken at 0 hour and 48 hours pre-treatment. Other recorded variables include presenting complaints, gestational age, progesterone levels, size of the ectopic mass and appearance of the ectopic on transvaginal sonography. Women were followed up until the outcome (success or failure) of management was known. Univariable analysis was performed to identify the variables associated with successful management using area under curves and relative risks. Thirty-nine women underwent expectant management (overall success rate 71.8%) and 42 had medical management (overall success rate 76.2%). The pre-treatment hCG ratio (hCG 48 hours/hCG 0 hour) was related to the failure of both expectant (area under curve 0.86, 95% CI 0.67-0.94) and medical (area under curve 0.79, 95% CI 0.58-0.90) management. History of ectopic pregnancy was related to failure of expectant management only (relative risk 0.46, 95% CI 0.16-0.92). The most important variable for predicting the likelihood of successful non-surgical management was the pre-treatment hCG ratio. New studies are required to validate the use of this variable and of history of ectopic pregnancy to predict the likelihood of successful non-surgical management in clinical practice. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

  20. A crucial role in fertility for the oyster angiotensin-converting enzyme orthologue CgACE.

    Directory of Open Access Journals (Sweden)

    Guillaume Riviere

    Full Text Available Angiotensin-converting enzyme (ACE is a highly conserved metallopeptidase. In mammals, the somatic isoform governs blood pressure whereas the germinal isoform (tACE is required for fertility. In Ecdysozoans, ACE-like enzymes are implicated in reproduction. Despite ACE orthologues being present from bacteria to humans, their function(s remain(s unknown in distant organisms such as Lophotrochozoans. In silico analysis of an oyster (Crassostrea gigas EST library suggested the presence of an ACE orthologue in molluscs. Primer walking and 5'-RACE revealed that the 1.9 kb cDNA encodes CgACE, a 632 amino acid protein displaying a conserved single active site and a putative C-terminal transmembrane anchor, thus resembling human tACE, as supported by molecular modelling. FRET activity assays and Maldi-TOF spectrometry indicated that CgACE is a functional dipeptidyl-carboxypeptidase which is active on Angiotensin I and sensitive to ACE inhibitors and chloride ion concentration. Immunocytochemistry revealed that, as its human counterpart, recombinant CgACE is synthesised as a transmembrane enzyme. RT-qPCR, in-situ hybridization and immunohistochemistry shed light on a tissue, and development stage, specific expression pattern for CgACE, which is increased in the gonad during spermatogenesis. The use of ACE inhibitors in vivo indicates that the dipeptidase activity of CgACE is crucial for the oyster fertilization. Our study demonstrates that a transmembrane active ACE is present in the oyster Crassostrea gigas, and for the first time ascribes a functional role for ACE in Lophotrochozoans. Its biological function in reproduction is conserved from molluscs to humans, a finding of particular evolutionary interest especially since oysters represent the most important aquaculture resource worldwide.

  1. Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides.

    Science.gov (United States)

    Pan, Xichun; Li, Bin; Kuang, Mei; Liu, Xin; Cen, Yanyan; Qin, Rongxin; Ding, Guofu; Zheng, Jiang; Zhou, Hong

    2016-02-22

    Toll-like receptor (TLR) 9 is an endosomal receptor recognizing bacterial DNA/CpG-containing oligodeoxynucleotides (CpG ODN). Blocking CpG ODN/TLR9 activity represents a strategy for therapeutic prevention of immune system overactivation. Herein, we report that a synthetic peptide (SP) representing the leucine-rich repeat 11 subdomain of the human TLR9 extracellular domain could attenuate CpG ODN/TLR9 activity in RAW264.7 cells by binding to CpG ODN and decreasing its internalization. Our results demonstrate that preincubation with SP specifically inhibited CpG ODN- but not lipopolysaccharide (LPS)- and lipopeptide (PAM3CSK4)-stimulated TNF-α and IL-6 release. Preincubation of SP with CpG ODN dose-dependently decreased TLR9-driven phosphorylation of IκBα and ERK and activation of NF-κB/p65. Moreover, SP dose-dependently decreased FAM-labeled CpG ODN internalization, whereas non-labeled CpG ODN reversed the inhibition. The KD value of SP-CpG ODN binding was within the micromolar range. Our results demonstrated that SP was a specific inhibitor of CpG ODN/TLR9 activity via binding to CpG ODN, leading to reduced ODN internalization and decreased activation of subsequent pathways within cells. Thus, SP could be used as a potential CpG ODN antagonist to block TLR9 signaling.

  2. Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides

    Directory of Open Access Journals (Sweden)

    Xichun Pan

    2016-02-01

    Full Text Available Toll-like receptor (TLR 9 is an endosomal receptor recognizing bacterial DNA/CpG-containing oligodeoxynucleotides (CpG ODN. Blocking CpG ODN/TLR9 activity represents a strategy for therapeutic prevention of immune system overactivation. Herein, we report that a synthetic peptide (SP representing the leucine-rich repeat 11 subdomain of the human TLR9 extracellular domain could attenuate CpG ODN/TLR9 activity in RAW264.7 cells by binding to CpG ODN and decreasing its internalization. Our results demonstrate that preincubation with SP specifically inhibited CpG ODN- but not lipopolysaccharide (LPS- and lipopeptide (PAM3CSK4-stimulated TNF-α and IL-6 release. Preincubation of SP with CpG ODN dose-dependently decreased TLR9-driven phosphorylation of IκBα and ERK and activation of NF-κB/p65. Moreover, SP dose-dependently decreased FAM-labeled CpG ODN internalization, whereas non-labeled CpG ODN reversed the inhibition. The KD value of SP-CpG ODN binding was within the micromolar range. Our results demonstrated that SP was a specific inhibitor of CpG ODN/TLR9 activity via binding to CpG ODN, leading to reduced ODN internalization and decreased activation of subsequent pathways within cells. Thus, SP could be used as a potential CpG ODN antagonist to block TLR9 signaling.

  3. New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

    Science.gov (United States)

    Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

    2009-09-01

    Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

  4. Dual activity of phosphorothioate CpG oligodeoxynucleotides on HIV: reactivation of latent provirus and inhibition of productive infection in human T cells.

    Science.gov (United States)

    Scheller, Carsten; Ullrich, Anett; Lamla, Stefan; Dittmer, Ulf; Rethwilm, Axel; Koutsilieri, Eleni

    2006-12-01

    CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor-9 (TLR-9) and activate immune cells with antigen-presenting activity, including B cells and dendritic cells. Here we show that treatment of the latently human immunodeficiency virus (HIV)-infected T cell line ACH-2 with the CpG ODNs 2006 or 2040 triggers activation of viral gene expression, demonstrating that CpG-signaling activity can also be found in T cells. The CpG ODNs g12AAC and g12GTC had no effect on virus reactivation. In contrast to the stimulating effects on viral gene expression in latently infected cells, CpG ODNs potently suppressed HIV replication in productively infected MT4 T cells or PBLs. Inhibition of virus replication was not related to the CpG motif but similarly occurred with non-CpG phosphorothioate (PTO)-ODNs. Thus, virus inhibition was likely caused by the PTO backbone of the CpG ODNs, probably by interfering with events prior to integration of the viral cDNA into the host genome. The ability of CpG PTO-ODNs to trigger reactivation of latent HIV in combination with their antiviral activity on productive infection makes this substance class an interesting candidate for further test to asses their potential as supplements in HIV therapy.

  5. Transcriptomic Insights into the Response of Placenta and Decidua Basalis to the CpG Oligodeoxynucleotide Stimulation in Non-Obese Diabetic Mice and Wild-Type Controls

    Directory of Open Access Journals (Sweden)

    Xiao-Rui Liu

    2016-08-01

    Full Text Available Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD mice but not in the wild-type (WT mice. To elucidate the molecular mechanisms of differential pregnancy outcomes, differentially expressed genes (DEGs in the placenta and decidua basalis was revealed by RNA-Seq with CpG ODN or control ODN treatment. Common DEGs in the WT and NOD mice were enriched in antimicrobial/antibacterial humoral responses that may be activated as a primary response to bacterial infection. The susceptibility to CpG ODN-induced embryo-resorption in the NOD mice might mainly be attributed to M1 macrophage polarization and the immunodeficient status, such as the down-regulation in antigen processing and presentation, allograft rejection, and natural killer cell mediated cytotoxicity. In contrast, the WT mice with normal immune systems could activate multiple immune responses and be resistant to CpG ODN-induced embryo-resorption, such as M2 macrophage differentiation and activation regulated by complement component C1q and peroxisome proliferation-activated receptor (PPAR signaling pathways. Collectively, this study suggests that the immunodeficient status of NOD mice and the macrophage polarization regulated by C1q and PPAR signaling might be the basis for differential pregnancy outcomes between the NOD and WT mice.

  6. Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo.

    Science.gov (United States)

    Kitajima, I; Shinohara, T; Minor, T; Bibbs, L; Bilakovics, J; Nerenberg, M

    1992-12-25

    We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale for the use of antisense ODN therapeutics in HTLV-I-associated diseases.

  7. Prevention and Treatment of Cutaneous Leishmaniasis in Primates by Using Synthetic Type D/A Oligodeoxynucleotides Expressing CpG Motifs

    Science.gov (United States)

    Flynn, Barbara; Wang, Vivian; Sacks, David L.; Seder, Robert A; Verthelyi, Daniela

    2005-01-01

    Oligodeoxynucleotides (ODN) containing CpG motifs mimic microbial DNA and are recognized by toll-like receptor 9 on immune cells. The resulting response limits the early spread of infectious organisms and promotes the development of adaptive immunity. In this regard, CpG ODN show promise as immunoprotective agents and as vaccine adjuvants. Previous studies of nonhuman primates showed that administration of CpG ODN type D (also known as type A) at the site of infection 3 days before and after a challenge with Leishmania major enhanced host resistance and reduced the lesion's severity. In this study, we show that systemic administration of D/A ODN limits the size of lesions following an intradermal infection with L. major. Importantly, the reduced morbidity was not associated with a reduction in long-term immunity, as such treated macaques were still protected following a secondary challenge. Finally, administration of D/A ODN to macaques that had established cutaneous lesions reduced the severity of the lesions, suggesting a potential role for CpG ODN in L. major treatment. Together, these findings support the development of clinical studies to assess the use of CpG ODN types D/A as immunoprotective and therapeutic agents. PMID:16041009

  8. Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo.

    Science.gov (United States)

    Del Bufalo, D.; Cucco, C.; Leonetti, C.; Citro, G.; D'Agnano, I.; Benassi, M.; Geiser, T.; Zon, G.; Calabretta, B.; Zupi, G.

    1996-01-01

    We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs. Images Figure 1 Figure 4 PMID:8695353

  9. Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG

    NARCIS (Netherlands)

    T.I.M. Korevaar (Tim); E.A.P. Steegers (Eric); L. Chaker (Layal); M. Medici (Marco); V.W.V. Jaddoe (Vincent); T.J. Visser (Theo); Y.B. de Rijke (Yolanda); R.P. Peeters (Robin)

    2017-01-01

    textabstractConclusion: In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in

  10. Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

    Science.gov (United States)

    Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

    2016-01-01

    The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of 0.5 and hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low ( 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

  11. First trimester β-hCG and estradiol levels in singleton and twin pregnancies after assisted reproduction.

    Science.gov (United States)

    Póvoa, Ana; Xavier, Pedro; Matias, Alexandra; Blicksttein, Isaac

    2017-07-28

    To compare levels of β-hCG and estradiol collected during the first trimester in singleton and twin pregnancies following assisted reproduction technologies (ART). We prospectively evaluated 50 singleton and 47 dichorionic twin pregnancies that eventually ended in live births. Patients were recruited from a single ART center with standard treatment protocols followed by fresh embryo transfers. Hormone measurements were performed within a narrow gestational age range and analyzed in a single laboratory thus minimizing inter- and intra-assay variability. We measured serum β-hCG at 13 days after embryo transfer as well as samples of β-hCG and estradiol at 8-9 weeks+6 days. No significant differences existed between singletons and twins in respect to demographic and cycle characteristics. β-hCG and estradiol were all significantly higher in twins (PhCG and estradiol in twins, pointing to the potential role of these placental hormones in early support of a twin pregnancy.

  12. Significance of pregnancy test false negative results due to elevated levels of β-core fragment hCG.

    Science.gov (United States)

    Johnson, Sarah; Eapen, Saji; Smith, Peter; Warren, Graham; Zinaman, Michael

    2017-01-01

    Very high levels of β-core fragment human chorionic gonadotrophin (βcf-hCG) are reported to potentially cause false negative results in point-of-care (POC)/over-the-counter (OTC) pregnancy tests. To investigate this further, women's daily early morning urine samples, collected prior to conception and during pregnancy, were analysed for intact, free β-, and βcf-hCG. The proportion of βcf-hCG was found to be related to that of hCG produced and in circulation. Therefore, best practice for accuracy testing of POC/OTC pregnancy tests would be to test devices against clinical samples containing high levels of βcf-hCG as well as standards spiked with biologically relevant ratios.

  13. Variation, Evolution, and Correlation Analysis of C+G Content and Genome or Chromosome Size in Different Kingdoms and Phyla

    Science.gov (United States)

    Li, Xiu-Qing; Du, Donglei

    2014-01-01

    C+G content (GC content or G+C content) is known to be correlated with genome/chromosome size in bacteria but the relationship for other kingdoms remains unclear. This study analyzed genome size, chromosome size, and base composition in most of the available sequenced genomes in various kingdoms. Genome size tends to increase during evolution in plants and animals, and the same is likely true for bacteria. The genomic C+G contents were found to vary greatly in microorganisms but were quite similar within each animal or plant subkingdom. In animals and plants, the C+G contents are ranked as follows: monocot plants>mammals>non-mammalian animals>dicot plants. The variation in C+G content between chromosomes within species is greater in animals than in plants. The correlation between average chromosome C+G content and chromosome length was found to be positive in Proteobacteria, Actinobacteria (but not in other analyzed bacterial phyla), Ascomycota fungi, and likely also in some plants; negative in some animals, insignificant in two protist phyla, and likely very weak in Archaea. Clearly, correlations between C+G content and chromosome size can be positive, negative, or not significant depending on the kingdoms/groups or species. Different phyla or species exhibit different patterns of correlation between chromosome-size and C+G content. Most chromosomes within a species have a similar pattern of variation in C+G content but outliers are common. The data presented in this study suggest that the C+G content is under genetic control by both trans- and cis- factors and that the correlation between C+G content and chromosome length can be positive, negative, or not significant in different phyla. PMID:24551092

  14. Predictive value of serum β-hCG for early pregnancy outcomes among women with recurrent spontaneous abortion.

    Science.gov (United States)

    Liu, Yinglin; Liu, Yukun; Li, Xuejiao; Jiao, Xuedan; Zhang, Rui; Zhang, Jianping

    2016-10-01

    To examine peak serum levels of the β-subunit of human chorionic gonadotropin (β-hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA). In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat-sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum β-hCG had been measured twice weekly from 5 to 13weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13(+6)weeks. Optimal cutoff for peak β-hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak β-hCG cutoff and pregnancy outcome (pregnancy at 13weeks or spontaneous abortion). Peak β-hCG levels and length of pregnancy at this peak were examined. Overall, 1240 patients were included. The optimal cutoff value of peak β-hCG was 88 468IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in β-hCG, higher peak β-hCG, and longer pregnancy length at peak β-hCG were associated with successful early pregnancy. A cutoff value of serum β-hCG of 88 000IU/L could be used to predict early pregnancy outcomes for women with a history of RSA. Copyright © 2016. Published by Elsevier Ireland Ltd.

  15. The Risk of Preeclampsia According to High Thyroid Function in Pregnancy Differs by hCG Concentration.

    Science.gov (United States)

    Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

    2016-12-01

    During pregnancy, there is an increased demand for thyroid hormone. The pregnancy hormone human chorionic gonadotropin (hCG) is an important physiological stimulator of thyroid function. Already high-normal maternal free T 4 concentrations are associated with a higher risk of preeclampsia. The objective of the investigation was to study our hypothesis that hCG concentrations can distinguish a physiological form of high thyroid function from a more pathological form of high thyroid function and that the risk of preeclampsia would differ accordingly. TSH, free T 4 , hCG, or thyroperoxidase antibody concentrations were determined in pregnant women participating in a population-based prospective cohort study. The study was conducted in the general community. A nonselected sample of 5146 pregnant women participated in the study. There were no interventions. Preeclampsia was measured. Women with high hCG-associated high thyroid function did not have a higher risk of preeclampsia than women with normal thyroid function. In contrast, women with low hCG and high thyroid function had a 3.4- to 11.1-fold higher risk of preeclampsia. These risk estimates were amplified in women with a high body mass index. Women with a low hCG and suppressed TSH (hCG was not associated with preeclampsia, and results remained similar after exclusion of thyroperoxidase antibody-positive women. This study suggests that, in contrast to women with a high hCG associated high thyroid function, women with low hCG and high thyroid function during pregnancy are at a higher risk of developing preeclampsia. The additional measurement of hCG may therefore help to distinguish a more pathological form of high thyroid function and women at a high risk of preeclampsia.

  16. Generation of a luciferase-based reporter for CHH and CG DNA methylation in Arabidopsis thaliana.

    Science.gov (United States)

    Dinh, Thanh Theresa; O'Leary, Michael; Won, So Youn; Li, Shengben; Arroyo, Lorena; Liu, Xigang; Defries, Andrew; Zheng, Binglian; Cutler, Sean R; Chen, Xuemei

    2013-04-05

    DNA methylation ensures genome integrity and regulates gene expression in diverse eukaryotes. In Arabidopsis, methylation occurs in three sequence contexts: CG, CHG and CHH. The initial establishment of DNA methylation at all three sequence contexts occurs through a process known as RNA-directed DNA methylation (RdDM), in which small RNAs bound by Argonaute4 (AGO4) guide DNA methylation at homologous loci through the de novo methyltransferase DRM2. Once established, DNA methylation at each of the three sequence contexts is maintained through different mechanisms. Although some players involved in RdDM and maintenance methylation have been identified, the underlying molecular mechanisms are not fully understood. To aid the comprehensive identification of players in DNA methylation, we generated a transgenic reporter system that permits genetic and chemical genetic screens in Arabidopsis. A dual 35S promoter (d35S) driven luciferase (LUC) reporter was introduced into Arabidopsis and LUCL, a line with a low basal level of luciferase activity, was obtained. LUCL was found to be a multi-copy, single-insertion transgene that contains methylated cytosines in CG, CHG and CHH contexts, with the highest methylation in the CG context. Methylation was present throughout the promoter and LUC coding region. Treatment with an inhibitor of cytosine methylation de-repressed luciferase activity. A mutation in MET1, which encodes the CG maintenance methyltransferase, drastically reduced CG methylation and de-repressed LUC expression. Mutations in AGO4 and DRM2 also de-repressed LUC expression, albeit to a smaller extent than loss of MET1. Using LUCL as a reporter line, we performed a chemical screen for compounds that de-repress LUC expression, and identified a chemical, methotrexate, known to be involved in biogenesis of the methyl donor. We developed a luciferase-based reporter system, LUCL, which reports both RdDM and CG maintenance methylation in Arabidopsis. The low basal level

  17. Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Chi-Huang; Tzeng, Chii-Ruey; Wang, Peng-Hui; Liu, Wei-Min; Chang, Heng-Yu; Chen, Huang-Hui; Chen, Ching-Hui

    2018-03-29

    To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

  18. BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

    Science.gov (United States)

    Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

    2017-09-04

    Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

  19. LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

    Science.gov (United States)

    Casarini, Livio; Lispi, Monica; Longobardi, Salvatore; Milosa, Fabiola; La Marca, Antonio; Tagliasacchi, Daniela; Pignatti, Elisa; Simoni, Manuela

    2012-01-01

    Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. PMID:23071612

  20. Alternative Fuels

    Science.gov (United States)

    Alternative fuels include gaseous fuels such as hydrogen, natural gas, and propane; alcohols such as ethanol, methanol, and butanol; vegetable and waste-derived oils; and electricity. Overview of alternative fuels is here.

  1. Cannonball lung metastases as a presenting feature of ectopic hCG expression

    Directory of Open Access Journals (Sweden)

    Rong-Hsin Yang

    2016-08-01

    Full Text Available Cannonball metastases refer to well-defined spherical nodules scattered over both lungs, being a classical presentation of hematogenous tumor spreading. Striking progression of lung metastases without established primary malignancy can raise a diagnostic challenge. We herein report three cases with cannonball metastases at initial presentation. Two patients ended up having a choriocarcinoma but no awareness of the presence of primary tumors, and the third had abrupt lung metastases of endometrial cancer while she was being asymptomatic. Relentless progression was illustrated by clinical and radiographic changes. Ectopic expression of human chorionic gonadotropin (hCG would seemingly go some way responsible for fulminant cancer spreading associated with poor prognosis in our patients. The goal of this presentation is to raise awareness of ectopic hCG expression in patients presenting with similar astonishing scenarios.

  2. Prediction of late failure after medical abortion from serial beta-hCG measurements and ultrasonography

    DEFF Research Database (Denmark)

    Rørbye, C; Nørgaard, M; Nilas, Lisbeth

    2004-01-01

    on day 15 were greater among late failures than successes. Used as a predictive test, the positive predictive values of these variables were low. CONCLUSION: Neither beta-hCG nor endometrial thickness can be used clinically as diagnostic tests in predicting late failure after medical abortion.......BACKGROUND: Surgical treatment of failed medical abortion may be performed several weeks after initiation of the abortion. There are no recognized methods for early identification of these late failures. We assessed the prognostic values of beta-hCG and ultrasonography in predicting late failure...... thickness by ultrasonography was performed on day 15 after induction of medical abortion. Failures diagnosed after day 15 and within 15 weeks were identified and classified as late failures. All interventions in this group were due to bleeding problems. The predictive values of different absolute...

  3. Kinetic Studies on the Total Human Chorionic Gonadotropin (hCG) IRMA Assay

    International Nuclear Information System (INIS)

    Moustafa, K.A.; Aly, M.A.M.; Al-Kolaly, M.T.; Abou El-Nour, F.

    2002-01-01

    Human chorionic gonadotropin (hCG) is a two chains glycoprotein hormone normally found in blood and urine, only during pregnancy. It is secreted by placental tissue, beginning with the primitive trophoblast, almost from the time of implantation. The kinetics of the interaction between the hCG antigen and two matched antibodies, one labelled with radioactive isotope 125 I (tracer) and the other is unlabelled and attached to a solid support (tube) , are studied using, two-sites (sandwich) Immunoradiometric assay (IRMA) technique. A new method for determining the rate constants, using an advanced computer program (RKY) based on the Nelder-Mead optimisation principle is introduced. The rate constants, at three variable temperatures and three different antigen concentrations as well as the half time of exchange (t) were calculated

  4. Abnormal hCG levels in a patient with treated stage I seminoma: a diagnostic dilemma.

    LENUS (Irish Health Repository)

    Aherne, Noel J

    2008-01-01

    BACKGROUND: We report the case of a patient with treated Stage Ia seminoma who was found to have an elevated beta human chorionic gonadotrophin (hCG) on routine follow - up. This instigated restaging and could have lead to commencement of chemotherapy. CASE PRESENTATION: The patient was a bodybuilder, and following a negative metastatic work - up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis. CONCLUSION: This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.

  5. Parallel performance of a preconditioned CG solver for unstructured finite element applications

    Energy Technology Data Exchange (ETDEWEB)

    Shadid, J.N.; Hutchinson, S.A.; Moffat, H.K. [Sandia National Labs., Albuquerque, NM (United States)

    1994-12-31

    A parallel unstructured finite element (FE) implementation designed for message passing MIMD machines is described. This implementation employs automated problem partitioning algorithms for load balancing unstructured grids, a distributed sparse matrix representation of the global finite element equations and a parallel conjugate gradient (CG) solver. In this paper a number of issues related to the efficient implementation of parallel unstructured mesh applications are presented. These include the differences between structured and unstructured mesh parallel applications, major communication kernels for unstructured CG solvers, automatic mesh partitioning algorithms, and the influence of mesh partitioning metrics on parallel performance. Initial results are presented for example finite element (FE) heat transfer analysis applications on a 1024 processor nCUBE 2 hypercube. Results indicate over 95% scaled efficiencies are obtained for some large problems despite the required unstructured data communication.

  6. Characterization of LH/hCG receptor by enzyme receptor assay in human ovarian cancer cell line 3AO

    International Nuclear Information System (INIS)

    Xing Yan; Liao Ying; Chen Manling

    2005-01-01

    To establish an enzyme receptor assay (ERA) for LH/hCG receptor on intact culture cells and study the characteristics of LH/hCG receptor of ovarian cancer cell line 3AO by ERA, the enzyme-ligand conjugate was prepared by the oxidation method of NaIO 4 . An ERA of marker ligand with embedded cells was established in suitable conditions, and applied to determine the maximum binding and affinity of LH/hCG receptor on 3AO cells as well as on an ovarian cancer cell line SKOV-3 serving as the negative control. The results showed that the B max and K d values of LH/hCG receptor were 3.65 mmol/g protein and 0.41 nmol/L, respectively. For competitive inhibition, the IC 50 of unlabelled hCG against HRP-hCG binding was 0.92 μmol/L. Our conclusion is that by competitive inhibition assay, saturation binding assay and Scatchard analysis, LH/hCG receptors with high affinity are present on 3AO cells. (authors)

  7. Serial hCG and progesterone levels to predict early pregnancy outcomes in pregnancies of uncertain viability: A prospective study.

    Science.gov (United States)

    Puget, Claire; Joueidi, Yolaine; Bauville, Estelle; Laviolle, Bruno; Bendavid, Claude; Lavoué, Vincent; Le Lous, Maela

    2018-01-01

    To assess the value of serial hCG and progesterone serum level in the diagnosis of early pregnancy viability. It was a prospective cohort study. Women with a pregnancy of uncertain viability (PUV), defined as the presence of an intra-uterine embryo with a crown-rump length hCG levels on the first day and 48h after as well as the initial progesterone level were evaluated to diagnose pregnancy viability. Pregnancy viability was assessed by TVS 7 to 14days after inclusion. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an hCG H48/H0 ratio increase hCG H48/H0 ratio increase >75% to diagnose a viable pregnancy were 100%, 31%, 45.9% and 100%, respectively. hCG H48/H0 ratio increase hCG H48/H0 ratio increase >75% was associated with 100% of viable pregnancies in 100% of the cases. Serial hCG levels alone permitted an early viability diagnosis within 48h for 41.1% of patients with PUV instead of 7 to 14days with TVS. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population.

    Science.gov (United States)

    Zidi, Inès; Dziri, Olfa; Zidi, Nour; Sebai, Refaat; Boujelebene, Nadia; Ben Hassine, Amna; Ben Yahia, Hamza; Laaribi, Ahmed Baligh; Babay, Wafa; Rifi, Hela; Mezlini, Amel; Chelbi, Hanene

    2016-08-01

    HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C>G polymorphisms. The mutations were identified with PCR and PCR-RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C>G polymorphism (p = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008-0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C>G polymorphism is maintained in young patients (HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081-0.895, p = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL (p HLA-G +3142 C>G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.

  9. Use of a rapid hCG-beta-subunit radioimmunoassay in acute gynaecological emergencies

    International Nuclear Information System (INIS)

    Seppala, M.; Tontti, K.; Ranta, T.; Stenman, U.-H.; Chard, T.

    1980-01-01

    Chorionic gonadotrophin (hCG) was measured by a rapid and sensitive radioimmunoassay in 100 female patients with lower abdominal pain attending an emergency department. Of the 24 subjects with a positive result, 22 had evidence of pregnancy (ectopic or uterine). Of the 76 patients with negative results, 3 had some evidence of pregnancy. This test may be of considerable practical value in the differential diagnosis of acute abdominal emergencies in women of reproductive age. (author)

  10. Analytical characterization of recombinant hCG and comparative studies with reference product.

    Science.gov (United States)

    Thennati, Rajamannar; Singh, Sanjay Kumar; Nage, Nitin; Patel, Yena; Bose, Sandip Kumar; Burade, Vinod; Ranbhor, Ranjit Sudhakar

    2018-01-01

    Regulatory agencies recommend a stepwise approach for demonstrating biosimilarity between a proposed biosimilar and reference biological product emphasizing for functional and structural characterization to trace if there is any difference which may impact safety and efficacy. We studied the comparative structural and biological attributes of recombinant human chorionic gonadotropin (rhCG), SB005, with reference product, Ovidrel ® and Ovitrelle ® . Recombiant hCG was approved in 2000 by the US Food and Drug Administration for the induction of final follicular maturation, early luteinization in infertile women as part of assisted reproductive technology program. It is also indicated for the induction of ovulation and pregnancy in ovulatory infertile patients whose cause of infertility is not due to ovarian failure. Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB005 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography and sialic acid analysis. Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Biological activity in term of potency of reference product and SB005 was studied by in vivo analysis. In this study we have compared analytical similarity of recombinant rhCG (SB005) produced at Sun Pharmaceuticals with the reference product with respect to its primary, higher order structure, isoforms, charge variants, glycosylation, sialyation

  11. CG Methylation Covaries with Differential Gene Expression between Leaf and Floral Bud Tissues of Brachypodium distachyon.

    Directory of Open Access Journals (Sweden)

    Kyria Roessler

    Full Text Available DNA methylation has the potential to influence plant growth and development through its influence on gene expression. To date, however, the evidence from plant systems is mixed as to whether patterns of DNA methylation vary significantly among tissues and, if so, whether these differences affect tissue-specific gene expression. To address these questions, we analyzed both bisulfite sequence (BSseq and transcriptomic sequence data from three biological replicates of two tissues (leaf and floral bud from the model grass species Brachypodium distachyon. Our first goal was to determine whether tissues were more differentiated in DNA methylation than explained by variation among biological replicates. Tissues were more differentiated than biological replicates, but the analysis of replicated data revealed high (>50% false positive rates for the inference of differentially methylated sites (DMSs and differentially methylated regions (DMRs. Comparing methylation to gene expression, we found that differential CG methylation consistently covaried negatively with gene expression, regardless as to whether methylation was within genes, within their promoters or even within their closest transposable element. The relationship between gene expression and either CHG or CHH methylation was less consistent. In total, CG methylation in promoters explained 9% of the variation in tissue-specific expression across genes, suggesting that CG methylation is a minor but appreciable factor in tissue differentiation.

  12. Visual and laser Doppler perfusion scanning assessments of Kathon CG patch test reactions.

    Science.gov (United States)

    Bjarnason, B; Fischer, T

    1998-12-01

    Testing procedure for Kathon CG (Diagnostics AB, Tygelsjö, Sweden) is not standardized. To improve test results for Kathon CG. Eleven subjects were tested with Kathon CG patch tests applied from 6 to 96 hours. Tests were read visually and by a laser Doppler perfusion scanning technique at time points ranging from 6 to 240 hours. There were large differences in the perfusion profiles of subjects tested in identical fashion. Beginning reactions were detected earlier with the laser Doppler scanning than with the visual assessment technique. There was no obvious agreement between peak perfusion values of reactions and application times. Both assessment techniques were effective at distinguishing between positive and negative subjects at an adequate dose and application time. This distinction was possible using a shorter reading time with the laser Doppler scanning for all subjects. Six-hour applications were sufficient to detect all positive subjects so tested regardless of assessment technique. With that application time, positive and negative subjects were most effectively identified using long reading times regardless of assessment technique. The shortest application time used on all subjects, 24 hours, was effective and 6-hour applications with long reading times for all subjects so tested. Doses lower than 0.0040 mg/cm2 resulted in false-negative tests.

  13. Iterative methods for solving Ax=b, GMRES/FOM versus QMR/BiCG

    Energy Technology Data Exchange (ETDEWEB)

    Cullum, J. [IBM Research Division, Yorktown Heights, NY (United States)

    1996-12-31

    We study the convergence of GMRES/FOM and QMR/BiCG methods for solving nonsymmetric Ax=b. We prove that given the results of a BiCG computation on Ax=b, we can obtain a matrix B with the same eigenvalues as A and a vector c such that the residual norms generated by a FOM computation on Bx=c are identical to those generated by the BiCG computations. Using a unitary equivalence for each of these methods, we obtain test problems where we can easily vary certain spectral properties of the matrices. We use these test problems to study the effects of nonnormality on the convergence of GMRES and QMR, to study the effects of eigenvalue outliers on the convergence of QMR, and to compare the convergence of restarted GMRES, QMR, and BiCGSTAB across a family of normal and nonnormal problems. Our GMRES tests on nonnormal test matrices indicate that nonnormality can have unexpected effects upon the residual norm convergence, giving misleading indications of superior convergence over QMR when the error norms for GMRES are not significantly different from those for QMR. Our QMR tests indicate that the convergence of the QMR residual and error norms is influenced predominantly by small and large eigenvalue outliers and by the character, real, complex, or nearly real, of the outliers and the other eigenvalues. In our comparison tests QMR outperformed GMRES(10) and GMRES(20) on both the normal and nonnormal test matrices.

  14. A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H1 immunity.

    Directory of Open Access Journals (Sweden)

    Jun-ichi Maeyama

    Full Text Available BACKGROUND: CpG oligodeoxynucleotides (ODNs, resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC-mediated T(H1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA. METHODS: T(H1 and T(H2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT through nasal vaccination. RESULTS: G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of T(H1, but not T(H2-type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. CONCLUSIONS: G9.1 is a promising mucosal adjuvant for induction of pDC-mediated T(H1 immunity.

  15. Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability

    Science.gov (United States)

    Mendez, Susana; Tabbara, Khaled; Belkaid, Yasmine; Bertholet, Sylvie; Verthelyi, Daniela; Klinman, Dennis; Seder, Robert A.; Sacks, David L.

    2003-01-01

    The inoculation of live, nonattenuated Leishmania major to produce a lesion in a selected site that heals, referred to as leishmanization, is to date the only vaccine against leishmaniasis that has proven to be effective in humans. Its use has been restricted or abandoned entirely, however, due to safety concerns. In an attempt to develop a leishmanization protocol that minimizes pathology while maintaining long-term protection, live parasites were coinjected with CpG-containing immunostimulatory oligodeoxynucleotides (CpG ODNs) alone or in combination with whole-cell lysates of heat-killed L. major promastigotes bound to alum (ALM). C57BL/6 mice infected intradermally by using L. major plus CpG ODN with or without ALM developed few or no dermal lesions and showed an early containment of parasite growth, while mice infected with L. major with or without ALM developed sizable dermal lesions that required up to 10 weeks to heal. The CpG ODNs provoked a transient inflammation that included an early recruitment and accumulation of gamma interferon-producing CD4+ lymphocytes in the site. Attenuation of the live vaccine did not compromise its ability to confer long-term immunity, as mice receiving L. major and CpG ODN plus ALM were totally protected against reinfection with L. major for up to 6 months. By comparison, the immunity elicited by two efficient nonlive vaccines began to wane by 6 months. Our results suggest that immune modulation using CpG ODNs might be a practical approach to improving the safety of a highly effective live vaccine that has already been widely applied. PMID:12933855

  16. In vitro and in vivo reversal of multidrug resistance in a human leukemia-resistant cell line by mdr1 antisense oligodeoxynucleotides.

    Science.gov (United States)

    Cucco, C; Calabretta, B

    1996-10-01

    A major obstacle to successful cancer chemotherapy is the development of multidrug resistance (MDR) by tumor cells. Overexpression of the mdrl gene product P-glycoprotein (P-170) is characteristic of such cells. In this study, in vitro and in vivo reversion of MDR was attempted in a human leukemia cell line resistant to vincristine (HL-60/Vinc) using an 18-mer mdr1 antisense phosphorothioate oligodeoxynucleotide ([S]ODN) in combination with vincristine. As control of sequence specificity, both sense and scrambled [S]ODNs were used. The ability of these [S]ODNs to reverse MDR was studied in vitro and in severe combined immunodeficient (SCID) mice. In vitro treatment with antisense [S]ODNs restored vincristine sensitivity of HL-60/Vinc cells, whereas no changes in drug sensitivity were observed upon treatment with the sense or scrambled sequence. The in vitro effects correlated with inhibition of P-170 expression in HL-60/Vinc cells exposed to the mdr1 antisense [S]ODNs. In vivo reversal of MDR was obtained in SCID mice given injections of HL-60/Vinc cells and systemically treated with [S]ODNs plus vincristine, as indicated by a significantly prolonged survival of SCID mice that received the combination therapy of mdr1 antisense [S]ODNs + vincristine. Treatments with mdr1 antisense or scrambled [S]ODNs, vincristine, or scrambled [S]ODNs + vincristine had no effect on survival. These results suggest that the use of mdr1 antisense ODNs in combination with standard antineoplastic drugs might be useful in reversing MDR in vitro and in vivo.

  17. Analytical characterization of recombinant hCG and comparative studies with reference product

    Directory of Open Access Journals (Sweden)

    Thennati R

    2018-01-01

    Full Text Available Rajamannar Thennati,1 Sanjay Kumar Singh,1 Nitin Nage,1 Yena Patel,1 Sandip Kumar Bose,1 Vinod Burade,2 Ranjit Sudhakar Ranbhor1 1Sun Pharmaceutical Industries Limited, 2Sun Pharmaceutical Advanced Research Center, Vadodara, Gujarat, India Introduction: Regulatory agencies recommend a stepwise approach for demonstrating biosimilarity between a proposed biosimilar and reference biological product emphasizing for functional and structural characterization to trace if there is any difference which may impact safety and efficacy. We studied the comparative structural and biological attributes of recombinant human chorionic gonadotropin (rhCG, SB005, with reference product, Ovidrel® and Ovitrelle®. Recombiant hCG was approved in 2000 by the US Food and Drug Administration for the induction of final follicular maturation, early luteinization in infertile women as part of assisted reproductive technology program. It is also indicated for the induction of ovulation and pregnancy in ovulatory infertile patients whose cause of infertility is not due to ovarian failure. Materials and methods: Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB005 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography and sialic acid analysis. Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Biological activity in term of potency of reference product

  18. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner

    NARCIS (Netherlands)

    Barjaktarovic, M. (Mirjana); T.I.M. Korevaar (Tim); V.W.V. Jaddoe (Vincent); Y.B. de Rijke (Yolanda); T.J. Visser (Theo); R.P. Peeters (Robin); E.A.P. Steegers (Eric)

    2017-01-01

    textabstractHuman chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth

  19. Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

    DEFF Research Database (Denmark)

    Thuesen, L L; Andersen, A Nyboe; Loft, A

    2014-01-01

    CONTEXT: The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied. OBJECTIVE: The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH...... protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. MAIN OUTCOME MEASURE: Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were...... measured. RESULTS: In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P

  20. Homebox Genes Mediates the Biological Functions of Human Chorionic Gonadotropin (hCG) in Human Breast Epithelial Cells

    National Research Council Canada - National Science Library

    Russo, Jose

    2000-01-01

    ... (hCG) has been found to be an efficacious physiological protector in rats against the initiation and progression of mammary tumors induced by carcinogen, accompanied by the induction of cellular differentiation and expression of the a and.

  1. Impacts of elevated level of hCG in serum on clinical course and radiotherapy results in the histology-confirmed intracranial germinomas

    Energy Technology Data Exchange (ETDEWEB)

    Shin, K.H.; Kim, I.H.; Choe, G. [Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Therapeutic Radiology

    2001-05-01

    The prognosis of intracranial germinoma producing the human chorionic gonadotropin (hCG) is controversial due to limited information. We undertook a retrospective analysis to determine whether this type of tumor has similar clinical course and prognosis to hCG non-secreting germinoma. Thirty-one histologically confirmed intracranial germinoma patients who had pretreatment hCG examination in serum/CSF were treated with radiotherapy between 1980 and 1996. hCG level was measured by immunoradioassay of beta subunit of hCG. Six patients had elevated serum hCG levels and were defined as having hCG secreting germinoma. All except three patients received craniospinal axis irradiation. The follow-up ranged from 19-175 months with a median of 63 months. hCG secreting germinoma accounted for 19% of intracranial germinoma cases. Elevated hCG levels ranged from 39-260 IU/l in serum. No difference was found between hCG non-secreting germinoma and hCG secreting germinoma in terms of patient or treatment characteristics. There was no recurrence among the six hCG secreting germinoma patients. The 5-year overall and disease-free survival rates were 96% for patients with hCG non-secreting germinomas and 100% for the patients with hCG secreting germinomas. The survival difference was not significant (p = 0. 59). Our results suggest that elevated level of hCG did not result in any differences in the clinical characteristics or survival after radical radiotherapy in histologically confirmed intracranial germinoma.

  2. Abnormal human chorionic gonadotropin (hCG) trends after transfer of multiple embryos resulting in viable singleton pregnancies.

    Science.gov (United States)

    Brady, Paula C; Farland, Leslie V; Missmer, Stacey A; Racowsky, Catherine; Fox, Janis H

    2017-12-19

    The purpose of this study is to investigate whether abnormal hCG trends occur at a higher incidence among women conceiving singleton pregnancies following transfer of multiple (two or more) embryos (MET), as compared to those having a single embryo transfer (SET). Retrospective cohort study was performed of women who conceived singleton pregnancies following fresh or frozen autologous IVF/ICSI cycles with day 3 or day 5 embryo transfers between 2007 and 2014 at a single academic medical center. Cycles resulting in one gestational sac on ultrasound followed by singleton live birth beyond 24 weeks of gestation were included. Logistic regression models adjusted a priori for patient age at oocyte retrieval and day of embryo transfer were used to estimate the Odds Ratio of having an abnormal hCG rise (defined as a rise or hCG rises between the first and second measurements, compared to 2.7% (n = 17) of patients undergoing SET (OR 2.16, 95% CI 1.26-3.71). Among patients with initially abnormal hCG rises who had a third level checked (89%), three-quarters had normal hCG rises between the second and third measurements. Patients who deliver singletons following MET were more likely to have suboptimal initial hCG rises, potentially due to transient implantation of other non-viable embryo(s). While useful for counseling, these findings should not change standard management of abnormal hCG rises following IVF. The third hCG measurements may clarify pregnancy prognosis.

  3. Assessment and association of two useful tumour markers: alpha feto protein and human chornionic gonodotropin (beta hCG) hormone

    International Nuclear Information System (INIS)

    Subhan, F.; Tahir, F.; Sultan, S.; Subhan, K.

    2008-01-01

    This study was designed to determine serum Alpha-fetoprotein (AFP) and beta-h Chornionic Gonodotropin hormone (beta-hCG) levels among adult Pakistani population, and to observe their correlation. Serum AFP and beta-hCG levels were evaluated, using Micro-particle Enzyme Immuno Assay (MEIA) technology of M/s Abbott Laboratories. Data were compared using students t-test and correlation was computed. In the patients advised serum AFP assessment, 52% had normal AFP levels. comprising 37% male and 63% female subjects. For patients having a non-pathological picture, AFP levels varied non-significantly (p>0.05) between the Genders however, age varied highly significantly (p 0.05) and highly significant (p 0.05). Comparison of the population in the same age groups of both genders revealed significant (p 0.05), due to a large standard error. Although the differences in beta-hCG levels were highly significant (p 0.05). Among the studied cases, 67% patients had normal and 33% patients had raised beta-hCG levels. Beta-hCG levels show a decreasing trend with increasing age and beta-hCG levels were statistically significant (p<0.05) when patients under 50 years of age were compared with patients above 50 years. The coefficient of correlation between serum AFP and beta- hCG levels was 0.996454, which indicated a very strong. Significant positive correlation between the two tumour markers. The study showed that both serum AFP and beta-hCG are useful tumour markers and had a very strong positive correlation. (author)

  4. Serum β-hCG levels post-treatment of ectopic pregnancy with a single dose of intramuscular methotrexate.

    Science.gov (United States)

    Hadinata, Ignatius E; Doyle, Lex W; Thompson, Derrick; Reti, Leslie

    2015-04-01

    The cytotoxic management of ectopic pregnancy using a single dose of intramuscular methotrexate injection has been well established as effective for a select number of women with unruptured tubal ectopic pregnancy where there are minimal symptoms. The purpose of this study was to create centile curves of serum β-hCG levels following successful treatment with a single dose of 50 mg/m(2) of intramuscular methotrexate to treat ectopic pregnancy. Data were retrieved from women treated at the Royal Women's Hospital for ectopic pregnancy between 2006 and 2012. Only women with minimal symptoms, initial serum β-hCG ≤5000 IU/L and ectopic mass size of ≤35 mm on ultrasound were included. Two hundred and fifty-three cases of ectopic pregnancy were analysed. Initial β-hCG of women in the study ranged from 18 to 3995 IU/L with a median of 497 (25th to 75th centiles; 222-1160) IU/L. The median levels of β-hCG levels at day 4, 7 and 14 postmethotrexate injection were 73.8, 47.2 and 10.4% of the initial β-hCG level, respectively. The 90th centiles of β-hCG levels at day 4, 7 and 14 were 124.7, 93.8 and 40.0% of initial β-hCG level, respectively. Whilst no comparison with those unsuccessfully treated was made, pending further validation studies, the use of these curves may reduce the reliance on specialist units and streamline care for many women with ectopic pregnancy, such as those whose β-hCG regress in line with centile values without crossing a certain threshold. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  5. Trichosanthin, a Chinese medicine for the medical treatment of ectopic pregnancy with high levels of β-hCG.

    Science.gov (United States)

    Xiang, D J; Chen, L M; Gu, J S; Stone, P; Chen, Qi

    2012-05-01

    This was a retrospective study of the effectiveness of trichosanthin (TCS), an active component isolated from the Chinese herb root tuber of Trichosanthes kirilowii on 140 cases of ectopic pregnancy with higher levels of β-human chorionic gonadotropin (β-hCG) managed with a single dose of TCS treatment. Trichosanthin has been used for medical treatment of ectopic pregnancy in China since the 1980s. This study was performed in a major teaching hospitals in China. The mean pretreatment level of β-hCG in the TCS treatment group was 3387.57 IU/L. The success rate of TCS treatment was 85% (119 of 140) which was similar to methotrexate (MTX) treatment. In 86 women with a high level of β-hCG (over 2000 IU/L), the success rate was 80.08% when treated with TCS. Of this group, 26 women who had a high level of β-hCG (over 5000 IU/L) showed a success rate of 73%. The level of β-hCG on days 4, 7, and 10 in TCS group was significantly decreased. This study has shown that TCS may be an option for the medical treatment of unruptured ectopic pregnancy or an option for the treatment of ectopic pregnancy with higher levels of β-hCG than currently recommended for medical management with MTX.

  6. Positive pregnancy tests in a nongravid, premenopausal woman due to hCG beta-chain production by multiple myeloma.

    Science.gov (United States)

    Slone, Stephen P; Ahmed, Zakaria; Cole, Laurence A; Elin, Ronald J; Martin, Alvin W; Herzig, Roger H; Herzig, Geoffrey P; Miller, James J

    2005-07-01

    Positive pregnancy test results occurred in a nongravid, premenopausal woman while she was receiving chemotherapy for multiple myeloma. We tested 2 hypotheses to account for this finding: (1) Heterophil antibodies caused positive interference in the immunoassays. (2) Genuine human chorionic gonadotropin (hCG) originated from a nonsyncytiotrophoblastic source. Paraprotein was eliminated as a source of positive interference because 3 different instruments with unique capture and signal antibodies gave similar results (83, 90, and 97 mIU/mL [83, 90, and 97 IU/L]). Human antimouse antibodies (HAMAs) were unlikely to cause positive interference because immunoreactivity was maintained after serum was treated to neutralize heterophil antibodies. Immunoassays performed after gel filtration of serum indicated that immunoreactivity was due to genuine hCG. The high-molecular-weight fraction (heterophil antibody) had 6 mIU/mL (6 IU/L) of hCG. The low-molecular-weight fraction (hCG) had 86 mIU/mL (86 IU/L) of hCG. Immunohistochemical stains revealed that myeloma cells expressed immunoreactive hCG. Hence, multiple myeloma caused positive pregnancy test results in a nongravid woman.

  7. LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

    Science.gov (United States)

    Noci, Ivo; Sorbi, Flavia; Mannini, Luca; Projetto, Elisabetta; Pillozzi, Serena; Ghizzoni, Viola; Lottini, Tiziano; Moncini, Daniela; Baroni, Gianna; Mungai, Francesco; Arcangeli, Annarosa; Fambrini, Massimiliano

    2016-01-01

    A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

  8. Embryo transfer day does not affect the initial maternal serum β-hCG levels: A retrospective cohort study.

    Science.gov (United States)

    Dahiya, Mona; Rupani, Karishma; Yu, Su Ling; Fook-Chong, Stephanie M C; Siew Fui, Diana Chia; Rajesh, Hemashree

    2017-05-01

    The aim of this study is to compare the serum β-hCG values post transfer of a cleavage stage embryo versus a blastocyst stage embryo at equal time intervals post oocyte retrieval (OR) in clinically pregnant patients, and to ascertain a β-hCG value to predict pregnancy outcomes. This is a retrospective cohort study of 560 women with clinical pregnancy who underwent an embryo transfer performed at either the cleavage stage or the blastocyst stage of embryo development between January 2003 and June 2014 at the Center for Assisted Reproduction (CARE), Singapore General Hospital. The serum β-hCG level was measured on day 17 post OR. The β-hCG values were not significantly different in the cleavage stage versus the blastocyst stage embryos (mean±SD: 387±486IU/L D3 vs. 352±268IU/L D5, p=0.96, median value 297 in both groups). Our study suggests that the initial maternal serum β-hCG values were not affected by the day of transfer of the embryos since assessing the β-hCG at equivalent points after transfer should not lead to a significant difference assuming the progress and development of the embryos occurred as expected. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels.

    Science.gov (United States)

    Gol, Mert; Tuna, Burçin; Dogan, Erbil; Gulekli, Bülent; Bagci, Mustafa; Altunyurt, Sabahattin; Saygili, Ugur

    2004-08-01

    Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67, a cell proliferation and activity marker, is confined mostly in the nuclei of villous cytotrophoblasts of the human placenta. In this study, we examined the effect of fetal gender on the cytotrophoblast cell activity in human term placenta, with special regard to maternal serum and cord blood hCG levels. Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17 female fetuses) were recruited in the study. hCG was measured in maternal peripheral serum and umbilical cord blood. Placental samples were collected in each patient during the cesarean section. Cytotrophoblast cell activity was measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index values of the cytotrophoblasts were compared between the female and male placentas. Maternal serum and cord blood hCG levels were higher in pregnant women with female fetuses than in those carrying male fetuses. There was no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells. There was no correlation between maternal serum and cord blood hCG levels and Ki-67 staining index values of the cytotrophoblast cells. The difference in maternal serum and cord blood hCG levels in correlation with the fetal gender is not associated with cytotrophoblast cell activity in the human term placenta. The gender of the fetus does not seem to affect the regulation of cytotrophoblast cell proliferation.

  10. Challenges in harmonizing integrated healthcare network laboratories: multi-center evaluation of the hCG5 assay.

    Science.gov (United States)

    Greene, Dina N; Baird, Geoffrey S; Kwong, Shiu-Land; Lorey, Thomas S; Holmes, Daniel T

    2016-01-01

    Beckman Coulter recently introduced a new hCG assay manufactured for the Access 2 and DxI platforms. This assay is the first to use the 5th International Standard (5th IS) as its primary calibration material. Clinical laboratories are required to validate the method performance before testing and reporting patient results. Beckman Coulter Access 2 instruments (n=41) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the hCG5 reagent. Precision, linearity, dilution verification, and patient sample comparisons were performed on each instrument. The assay was linear up to 1350IU/L. Intra-day and inter-day precision ranged from 1.0%-3.3% and 1.8-7.3%, respectively, for the low QC material (mean concentration 4.6IU/L). Percent bias between the previous assay (hCG2) and the hCG5 assay was 3.2 to 22.7% for hCG concentrations 1000IU/L. On board and manual dilutions agreed within 15% following proper adjustment of the instrument dilution factor. Achieving Access 2 inter-instrument agreement on specimens needing dilutions (hCG>1350IU/L) requires validation of the on board dilution factor. Laboratories should use QC material above the linear range to monitor instrument dilution accuracy and precision. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

    Directory of Open Access Journals (Sweden)

    Paraskevis Dimitris

    2009-10-01

    Full Text Available Abstract A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58 were administered hCG and Group B rLH (n = 56 in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures.

  12. The molecular relationship between antigenic domains and epitopes on hCG.

    Science.gov (United States)

    Berger, Peter; Lapthorn, Adrian J

    2016-08-01

    Antigenic domains are defined to contain a limited number of neighboring epitopes recognized by antibodies (Abs) but their molecular relationship remains rather elusive. We thoroughly analyzed the antigenic surface of the important pregnancy and tumor marker human chorionic gonadotropin (hCG), a cystine knot (ck) growth factor, and set antigenic domains and epitopes in molecular relationships to each other. Antigenic domains on hCG, its free hCGα and hCGβ subunits are dependent on appropriate inherent molecular features such as molecular accessibility and protrusion indices that determine bulging structures accessible to Abs. The banana-shaped intact hCG comprises ∼7500Å(2) of antigenic surface with minimally five antigenic domains that encompass a continuum of overlapping non-linear composite epitopes, not taking into account the C-terminal peptide extension of hCGβ (hCGβCTP). Epitopes within an antigenic domain are defined by specific Abs, that bury nearly 1000Å(2) of surface accessible area on the antigen and recognize a few up to 15 amino acid (aa) residues, whereby between 2 and 5 of these provide the essential binding energy. Variability in Ab binding modes to the contact aa residues are responsible for the variation in affinity and intra- and inter-species specificity, e.g. cross-reactions with luteinizing hormone (LH). Each genetically distinct fragment antigen binding (Fab) defines its own epitope. Consequently, recognition of the same epitope by different Abs is only possible in cases of genetically identical sequences of its binding sites. Due to combinatorial V(D)J gene segment variability of heavy and light chains, Abs defining numerous epitopes within an antigenic domain can be generated by different individuals and species. Far more than hundred Abs against the immuno-dominant antigenic domains of either subunit at both ends of the hCG-molecule, the tips of peptide loops one and three (Ł1+3) protruding from the central ck, encompassing h

  13. The effect of post-mating hCG or progesterone administration on reproductive performance of Afshari × Booroola-Merino crossbred ewes.

    Science.gov (United States)

    Rostami, Behnam; Hajizadeh, Rahman; Shahir, Mohammad-Hossein; Aliyari, Davood

    2017-02-01

    To investigate the efficiency of hCG/CIDR after breeding to increase the reproductive performance, 35 synchronized ewes were mated with fertile rams and were assigned to three treatment groups. Ewes in hCG group (n = 12) received 400 IU hCG on day 11 post-mating, and ewes in CIDR group (n = 11) received CIDR from day 7 until day 19 post-mating. Ewes in the control group (n = 12) did not receive any treatment. Blood samples were collected on days 7, 12, 17, and 22 post-mating. Plasma P 4 concentrations were higher on days 12 and 17 post-mating in hCG- and CIDR-treated groups (P hCG and control groups were higher than that in CIDR group (P hCG group produced more quadruplets (P hCG group (3.6%) was less than that in control (11.8%; P  0.05) groups. Post-mating administration of hCG or CIDR did not affect the lamb birth weight in single and quadruplet births (P > 0.05), but the birth weight of twin lambs was higher in the hCG and CIDR groups (P hCG and CIDR groups (P hCG/CIDR administration post-mating increased the maternal P 4 concentrations and enhanced reproductive performance.

  14. Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.

    Science.gov (United States)

    Chowdhury, Kaushik; Kumar, Suresh; Sharma, Tanu; Sharma, Ankit; Bhagat, Meenakshi; Kamai, Asangla; Ford, Bridget M; Asthana, Shailendra; Mandal, Chandi C

    2018-01-10

    Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing

  15. [Contact hypersensitivity to Kathon CG. Apropos of 35 cases among 977 tested subjects].

    Science.gov (United States)

    Ledieu, G; Martin, P; Thomas, P

    1991-01-01

    Kathon CG (Rohm and Haas) is a mixture of two isothiazolinones: chloromethylisothiazolinone and methylisothiazolinone. It is widely used in aqueous solution as antimicrobial agent in cosmetics (CG means cosmetic grade) instead of parabens. Routine testing is effected with Kathon CG in aqueous solution at 100 ppm (Trolab) in finn chamber tests on scanpor (ICDRG directives). Between September 1987 and September 1989, 977 patients (538 women, 439 men) referred for suspected contact allergy were tested. Thirty-five patients (77 p. 100 of whom were young women) with a history of allergy to cosmetics were found to be positive. Face, hands or both were involved in 15, 7 and 9 cases respectively, and a lupus-like reaction was observed in one patient. Our results (frequency: 3.6 p. 100) were compared with previously published results ranging from 0.67 p. 100 to 16.1 p. 100 (tables IV and V). Such wide variations can be explained by different selections of patients, different uses of cosmetics and lack of standardization in testing. Patch tests were strongly positive (quoted + +) in all cases. None of the irritant effects previously reported (3, 8, 28) was detected. In a control study carried out two months later, diluted patch tests (100, 50, 25, 15 and 7.5 ppm) were performed in 15 patients and were positive in 11 of them: 5 at 25 ppm, 1 at 15 ppm and 5 only at 100 ppm. Contrary to previous suggestions (7, 28, 36), there was no correlation between allergenic potential and minimal concentration, so that the "no response concentration" concept could not be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Prediction of late failure after medical abortion from serial beta-hCG measurements and ultrasonography

    DEFF Research Database (Denmark)

    Rørbye, C; Nørgaard, M; Nilas, Lisbeth

    2004-01-01

    BACKGROUND: Surgical treatment of failed medical abortion may be performed several weeks after initiation of the abortion. There are no recognized methods for early identification of these late failures. We assessed the prognostic values of beta-hCG and ultrasonography in predicting late failure...... after medical abortion. METHODS: A total of 694 consecutive women with gestational age (GA) abortion with mifepristone and gemeprost. Measurement of the endometrial...... thickness by ultrasonography was performed on day 15 after induction of medical abortion. Failures diagnosed after day 15 and within 15 weeks were identified and classified as late failures. All interventions in this group were due to bleeding problems. The predictive values of different absolute...

  17. Reproductive performance of lactating dairy cows after inducing ovulation using hCG in a five-day progesterone-based fixed-time AI protocol.

    Science.gov (United States)

    Garcia-Ispierto, I; De Rensis, F; Casas, X; Caballero, F; Mur-Novales, R; López-Gatius, F

    2018-02-01

    This study compares the effects of inducing ovulation using human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) at the end of a 5-day progesterone(P4)-based protocol for fixed-time artificial insemination (FTAI) in lactating dairy cows on ovarian dynamics and fertility. A P4 intravaginal device (PRID) was fitted for five days and GnRH administered upon PRID insertion and a double dose (24 h apart) of prostaglandin F 2α upon PRID removal. Cows received either GnRH (GnRH group; n = 98), 1000 IU hCG (hCG-1 group; n = 97), or 3000 IU hCG (hCG-2 group; n = 104) 36 h after PRID removal and were inseminated 50-56 h after PRID removal. Based on Tukey-Kramer tests, cows in hCG-1 and hCG-2 showed a larger follicle diameter at AI than cows in GnRH (P HCG-2 treatment increased corpus luteum (CL) size on Day 7 post-AI compared with the GnRH and hCG-1 treatments (P hCG-1 or hCG-2 that did not become pregnant were more likely to return to estrus than cows in GnRH (P hCG-2 treatment showed a 1.9-fold cumulative pregnancy rate after two rounds of AI compared to cows receiving GnRH. Our results indicate that hCG treatment hCG treatment used to induce ovulation at the end of a short protocol for FTAI improves follicular/luteal dynamics compared to GnRH treatment. Of the two hCG treatments tested, better results were obtained with the 3000 IU dose. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    International Nuclear Information System (INIS)

    Liu, Xin; Zhu, Yanming; Zhai, Hong; Cai, Hua; Ji, Wei; Luo, Xiao; Li, Jing; Bai, Xi

    2012-01-01

    Highlights: ► AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. ► AtPP2CG1 up-regulates the expression of marker genes in different pathways. ► AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2–3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter–GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  19. How alternative are alternative fuels?

    OpenAIRE

    Soffritti, Tiziana; Danielis, Romeo

    1998-01-01

    Could alternative fuel vehicles contribute to a substantial reduction of air pollution? Is there a market for alternative fuel vehicles? Could a market be created via a pollution tax? The article answers these questions on the basis of the available estimates.

  20. A single, low dose oral antigen exposure in newborn piglets primes mucosal immunity if administered with CpG oligodeoxynucleotides and polyphosphazene adjuvants.

    Science.gov (United States)

    Pasternak, J Alex; Ng, Siew Hon; Wilson, Heather L

    2014-10-15

    By definition, soluble antigens ingested orally trigger mucosal tolerance such that any subsequent re-exposure by a systemic route results in suppression of immunity. We propose that antigens introduced in extreme early life can readily traverse the gut wall and therefore circumvent induction of mucosal tolerance and instead induce immunity. Piglets were drenched with low-doses of ovalbumin (OVA; 5mg or 0.05 mg) alone, OVA plus adjuvants (CpG oligodeoxynucleotides and PCEP polyphosphazene) or saline within 6h of birth. At 28 days of age, they were administered 10mg OVA plus 1:1 Montanide adjuvant (or saline) via the intraperitoneal (i.p.) route or via the oral route. Serum was obtained on day 28 and day 49 to measure OVA-specific antibodies titres. All piglets boosted orally with OVA plus Montanide, regardless of prior OVA exposure, failed to induce immunity. As expected, piglets drenched with saline but boosted via the i.p. route with OVA plus Montanide showed significant induction of anti-OVA IgA, IgG, IgG1 and IgG2 relative to saline control piglets. Newborn animals drenched with 5mg or 0.05 mg OVA failed to induce oral immunity. A second intramuscular injection in adulthood triggered immunity in the piglets that were drenched with 0.05 mg OVA and boosted initially by the i.p. route suggesting that some systemic lymphocytes were primed despite initial lack of induction of humoral immunity. In contrast, piglets orally immunized with 5mg or 0.05 mg OVA plus adjuvants resulted in significant induction of anti-OVA IgA (5mg only), IgM, IgG, IgG1 and IgG2 in serum relative to saline control piglets as well as significant induction of anti-OVA IgA, IgM (5mg only) IgG, IgG1 (5mg only) or IgG2 relative to piglets drenched with OVA alone. These data clearly show that the response was sensitive to the oral vaccine components and was not simply a response to the i.p. immunization at day 28. This work demonstrates that newborn piglets respond to oral antigens with immunity

  1. [Immunostimulatory CpG oligodeoxynucleotides (CpG-ODN) in an orthotopic murine transitional cell carcinoma (TCC) model. Effect on local cytokine expression].

    Science.gov (United States)

    Olbert, P J; Schrader, A J; Hofmann, R; Hegele, A

    2008-09-01

    CpG-oligodeoxynucleotides (CpG-ODN) are potent stimulators of the innate immune system. They promote a Th1-biased immune response with antineoplastic potential. We recently demonstrated antitumoral effects of CpG-ODN in murine transitional cell carcinoma (TCC) models. The purpose of the present work was to more precisely define the immunological nature of this immunotherapeutic approach to TCC.MB-49 TCC was established in female C57/Bl6 mice by intravesical tumor cell instillation after poly-L-lysine conditioning of the bladder (day 0) as described previously. Three groups of six mice were treated: intravesical instillation of 50 microl PBS on days 1, 3, 5, and 7 (group 1, untreated control); 10 nmol CpG 1668 on days 1, 3, 5, and 7 (group 2); and 10 nmol GpC 1668 on days 1, 3, 5, and 7 (group 3). Six native bladders served as no-treatment/no-tumor controls (group 4). Mice were sacrificed on day 11; bladders and draining lymph nodes were removed, and mRNA was prepared for quantitative real-time polymerase chain reaction. Samples were analyzed on a Bio-Rad iCycler for IL 10, TGF-beta, IL 12, and IFNgamma expression; threshold values were compared to beta-actin as housekeeping gene.Tumor take was 100%. Three animals in group 1 had to be sacrificed in advance due to rapid tumor progression. Relative cytokine expression was comparable in groups 1 and 4. IL-10, IL-12, TGF-beta, and IFNgamma were overexpressed in groups 2 and 3. CpG-ODN treatment of murine TCC results in overexpression of both classic Th1 cytokines (IL 12 and IFNgamma) and the Th2 marker IL 10. TGF-beta expression is increased as well. These phenomena are not induced by the growing TCC but by CpG-ODN therapy. They are accompanied by an objective clinical response, as we were able to show recently. Immunostimulatory DNA holds promise to be a novel therapeutic agent in TCC.

  2. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

    Directory of Open Access Journals (Sweden)

    Wang Yu-Zhu

    2009-08-01

    Full Text Available Abstract To determine if nuclear factor-κB (NF-κB activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs, and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-κB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC-labeled NF-κB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-κB and activator protein 1(AP-1 activity was detected by the electrophoretic motility shift assay (EMSA. Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA in bronchoalveolar lavage fluid (BALF and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 ± 3.30%. Analysis of respiratory function indicated that transfection of NF-κB decoy ODNs significantly impacted peak expiratory flow (PEF, and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-κB decoy ODNs smoke exposed mice. NF-κB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP 1α and monocyte chemoattractant protein 1(MCP-1 in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-κB decoy ODNs-treated mice showed significant increase in the

  3. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice.

    Science.gov (United States)

    Li, Yu-Tao; He, Bei; Wang, Yu-Zhu; Wang, Jing

    2009-08-25

    To determine if nuclear factor-kappaB (NF-kappaB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-kappaB can be blocked by intratracheal administration of NF-kappaB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-kappaB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-kappaB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-kappaB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-kappaB and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 +/- 3.30%. Analysis of respiratory function indicated that transfection of NF-kappaB decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-kappaB decoy ODNs smoke exposed mice. NF-kappaB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1alpha and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-kappaB decoy ODNs-treated mice showed

  4. TLR9 ligand (CpG oligodeoxynucleotide induces CLL B-cells to differentiate into CD20+ antibody-secreting cells

    Directory of Open Access Journals (Sweden)

    Hussein eGhamlouch

    2014-06-01

    Full Text Available B-cell chronic lymphocytic leukemia (CLL is the most frequent adult leukemia in the Western world. It is a heterogeneous disease characterized by clonal proliferation and the accumulation of CD5+ mature B lymphocytes. However, the normal counterpart from which the latter cells arise has not yet been identified. CD27 expression and gene expression profiling data suggest that CLL cells are related to memory B-cells. In vitro, memory B-cells differentiate into plasma cells when stimulated with CpG oligodeoxynucleotide (CpG. The objective of the present study was therefore to investigate the ability of CpG, in the context of CD40 ligation, to induce the differentiation of CLL B-cells into antibody-secreting cells (ASCs. CD20+CD38− CLL B-cells were stimulated with a combination of CpG, CD40 ligand and cytokines (CpG/CD40L/c in a two-step, seven-day culture system. We found that the CpG/CD40L/c culture system prompted CLL B-cells to differentiate into CD19+CD20+CD27+CD38- ASCs. These cells secreted large amounts of IgM and had the same shape as plasma cells. However, only IgMs secreted by ASCs that had differentiated from unmutated CLL B-cells were poly/autoreactive. Class-switch recombination to IgG and IgA was detected in cells expressing the activation-induced cytidine deaminase gene (AICDA. Although these ASCs expressed high levels of the transcription factors PRDM1 (BLIMP1, IRF4 and XBP1s, they did not downregulate expression of PAX5. Our results suggest that CLL B-cells can differentiate into ASCs, undergo class-switch recombination and produce poly/autoreactive antibodies. Furthermore, our findings may be relevant for (i identifying the normal counterpart of CLL B-cells and (ii developing novel treatment strategies in CLL.

  5. Different processing of LH/hCG receptors in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1)

    International Nuclear Information System (INIS)

    Kellokumpu, S.

    1987-01-01

    The metabolic fate of LH/hCG receptors after exposure to human chorionic gonadotropin (hCG) was examined in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1). Kinetic studies performed after pulse-labelling of the cells with [ 125 I]hCG indicated that the bound hormone was lost much more rapidly from the tumor cells than from the luteal cells. The tumor cells were also found to internalize and degrade the hormone more effectively than the luteal cells. Chemical cross-linking and analyses by SDS-PAGE of this material revealed that both cell types also released, in addition to intact hCG, two previously characterized receptor fragment-[ 125 I]hCG complexes (M/sub r/ 96,000 and 74,000) into the medium, although their amount was negligible in MLTC-1 cells. Possibly due to rapid discharge of the ligand from its receptor, no similar complexes could be detected inside the MLTC-1 cells, suggesting that they were released directly from the cell surface. However, the M/sub r/ 74,000 complex was observed inside MLTC-1 cells if chloroquine, a lysosomotropic agent, was present during the incubations. This suggests that the internalized receptor also becomes degraded, at least when complexed to hCG. The results thus provide evidence that there exist two different mechanisms for proteolytic processing of LH/hCG receptors in these target cells. In tumor cells, the degradation seems to occur almost exclusively intracellularly, whereas in luteal cells a substantial portion of the receptors is also degraded at the cell surface

  6. Proteomic Profiling of β-hCG-Induced Spheres in BRCA1 Defective Triple Negative Breast Cancer Cells.

    Science.gov (United States)

    Sengodan, Satheesh Kumar; Rajan, Arathi; Hemalatha, Sreelatha Krishnakumar; Nadhan, Revathy; Jaleel, Abdul; Srinivas, Priya

    2018-01-05

    Previously, we identified that β-hCG is expressed by BRCA1 mutated but not wild type breast cancers in vitro/in vivo and exhibited a novel event in β-hCG overexpressing BRCA1 mutated HCC1937 cells where the cells were able to form spheres (HCC1937 β spheres) in adherent cell culture plates even in the absence of any growth factors. These spheres express stem cell and EMT markers. In the present study, we carried out the total proteomic profiling of these HCC1937 β spheres obtained from BRCA1 defective β-hCG expressing stable breast cancer cells to analyze the cell signaling pathways that are active in these cells. Functional annotation revealed proteins (164 cellular and 97 secretory) predominantly involved in oxygen binding, nucleosome assembly, cytoskeleton organization, protein folding, etc. Many of the proteins identified from HCC1937 β spheres in this study are also up regulated in breast cancers, which are directly linked with poor prognosis in human cancer samples as analyzed using TCGA data set. Survival analysis shows that β-hCG expressing cancer patients are linked with poor survival rate. Interestingly, hemoglobins were identified at both cellular and secretory level in HCC1937 β spheres and experiments after treating with ROS inducers revealed that β-hCG induces hemoglobin and protects the cancer cells during oxidative stress. Our proteomic data strongly propose β-hCG as an oncogenic molecule associated with BRCA1 mutation, and hence, targeting β-hCG could be a strategy to treat BRCA1 defective breast cancers.

  7. Effect of kisspeptin-10, LH and hCG on serum testosterone concentrations in stallions, donkeys and mules.

    Science.gov (United States)

    Akhtar, Rana Waseem; Shah, Syed Aftab Hussain; Qureshi, Irfan Zia

    2017-10-15

    This study was conducted to determine the response of serum testosterone (T) in male equines (stallions, donkeys and mules) after administering intravenous doses of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing hormone (LH) and saline as a control. The animals were divided into four groups of three each: Group I, 3 ml of 0.95% saline; Group II, 50 μg KP-10; Group III, 2500 IU hCG and group IV, 400 μg LH. The administration of KP-10 and hCG to stallions resulted in a significant increase in serum T concentration at 240 min; whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was significantly higher at 60, 120, and 240 min with LH treatment as compared to pre-dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as compared to the control and hCG concentrations. After 120 and 240 min, T concentrations in mules were higher (p hCG and LH as compared to the control. In conclusion, the administration of KP-10, hCG and LH elevate the serum T concentration in normal male equines. It is suggested that KP-10 may be useful in situations where an increase in T is desired. Further work is required to determine the effect of KP-10 on T in male equids with reproductive abnormalities before it can be used in clinical situations. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Viewing MORSE-CG radiation transport with 3-D color graphics

    International Nuclear Information System (INIS)

    Namito, Yoshihito; Jenkins, T.M.; Nelson, W.R.

    1990-01-01

    In this paper we present the coupling of MORSE-CG with the SLAC Unified Graphics System (UGS77) through an add-on package called MORSGRAF which allows for real-time display of neutron and photon tracks in the Monte Carlo simulation. In addition to displaying the myriad of complicated geometries that can be created with the MORSE Combinatorial Geometry program, MORSGRAF permits color tagging of neutrons (green) and photons (red) with the variation of track intensity an indicator of the energy of the particle. Particle types can be switched off and on by means of a mouse-icon system, and the perspective can be changed (i.e., rotated, translated, and zoomed). MORSGRAF also allows one to display the propagation of radiation through shields and mazes on an ordinary graphics terminal, as well as in documents printed on a laser printer. Several examples will be given to demonstrate the various capabilities of MORSGRAF coupled to MORSE-CG. 12 refs., 8 figs

  9. Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

    Science.gov (United States)

    Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

    2016-09-01

    To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen

  10. Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease.

    Science.gov (United States)

    González Aguilera, B; Syrios, P; Gadisseur, R; Luyckx, F; Cavalier, E; Beckers, A; Valdes-Socin, H

    2016-06-01

    Phantom hCG refers to persistent mild elevations of hCG, leading physicians to unnecessary treatments whereas neither a true hCG nor a trophoblastic disease is present. We report the case of a 23-year-old woman with persistent low levels of serum hCG detected one month after miscarriage. As choriocarcinoma was suspected, a chemotherapy trial of methotrexate was prescribed, without any hCG reduction. Subsequently, laparoscopy ruled out a trophoblastic residue and the patient was referred to the Endocrine Unit for further investigations. While low levels of hCG were still detected in serum, no hCG was detected in the urine. In addition, when serum was processed in a HBT tube for revealing heterophilic antibodies, hCG was no longer detected. Such finding indicated the presence of phantom hCG due to heterophilic mouse antibodies interaction. This case raises the need of clinico-biological discussion to avoid inappropriate therapeutic decisions. Based on this case experience and after review of the literature, we suggest that current gynecological protocols for the diagnosis and treatment of trophoblastic disease should consider the inclusion of urinary hCG and/or a test for serum heterophilic antibodies when appropriate.

  11. Analysis of human chorionic gonadotropin (hCG): application of routine immunological methods for initial testing and confirmation analysis in doping control.

    Science.gov (United States)

    Kuuranne, Tiia; Ahola, Liisa; Pussinen, Christel; Leinonen, Antti

    2013-08-01

    Human chorionic gonadotropin (hCG) is dimeric glycoprotein produced by placenta in pregnancy and also in low levels by pituitary gland. The main clinical use for exogenous hCG-administration is typically linked to infertility. The desired effect of hCG misuse in sport is due to the enhancement of testicular production of testosterone. Therefore, hCG is listed by the World Anti-Doping Agency (WADA) as a prohibited substance in male athletes and according to the recently published WADA guideline urinary concentrations of hCG > 5 IU/L may be an indicator of doping. In this study two independent immunoassays were used to implement the new WADA guideline. The assay for initial testing (Siemens Immulite 2000 XPi hCG assay) recognizes various hCG variants (e.g. hCG and β-core fragment of hCG) whereas the confirmatory assay (PerkinElmer DELFIA Xpress hCG) is sensitive to intact and nicked hCG only. Both assays showed adequate sensitivity and were proven fit-for-purpose in routine doping control. Population-based distribution of the assays was in good agreement with results of earlier studies and supported well the current threshold of 5 IU/L. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

    Science.gov (United States)

    Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

    2015-01-01

    Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

  13. Modulation of rat testes lipid composition by hormones: Effect of PRL [prolactin] and hCG [human chorionic gonadotropin

    International Nuclear Information System (INIS)

    Sebokova, E.; Wierzbicki, A.; Clandinin, M.T.

    1988-01-01

    The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for 125 I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3',5'-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptor but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions

  14. Induction of ovulation in quarter horse mares through the use of deslorelin acetate and human chorionic gonadotrophin (hCG

    Directory of Open Access Journals (Sweden)

    Tatiana Figueiredo

    2011-06-01

    Full Text Available The aim this study was to compare two protocols of induction for ovulation by desloreline acetate and hCG in Quarter Horse mares. The choice of the animals was based on the observations by the estrus, by rectal palpation of the ovaries and by ultrassonography of the follicular dynamics. After estrus detection and follicle control, the measurement of the follicles and the classification of uterus were carried out. The animals that had dominant follicle (diameter more than 35 mm and swollen uterus were used. In these conditions, the mares received hCG or desloreline acetate. Once ovulation occurred, the artificial insemination was carried. Two groups were performed: G1 (20 animals received 1.5 mg desloreline acetate and G2 (20 animals received 1700 IU of hCG. Following 6h intervals, the control follicular was performed by ultrasonography. The follicular average diameter was 42.6 cm for the groups and set up a score of 0 to 3 of uterine edema displayed by the device as well as the time of ovulation. In conclusion, the desloreline acetate showed better performance than hCG, because the ovulation was induced in less time (nine hours than hCG (p<0.05.The pregnancy rate was 80 and 75 %, respectively in G1 and G2.

  15. Extending the eigCG algorithm to nonsymmetric Lanczos for linear systems with multiple right-hand sides

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Rehim, A M; Stathopoulos, Andreas; Orginos, Kostas

    2014-08-01

    The technique that was used to build the EigCG algorithm for sparse symmetric linear systems is extended to the nonsymmetric case using the BiCG algorithm. We show that, similarly to the symmetric case, we can build an algorithm that is capable of computing a few smallest magnitude eigenvalues and their corresponding left and right eigenvectors of a nonsymmetric matrix using only a small window of the BiCG residuals while simultaneously solving a linear system with that matrix. For a system with multiple right-hand sides, we give an algorithm that computes incrementally more eigenvalues while solving the first few systems and then uses the computed eigenvectors to deflate BiCGStab for the remaining systems. Our experiments on various test problems, including Lattice QCD, show the remarkable ability of EigBiCG to compute spectral approximations with accuracy comparable to that of the unrestarted, nonsymmetric Lanczos. Furthermore, our incremental EigBiCG followed by appropriately restarted and deflated BiCGStab provides a competitive method for systems with multiple right-hand sides.

  16. 76 FR 5319 - Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline

    Science.gov (United States)

    2011-01-31

    ... producing gasoline are required to test Reformulated Gasoline (RFG), and conventional gasoline (CG) for... Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline AGENCY: Environmental... gasoline. This proposed rule will provide flexibility to the regulated community by allowing an additional...

  17. 76 FR 65382 - Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline

    Science.gov (United States)

    2011-10-21

    ... blenders producing gasoline are required to test Reformulated Gasoline (RFG), and conventional gasoline (CG... Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline AGENCY: Environmental... gasoline. This final rule will provide flexibility to the regulated community by allowing an additional...

  18. Rhipicephalus (Boophilus microplus: expression and characterization of Bm86-CG in Pichia pastoris Rhipicephalus (Boophilus microplus: expressão e caracterização da Bm86-CG em Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Rodrigo Casquero Cunha

    2011-06-01

    Full Text Available The cattle tick Rhipicephalus (Boophilus microplus is responsible for great economic losses. It is mainly controlled chemically, with limitations regarding development of resistance to the chemicals. Vaccines may help control this parasite, thereby reducing tick pesticide use. In this light, we performed subcloning of the gene of the protein Bm86-GC, the homologue protein that currently forms the basis of vaccines (GavacTM and TickGardPLUS that have been developed against cattle ticks. The subcloning was done in the pPIC9 expression vector, for transformation in the yeast Pichia pastoris. This protein was characterized by expression of the recombinant Mut+ strain, which expressed greater quantities of protein. The expressed protein (rBm86-CG was recognized in the Western-blot assay using anti-Gavac, anti-TickGard, anti-larval extract and anti-rBm86-CG polyclonal sera. The serum produced in cattle vaccinated with the antigen CG rBm86 presented high antibody titers and recognized the native protein. The rBm86-GC has potential relevance as an immunogen for vaccine formulation against cattle ticks.O carrapato-do-boi Rhipicephalus (Boophilus microplus é responsável por grandes perdas econômicas. Seu controle é principalmente químico e apresenta limitações quanto ao desenvolvimento de resistência aos princípios ativos. As vacinas podem auxiliar no controle deste parasita diminuindo as aplicações de carrapaticidas. Considerando isso, foi realizada a subclonagem do gene da proteína Bm86-CG, proteína homologa a que atualmente é a base das vacinas desenvolvidas (GavacTM e TickGardPLUS contra o carrapato-do-boi, no vetor de expressão pPIC9, para ser transformado em levedura, Pichia pastoris. Esta proteína foi caracterizada pela expressão da cepa recombinante Mut+ que expressou maior quantidade de proteína. A proteína expressa, rBm86-CG, foi reconhecida no ensaio de Western-blot pelos soros policlonais anti-Gavac, anti-TickGard, anti

  19. A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

    DEFF Research Database (Denmark)

    Loft, A; Egeberg, Anne Noes; Smitz, J

    2012-01-01

    Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses...... of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity...... low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF....

  20. A Live Birth Subsequent to IVF following Egg Retrieval Only 12 Hours after hCG Priming

    Directory of Open Access Journals (Sweden)

    Limor Man

    2013-01-01

    Full Text Available Introduction. To report a live birth following egg retrieval after only 12 hours from hCG priming. Patients. A childless couple with five-years-lasting secondary infertility. Methods. IVF was performed according to the long protocol. Two immature oocytes were retrieved following only 12 hours after hCG priming due to the patient misunderstanding. The eggs were cultured in vitro and ICSI was performed following polar body extruded after 24 hours in culture. After additional 24 hours a 4-cell embryo was developed and ET was performed. Results. A viable pregnancy was achieved and a healthy baby girl was delivered at 38 weeks of gestation. Conclusion. In a rare and unexpected situation when immature oocytes are retrieved following a short hCG priming, the eggs should be cultured in vitro, late ICSI should be performed, and a pregnancy may be expected.

  1. An Efficient Algorithm for EM Scattering from Anatomically Realistic Human Head Model Using Parallel CG-FFT Method

    Directory of Open Access Journals (Sweden)

    Lei Zhao

    2014-01-01

    Full Text Available An efficient algorithm is proposed to analyze the electromagnetic scattering problem from a high resolution head model with pixel data format. The algorithm is based on parallel technique and the conjugate gradient (CG method combined with the fast Fourier transform (FFT. Using the parallel CG-FFT method, the proposed algorithm is very efficient and can solve very electrically large-scale problems which cannot be solved using the conventional CG-FFT method in a personal computer. The accuracy of the proposed algorithm is verified by comparing numerical results with analytical Mie-series solutions for dielectric spheres. Numerical experiments have demonstrated that the proposed method has good performance on parallel efficiency.

  2. Alternative Therapies

    Science.gov (United States)

    ... the widespread and erroneous belief that they are natural and do no harm, and because their use offers the opportunity for more control over treatment options and procedures. Alternative therapies can reduce stress, pain, and/or fatigue. Some therapies are covered ...

  3. Growing Alternatives

    DEFF Research Database (Denmark)

    Bagger-Petersen, Mai Corlin

    2014-01-01

    From 2014, Anhui Province will pilot a reform of the residential land market in China, thus integrating rural Anhui in the national housing market. In contrast, artist and activist Ou Ning has proposed the Bishan time money currency, intending to establish an alternative economic circuit in Bishan...

  4. Magnetostrictive Alternator

    Science.gov (United States)

    Dyson, Rodger; Bruder, Geoffrey

    2013-01-01

    This innovation replaces the linear alternator presently used in Stirling engines with a continuous-gradient, impedance-matched, oscillating magnetostrictive transducer that eliminates all moving parts via compression, maintains high efficiency, costs less to manufacture, reduces mass, and eliminates the need for a bearing system. The key components of this new technology are the use of stacked magnetostrictive materials, such as Terfenol-D, under a biased magnetic and stress-induced compression, continuous-gradient impedance-matching material, coils, force-focusing metallic structure, and supports. The acoustic energy from the engine travels through an impedancematching layer that is physically connected to the magnetostrictive mass. Compression bolts keep the structure under compressive strain, allowing for the micron-scale compression of the magnetostrictive material and eliminating the need for bearings. The relatively large millimeter displacement of the pressure side of the impedance-matching material is reduced to micron motion, and undergoes stress amplification at the magnetostrictive interface. The alternating compression and expansion of the magnetostrictive material creates an alternating magnetic field that then induces an electric current in a coil that is wound around the stack. This produces electrical power from the acoustic pressure wave and, if the resonant frequency is tuned to match the engine, can replace the linear alternator that is commonly used.

  5. The Drosophila gene CG9918 codes for a pyrokinin-1 receptor

    DEFF Research Database (Denmark)

    Cazzamali, Giuseppe; Torp, Malene; Hauser, Frank

    2005-01-01

    The database from the Drosophila Genome Project contains a gene, CG9918, annotated to code for a G protein-coupled receptor. We cloned the cDNA of this gene and functionally expressed it in Chinese hamster ovary cells. We tested a library of about 25 Drosophila and other insect neuropeptides......, and seven insect biogenic amines on the expressed receptor and found that it was activated by low concentrations of the Drosophila neuropeptide, pyrokinin-1 (TGPSASSGLWFGPRLamide; EC50, 5 x 10(-8) M). The receptor was also activated by other Drosophila neuropeptides, terminating with the sequence PRLamide...... (Hug-gamma, ecdysis-triggering-hormone-1, pyrokinin-2), but in these cases about six to eight times higher concentrations were needed. The receptor was not activated by Drosophila neuropeptides, containing a C-terminal PRIamide sequence (such as ecdysis-triggering-hormone-2), or PRVamide (such as capa...

  6. The Role of Serum Beta hCG in Early Diagnosis and Management Strategy of Ectopic Pregnancy.

    Science.gov (United States)

    Surampudi, Kameswari; Gundabattula, Sirisha Rao

    2016-07-01

    The presentation of Ectopic Pregnancy (EP) can be highly variable and serum Beta hCG estimation plays an important role in early diagnosis. Aim of the study was to determine the trends of hCG levels in EP and to explore the role of hCG in decisions related to management and follow-up of EPs. A retrospective study of women who had EPs from January 2006 to December 2012 at an advanced tertiary care centre in southern India was carried out. These women had undergone treatment based on the hospital protocol. The study identified 337 women with EP. Thirty one surgically confirmed cases were diagnosed below the discriminatory zone of 1500 mIU/ml. Among women who had Beta hCG estimations 48 hours apart, plateauing was observed in 22.5% while decrease >15% was noted in 26.8%. Almost half (47.9%) of the cases had an increase >15% and a few (2.8%) demonstrated an initial fall followed by a rise in titres. In 23.9% of these women, there was a rise >53% similar to intrauterine pregnancy. The average pre-treatment Beta hCG was 429.8, 3866.2 and 12961.5 mIU/ml for those who received expectant, medical and direct surgical treatment respectively. 43 women with relative contraindications received medical management and 39 were lost to follow-up after medical and expectant management. Excluding them, the success rate of these two modalities was 76.6% and 85.0% respectively. No single level of Beta hCG is diagnostic of EP and serial levels can demonstrate atypical trends in some cases. Hence, interpretation of these results should be done in conjunction with clinical and sonographic findings to arrive at a correct diagnosis.

  7. Binding and internalization in vivo of [125I]hCG in Leydig cells of the rat

    International Nuclear Information System (INIS)

    Hermo, L.; Lalli, M.

    1988-01-01

    The present study was performed to demonstrate the binding, mode of uptake, pathway and fate of iodinated human chorionic gonadotropin ([ 125 I]hCG) by Leydig cells in vivo using electron microscope radioautography. Following a single injection of [ 125 I]hCG into the interstitial space of the testis, the animals were fixed by perfusion with glutaraldehyde at 20 minutes, 1, 3, 6 and 24 hours. The electron microscope radioautographs demonstrated a prominent and qualitatively similar binding of the labeled hCG on the microvillar processes of the Leydig cells at 20 minutes, 1, 3, and 6 hours. The specificity of the [ 125 I]hCG binding was determined by injecting a 100-fold excess of unlabeled hormone concurrently with the labeled hormone. Under these conditions, the surface, including the microvillar processes of Leydig cells, was virtually unlabeled, indicating that the binding was specific and receptor-mediated. In animals injected with labeled hCG and sacrificed 20 minutes later, silver grains were also seen overlying the limiting membrane of large, uncoated surface invaginations and large subsurface vacuoles with an electron-lucent content referred to as endosomes. A radioautographic reaction was also seen within multivesicular bodies with a pale stained matrix. At 1 hour, silver grains appeared over dense multivesicular bodies and occasionally over secondary lysosomes, in addition to the structures mentioned above, while at 3 and 6 hours, an increasing number of secondary lysosomes became labeled. At 24 hours, binding of [ 125 I]hCG to the microvillar processes of Leydig cells persisted but was diminished, although a few endosomes, multivesicular bodies and secondary lysosomes still showed a radioautographic reaction. No membranous tubules that were seen in close proximity to, or in continuity with, endosomes and multivesicular bodies were observed to be labeled at any time interval

  8. Association of ß-hCG Surveillance with Emotional, Reproductive, and Sexual Health in Women Treated for Gestational Trophoblastic Neoplasia.

    Science.gov (United States)

    Jewell, Elizabeth L; Aghajanian, Carol; Montovano, Margaret; Lewin, Sharyn N; Baser, Raymond E; Carter, Jeanne

    2018-03-01

    To assess the emotional, reproductive, sexual health, and relationship concerns of women treated for gestational trophoblastic neoplasia (GTN) and examine associations with ß-hCG surveillance. This institutional review board approved study surveyed GTN survivors (n = 51) who received treatment from 1996 to 2008. Fifty-one women, including those actively followed or formerly treated, were surveyed. The survey consisted of background/medical information, the Reproductive Concerns Scale, the Female Sexual Function Index, an item from the Abbreviated Dyadic Adjustment Scale, the Center for Epidemiologic Studies-Depression scale, the Menopausal Symptom Checklist, the Impact of Life Events Scale, and exploratory items. Mean age at diagnosis was 37.1 years; 41.6 years at study enrollment. Twenty-seven patients (56%) expressed worry about treatment harm and 30 (60%) about recurrence. Twenty percent reported significant depressive symptomatology. Mild cancer-related distress, reproductive concerns, sexual dysfunction, and bothersome menopausal symptoms were noted. Nineteen patients (40%) rated their ß-hCG surveillance worry as "high." Among patients who attempted conception after treatment, 3 of 12 (25%) succeeded in the ß-hCG high-worry group versus 13 of 19 (68%) in the ß-hCG low-worry group. Survivors with high ß-hCG worry had greater reproductive concerns than those with low worry (p = 0.002) and reported less sexual desire (p = 0.025). There was no difference in the number of low-worry versus high-worry participants in active surveillance (p = 0.09). Our study suggests that cancer-specific distress, sexual health, and reproductive concerns continue to impact women years after treatment. High worry about ß-hCG surveillance is negatively associated with the emotional well-being of GTN survivors and possibly influences reproductive attempts and success.

  9. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

    Science.gov (United States)

    Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

    2017-02-01

    Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

  10. Polymorphism +17 C/G in Matrix Metalloprotease MMP8 decreases lung cancer risk

    Directory of Open Access Journals (Sweden)

    Tardón Adonina

    2008-12-01

    Full Text Available Abstract Background Matrix metalloproteases (MMPs constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer. Methods A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method. Results The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45–0.93. The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival. Conclusion This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.

  11. Successful Pregnancy Outcome in Women with Recurrent IVF Failure and Anti-hCG Autoimmunity: A Report of Three Cases

    Directory of Open Access Journals (Sweden)

    Valeria Muller

    2016-01-01

    Full Text Available We report three cases of effective management of infertility in women with a history of repeated unsuccessful IVF attempts, who have developed antibodies to hCG. A novel approach to conservative treatment of immunologic reproductive failure, suggested for selected patients, included membrane plasmapheresis, combined prednisolone, and intravenous immunoglobulin therapy. No adverse side effects were observed; all cases resulted in pregnancy and subsequent life births. In order to be given an adequate efficient treatment, women with recurrent implantation failure should be suspected for autoimmune factor of infertility and its possible association with anti-hCG autoimmunity.

  12. Demonstration of Z-d(5BrCGAT5BrCG) and B-d(CGCGATCGCG) form crystal structures in DNA-cobalt hexammine complexes by Kr 647.1 nm excitation of Raman spectra.

    Science.gov (United States)

    Benevides, J M; Wang, A H; Thomas, G J

    1993-03-25

    Cobalt hexammine [Co(NH3)6(3+)] is an efficient DNA complexing agent which significantly perturbs nucleic acid secondary structure. We have employed red excitation (647.1 nm) from a krypton laser to obtain Raman spectra of the highly colored complexes formed between cobalt hexammine and crystals of the DNA oligomers, d(5BrCGAT5BrCG) and d(CGCGATCGCG), both of which incorporate out-of-alternation pyrimidine/purine sequences. The Co(NH3)6(3+) complex of d(5BrCGAT5BrCG) exhibits a typical Z-form Raman signature, similar to that reported previously for the alternating d(CGCGCG) sequence. Comparison of the Raman bands of d(5BrCGAT5BrCG) with those of other oligonucleotide and polynucleotide structures suggests that C3'-endo/syn and C3'-endo/anti thymidines may exhibit distinctive nucleoside conformation markers, and tentative assignments are proposed. The Raman markers for C2'-endo/anti adenosine in this Z-DNA are consistent with those reported previously for B-DNA crystals containing C2'-endo/anti dA. Raman bands of the cobalt hexammine complex of d(CGCGATCGCG) are those of B-DNA, but with significant differences from the previously characterized B-DNA dodecamer, d(CGCAAATTTGCG). The observed differences suggest an unusual deoxyguanosine conformer, possibly related to a previously characterized structural intermediate in the B-->Z transition. The present results show that crystallization of d(CGCGATCGCG) in the presence of cobalt hexammine is not alone sufficient to induce the left-handed Z-DNA conformation. This investigation represents the first application of off-resonance Raman spectroscopy for characterization of highly chromophoric DNA and illustrates the feasibility of the Raman method for investigating other structurally perturbed states of DNA-cobalt hexammine complexes.

  13. Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

    Science.gov (United States)

    Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

    2017-12-01

    The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

  14. DNA adducts of acrolein: site-specific synthesis of an oligodeoxynucleotide containing 6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one, an acrolein adduct of guanine.

    Science.gov (United States)

    Nechev, Lubomir V; Kozekov, Ivan D; Brock, Angela K; Rizzo, Carmelo J; Harris, Thomas M

    2002-05-01

    3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one is formed in low yield by the reaction of acrolein with 2'-deoxyguanosine. The nucleoside and an oligodeoxynucleotide containing it have been synthesized. For preparation of the nucleoside 2'-deoxyguanosine was alkylated at the N1 position using 1-bromo-3-butene to give 1-(3-butenyl)-2'-deoxyguanosine. Oxidation with OsO(4) and N-methylmorpholine-N-oxide to give the 3,4-dihydroxybutyl adduct followed by oxidation with NaIO(4) gave the 1-(3-oxopropyl) adduct which cyclized spontaneously to yield the title compound as a rapidly epimerizing mixture of two diastereomers. Reduction of the nucleoside with NaBH(4) gave the unfunctionalized compound plus 1-(3-hydroxypropyl)-2'-deoxyguanosine showing that epimerization was occurring via both the imine and the 1-(3-oxopropyl) adduct. Reduction with NaCNBH(3) gave exclusively unfunctionalized 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one. The phosphoramidite reagent needed for preparation of oligonucleotides was prepared from 1-(3-butenyl)-2'-deoxyguanosine by glycolation after protection of the 3' and 5' hydroxyl groups as silyl derivatives. Acetylation of the vicinal hydroxyl groups and the exocyclic amino group followed by removal of silyl protection gave the protected nucleoside. Protection of the 5' hydroxyl group as the 4,4'-dimethoxytrityl ether followed by phosphitylation with 2-cyanoethyl-N,N,N',N'-tetraisopropylphosphorodiamidite gave the prosphoramidite reagent which was used to prepare a 12-mer oligodeoxynucleotide.

  15. The Association Between LH Serum Levels at the time of hCG Injection and Clinical Pregnancy during IVF

    Directory of Open Access Journals (Sweden)

    Budi Wiweko

    2015-12-01

    Full Text Available Some studies showed that recombinant follicle stimulating hormone (r-FSH administration without LH supplementation has a good success rate on in vitro fertilization (IVF. However, LH role in IVF has been controversial. This study was conducted to evaluate the association between serum LH levels at the time of hCG injection and clinical pregnancy during IVF. This retrospective study included 136 patients underwent long protocol IVF from January 2005 to December 2009 in Yasmin Clinic, Cipto Mangunkusumo Hospital, Jakarta. The controlled ovarian hyper-stimulation protocol used in this study was gonadotropin-releasing hormone (GnRH agonist and r-FSH.  Serum LH level was measured on the day of hCG administration and the outcome evaluated was the clinical pregnancy following IVF cycles. There were 32 IVF cycles resulted in pregnancy out of 136 cycles (23.5%. There was significant difference between serum LH levels on the day of hCG administration and clinical pregnancy outcome (p=0.036. LH serum level cut-off value of ≥1.050 IU/l was the best value to predict pregnancy outcome with 62.5% sensitivity, 59.4% specificity, 83.3% positive predictive value, and 32.76% negative predictive value. It was concluded that there was an association between serum LH levels at the time of hCG injection and clinical pregnancy during IVF. Keywords: IVF cycles, LH levels serum, hCG administration   Hubungan Kadar LH saat Penyuntikan hCG dengan Kejadian Kehamilan pada Fertilisasi In vitro Abstrak Pemberian follicles stimulating hormone rekombinan (r-FSH tanpa suplementasi LH memiliki tingkat keberhasilan fertilisasi in vitro (FIV yang baik namun, peran LH pada FIV masih kontroversial. Tujuan penelitian ini adalah untuk mengevaluasi hubungan antara kadar serum LH pada hari penyuntikan hCG dengan kehamilan klinis selama FIV. Penelitian retrospektif ini melibatkan 136 perempuan yang menjalani FIV siklus pertama dengan protokol panjang mulai bulan Januari 2005 sampai

  16. Diagnosis of hydatidiform mole and persistent trophoblastic disease: diagnostic accuracy of total human chorionic gonadotropin (hCG), free hCG {alpha}- and {beta}-subunits, and their ratios.

    NARCIS (Netherlands)

    Trommel, N.E. van; Sweep, C.G.J.; Schijf, C.P.T.; Massuger, L.F.A.G.; Thomas, C.M.G.

    2005-01-01

    OBJECTIVE: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Predicting PTD after molar pregnancy might be beneficial since prophylactic chemotherapy reduces the incidence of PTD. DESIGN: A retrospective study based

  17. Alternative 23

    OpenAIRE

    Jackson, Mark

    2014-01-01

    Alternative 23 is a curated exhibition of works by Steve Aylett, David Blandy & Daniel Locke, Let Me Feel Your Finger First, Laura Oldfield Ford, Plastique Fantastique and Henrik Schrat, including the first screening of Let Me Feel Your Finger First’s Postcolonial Capers.\\ud \\ud In 1985 DC Comics in the US had taken the commercial decision to unify the complex and contradictory character story arcs from its various strips such as Superman, Batman and Green Lantern. The resultant crossover ser...

  18. Ten tandem repeats of β-hCG 109-118 enhance immunogenicity and anti-tumor effects of β-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

    International Nuclear Information System (INIS)

    Zhang Yankai; Yan Rong; He Yi; Liu Wentao; Cao Rongyue; Yan Ming; Li Taiming; Liu Jingjing; Wu Jie

    2006-01-01

    The β-subunit of human chorionic gonadotropin (β-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of β-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with β-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-βhCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residue sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-βhCGCTP37 and HSP65-βhCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-βhCGCTP37 elicited much higher levels of specific anti-β-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-βhCGCTP37, which should suggest that HSP65-X10-βhCGCTP37 may be an effective protein vaccine for the treatment of β-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens

  19. An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors.

    Science.gov (United States)

    Hu, Mingming; Guan, Hongzhi; Lau, Ching C; Terashima, Keita; Jin, Zimeng; Cui, Liying; Wang, Yuzhou; Li, Guilin; Yao, Yong; Guo, Yi; Li, Yan Michael; Zhong, Dingrong; Xiao, Juan; Wan, Xirun; Lian, Xin; Feng, Feng; Ren, Haitao; Zhao, Yanhuan; Cheng, Xinqi; Gu, Feng

    2016-03-12

    Pathological examination combined with tumor markers has become a standard for the diagnosis of intracranial germ cell tumors (ICGCTs), but the current concept of 'secreting germ cell tumors' and three empirically highly specific diagnostic criteria (β-hCG ≥ 50 IU/L or αFP ≥ 10 ng/mL; β-hCG ≥ 100 IU/L or αFP ≥ 50 ng/mL; β-hCG > 50 IU/L or αFP > 25 ng/mL) are not based upon pathology examination or CSF cytology. Further investigation is needed to re-evaluate their value. A multidisciplinary diagnostic team was created. Valid β-hCG/αFP data were collected from cases of ICGCTs confirmed by pathology and CSF cytology (n = 58) between 1991 and 2012, and from suspected ICGCTs cases (n = 17) between 2011 and 2012 as controls [Langerhans cell histiocytosis (LCH), n = 12; and other intracranial tumor (ICT), n = 5]. The cut-off points for β-hCG and αFP were calculated using receiver operating characteristic (ROC) curves. This study clarifies the relative rationality of one criteria (β-hCG > 50 IU/L and αFP > 25 ng/mL); confirms new β-hCG diagnostic cut-off points: CSF β-hCG ≥ 8.2 IU/L and serum β-hCG ≥ 2.5 IU/L (sensitivity of 47 and 34%, respectively, specificity of 100%, both; P hCG exceeds 90%). Subtype diagnosis improved with αFP in 16.7% of non-geminomatous germ cell tumor cases. New evidence-based criteria of β-hCG and αFP can help improving early and formal diagnosis of ICGCTs, and is of great clinical significance.

  20. Structural Characterization of Heme Environmental Mutants of CgHmuT that Shuttles Heme Molecules to Heme Transporters

    Directory of Open Access Journals (Sweden)

    Norifumi Muraki

    2016-05-01

    Full Text Available Corynebacteria contain a heme uptake system encoded in hmuTUV genes, in which HmuT protein acts as a heme binding protein to transport heme to the cognate transporter HmuUV. The crystal structure of HmuT from Corynebacterium glutamicum (CgHmuT reveals that heme is accommodated in the central cleft with His141 and Tyr240 as the axial ligands and that Tyr240 forms a hydrogen bond with Arg242. In this work, the crystal structures of H141A, Y240A, and R242A mutants were determined to understand the role of these residues for the heme binding of CgHmuT. Overall and heme environmental structures of these mutants were similar to those of the wild type, suggesting that there is little conformational change in the heme-binding cleft during heme transport reaction with binding and the dissociation of heme. A loss of one axial ligand or the hydrogen bonding interaction with Tyr240 resulted in an increase in the redox potential of the heme for CgHmuT to be reduced by dithionite, though the wild type was not reduced under physiological conditions. These results suggest that the heme environmental structure stabilizes the ferric heme binding in CgHmuT, which will be responsible for efficient heme uptake under aerobic conditions where Corynebacteria grow.

  1. Effect of Repeated Administration of hCG on Ovarian Response in PMSG-superovulated Ouled Djellal Ewes (Algeria

    Directory of Open Access Journals (Sweden)

    Lamraoui, R.

    2014-01-01

    Full Text Available The objective of this study was to evaluate the effect of repeated administration of hCG on ovarian response in PMSG-superovulated ewes. Intravaginal pessaries containing 40 mg fluorogestone acetate (FGA were inserted in all ewes (n=9 and remained in situ for 14 days. Two days prior to pessary removal, all ewes were treated with 1000 IU of PMSG. On the day of sponge removal (day 0, the females were randomly assigned to 2 treatments. The first group (n=3 did not receive any hCG, while the second group (n=6 treated inter-muscular with hCG (500 IU during days 0-2. On day 8, laparotomy was performed to assess numbers of corpora lutea (CL and anovulatory follicles (AF. Blood samples were collected for analysis of serum progesterone (P4 using radioimmunoassay (RIA method. The results obtained for first and second group was in number of CL (6.33±1.15 and 10.50±5.54, number of AF (2 ±3.46 and 4.16±5.70, then the levels of P4 (5.75± 4.45 and 13.22±6.80 ng/ml, respectively. These results indicate that the repeated administration of hCG post-sponge removal increases number of CL and improves luteal function in ewes after PMSG-superovulatory treatment.

  2. The use of melatonin and progestagen-eCG to initiate reproductive activity in prepuberal Awassi ewe lambs.

    Science.gov (United States)

    Sawalha, Mohammad N; Kridli, Rami T; Jawasreh, Khalil I; Meza-Herrera, Cesar A

    2011-10-01

    This experiment was conducted to evaluate the effect of administering hormonal treatments (melatonin and progestagen/equine chronic gonadotropin (eCG)) on advancing puberty in Awassi ewe lambs. Fifty-one 6-month-old ewe lambs of similar body weights (around 28 kg) were randomly assigned into four treatment groups; control (CON; n = 14), melatonin (MEL; n = 13), melatonin plus progestagen-eCG (MELPP; n = 11), and progestagen-eCG (PP; n = 13). Ewe lambs in the PP and MELPP groups were fitted with intravaginal progestagen sponges containing 60 mg medroxyprogesterone acetate for 14 days; 400 IU eCG were administered to each of these ewe lambs on the day of sponge removal. Ewe lambs in the MEL and MELPP groups received subcutaneous melatonin implants (Regulin®, 18 mg melatonin) 36 days before sponge insertion. Hormonal treatment had no effect on ewe lamb body weight change. Estrous behavior was greater (p ewe lambs. The duration from ram introduction to onset of estrus was shorter (p ewe lambs. The number of ewe lambs showing luteal activity was greater (p ewe lambs in the current study either failed to cycle or stopped cycling following the induced estrus. Such failure in advancing puberty may be related to body weight of ewe lambs at the time of mating.

  3. Combination of serum hCG beta and p53 tissue expression defines distinct subgroups of serous ovarian carcinoma.

    Science.gov (United States)

    Vartiainen, Juhani; Lassus, Heini; Lehtovirta, Pentti; Finne, Patrik; Alfthan, Henrik; Butzow, Ralf; Stenman, Ulf-Håkan

    2008-05-01

    Serous ovarian carcinoma comprises a clinically heterogenous group of tumors, and molecular markers stratifying patients into clinically meaningful subgroups are needed. Numerous markers have been evaluated, but none of them has yet been routinely incorporated into clinical practice. Previously we have found that elevated serum levels of the free beta subunit of human chorionic gonadotropin (hCG beta) and aberrant p53 expression confer poor prognosis in ovarian carcinoma. The aim of our study was to evaluate their combined effect in predicting the outcome of patients with serous ovarian carcinoma. The study material consisted of 173 consecutive patients treated for primary serous ovarian carcinoma in 1 institution between 1990 and 2000. The preoperative serum level of hCG beta was analyzed by a ultrasensitive and specific immunofluorometric assay, and p53 tumor tissue expression by immunohistochemistry using a novel classification. Elevated serum hCG beta (>or=2.0 pmol/L) was detected in 57 (33%) of 173 patients, and aberrant p53 expression in 103 (62%) of 167 interpretable cancers. Elevated hCG beta and aberrant p53 expression were strongly associated with poor prognosis (p p53 expression are feasible markers that divide serous ovarian carcinomas into clinically relevant subgroups. (c) 2007 Wiley-Liss, Inc.

  4. Study on the relationship between the levels of serum cholylglycine (CG) and blood lipids in pregnant women

    International Nuclear Information System (INIS)

    You Jianfei; Lv Shiming; Wang Qiong; Zhu Yuning

    2005-01-01

    Objective: To investigate the prevalence of intrahepatic cholestasis during pregnancy and the relationship between levels of serum CG and blood lipids. Methods: Serum CG, blood lipid and liver function profile were examined in 2040 women with pregnancy during the second or third trimester. Among these pregnant women, 57 were diagnosed as with intrahepatic cholestasis. Blood lipids (TG, cholesterol, HDL, LDL) and ALP levels in 50 of the 57 pregnant women were studied and compared with those in 50 otherwise normal pregnant women as controls. Results: Serum CG levels were above normal range in 372 of the 2040 pregnant women (18.5%). Fifty seven of these 372 pregnant women were confirmed to be with intrahepatic cholestasis (2.8% of the 2040 pregnancies). The TG, cholesterol, LDL contents and ALP levels in the pregnant women with intrahepatic cholestasis were significantly higher (P 0.05) than those in controls. Conclusion: Intrahepatic cholestasis developed in a substantial proportion of pregnant women (2.8% in this study) and should be carefully monitored due to possible damage to the fetus. Serum CG was shown to be an early and sensitive marker for the diagnosis of intrahepatic cholestasis. Changes of blood lipid and ALP levels were related to disease status. (authors)

  5. Rising serum values of beta-subunit human chorionic gonadotrophin (hCG) in patients with progressive vulvar carcinomas

    NARCIS (Netherlands)

    deBruijn, HWA; tenHoor, KA; Krans, M; vanderZee, AGJ

    Elevated serum levels of the beta-subunit of human chorionic gonadotrophin (hCG) were measured in 50% of patients with locoregional recurrences or progressive Vulvar carcinoma (n = 14). At diagnosis of vulvar cancer, however, the incidence of elevated serum levels was low (5%) in 104 patients. The

  6. Clinical utility of hyperglycosylated hCG in serum taken before hydatidiform mole evacuation to predict persistent trophoblastic disease.

    NARCIS (Netherlands)

    Duc, H.N.; Trommel, N.E. van; Sweep, C.G.J.; Massuger, L.F.A.G.; Thomas, C.M.G.

    2006-01-01

    OBJECTIVE: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation

  7. Hormonal characteristics of follicular fluid from women receiving either GnRH agonist or hCG for ovulation induction

    DEFF Research Database (Denmark)

    Andersen, C Yding; Al Humaidan, Peter Samir Heskjær; Ejdrup, H Bredkjaer

    2006-01-01

    BACKGROUND: A recent prospective randomized study from our group compared GnRH agonist (0.5 mg buserelin) and hCG (10,000 IU) for triggering of ovulation following a flexible antagonist protocol. The agonist group showed a poor reproductive outcome despite luteal phase support with progesterone......-ovulatory follicular maturation resulting in oocytes with a compromised developmental competence. METHODS: Hormone concentrations were measured in two individual follicular fluid samples from each of 32 women receiving buserelin and 37 receiving hCG, thus representing a subset of the follicles retrieved. RESULTS......: Follicular fluid levels of LH in the agonist group as compared with the hCG group was 11.1 +/- 0.5 versus 3.6 +/- 0.3 IU/l (mean +/- SEM; P hCG, not determined versus 139+/-8 IU/l; E(2), 1.9 +/- 0.2 versus 1.8 +/- 0.2 micromol/l (P > 0...

  8. Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and their preference for a CG closing base pair

    Directory of Open Access Journals (Sweden)

    Kaethe N. Leonard

    2018-02-01

    Full Text Available Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo. To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair. The thermal denaturation of model hairpins containing GAAA loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG 200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic preference for a CG base pair by destabilizing the loop with a CG closing base pair relative to the loop with a GC closing base pair. This result also extended to a related DNA triloop, which provides further evidence that the interactions between the loop and closing base pair are identical for the d(GCA triloop and the GAAA tetraloop. Our results suggest that in the presence of model PEG molecules, loops with a GC closing base pair may retain some preferential interactions with the cosolutes that are lost in the presence of the CG closing base pair. These results reveal that relatively small structural changes could influence how neutral cosolutes tune the stability and function of secondary structure motifs in vivo.

  9. Evaluation of the frequency of contact allergic reactions to Kathon CG in the Maastricht area--1987-1990.

    Science.gov (United States)

    Lucker, G P; Hulsmans, R F; van der Kley, A M; van de Staak, W J

    1992-01-01

    In the period 1987-1990, 999 patients suspected of a contact allergy were patch-tested with Kathon CG 100 ppm active ingredients aq. Of these patients, 84 (8.4%) showed a positive reaction (70% females). In 62% of these cases clinical relevance was established. Most of them suffered from contact dermatitis of the face, the hands or the perianal region.

  10. The HELLP syndrome : Its association with unexplained elevation of MSAFP and MShCG in the second trimester

    NARCIS (Netherlands)

    Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

    In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the 'haemolysis, elevated liver enzymes, low platelet count' (HELLP) syndrome. The concentrations of both

  11. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation

    DEFF Research Database (Denmark)

    Humaidan, Peter; Polyzos, N P; Alsbjerg, B

    2013-01-01

    of OHSS the administration of two boluses of 1.500 IU hCG after GnRHa trigger should be avoided as it may induce OHSS. STUDY FUNDING/POTENTIAL COMPETING INTERESTS: The study was supported by a research grant by MSD, Denmark. No conflict of interest was declared. TRIAL REGISTRATION NUMBER: Project number...

  12. Suspected ectopic pregnancy: expectant management in patients with negative sonographic findings and low serum hCG concentrations

    NARCIS (Netherlands)

    Hajenius, P. J.; Mol, B. W.; Ankum, W. M.; van der Veen, F.; Bossuyt, P. M.; Lammes, F. B.

    1995-01-01

    Between July 1989 and December 1994, we performed a prospective study in 265 patients with suspected ectopic pregnancy to assess the value of expectant management in patients with negative transvaginal sonographic findings and low serum human chorionic gonadotropin (hCG) concentrations. All patients

  13. Alternative detente

    International Nuclear Information System (INIS)

    Soper, K.; Ryle, M.

    1988-01-01

    The influence of the Chernobyl accident on the disarmament and anti-nuclear movements is discussed. The accident directed attention towards the areas in common rather than the areas of disagreement. It also demonstrated the environmental impact of radioactivity, strengthening the ecological case of the anti-nuclear movement. The issues are discussed for the Western and Eastern bloc countries and the relationship between the two. Sections focus on the Eco-protest, Green politics and economics and on the politics of minority protest and the Green alternative. (U.K.)

  14. RNAi, DRD1, and histone methylation actively target developmentally important non-CG DNA methylation in arabidopsis.

    Directory of Open Access Journals (Sweden)

    Simon W-L Chan

    2006-06-01

    Full Text Available Cytosine DNA methylation protects eukaryotic genomes by silencing transposons and harmful DNAs, but also regulates gene expression during normal development. Loss of CG methylation in the Arabidopsis thaliana met1 and ddm1 mutants causes varied and stochastic developmental defects that are often inherited independently of the original met1 or ddm1 mutation. Loss of non-CG methylation in plants with combined mutations in the DRM and CMT3 genes also causes a suite of developmental defects. We show here that the pleiotropic developmental defects of drm1 drm2 cmt3 triple mutant plants are fully recessive, and unlike phenotypes caused by met1 and ddm1, are not inherited independently of the drm and cmt3 mutations. Developmental phenotypes are also reversed when drm1 drm2 cmt3 plants are transformed with DRM2 or CMT3, implying that non-CG DNA methylation is efficiently re-established by sequence-specific signals. We provide evidence that these signals include RNA silencing though the 24-nucleotide short interfering RNA (siRNA pathway as well as histone H3K9 methylation, both of which converge on the putative chromatin-remodeling protein DRD1. These signals act in at least three partially intersecting pathways that control the locus-specific patterning of non-CG methylation by the DRM2 and CMT3 methyltransferases. Our results suggest that non-CG DNA methylation that is inherited via a network of persistent targeting signals has been co-opted to regulate developmentally important genes.

  15. Alternative crops

    International Nuclear Information System (INIS)

    Andreasen, L.M.; Boon, A.D.

    1992-01-01

    Surplus cereal production in the EEC and decreasing product prices, mainly for cereals, has prompted considerable interest for new earnings in arable farming. The objective was to examine whether suggested new crops (fibre, oil, medicinal and alternative grains crops) could be considered as real alternatives. Whether a specific crop can compete economically with cereals and whether there is a market demand for the crop is analyzed. The described possibilities will result in ca. 50,000 hectares of new crops. It is expected that they would not immediately provide increased earnings, but in the long run expected price developments are more positive than for cereals. The area for new crops will not solve the current surplus cereal problem as the area used for new crops is only 3% of that used for cereals. Preconditions for many new crops is further research activities and development work as well as the establishment of processing units and organizational initiatives. Presumably, it is stated, there will then be a basis for a profitable production of new crops for some farmers. (AB) (47 refs.)

  16. Effect of GnRH and hCG on progesterone concentration and ovarian and luteal blood flow in diestrous mares.

    Science.gov (United States)

    Brito, L F C; Baldrighi, J M; Wolf, C A; Ginther, O J

    2017-01-01

    The objective of the present study was to investigate the effect of reproductive hormones (GnRH, hCG, LH and progesterone) on the regulation of corpus luteum (CL) and ovarian blood flow. Diestrous mares received a single treatment of saline, 100μg gonadorelin (GnRH), or 1500IU hCG 10days after ovulation. Plasma LH and progesterone concentrations, resistance index (RI) for ovarian artery blood-flow, and percentage of corpus luteum (CL) with color-Doppler signals of blood flow were determined immediately before treatment (hour 0) and at hours 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6. In the GnRH group, LH increased (PhCG groups. Progesterone concentration was not different among groups. In the GnRH group, RI tended (PhCG group, two transient RI decreases (PhCG group. The similarity among groups in progesterone concentration indicated that changes in progesterone were not involved in the GnRH and hCG stimulation of ovarian vascular perfusion. Effects of treatment might have been mediated through LH; however, since hCG biological activity is primarily LH-like, the differences in timing and degree of ovarian and luteal blood flow changes after GnRH or hCG administration in the present study suggest that GnRH might have a direct effect on ovarian blood vessels and vascular control. Copyright © 2016. Published by Elsevier B.V.

  17. Repeated Superovulation via PMSG/hCG Administration Induces 2-Cys Peroxiredoxins Expression and Overoxidation in the Reproductive Tracts of Female Mice.

    Science.gov (United States)

    Park, Sun-Ji; Kim, Tae-Shin; Kim, Jin-Man; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

    2015-12-01

    Superovulation induced by exogenous gonadotropin treatment (PMSG/hCG) increases the number of available oocytes in humans and animals. However, Superovulatory PMSG/hCG treatment is known to affect maternal environment, and these effects may result from PMSG/hCG treatment-induced oxidative stress. 2-Cys peroxiredoxins (2-Cys Prxs) act as antioxidant enzymes that protect cells from oxidative stress induced by various exogenous stimuli. Therefore, the objective of this study was to test the hypothesis that repeated PMSG/hCG treatment induces 2-Cys Prx expression and overoxidation in the reproductive tracts of female mice. Immunohistochemistry and western blotting analyses further demonstrated that, after PMSG/hCG treatment, the protein expression levels of 2-Cys Prxs increased most significantly in the ovaries, while that of Prx1 was most affected by PMSG/hCG stimulation in all tissues of the female reproductive tract. Repeated PMSG/hCG treatment eventually leads to 2-Cys Prxs overoxidation in all reproductive organs of female mice, and the abundance of the 2-Cys Prxs-SO2/3 proteins reported here supports the hypothesis that repeated superovulation induces strong oxidative stress and damage to the female reproductive tract. Our data suggest that excessive oxidative stress caused by repeated PMSG/hCG stimulation increases 2-Cys Prxs expression and overoxidation in the female reproductive organs. Intracellular 2-Cys Prx therefore plays an important role in maintaining the reproductive organ environment of female mice upon exogenous gonadotropin treatment.

  18. The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hCG and alpha-fetoprotein

    NARCIS (Netherlands)

    Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

    Objective: To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. Methods: The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced

  19. Leydig cell number and function in the adult cynomolgus monkey (Macaca fascicularis) is increased by daily hCG treatment but not by daily FSH treatment

    NARCIS (Netherlands)

    Teerds, K. J.; Rommerts, F. F.; van de Kant, H. J.; de rooij, D. G.

    1989-01-01

    Daily treatment of adult cynomolgus monkeys with 450 i.u. hCG for 16 days resulted in a significant 163% increase in the number of Leydig cells, and a 9-fold rise in plasma testosterone concentrations. The number of proliferating Leydig cells was very low, even after 16 days of treatment with hCG.

  20. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin, E-mail: fangfei6073@126.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn [Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin 150040 (China); Cai, Hua, E-mail: small-big@sohu.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Ji, Wei, E-mail: iwei_j@hotmail.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Luo, Xiao, E-mail: luoxiao2010@yahoo.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Li, Jing, E-mail: lijing@neau.edu.cn [Plant Secondary Metabolism Laboratory, Northeast Agricultural University, Harbin 150030 (China); Bai, Xi, E-mail: baixi@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  1. Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARalpha.

    Science.gov (United States)

    Sukhai, Mahadeo A; Wu, Xuemei; Xuan, Yali; Zhang, Tong; Reis, Patricia P; Dubé, Karina; Rego, Eduardo M; Bhaumik, Mantu; Bailey, Denis J; Wells, Richard A; Kamel-Reid, Suzanne; Pandolfi, Pier Paolo

    2004-01-22

    Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in the bone marrow (BM), and by the presence of a reciprocal chromosomal translocation involving retinoic acid receptor alpha (RARalpha). To date, five RARalpha partner genes have been identified in APL. NuMA-RARalpha was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARalpha fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARalpha), two transgenic mouse lines were generated. Transgenic mice were observed to have a genetic myeloproliferation (increased granulopoiesis in BM) at an early age, and rapidly developed a myeloproliferative disease-like myeloid leukemia. This leukemia was morphologically and immunophenotypically indistinguishable from human APL, with a penetrance of 100%. The phenotype of transgenic mice was consistent with a blockade of neutrophil differentiation. NuMA-RARalpha is therefore sufficient for disease development in this APL model.

  2. Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

    Science.gov (United States)

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Mizugaki, Asumi; Katabami, Kenichi; Maekawa, Kunihiko; Miyamoto, Daisuke; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi

    2015-04-01

    Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. CG gene body DNA methylation changes and evolution of duplicated genes in cassava.

    Science.gov (United States)

    Wang, Haifeng; Beyene, Getu; Zhai, Jixian; Feng, Suhua; Fahlgren, Noah; Taylor, Nigel J; Bart, Rebecca; Carrington, James C; Jacobsen, Steven E; Ausin, Israel

    2015-11-03

    DNA methylation is important for the regulation of gene expression and the silencing of transposons in plants. Here we present genome-wide methylation patterns at single-base pair resolution for cassava (Manihot esculenta, cultivar TME 7), a crop with a substantial impact in the agriculture of subtropical and tropical regions. On average, DNA methylation levels were higher in all three DNA sequence contexts (CG, CHG, and CHH, where H equals A, T, or C) than those of the most well-studied model plant Arabidopsis thaliana. As in other plants, DNA methylation was found both on transposons and in the transcribed regions (bodies) of many genes. Consistent with these patterns, at least one cassava gene copy of all of the known components of Arabidopsis DNA methylation pathways was identified. Methylation of LTR transposons (GYPSY and COPIA) was found to be unusually high compared with other types of transposons, suggesting that the control of the activity of these two types of transposons may be especially important. Analysis of duplicated gene pairs resulting from whole-genome duplication showed that gene body DNA methylation and gene expression levels have coevolved over short evolutionary time scales, reinforcing the positive relationship between gene body methylation and high levels of gene expression. Duplicated genes with the most divergent gene body methylation and expression patterns were found to have distinct biological functions and may have been under natural or human selection for cassava traits.

  4. Energy alternatives

    International Nuclear Information System (INIS)

    1981-01-01

    English. A special committe of the Canadian House of Commons was established on 23 May 1980 to investigate the use of alternative energy sources such as 'gasohol', liquified coal, solar energy, methanol, wind and tidal power, biomass, and propane. In its final report, the committee envisions an energy system for Canada based on hydrogen and electricity, using solar and geothermal energy for low-grade heat. The committe was not able to say which method of generating electricty would dominate in the next century, although it recommends that fossil fuels should not be used. The fission process is not specifically discussed, but the outlook for fusion was investigated, and continued governmental support of fusion research is recommended. The report proposes some improvements in governmental energy organizations and programs

  5. Multi-Sensory Approach to Search for Young Stellar Objects in CG4

    Science.gov (United States)

    Hoette, Vivian L.; Rebull, L. M.; McCarron, K.; Johnson, C. H.; Gartner, C.; VanDerMolen, J.; Gamble, L.; Matche, L.; McCartney, A.; Doering, M.; Crump, R.; Laorr, A.; Mork, K.; Steinbergs, E.; Wigley, E.; Caruso, S.; Killingstad, N.; McCanna, T.

    2011-01-01

    Individuals with disabilities - specifically individuals who are deaf or hard of hearing (DHH) and/or blind and visually-impaired (BVI) - have traditionally been underrepresented in the fields of Science, Technology, Engineering, and Math (STEM). The low incidence rate of these populations, coupled with geographic isolation, creates limited opportunities for students to work with and receive mentoring by professionals who not only have specialty knowledge in disability areas but also work in STEM fields. Yerkes Observatory scientists, along with educators from the Wisconsin School for the Deaf, the Wisconsin Center for the Blind and Visually Impaired, Breck School, and Oak Park and River Forest High School, are engaged in active research with a Spitzer Science Center (SSC) scientist. Our ultimate goals are threefold; to engage DHH and BVI students with equal success as their sighted and hearing peers, to share our techniques to make astronomy more accessible to DHH and BVI youth, and to generate a life-long interest which will lead our students to STEM careers. This poster tracks our work with an SSC scientist during the spring, summer, and fall of 2010. The group coauthored another AAS poster on finding Young Stellar Objects (YSO) in the CG4 Nebula in Puppis. During the project, the students, scientists and teachers developed a number of techniques for learning the necessary science as well as doing the required data acquisition and analysis. Collaborations were formed between students with disabilities and their non-disabled peers to create multi-media projects. Ultimately, the projects created for our work with NITARP will be disseminated through our professional connections in order to ignite a passion for astronomy in all students - with and without disabilities. This research was made possible through the NASA/IPAC Teacher Archive Research Project (NITARP) and was funded by NASA Astrophysics Data Program and Archive Outreach funds.

  6. Practice of the Education for the Principle of Otto Cycle by the E-Learning CG-Content

    Science.gov (United States)

    Sato, Tomoaki; Nagaoka, Keizo; Oguchi, Kosei

    A CG-animation content which supports the learning of the Otto cycle was developed. This content has a piston assembly and the diagrams of PV, VS, TP and TS. The each diagram has a pointer which moves along the line of the graph and they are synchronized with the movement of the piston. The learners can operate this content directly on the e-learning system. While watching the movements of the piston assembly, the learners can confirm the state of the engine about temperature, pressure, volume, and entropy by the synchronized pointer on the diagrams. This content was used for the class of the machining practice exercise. The learning effect of the content was examined by the score of the short test. As the result of this examination, the CG-animation content was effective in the learning of the Otto cycle.

  7. The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles.

    Science.gov (United States)

    Huang, Chen-Yu; Shieh, Miawh-Lirng; Li, Hsin-Yang

    2016-07-01

    To assess the pregnancy outcome and ovarian hyperstimulation syndrome (OHSS) incidence in high responders receiving gonadotropin-releasing hormone agonist (GnRHa) trigger plus individualized support of low-dose human chorionic gonadotropin (hCG). Such support includes 500-1000 IU hCG given at trigger and, if serum estradiol (E2) dropped to below 800 pg/mL before the 6(th) day after oocyte retrieval, an additional rescue dose of 300 IU hCG. This was a retrospective study of potential high responders aged from 28 years to 40 years at a tertiary fertility center in Taiwan. By means of chart review, we assessed the pregnancy outcome and OHSS incidence in high responders receiving GnRHa trigger plus individualized low-dose hCG support. The main outcomes were measured by ongoing pregnancy rate and OHSS incidence (SPSS), in which statistical significance was determined by Chi-square test. Moderate to severe OHSS did not develop in any patient receiving GnRHa trigger plus individualized low-dose hCG support. In fact, a satisfactory ongoing pregnancy rate (46.9%) was noted in patients receiving GnRHa trigger plus individualized low-dose hCG support. Our study suggested that GnRHa trigger combined with individualized low-dose hCG support appears to be a safe approach with a satisfactory pregnancy outcome. Copyright © 2016. Published by Elsevier Taiwan LLC.

  8. Different maternal serum hCG levels in pregnant women with female and male fetuses: does fetal hypophyseal--adrenal--gonadal axis play a role?

    Science.gov (United States)

    Gol, Mert; Altunyurt, Sabahattin; Cimrin, Dilek; Guclu, Serkan; Bagci, Mustafa; Demir, Namik

    2004-01-01

    Fetal gender has a significant effect on maternal and cord blood hCG levels, particularly during the last trimester of the pregnancy. However, the reason for this difference is obscure. The aim of the present study was to investigate whether term fetal hypophyseal - adrenal - gonadal axis differs between female and male fetuses thereby causing different hCG levels. The study consisted of 60 women with singleton pregnancies in the third trimester. Thirty-one pregnant women were carrying female fetuses, whereas 29 were carrying male. Human chorionic gonadotropin (hCG), estradiol, progesterone, testosterone, dehydro-epiandrosteron-sulfate (DHEAS), prolactin and growth hormone levels were measured in maternal serum and umbilical cord blood. In female bearing pregnancies maternal and cord blood hCG levels were significantly higher than in male bearing pregnancies (P<0.001). Maternal and cord blood estradiol, progesterone, testosterone, DHEAS, prolactin and growth hormone levels were not significantly different in either fetal gender. When all patients were considered as a group there were no correlations between fetal hCG levels and any of the measured hormones. Term fetal DHEAS, estrogen, progesterone, testosterone, growth hormone and prolactin levels do not contribute to different hCG levels between female and male fetuses. It is possible that fetal hypophyseal-adrenal gonadal axis does not play a central role as the cause of different hCG levels.

  9. Luteal P4 synthesis in early pregnant gilts after induction of estrus with PMSG/hCG.

    Science.gov (United States)

    Blitek, Agnieszka; Szymanska, Magdalena; Pieczywek, Marta; Morawska-Pucinska, Ewa

    2016-03-01

    The present study was designed to examine whether an estrus induction with gonadotropins could affect luteal P4 synthesis in early pregnant gilts. Sixteen prepubertal gilts received 750IU of PMSG and 500IU of hCG 72h later. Prepubertal gilts in the control group (n=17) were observed daily for estrus behavior. All gilts were inseminated in their first estrus. Corpora lutea (CLs) were collected on days 10, 12 and 15 of pregnancy and analyzed for (1) the mRNA and protein expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), and 3β-hydroxysteroid dehydrogenase (3βHSD); (2) the tissue concentration of P4; and (3) the mRNA expression of luteinizing hormone receptor (LHR) and estrogen receptors (ESR1 and ESR2). Additionally, P4 concentration was analyzed in blood serum of all animals. PMSG/hCG injections to induce estrus decreased mRNA expression of StAR, CYP11A1 and 3βHSD on day 10 and CYP11A1 on day 12 of pregnancy compared with the control group, while CYP11A1 and 3βHSD proteins were down-regulated on day 10 in the hormonally-treated gilts. Concentrations of P4 in luteal tissue and blood serum were also lower in animals after gonadotropin-induced estrus. In contrast, LHR and ESR1 mRNA expression was greater in PMSG/hCG-treated than control gilts on day 15 of gestation. In conclusion, induction of estrus with a PMSG/hCG protocol in prepubertal gilts impaired expression of the luteal P4 synthesis system. Low P4 content may, in turn, induce local mechanisms involving LHR and ESR1 expression to support CL function. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The Use of rLH, HMG and hCG in Controlled Ovarian Stimulation for Assisted Reproductive Technologies

    Science.gov (United States)

    2012-11-21

    if the addition of rLH increases pregnancy outcomes in ART 5. Human chorionic gonadotropin : hCG and LH have a significant degree of structural...The expression of human chorionic - gonadotropin luteinizing-hormone receptors in human endometrial and myometrial blood-vessels. Journal of Clinical...Retzloff MG. Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels

  11. Tandem repeats upstream of the Arabidopsis endogene SDC recruit non-CG DNA methylation and initiate siRNA spreading.

    Science.gov (United States)

    Henderson, Ian R; Jacobsen, Steven E

    2008-06-15

    Plants use siRNAs to target cytosine DNA methylation to both symmetrical CG and nonsymmetrical (CHG and CHH) sequence contexts. DNA methylation and siRNA clusters most frequently overlap with transposons in the Arabidopsis thaliana genome. However, a significant number of protein-coding genes also show promoter DNA methylation, and this can be used to silence their expression. Loss of the majority of non-CG DNA methylation in drm1 drm2 cmt3 triple mutants leads to developmental phenotypes. We identified the gene responsible for these phenotypes as SUPPRESSOR OF drm1 drm2 cmt3 (SDC), which encodes an F-box protein and possesses seven promoter tandem repeats. The SDC repeats show a unique silencing requirement for non-CG DNA methylation directed redundantly by histone methylation and siRNAs, and display spreading of siRNAs and methylation beyond the repeated region. In addition to revealing the complexity of DNA methylation control in A. thaliana, SDC has important implications for how plant genomes utilize gene silencing to repress endogenous genes.

  12. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

    Science.gov (United States)

    Gala, Anna; Assou, Said; Perrochia, Hélène; Dechaud, Hervé; Hugues, Jean-Noel; Hamamah, Samir

    2014-01-01

    The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity. PMID:24877150

  13. Maternal hCG concentrations in early IVF pregnancies: associations with number of cells in the Day 2 embryo and oocytes retrieved.

    Science.gov (United States)

    Tanbo, T G; Eskild, A

    2015-12-01

    Do number of cells in the transferred cleavage stage embryo and number of oocytes retrieved for IVF influence maternal hCG concentrations in early pregnancies? Compared with transfer of a 2-cell embryo, transfer of a 4-cell embryo results in higher hCG concentrations on Day 12 after transfer, and more than 20 oocytes retrieved were associated with low hCG concentrations. Maternal hCG concentration in very early pregnancy varies considerably among women, but is likely to be an indicator of time since implantation of the embryo into the endometrium, in addition to number and function of trophoblast cells. We followed 1047 pregnancies after IVF/ICSI from oocyte retrieval until Day 12 after embryo transfer. Women were recruited in Norway during the years 2005-2013. Successful pregnancies after transfer of one single embryo that had been cultured for 2 days were included. Maternal hCG was quantified on Day 12 after embryo transfer by chemiluminescence immunoassay, which measures intact hCG and the free β-hCG chain. Information on a successful pregnancy, defined as birth after >16 weeks, was obtained by linkage to the Medical Birth Registry of Norway. Transfer of a 4-cell embryo resulted in higher maternal hCG concentrations compared with transfer of a 2-cell embryo (134.8 versus 87.8 IU/l, P 20) was associated with low hCG concentrations (P hCG concentrations in early pregnancy. Although embryo transfer was performed at the same time after fertilization, we do not know the exact time of implantation. A further limitation to our study is that the number of pregnancies after transfer of a 2-cell embryo was small (27 cases). Number of cells in the transferred embryo and number of oocytes retrieved may influence the conditions and timing for embryo implantation in different ways and thereby influence maternal hCG concentrations. Such knowledge may be important for interpretation of hCG concentrations in early pregnancy. © The Author 2015. Published by Oxford University

  14. Large-scale genomic 2D visualization reveals extensive CG-AT skew correlation in bird genomes

    Directory of Open Access Journals (Sweden)

    Deng Xuemei

    2007-11-01

    Full Text Available Abstract Background Bird genomes have very different compositional structure compared with other warm-blooded animals. The variation in the base skew rules in the vertebrate genomes remains puzzling, but it must relate somehow to large-scale genome evolution. Current research is inclined to relate base skew with mutations and their fixation. Here we wish to explore base skew correlations in bird genomes, to develop methods for displaying and quantifying such correlations at different scales, and to discuss possible explanations for the peculiarities of the bird genomes in skew correlation. Results We have developed a method called Base Skew Double Triangle (BSDT for exhibiting the genome-scale change of AT/CG skew as a two-dimensional square picture, showing base skews at many scales simultaneously in a single image. By this method we found that most chicken chromosomes have high AT/CG skew correlation (symmetry in 2D picture, except for some microchromosomes. No other organisms studied (18 species show such high skew correlations. This visualized high correlation was validated by three kinds of quantitative calculations with overlapping and non-overlapping windows, all indicating that chicken and birds in general have a special genome structure. Similar features were also found in some of the mammal genomes, but clearly much weaker than in chickens. We presume that the skew correlation feature evolved near the time that birds separated from other vertebrate lineages. When we eliminated the repeat sequences from the genomes, the AT and CG skews correlation increased for some mammal genomes, but were still clearly lower than in chickens. Conclusion Our results suggest that BSDT is an expressive visualization method for AT and CG skew and enabled the discovery of the very high skew correlation in bird genomes; this peculiarity is worth further study. Computational analysis indicated that this correlation might be a compositional characteristic

  15. Alternative Gravity Rotation Curves for the LITTLE THINGS Survey

    Science.gov (United States)

    O’Brien, James G.; Chiarelli, Thomas L.; Dentico, Jeremy; Stulge, Modestas; Stefanski, Brian; Moss, Robert; Chaykov, Spasen

    2018-01-01

    Galactic rotation curves have proven to be the testing ground for dark matter bounds in spiral galaxies of all morphologies. Dwarf galaxies serve as an increasingly interesting case of rotation curve dynamics due to their typically rising rotation curve as opposed to the flattening curve of large spirals. Dwarf galaxies usually vary in galactic structure and mostly terminate at small radial distances. This, coupled with the fact that Cold Dark Matter theories struggle with the universality of galactic rotation curves, allow for exclusive features of alternative gravitational models to be analyzed. Recently, The H I Nearby Galactic Survey (THINGS) has been extended to include a sample of 25 dwarf galaxies now known as the LITTLE THINGS Survey. Here, we show an application of alternative gravitational models to the LITTLE THINGS survey, specifically focusing on conformal gravity (CG) and Modified Newtonian Dynamics (MOND). In this work, we provide an analysis and discussion of the rotation curve predictions of each theory to the sample. Furthermore, we show how these two alternative gravitational models account for the recently observed universal trends in centripetal accelerations in spiral galaxies. This work highlights the similarities and differences of the predictions of the two theories in dwarf galaxies. The sample is not large or diverse enough to strongly favor a single theory, but we posit that both CG and MOND can provide an accurate description of the galactic dynamics in the LITTLE THINGS sample without the need for dark matter.

  16. Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response.

    Science.gov (United States)

    Lohmann, Katharina L; Lopez, A Marianela; Manning, Stephen T; Marques, Fernando J; Brownlie, Robert; Allen, Andrew L; Sangster, Anna E; Mutwiri, George; Gerdts, Volker; Potter, Andrew; Townsend, Hugh G G

    2013-07-01

    We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain.

  17. The relation between plasmatic triglycerides levels and polymorphisms -133T>C and 56C>G of ApoA5 codifying gene

    Directory of Open Access Journals (Sweden)

    Ismael San Mauro Martín

    2016-06-01

    Full Text Available Aim. The aim was to evaluate the association between polymorphisms -113C>T (rs662799 and 56C>G (rs3135506 and plasmatic triglycerides levels in adults. Methods. A randomized clinical trial of 44 subjects from two hospital centers from Madrid (Spain. Anthropometric survey, blood test genetic analysis and an Ad hoc survey (lifestyle habits: nutrition, physical activity, sleep were conducted. Results. No statistically significant differences were observed between polymorphism 113G>T or 56C>G and plasmatic triglycerides concentrations (p>0.05. However, statistically significant differences were found between gene variant 56C>G and total cholesterol levels and low-density lipoproteins (p=0.015 and p=0.036, respectively. Conclusion. This trial brings to light no association between plasmatic triglycerides levels and polymorphic variants 56C>G and - 1131T>C of Apo5 coding gene.

  18. Desempenho reprodutivo de cabras alpinas tratadas com hCG cinco dias após o acasalamento Reproductive performance of alpine goats treated with hCG five days after breeding

    Directory of Open Access Journals (Sweden)

    Jeferson Ferreira da Fonseca

    2005-04-01

    Full Text Available Objetivou-se com este estudo avaliar o efeito da administração de hCG sobre o desempenho reprodutivo de cabras Alpinas durante a estação de acasalamento natural. Trinta e duas fêmeas nulíparas e 124 lactantes, após a identificação de estro e acasalamento, foram aleatoriamente divididas, de acordo com a categoria, em dois tratamentos. Em T1 (n=75 e T2 (n=81, os animais receberam 1 mL de solução salina ou 250 UI de hCG, respectivamente, por via intramuscular cinco dias após o acasalamento. A gestação foi verificada por ultra-sonografia transabdominal (probe de 3,5 MHz nos dias 35 e 70 após o acasalamento, para detecção e confirmação da gestação, respectivamente. As taxas de gestação não diferiram entre T1 (86,7% e T2 (70,6% para nulíparas e T1 (78,3 % e T2 (84,4 % para lactantes. Não houve diferença entre a taxa de parição (75,0 e 75,7%, o período de gestação (150,47 e 150,80 dias e a prolificidade (1,75 e 1,80 fetos entre os animais do T1 e T2, respectivamente. A prolificidade foi superior em cabras lactantes (1,90 que em nulíparas (1,41. A administração de hCG cinco dias após o acasalamento não elevou o desempenho reprodutivo em cabras da raça Alpina.The effect of hCG administration on reproductive performance of Alpine goats during the natural breeding season was evaluated. Thirty-two nulliparous and 124 lactating goats, after estrus identification and breeding, were randomly assigned according to the categories to two treatments. In T1 (n=75 and T2 (n=81 the animals received 1 mL of saline solution or 250 IU of hCG intramuscularly, respectively, five days after breeding. Pregnancy was detected and confirmed on days 35 and 70 after breeding by transabdominal ultrasonography (3.5 MHz probe, respectively. Pregnancy rate did not differ between T1 (86.7 % and T2 (70.6% for nulliparous and T1 (78.3% and T2 (84.4% for lactating does. There were no differences for kidding rate (75.0 and 75.7%, gestation period

  19. Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial.

    Science.gov (United States)

    Navali, N; Gassemzadeh, A; Farzadi, L; Abdollahi, S; Nouri, M; Hamdi, K; Mallah, F; Jalilvand, F

    2016-11-01

    Does the intrauterine administration of hCG immediately after oocyte retrieval in antagonist cycles with ICSI and fresh embryo transfer (ET) influence the implantation rate or chemical and clinical pregnancy rates? The intrauterine administration of hCG after oocyte retrieval increases the implantation rate and chemical and clinical pregnancy rates. Over half of IVF/ICSI cycles fail due to implantation failure. Intrauterine administration of hCG, a few minutes before ET, increased the implantation and pregnancy rates in most but not in all studies. The effect of intrauterine administration of hCG, after oocyte retrieval, has not yet been studied. The study was a parallel, triple-blind randomized clinical trial (RCT) performed from September 2015 to February 2016, in a university hospital. We recruited women undergoing antagonist ovarian stimulation, ICSI and ET. For an effect size of 0.2, power of 80% at a significance level of 0.05, we needed 150 participants. Accounting for a 7% dropout rate, a total of 160 women was considered appropriate. A computer-generated randomization list with a block size of 4, with 1:1 allocation was used. The treatment allocation was placed in a sealed, opaque, envelope and picked up consecutively. Immediately after oocyte retrieval, patients in the intervention and control groups were treated with intrauterine injection of hCG and saline, respectively. Participants underwent ET on Day 3. A beta-hCG test was done at 2 weeks. If positive, three transvaginal-ultrasonographies (TVSs) were done at 3, 4 and 10 weeks after ET. The participants were called up thereafter and questioned about the continuity of their pregnancy. Of 1990 women attending the infertility clinic of our university hospital, 508 were IVF/ICSI candidates during the study period, and 245 of the patients on an antagonist cycle met the criteria to be invited into our trial. Inclusion criteria were normal ovarian reserve, age ≤41, undergoing ICSI, and fresh ET and normal

  20. Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery.

    Science.gov (United States)

    Soni, Shelly; Krantz, David A; Blitz, Matthew J; Vohra, Nidhi; Rochelson, Burton

    2018-04-12

    To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

  1. Endocrine effects of hCG supplementation to recombinant FSH throughout controlled ovarian stimulation for IVF: a dose–response study

    DEFF Research Database (Denmark)

    Thuesen, Leif; Smitz, J; Loft, A

    2013-01-01

    To analyse the endocrine response in relation to the Δ-4 and Δ-5 pathways of ovarian steroidogenesis after different doses of human chorionic gonadotrophin (hCG) supplementation to recombinant FSH from Day 1 of controlled ovarian stimulation for IVF.......To analyse the endocrine response in relation to the Δ-4 and Δ-5 pathways of ovarian steroidogenesis after different doses of human chorionic gonadotrophin (hCG) supplementation to recombinant FSH from Day 1 of controlled ovarian stimulation for IVF....

  2. Assessment of serum β-hCG and lipid profile in early second trimester as predictors of hypertensive disorders of pregnancy.

    Science.gov (United States)

    Revankar, Vijaya M; Narmada, Lavu

    2017-09-01

    To assess and compare the ability of serum β-human chorionic gonadotropin (β-hCG) and serum lipid profile in early second trimester as predictors of hypertensive disorders of pregnancy. The present hospital-based prospective study was conducted between November 24, 2012, and April 30, 2014, at a tertiary hospital in Mangalore, India. Women of any parity with a pregnancy of 14-20 weeks were included. Venous blood (3 mL) was collected, and serum β-hCG and lipid profile were estimated by enzyme-linked immunosorbent assay and an enzymatic colorimetric test with lipid clearing factor, respectively. A cutoff value of β-hCG for predicting hypertensive disorders was obtained by receiver operating curve analysis. Serum β-hCG was significantly higher among women who subsequently developed hypertension (71 142 IU/L [n=27]) than among those who did not (20 541 IU/L [n=137]; PhCG to predict hypertension were 92.6% and 94.9% respectively. The positive and negative predictive values were 78.1% and 98.5%, respectively. Serum β-hCG might be used as a predictor of hypertensive disorders that complicate pregnancy. Dyslipidemia was not found to be a useful marker. © 2017 International Federation of Gynecology and Obstetrics.

  3. Estrogen-2/4-hydroxylase activity is stimulated during germinal vesicle breakdown induced by hCG, IGF-1, GH and insulin in the catfish Heteropneustes fossilis.

    Science.gov (United States)

    Chourasia, T K; Joy, K P

    2008-01-15

    Estrogen-2/4-hydroxylase (EH) activity was measured radiometrically in ovaries of catfish injected with hCG intraperitoneally and in postvitellogenic follicles incubated with different concentrations of hCG, catfish (Clarias batrachus) growth hormone (GH), bovine insulin or recombinant human insulin-like growth factor-I (rhIGF-I). The change in enzyme activity was correlated with germinal vesicle breakdown (GVBD), an index of oocyte maturation. A single intraperitoneal injection of hCG (100 IU/fish) stimulated EH activity both at 8 and 16 h prior to stripping of eggs. The activity decreased significantly at 24 h, following ovulation. The follicles incubated with hCG, rhIGF-I, insulin or GH elicited biphasic effects on EH activity. rhIGF-I, insulin and GH increased enzyme activity at the lower or median concentrations. hCG and rhIGF-I stimulated EH activity higher than GH or insulin. All the hormones elicited a dose-dependent increase in GVBD, the effect was greater with rhIGF-I (100 nM) and hCG (5.0 IU/ml). The significance of changes in EH activity (E2 hydroxylation) and GVBD were discussed.

  4. Water and Carbon Dioxide Ices-Rich Areas on Comet 67P/CG Nucleus Surface

    Science.gov (United States)

    Filacchione, G.; Capaccioni, F.; Raponi, A.; De Sanctis, M. C.; Ciarniello, M.; Barucci, M. A.; Tosi, F.; Migliorini, A.; Capria, M. T.; Erard, S.; Bockelée-Morvan, D.; Leyrat, C.; Arnold, G.; Kappel, D.; McCord, T. B.

    2017-01-01

    fields ice grains [3]; 3) different combinations of water ice and dark terrain in intimate mixing with small grains (tens of microns) or in areal mixing with large grains (mm- sized) are seen on the eight bright areas discussed in [4]; 4) the CO2 ice in the Anhur region appears grouped in areal patches made of 50 μm sized grains [5]. While the spectroscopic identification of water and carbon dioxide ices is made by means of diagnostic infrared absorption features, their presence cause significant effects also at visible wavelengths, including the increase of the albedo and the reduction of the spectral slope which results in a more blue color [9,10]. In summary, thermodynamic conditions prevailing on the 67P/CG nucleus surface allow the presence of only H2O and CO2 ices. Similar properties are probably common among other Jupiter family comets.

  5. Association of vascular endothelial growth factor -634C/G polymorphism and diabetic retinopathy in type 2 diabetic Han Chinese.

    Science.gov (United States)

    Yang, Ying; Andresen, Bradley T; Yang, Ke; Zhang, Ying; Li, Xiaojin; Li, Xianli; Wang, Hui

    2010-10-01

    Genetic factors are important in the pathogenesis of diabetic retinopathy (DR); there is a clear association of increased expression of vascular endothelial growth factor (VEGF) with DR as well as numerous VEGF polymorphisms that are linked to increased VEGF levels and DR. In this study, the relationships between the VEGF promoter polymorphism -634C/G, plasma VEGF levels and DR were examined in the Han Chinese. Ninety-six healthy subjects and 285 subjects with type 2 diabetes were enrolled in this study. The diabetic subjects were divided into three groups depending on the degree of DR as determined by fundus photography and fluorescent angiography. Along with standard clinical characteristics, the -634C/G polymorphism was examined using TaqMan allelic discrimination, and plasma VEGF levels were analyzed by enzyme-linked immunosorbent assay. The distribution of the polymorphism differed significantly between patients with and without retinopathy; this was most pronounced between the no DR and proliferative DR groups. Significantly greater plasma VEGF levels were present in those with the -634CC genotype, and only the proliferative DR group had elevated plasma VEGF levels. Logistic regression revealed that the -634C/G polymorphism is strongly associated with DR. This study suggests that diabetic Han Chinese carrying the -634CC VEGF promoter polymorphism have a genetic risk of DR, and this polymorphism may be a major factor influencing plasma VEGF levels. Therefore, this polymorphism may be used as a biomarker at the onset of diabetes in the Han Chinese to predict the risk of DR, allowing for clinicians to treat these patients more aggressively.

  6. Embryo yield in llamas synchronized with two different intravaginal progesterone-releasing devices and superovulated with eCG

    Energy Technology Data Exchange (ETDEWEB)

    Aller, J.F.; Abalos, M.C.; Acuña, F.A.; Virgili, R.; Requena, F.; Cancino, A.K.

    2015-07-01

    The objectives of this study were to compare the effects of two intravaginal devices (ID) containing the same dose (0.5 g) of progesterone (P4) on subsequent ovarian response, embryo production and circulating P4 concentration profile in llamas (Lama glama) treated with equine chorionic gonadotropin (eCG) for ovarian superstimulation. Female llamas were randomly assigned (n = 10 llamas per group) to one of the following groups and treated (Day 0) with an ID containing 0.5 g of vegetal P4 to synchronize the emergence of a new follicular wave: i) DIB 0.5® and ii) Cronipres M15®. On Day 3 llamas were intramuscularly treated with 1000 IU of eCG. The IDs were removed on Day 7. Llamas were naturally mated (Day 9) and treated with GnRH analogue to induce ovulation. A second mating was allowed 24 h later. Embryos were collected between 7 and 8 days after the first mating. Blood samples were taken every day from Day 0 to Day 7 to measure circulating P4 concentrations. The results indicated that DIB device maintained greater plasma P4 levels as compared to Cronipres until Day 2. However, the mean (± SD) number of corpora lutea and recovered embryos was not affected (p < 0.05) by the type of ID (5.3 ± 2.6 vs 4.2 ± 2.2 and 3.5 ± 2.7 vs 2.6 ± 3.0 for DIB and Cronipres, respectively). In conclusion, both DIB and Cronipres devices can be successfully used to synchronize the emergence of follicular wave prior to a single dose of eCG in superovulation protocol in llamas. (Author)

  7. Embryo yield in llamas synchronized with two different intravaginal progesterone-releasing devices and superovulated with eCG

    Directory of Open Access Journals (Sweden)

    Juan F. Aller

    2015-09-01

    Full Text Available The objectives of this study were to compare the effects of two intravaginal devices (ID containing the same dose (0.5 g of progesterone (P4 on subsequent ovarian response, embryo production and circulating P4 concentration profile in llamas (Lama glama treated with equine chorionic gonadotropin (eCG for ovarian superstimulation. Female llamas were randomly assigned (n = 10 llamas per group to one of the following groups and treated (Day 0 with an ID containing 0.5 g of vegetal P4 to synchronize the emergence of a new follicular wave: i DIB 0.5® and ii Cronipres M15®. On Day 3 llamas were intramuscularly treated with 1000 IU of eCG. The IDs were removed on Day 7. Llamas were naturally mated (Day 9 and treated with GnRH analogue to induce ovulation. A second mating was allowed 24 h later. Embryos were collected between 7 and 8 days after the first mating. Blood samples were taken every day from Day 0 to Day 7 to measure circulating P4 concentrations. The results indicated that DIB device maintained greater plasma P4 levels as compared to Cronipres until Day 2. However, the mean (± SD number of corpora lutea and recovered embryos was not affected (p < 0.05 by the type of ID (5.3 ± 2.6 vs 4.2 ± 2.2 and 3.5 ± 2.7 vs 2.6 ± 3.0 for DIB and Cronipres, respectively. In conclusion, both DIB and Cronipres devices can be successfully used to synchronize the emergence of follicular wave prior to a single dose of eCG in superovulation protocol in llamas.

  8. The CG-1D Neutron Imaging Beamline at the Oak Ridge National Laboratory High Flux Isotope Reactor

    Science.gov (United States)

    Santodonato, Lou; Bilheux, Hassina; Bailey, Barton; Bilheux, Jean; Nguyen, Phong; Tremsin, Anton; Selby, Doug; Walker, Lakeisha

    The Oak Ridge National Laboratory Neutron Sciences Directorate has installed a neutron imaging beamline at the High Flux Isotope Reactor (HFIR) cold guide hall. CG-1D is one of the three instruments that make up the CG1 instrument suite. The beamline optics and detector have recently been upgraded to meet the needs of the neutron imaging community (better ;smoothing; of guide system artifacts, higher flux or spatial resolution). These upgrades comprise a new diffuser/aperture system, two new detectors, a He-filled flight tube and silicon (Si) windows. Shielding inside the flight tube, beam scrapers and a beam stop ensure that biological dose is less than 50 μSv/hr outside of the radiation boundary. A set of diffusers and apertures (pinhole geometry) has been installed at the exit of the guide system to allow motorized L/D variation. Samples sit on a translation/rotation stage for alignment and tomography purposes. Detectors for the CG-1D beamline are (1) an ANDOR DW936 charge coupled device (CCD) camera with a field of view of approximately 7 cm x 7 cm and ∼ 80 microns spatial resolution and 1 frame per second time resolution, (2) a new Micro-Channel Plate (MCP) detector with a 2.8 cm x 2.8 cm field of view and 55 microns spatial resolution, and 5 μs timing capability. 6LiF/ZnS scintillators of thickness varying from 50 to 200 microns are being used at this facility. An overview of the beamline upgrade and preliminary data is presented here.

  9. Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258.

    Science.gov (United States)

    Breurec, S; Guessennd, N; Timinouni, M; Le, T A H; Cao, V; Ngandjio, A; Randrianirina, F; Thiberge, J M; Kinana, A; Dufougeray, A; Perrier-Gros-Claude, J D; Boisier, P; Garin, B; Brisse, S

    2013-04-01

    The molecular epidemiology of third-generation cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in developing countries is poorly documented. From February 2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven major towns in Maghreb (Morocco), West Africa (Senegal, Côte d'Ivoire), Central Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their genetic diversity, assessed by multilocus sequence typing, was high (60 sequence types), reflecting multiclonality. However, two major clonal groups, CG15 (n = 23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all participating centres. The two major clonal groups have previously been described in other parts of the world, indicating their global spread. The high diversity of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns at the local level indicates that most isolates were epidemiologically unrelated. The isolates were characterized by the presence of multiple resistance determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and blaCTX-M-15 genes in 61 isolates (45%) belonging to 31 sequence types. These isolates were detected across a large geographical area including Cameroon (n = 1), Vietnam (n = 4), Madagascar (n = 10), Côte d'Ivoire (n = 12), Morocco (n = 13) and Senegal (n = 21). These results have major implications for patient management and highlight a potential reservoir for resistance determinants. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  10. Heterogeneous hCG and hMG commercial preparations result in different intracellular signalling but induce a similar long-term progesterone response in vitro.

    Science.gov (United States)

    Riccetti, Laura; Klett, Danièle; Ayoub, Mohammed Akli; Boulo, Thomas; Pignatti, Elisa; Tagliavini, Simonetta; Varani, Manuela; Trenti, Tommaso; Nicoli, Alessia; Capodanno, Francesco; La Sala, Giovanni Battista; Reiter, Eric; Simoni, Manuela; Casarini, Livio

    2017-10-01

    Are four urinary hCG/menotropin (hMG) and one recombinant preparation characterized by different molecular features and do they mediate specific intracellular signaling and steroidogenesis? hCG and hMG preparations have heterogeneous compositions and mediate preparation-specific cell signaling and early steroidogenesis, although similar progesterone plateau levels are achieved in 24 h-treated human primary granulosa cells in vitro. hCG is the pregnancy hormone marketed as a drug for ARTs to induce final oocyte maturation and ovulation, and to support FSH action. Several hCG formulations are commercially available, differing in source, purification methods and biochemical composition. Commercial hCG preparations for ART or research purposes were compared in vitro. The different preparations were quantified by immunoassay with calibration against the hCG standard (Fifth IS; NIBSC 07/364). Immunoreactivity patterns, isoelectric points and oligosaccharide contents of hCGs were evaluated using reducing and non-reducing Western blotting, capillary isoelectric-focusing immunoassay and lectin-ELISA, respectively. Functional studies were performed in order to evaluate intracellular and total cAMP, progesterone production and β-arrestin 2 recruitment by ELISA and BRET, in both human primary granulosa lutein cells (hGLC) and luteinizing hormone (LH)/hCG receptor (LHCGR)-transfected HEK293 cells, stimulated by increasing hormone concentrations. Statistical analysis was performed using two-way ANOVA and Bonferroni post-test or Mann-Whitney's U-test as appropriate. Heterogeneous profiles were found among preparations, revealing specific molecular weight patterns (20-75 KDa range), isoelectric points (4.0-9.0 pI range) and lectin binding (P hCG/hMG preparations is provided in International Units (IU) by in-vivo bioassay and calibration against an International Standard, although it is an unsuitable unit of measure for in-vitro studies. The re-calibration against recombinant hCG

  11. Overcoming the heterologous bias: An in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Puri, Nidhi; Manoharlal, Raman; Sharma, Monika [Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067 (India); Sanglard, Dominique [Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne (Switzerland); Prasad, Rajendra, E-mail: rp47jnu@gmail.com [Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067 (India)

    2011-01-07

    Research highlights: {yields} First report to demonstrate an in vivo expression system of an ABC multidrug transporter CgCdr1p of C. glabrata. {yields} First report on the structure and functional characterization of CgCdr1p. {yields} Functional conservation of divergent but typical residues of CgCdr1p. {yields} CgCdr1p elicits promiscuity towards substrates and has a large drug binding pocket with overlapping specificities. -- Abstract: We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplished by tagging a green fluorescent protein (GFP) downstream of ORF of CgCDR1 and integrating the resultant fusion protein at its native chromosomal locus in AS and AR backgrounds. The characterization confirmed that in comparison to AS isolate, CgCdr1p-GFP was over-expressed in AR isolates due to its hyperactive native promoter and the GFP tag did not affect its functionality in either construct. We observed that in addition to Rhodamine 6 G (R6G) and Fluconazole (FLC), a recently identified fluorescent substrate of multidrug transporters Nile Red (NR) could also be expelled by CgCdr1p. Competition assays with these substrates revealed the presence of overlapping multiple drug binding sites in CgCdr1p. Point mutations employing site directed mutagenesis confirmed that the role played by unique amino acid residues critical to ATP catalysis and localization of ABC drug transporter proteins are well conserved in C. glabrata as in other yeasts. This study demonstrates a first in vivo novel system where over-expression of GFP tagged MDR transporter protein can be driven by its own hyperactive promoter of AR isolates. Taken together, this in vivo system can be exploited for the structure and functional analysis of CgCdr1p and similar proteins wherein the arte-factual concerns

  12. The hCG ratio can predict the ultimate viability of the intrauterine pregnancies of uncertain viability in the pregnancy of unknown location population.

    Science.gov (United States)

    Bignardi, Tommaso; Condous, George; Alhamdan, Dalya; Kirk, Emma; Van Calster, Ben; Van Huffel, Sabine; Timmerman, Dirk; Bourne, Tom

    2008-09-01

    To determine whether hCG ratio at 48 h can predict ultimate viability of intrauterine pregnancies of uncertain viability (IPUVs) in the pregnancy of unknown location (PUL) population. Prospective observational study from June 2001 to October 2004. All women classified with PUL had serum hCG levels measured at 0 and 48 h to calculate hCG ratio (hCG 48/hCG 0 h). All women were followed up until final diagnosis: failing PUL, viable and non-viable intrauterine pregnancy (IUP), ectopic pregnancy. Those PULs found to have an IPUV at follow-up transvaginal ultrasound scan (TVS) were included in final analysis. During the study period, 12,572 consecutive first trimester women were scanned. One thousand and three (8%) women were classified PULs. Three hundred and seventy-nine (37.8%) PULs were confirmed IPUVs at follow-up scan. Complete data from 334 IPUVs were analyzed: 82.6% (276/334) viable IUPs and 17.4% (58/334) non-viable IUPs. Median hCG ratio was greater in viable IUPs [2.32, inter-quartile range (IQR) 1.16-4.77] compared with non-viable IUPs 1.83 (IQR 0.97-4.60). Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratios of an hCG ratio >2.00 for the prediction of a viable IUP are 77.2%, 95.8%, 86.6%, 90.9%, 15.5, 0.24, respectively. In our population, an hCG ratio >2.00 increases the odds for a viable IUP from 0.42 to 6.46 post-test. The hCG ratio is significantly higher in those IPUVs which become viable IUPs compared with non-viable IUPs. New cut-offs for the hCG ratio need to be evaluated for the prediction of viability in the IPUV group of PULs.

  13. hCG activates Epac-Erk1/2 signaling regulating Progesterone Receptor expression and function in human endometrial stromal cells.

    Science.gov (United States)

    Tapia-Pizarro, Alejandro; Archiles, Sebastián; Argandoña, Felipe; Valencia, Cecilia; Zavaleta, Keyla; Cecilia Johnson, M; González-Ramos, Reinaldo; Devoto, Luigi

    2017-06-01

    How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? hCG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cyclic AMP (cAMP) (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors. hCG signals through cAMP/protein kinase A (PKA) in gonadal cells, but in endometrial epithelial cells, hCG induces Erk1/2 activation independent of the cAMP/PKA pathway. Few data exist concerning the signal transduction pathways triggered by hCG in ESCs and their role in regulation of ESC function. This is an in vitro study comprising patients undergoing benign gynecological surgery (n = 46). Endometrial samples were collected from normal cycling women during the mid-secretory phase for ESCs isolation. The study conducted in an academic research laboratory within a tertiary-care hospital. The activation of the Erk1/2 signal transduction pathway elicited by hCG was evaluated in ESC. Signaling pathway inhibitors were used to examine the roles of PKA, PI3K, PKC, adenylyl cyclase and Epac on the hCG-stimulated up-regulation of phospho-Erk1/2 (pErk1/2). Erk1/2 phosphorylation was determined by immunoblot. siRNA targeting Epac was used to investigate the molecular mechanisms. To assess the role of Erk1/2 signaling induced by hCG on ESC function, gene expression regulation was examined by immunofluorescence and real-time quantitative PCR. The role of PR on the regulation of transcript levels was studied using progesterone and the PR antagonist RU486. All experiments were conducted using at least three different cell culture preparations in triplicate. Addition of hCG to ESCs in vitro induced the phosphorylation of Erk1/2 through cAMP accumulation. Such

  14. Effects of eCG are more pronounced in primiparous than multiparous Bos indicus cows submitted to a timed artificial insemination protocol.

    Science.gov (United States)

    Sales, J N S; Bottino, M P; Silva, L A C L; Girotto, R W; Massoneto, J P M; Souza, J C; Baruselli, P S

    2016-12-01

    The effects of eCG on follicular growth, ovulation, and pregnancy per artificial insemination (P/AI) in multiparous and primiparous Bos indicus beef cows submitted to timed artificial insemination (TAI) were evaluated in three experiments. In experiments 1 (follicular responses; n = 64), 2 (follicular growth and ovulation rate; n = 662), and 3 (P/AI; n = 2092), cows submitted to TAI were assigned to receive one of two treatments on Day 8 of the synchronization protocol: control (no additional treatment) or eCG (300-IU of eCG intramuscularly). In experiment 1, largest follicle (LF) diameter on Day 8 (P = 0.56) and the interval from progesterone (P4)-device removal to ovulation (P = 0.79) did not differ between treatments. However, the maximum diameter of the LF (P = 0.05) and ovulation rate (P = 0.03) were greater in cows that received eCG. In experiment 2, the diameter of the LF on Day 10, follicular growth, and ovulation rate were greater in eCG-treated cows (P < 0.01). However, CL diameter was similar between treatments (P = 0.11). In experiment 3, there was a treatment-by-parity interaction (P = 0.003) on P/AI, such that treatment with eCG was more effective in primiparous cows. In conclusion, eCG treatment resulted in increased final follicular growth, ovulation rate, and fertility in B indicus cows submitted to TAI protocols, especially in primiparous cows. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Progesterone concentration, pregnancy and calving rate in Simmental dairy cows after oestrus synchronisation and hCG treatment during the early luteal phase.

    Science.gov (United States)

    Šuluburić, Adam; Milanović, Svetlana; Vranješ-Đurić, Sanja; Jovanović, Ivan B; Barna, Tomislav; Stojić, Milica; Fratrić, Natalija; Szenci, Ottó; Gvozdić, Dragan

    2017-09-01

    Early embryonic development may be negatively affected by insufficient progesterone (P4) production. Therefore, the aim of our study was to increase P4 by gonadotropin-releasing hormone (GnRH) and/or human chorionic gonadotropin (hCG) treatments after inducing oestrus by prostaglandin (PG) treatment. Lactating Simmental dairy cows (n = 110), between 1 to 5 lactations, with an average milk production of 6,500 1/305 days, at 40-80 days postpartum were used and grouped as follows: (1) PG + GnRH treatment at AI (GnRH group), (2) PG + hCG treatment at day 7 after AI (hCG group), (3) PG + GnRH at AI + hCG treatment at day 7 after AI (GnRH/hCG group), and (4) spontaneous oestrus (C: control group). All animals were double inseminated (at the time of oestrus detection and 12 ± 2 h thereafter). Blood serum and milk samples were collected at the day of observed oestrus (day 0), and 14, 21 and 28 days after AI. Serum P4 was determined using a commercial radioimmunoassay (RIA) test (INEP, Zemun), and milk P4 was determined using enzyme-linked immunoassay (ELISA) test (NIV Novi Sad). Pregnancy status was confirmed by ultrasonography between days 28 and 35 after AI. Differences of serum or milk P4 medians, pregnancy (and calving) rate were determined using Dunn's Multiple Comparison Tests and Z test, respectively. Serum P4 medians were significantly higher at days 14, 21 and 28 after AI in the hCG-treated animals, indicating increased luteal activity, with a similar tendency in whole milk P4 values. Treatment with hCG during the early luteal phase significantly contributed to the maintenance of gestation at days 28-35 after AI, and also increased the calving rate in Simmental dairy cows.

  16. Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.

    Science.gov (United States)

    Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Potì, Francesco; Giva, Lavinia Beatrice; Marino, Marco; Tagliavini, Simonetta; Trenti, Tommaso; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Simoni, Manuela; Casarini, Livio

    2017-01-05

    Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG. Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. We found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis. These data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

  17. Early maternal serum ß-human chorionic gonadotropin (ß-hCG) levels and sex-related growth difference of IVF embryos.

    Science.gov (United States)

    Esh-Broder, Efrat; Oron, Galia; Son, Weon-Young; Holzer, Hananel; Tulandi, Togas

    2015-10-01

    Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer. We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer. Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables. Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.

  18. Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.

    Directory of Open Access Journals (Sweden)

    Qun Shu

    Full Text Available Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2 in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 or p38 mitogen-activated protein kinase (MAPK pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.

  19. cgDNA: a software package for the prediction of sequence-dependent coarse-grain free energies of B-form DNA.

    Science.gov (United States)

    Petkevičiūtė, D; Pasi, M; Gonzalez, O; Maddocks, J H

    2014-11-10

    cgDNA is a package for the prediction of sequence-dependent configuration-space free energies for B-form DNA at the coarse-grain level of rigid bases. For a fragment of any given length and sequence, cgDNA calculates the configuration of the associated free energy minimizer, i.e. the relative positions and orientations of each base, along with a stiffness matrix, which together govern differences in free energies. The model predicts non-local (i.e. beyond base-pair step) sequence dependence of the free energy minimizer. Configurations can be input or output in either the Curves+ definition of the usual helical DNA structural variables, or as a PDB file of coordinates of base atoms. We illustrate the cgDNA package by comparing predictions of free energy minimizers from (a) the cgDNA model, (b) time-averaged atomistic molecular dynamics (or MD) simulations, and (c) NMR or X-ray experimental observation, for (i) the Dickerson-Drew dodecamer and (ii) three oligomers containing A-tracts. The cgDNA predictions are rather close to those of the MD simulations, but many orders of magnitude faster to compute. Both the cgDNA and MD predictions are in reasonable agreement with the available experimental data. Our conclusion is that cgDNA can serve as a highly efficient tool for studying structural variations in B-form DNA over a wide range of sequences. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2015-04-01

    Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

  1. Induction of puberty with human chorionic gonadotropin (hCG) followed by reversal of hypogonadotropic hypogonadism in Kallmann syndrome.

    Science.gov (United States)

    Pierzchlewska, Malgorzata M; Robaczyk, Maciej G; Vogel, Ida

    2017-01-01

    Kallmann syndrome (KS) is a rare, congenital disorder combining hypogonadotropic hypogonadism (HH) due to GnRH-deficiency with anosmia. Traditionally thought to require lifelong therapy it turns out to be a reversible condition in some patients. We present a case of a 22-year old man with absent puberty due to KS, in whom genetic testing revealed heterozygosity for a mutation in the PROK2 gene. Pubertal development and virilisation was achieved by using human chorionic gonadotropin (hCG) injections followed by testosterone replacement. During the follow-up we observed reversal of hypogonadism allowing discontinuation of testosterone treatment. Normalisation of testicular volume as well as gonadotropin and inhibin B levels through a 2-year postreversal period was seen. Treatment with hCG is effective in inducing pubertal development and may have advantage over testosterone replacement due to a potential of gonadal maturation. A regular assessment of testicular volume and biochemical surveillance including measuring of serum inhibin B and gonadotropins are necessary for a timely detection of reversal of GnRH deficiency.

  2. CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils.

    Science.gov (United States)

    Spinner, Daryl S; Kascsak, Regina B; Lafauci, Giuseppe; Meeker, Harry C; Ye, Xuemin; Flory, Michael J; Kim, Jae Il; Schuller-Levis, Georgia B; Levis, William R; Wisniewski, Thomas; Carp, Richard I; Kascsak, Richard J

    2007-06-01

    Prion diseases are characterized by conversion of the cellular prion protein (PrP(C)) to a protease-resistant conformer, the srapie form of PrP (PrP(Sc)). Humoral immune responses to nondenatured forms of PrP(Sc) have never been fully characterized. We investigated whether production of antibodies to PrP(Sc) could occur in PrP null (Prnp(-/-)) mice and further, whether innate immune stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN) 1826 could enhance this process. Whether such stimulation could raise anti-PrP(Sc) antibody levels in wild-type (Prnp(+/+)) mice was also investigated. Prnp(-/-) and Prnp(+/+) mice were immunized with nondenatured 139A scrapie-associated fibrils (SAF), with or without ODN 1826, and were tested for titers of PrP-specific antibodies. In Prnp(-/-) mice, inclusion of ODN 1826 in the immunization regime increased anti-PrP titers more than 13-fold after two immunizations and induced, among others, antibodies to an N-terminal epitope, which were only present in the immune repertoire of mice receiving ODN 1826. mAb 6D11, derived from such a mouse, reacts with the N-terminal epitope QWNK in native and denatured forms of PrP(Sc) and recombinant PrP and exhibits a K(d) in the 10(-)(11) M range. In Prnp(+/+) mice, ODN 1826 increased anti-PrP levels as much as 84% after a single immunization. Thus, ODN 1826 potentiates adaptive immune responses to PrP(Sc) in 139A SAF-immunized mice. These results represent the first characterization of humoral immune responses to nondenatured, infectious PrP(Sc) and suggest methods for optimizing the generation of mAbs to PrP(Sc), many of which could be used for diagnosis and treatment of prion diseases.

  3. Ex vivo gene editing of the dystrophin gene in muscle stem cells mediated by peptide nucleic acid single stranded oligodeoxynucleotides induces stable expression of dystrophin in a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Nik-Ahd, Farnoosh; Bertoni, Carmen

    2014-07-01

    Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutations in the dystrophin gene, which result in the complete absence of dystrophin protein throughout the body. Gene correction strategies hold promise to treating DMD. Our laboratory has previously demonstrated the ability of peptide nucleic acid single-stranded oligodeoxynucleotides (PNA-ssODNs) to permanently correct single-point mutations at the genomic level. In this study, we show that PNA-ssODNs can target and correct muscle satellite cells (SCs), a population of stem cells capable of self-renewing and differentiating into muscle fibers. When transplanted into skeletal muscles, SCs transfected with correcting PNA-ssODNs were able to engraft and to restore dystrophin expression. The number of dystrophin-positive fibers was shown to significantly increase over time. Expression was confirmed to be the result of the activation of a subpopulation of SCs that had undergone repair as demonstrated by immunofluorescence analyses of engrafted muscles using antibodies specific to full-length dystrophin transcripts and by genomic DNA analysis of dystrophin-positive fibers. Furthermore, the increase in dystrophin expression detected over time resulted in a significant improvement in muscle morphology. The ability of transplanted cells to return into quiescence and to activate upon demand was confirmed in all engrafted muscles following injury. These results demonstrate the feasibility of using gene editing strategies to target and correct SCs and further establish the therapeutic potential of this approach to permanently restore dystrophin expression into muscle of DMD patients. © 2014 AlphaMed Press.

  4. Effect of sublingual administration with a native or denatured protein allergen and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic T(H)2 immune responses and mucosal immunity in mice.

    Science.gov (United States)

    Huang, Ching-Feng; Wang, Chih-Chien; Wu, Tzee-Chung; Chu, Chia-Hsiang; Peng, Ho-Jen

    2007-11-01

    Sublingual immunotherapy has been recently used for allergic diseases, but its mechanisms are still unclear. To examine the effect of sublingual administration of a native or denatured allergen alone or plus adjuvant on systemic T(H)2 responses and mucosal immunity in mice. Naive or sensitized BALB/c mice were sublingually vaccinated biweekly for 3 weeks with ovalbumin (OVA) or urea-denatured OVA (CM-OVA) only or plus adjuvant CpG oligodeoxynucleotides (CpG) or cholera toxin (CT). Two weeks later, their specific serum IgG, IgG1, IgG2a, IgE, and saliva secretory IgA (SIgA) antibody responses and the cytokine profiles of spleen and cervical lymph node cells were investigated. Specific SIgA antibody responses were induced by vaccination with CM-OVA plus CpG or CT. Whereas vaccination with CM-OVA and CpG enhanced T(H)1 responses but inhibited IgE production, vaccination with CT and CM-OVA or OVA increased cervical lymph node cell production of interleukin (IL) 4, IL-5, and IL-6 and serum IgG1 antibody responses. In previously sensitized mice, sublingual vaccination with OVA or CM-OVA plus CT or CpG stimulated mucosal SIgA antibody responses, but did not enhance ongoing IgE antibody responses. Sublingual vaccination with OVA or CM-OVA plus adjuvant CT or CpG all can induce systemic and mucosal immunity, but CM-OVA plus CpG had the best prophylactic and therapeutic effects on IgE antibody production. It is likely that sublingual vaccines may have a role for the prophylaxis and immunotherapy of allergic reactions.

  5. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ji-meng [School of Medicine, Nankai University, Tianjin 300071 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hong-xi [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Wang, Li [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Gao, Zhi-ying, E-mail: gaozy301@yahoo.com.cn [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Yao, Yuan-qing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China)

    2013-05-10

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

  6. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    International Nuclear Information System (INIS)

    Wang, Ji-meng; Zhao, Hong-xi; Wang, Li; Gao, Zhi-ying; Yao, Yuan-qing

    2013-01-01

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion

  7. Day two post retrieval 1500 IUI hCG bolus, progesterone-free luteal support post GnRH agonist trigger - a proof of concept study.

    Science.gov (United States)

    Vanetik, Sharon; Segal, Linoy; Breizman, Tatiana; Kol, Shahar

    2018-02-01

    Small dose of hCG (1500 IU) on the day of oocyte retrieval, followed by daily progesterone administration, is currently the preferred way to secure adequate luteal support following GnRH agonist trigger. In the current proof-of-concept study, we explored the possibility that a bolus of 1500 IU hCG, given two days after oocyte retrieval, may be sufficient to sustain adequate luteal support without additional progesterone treatment. From February 2015 to August 2016, we obtained 44 pregnancies following GnRHa trigger followed by day 2 hCG (1500 IU) support only (study group). Data from these 44 cycles were compared with the latest 44 pregnancies obtained following hCG (6500 IU) trigger followed by conventional progesterone luteal documented (control group). Mean progesterone levels (14 days postoocyte retrieval) in the study and control groups were 197 nmol/l and 173 nmol/l, respectively (NS). Mean E 2 levels (14 days post oocyte retrieval) in the study group was 6937 pmol/l, significantly higher (p hCG, administered 2 days after retrieval, can provide excellent support, without the need to further supplement with progesterone.

  8. Development and clinical application of a highly sensitive hCG-β radioimmuno assay with a critical view to cross-reaction with LH

    International Nuclear Information System (INIS)

    Schuessler, B.

    1979-01-01

    A highly sensitive hCG-β-RIA with a lower detection limit of 1 mIU/ml was developed with an hCG-β-antiserum. Despite the crossreaction with LH-concentrations of 30 mIU/ml - 150mIU/ml ocurring between 1 mIU/ml and 5 mIU/ml, also in this region a definite statement on the hCG-concentration could be made, by comparison with the values developed in LH-RIA. The assay for the hCG-determination was applied in carcinomas of the uterine cervix (47%), ovaries (25%), body of the uterus (25%), mamma (17,6B), and prostate (5,8%). Another assay with a sensitivity of 5 mIU/ml was arranged for clinical routine examinations of chorionepithelioma and testis-carcinoma. In contrast to the first two systems which had a reaction time of appr. 100 hrs, we obtained safe results with another hCG-β-RIA with low antibodytiters after 110 min. The sensitivity was 15 mIU/ml. The procedure was found to be valuable for the exclusion of EU-gravidities. (orig.) [de

  9. Production of specific antisera for radioimmunoassay of human luteinizing hormone (LH) in the presence of human chorionic gonadotropin (hCG)

    International Nuclear Information System (INIS)

    Thorell, J.I.; Jeppsson, S.; Holmstrom, B.

    1976-01-01

    A specific radioimmunoassay for LH, which measures plasma LH in the presence of human chorionic gonadotropin (hCG) is described. Rabbits were immunized with highly purified native LH. One of the antisera with a difference in its reactivity against LH and hCG was further purified by affinity chromatography on a column with hCG coupled to Sepharose 4B. The adsorbed antiserum and 125 I-LH was used in a double antibody assay. The LH standard (MRC/68/40) efficiently inhibited the binding of 125 I-LH, and the standard curve showed a sensitivity of 0.5 ng/ml in the sample. hCG up to 10,000 ng/ml did not inhibit the binding of 125 I-LH. The plasma level of LH in pregnant women in the first trimester was low (1.3 +- 0.1 ng/ml). When LH was measured in fertile or menopausal women with or without stimulation with LH/FSH releasing hormone (LH-RH)/sup x/ the results agreed to those found with our conventional LH-assay based on antiserum against hCG

  10. Do high progesterone concentrations decrease pregnancy rates in embryo recipients synchronized with PGF2alpha and eCG?

    Science.gov (United States)

    Nogueira, Marcelo F Gouveia; Melo, Danilas S; Carvalho, Luciano M; Fuck, Egon J; Trinca, Luzia A; Barros, Ciro Moraes

    2004-05-01

    The objective of this study was to evaluate the effects of equine chorionic gonadotropin (eCG) treatment on the number of induced accessory corpora lutea (CL), plasma progesterone concentrations and pregnancy rate in cross-bred heifers after transfer of frozen-thawed (1.5M ethylene glycol) embryos. All recipients received 500 microg PGF2alpha (dl-cloprostenol, i.m.) at random stages of the estrous cycle (Day 0) and were observed for estrus for 7 days. On Day 14, heifers detected in estrus between 2 and 7 days after PGF2alpha treatment were randomly allocated to four groups ( n=83 per group) and given 0 (control), 200, 400, or 600 IU of eCG. Two days later (Day 16), these recipients were given PGF2alpha and observed for estrus. Six to eight days after detection of estrus, plasma samples were collected to determine progesterone concentration and ultrasonography was performed to observe ovarian structures. Heifers with multiple CL or a single CL >15 mm in diameter received an embryo by direct transfer. Embryos of excellent and good quality were thawed and transferred to the recipients by the same veterinarian. Pregnancy was diagnosed by ultrasonography and confirmed by transrectal palpation 21 and 83 days after embryo transfer (ET), respectively. Plasma progesterone concentrations on the day of transfer (Day 7 of the estrous cycle) were 3.9+/-0.7, 4.2+/-0.4,6.0+/-0.4 and 7.8+/-0.6 ng/ml for groups Control, 200, 400, and 600, respectively (Control versus treated groups P=0.009; 200 versus 400 and 600 groups P=0.0001; and 400 versus 600 P=0.012 ). Conception rates 83 days after ET were 41.9, 50.0, 25.0, and 20.9% for groups Control, 200, 400, and 600, respectively (200 versus 400 and 600 groups P=0.0036 ). In conclusion, an increase in progesterone concentration, induced by eCG treatment, did not improve pregnancy rates in ET recipients. Conversely, there was a decline in conception rates in the animals with the highest plasma progesterone concentrations.

  11. Alternate superior Julia sets

    International Nuclear Information System (INIS)

    Yadav, Anju; Rani, Mamta

    2015-01-01

    Alternate Julia sets have been studied in Picard iterative procedures. The purpose of this paper is to study the quadratic and cubic maps using superior iterates to obtain Julia sets with different alternate structures. Analytically, graphically and computationally it has been shown that alternate superior Julia sets can be connected, disconnected and totally disconnected, and also fattier than the corresponding alternate Julia sets. A few examples have been studied by applying different type of alternate structures

  12. First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses

    DEFF Research Database (Denmark)

    Pihl, Kasper; Larsen, Torben; Krebs, Lone

    2008-01-01

    trimester. METHODS: In all,36 cases being SGA (birth weight controls being non-SGA were matched on ethnicity (only Caucasians), smoking status (only nonsmokers), body mass index (BMI), age and parity. Stored blood samples from PAPP-A and beta-hCG testing obtained at gestational age......-hCG (0.74 vs 1.04, p = 0.007) and ADAM12 (0.74 vs 0.97, p = 0.004) were significantly reduced in cases compared to controls. The combination of PAPP-A MoM and beta-hCG MoM yielded a detection rate (DR) for SGA of 26% for a 5% false-positive rate (FPR). Addition of ADAM12 only improved (28% DR for a 5...

  13. Production and testing of HENDL-2.1/CG coarse-group cross-section library based on ENDF/B-VII.0

    International Nuclear Information System (INIS)

    Xu Dezheng; He Zhaozhong; Zou Jun; Zeng Qin

    2010-01-01

    A coarse-group coupled neutron and photon (27n + 21γ) cross-section library HENDL-2.1/CG, based on ENDF/B-VII.0 evaluate data source, has been produced by FDS Team in Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). HENDL-2.1/CG containing 350 nuclide cross-section files (from 1 H to 252 Cf) was generated in MATXS format with the NJOY processing system and then by compiling coarse-group problem-dependent format using the TRANSX code. In order to verify the availability and reliability of the HENDL-2.1/CG data library, requisite benchmark calculations were performed and compared with HENDL-2.0/MG fine-group coupled neutron and photon (175n + 42γ) cross-section library. In general, results using the coarse-group library showed similarly believable as fine-group library.

  14. GnRH agonist ovulation trigger and hCG-based, progesterone-free luteal support: a proof of concept study

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Itskovitz-Eldor, Joseph

    2011-01-01

    BACKGROUND It is now well established that a GnRH agonist (GnRHa) ovulation trigger completely prevents ovarian hyperstimulation syndrome. However, early studies, using conventional luteal support, showed inferior clinical results following a GnRHa trigger compared with a conventional hCG trigger...... in normal responder IVF patients. We here present a novel approach for luteal support after a GnRHa trigger. METHODS Normal responder patients who failed at least one previous IVF attempt, during which a conventional hCG trigger was used, were consecutively enrolled in the study. A GnRH antagonist......-based ovarian stimulation protocol was used in combination with a GnRHa trigger (Triptorelin 0.2 mg). The luteal phase was supported with a total of two boluses of 1500 IU hCG: on the day of oocyte retrieval and 4 days later. Neither progesterone nor estradiol was administered for luteal support. RESULTS...

  15. Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

    DEFF Research Database (Denmark)

    Thuesen, L L; Andersen, A Nyboe; Loft, A

    2014-01-01

    : 72; D150: 56 (P ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione...... for controlled ovarian stimulation. SETTING: This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. PATIENTS: From 62 in vitro fertilization patients, 334 FFs were selected for analyses. INTERVENTIONS: Patients were treated using a GnRH agonist......, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos. CONCLUSIONS: Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles...

  16. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    Energy Technology Data Exchange (ETDEWEB)

    Cha Gon, Lee, E-mail: leechagon@eulji.ac.kr [Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University, 68 Hangeulbiseok-ro, Nowon-gu, Seoul 139-711 (Korea, Republic of)

    2016-03-21

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  17. Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR from transfected cells and placenta explants

    Directory of Open Access Journals (Sweden)

    Randeva Harpal

    2011-05-01

    Full Text Available Abstract Placental hCG and pitutary LH transduce signals in target tissues through a common receptor (LHCGR. We demonstrate that recombinant LHCGR proteins which include the hormone-binding domain are secreted from transfected cells and that natural LHCGR is also secreted from human placental explants. LHCGR recombinant proteins representing varying lengths of the N-terminal extracellular domain were expressed in Chinese Hamster Ovary cells in suspension culture. Secretion was minimal up to 72h but by 96h 24-37% of the LHCGR had been released into the culture medium. The secreted proteins were folded and sensitive to glycosidases suggesting N-linked glycosylation. Secretion was independent of recombinant size and was mediated via structurally defined membrane vesicles (50-150nm. Similarly cultured human early pregnancy placental explants also released LHCGR via microvesicles. These studies provide the first experimental evidence of the possible mechanistic basis of the secretion of LHCGR.

  18. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    International Nuclear Information System (INIS)

    Cha Gon, Lee

    2016-01-01

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  19. A Comparative Study of CG CryoDerm and AlloDerm in Direct-to-Implant Immediate Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Jun Ho Lee

    2013-07-01

    Full Text Available Background  To date, various types of acellular dermal matrix (ADM have been developedfor clinical use. AlloDerm is the most familiar type of ADM to most surgeons in breastreconstruction. It is prepared by freeze-drying. CG CryoDerm is the first form of ADM thatrequires no drying process. Therefore,theoretically, it has a higher degree of preservation ofthedermalstructuresthan AlloDerm. We conducted thisstudy to compare the clinical course andpostoperative outcomes of patientswho underwent direct-to-implant breastreconstructionsusing AlloDermand thosewho did using CGCryoDerm.Methods  We performed a retrospective analysis ofthemedicalrecordsin a consecutive seriesof 50 patientswho underwent direct-to-implant breastreconstruction usingAlloDerm(n= 31or CryoDerm (n= 19. We then compared the clinical course and postoperative outcomes ofthe two groups based on the overall incidence of complications

  20. Fixed-time post-cervical artificial insemination in weaned sows following buserelin use combined with/without eCG.

    Science.gov (United States)

    Baroncello, E; Bernardi, M L; Kummer, A D; Wentz, I; Bortolozzo, F P

    2017-02-01

    Fixed-time post-cervical artificial insemination (FTAI) drastically reduces labour requirements and increases the use of boars with higher genetic merit. This study evaluated the efficiency of eCG administration combined with/without the GnRH agonist buserelin for the induction and synchronization of ovulation in weaned sows submitted to FTAI. The sows were allocated into three groups. In the control group, the first artificial insemination was performed at the onset of oestrus and repeated every 24 hr. In the eCG+GnRH group, sows received 600 IU eCG at weaning and buserelin (10 μg) after 86-89 hr of eCG, and in the GnRH group, sows received only buserelin after 86-89 hr of weaning. The hormone-treated sows received a single FTAI after 30-33 hr of buserelin application. All the sows were inseminated with homospermic doses (1.5 × 10 9  sperm cells/50 ml). The interval between weaning and ovulation was shorter (p insemination were considered, but lower farrowing rate and smaller litter size were observed in eCG+GnRH sows. The reproductive performance of eCG+GnRH sows was primarily compromised because the insemination was performed outside the optimal time relative to ovulation; therefore, it is advisable to inseminate them before 116-122 hr after weaning. © 2016 Blackwell Verlag GmbH.

  1. Dehydroepiandrosterone sulfate (DHEAS) levels reflect endogenous LH production and response to human chorionic gonadotropin (hCG) challenge in the older female macaque (Macaca fascicularis)

    Science.gov (United States)

    Moran, Francisco M.; Chen, Jiangang; Gee, Nancy A.; Lohstroh, Pete; Lasley, Bill L.

    2012-01-01

    Hypothesis We propose that the adrenal gland of an older higher primate female animal model will respond to a human chorionic gonadotropic (hCG) hormone challenge by secreting additional dehydroepiandrosterone sulfate (DHEAS). Such a response in surgically and chemically-castrated animals will provide proof-of-concept and a validated animal model for future studies to explore the rise of DHEAS during the menopausal transition of women. Methods Twenty four 18–26 y/o female cynomolgus monkeys were screened for ovarian function then either ovariectomized (n=4) or treated with a gonadotropic releasing hormone agonist (GnRHa) (n=20) to block ovarian steroid production. Following a recovery period from surgery or down-regulation, a single dose challenge (1,000 IU; IM) of human chorionic gonadotropin (hCG) was then administered in order to determine if LH/CG could accelerate circulating DHEAS production. Serum DHEAS, bioactive LH and urinary metabolites of ovarian sex steroids were monitored before, during and following these treatments. Results Circulating LH bioactivity and immunoreactive DHEAS concentrations were suppressed in all animals 14 days post administration of GnRHa. Urinary metabolites of estradiol and progesterone remained low following surgery or the flare reaction to GnRHa. Circulating DHEAS levels were increased following hCG administration and the increase in individual animals was proportional to the pre-treatment DHEAS baseline. Circulating DHEAS concentrations were positively correlated to endogenous LH bioactive concentrations prior to, and were increased by hCG challenge while no concomitant change was observed in ovarian steroid hormone excretion. Conclusion These data demonstrate a positive adrenal androgen response to LH/CG in older female higher primates and suggests a mechanism for the rise in adrenal androgen production during the menopausal transition in women. These results also illustrate that the nonhuman primate animal model can be

  2. Roles of hCG in Advancing Follicular Growth to Ovulation after Concurrent Injections of PGF and GnRH in Postpubertal Holstein Heifers Bearing a CL

    Directory of Open Access Journals (Sweden)

    Ricky Johnson

    2010-01-01

    Full Text Available A study was conducted to test the hypothesis that injecting Gonadotropin-releasing hormone (GnRH concurrently with Prostaglandin F2 alpha (PGF2 followed by an injection of human Chorionic Gonadotropin (hCG, would advance follicular growth to ovulation in Holstein heifers bearing a corpus luteum (CL. After manual examination of the CL, group 1 (PGF; =12 received an injection of PGF2 (25 mg, im. Group 2 (PGF + GnRH; =13 received an injection of GnRH (100 μg, im immediately after an injection of PGF2. Group 3 (PGF + GnRH + hCG; =12 received concurrent injections of PGF2 and GnRH followed with hCG (1500 IU, im two days later. Follicular size and day of ovulation were monitored by daily ultrasonographic examination from days 1 to 10. Blood was collected on days-7, 0 (PGF2 administration, 2, and 7. Progesterone was not different (>.05 on days-7, 0, and 2 between the experimental groups. However, it was higher (<.005 in the PGF + GnRH + hCG group on day 7 compared to PGF + GnRH heifers, but not significantly higher than the PGF. Additionally, heifers in the PGF + GnRH + hCG group ovulated earlier (<.05 than heifers in the PGF + GnRH and the PGF group. This data indicates that hCG advances follicular growth to ovulation in spite of high levels of progesterone when injected 48 h after concurrent treatments of GnRH and PGF2 on heifers bearing a CL.

  3. Conspiracies of immanence: Paul Tillich, Pierre Teilhard de Chardin and C.G. Jung.

    Science.gov (United States)

    Dourley, John

    2015-02-01

    Jung's psychology proffers a sustained reflection on the traditional religious question of the relation of divine transcendence to immanence. On this issue his psychology affirms a position of radical immanence in its contention that the experience of divinity is initially wholly from within. Though this position remains on the periphery of religious and theological orthodoxy Jung is not alone in holding it among moderns. Paul Tillich adopts a similar stance with his controlling symbols of the divine as 'Ground of Being' and 'Depth of Reason'. Pierre Teilhard de Chardin understands divinity as the experiential energy of evolution itself working within nature and humanity toward greater configurations of universal communion as the basis of community. All of Jung's master symbols of individuation assume such an understanding of immanence uniting individual and totality. His psychology strongly suggests and contributes to the current emergence of a new religious sensitivity based on the awareness of the intra-psychic origin of all religions. In his later writings he held out such a position as a significant alternative to genocide. © 2015, The Society of Analytical Psychology.

  4. Mechanistic assessment of peptide reactivity assay to predict skin allergens with Kathon CG isothiazolinones.

    Science.gov (United States)

    Mutschler, Julien; Giménez-Arnau, Elena; Foertsch, Leslie; Gerberick, G Frank; Lepoittevin, Jean-Pierre

    2009-04-01

    Assessment of skin sensitization hazard of chemicals currently depends on in vivo methods. Considering the forthcoming European Union ban on in vivo testing of cosmetic/toiletry ingredients, the search for alternative non-animal approaches is an urgent challenge for investigators today. For the skin sensitization end-point the concept of protein/peptide haptenation, that could reflect the chemical modification of skin proteins, crucial to form immunogenic structures, has been used to develop in vitro assays to predict the sensitization potential of new chemicals. Using glutathione and nucleophile-containing synthetic peptides we confirmed previously the possibility to screen for skin sensitization potential by measuring peptide depletion following incubation with a set of allergens and non-allergens. In this paper, additionally to our model development work, we performed mechanistic based studies to confirm the peptide reactivity concept under the specific conditions used for haptens in the screening assay as they were somewhat different from the ones expected to happen in vivo. Following the reactivity toward the peptides of 13C labelled MI and MCI, models of true haptens, we showed that the initial step leading to the biological end-point was similar regardless the conditions used even if final adducts could be different. This confirmed the validity of the peptide reactivity concept as well as the choice made to look at peptide depletion rather than at adduct formation.

  5. p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China.

    Science.gov (United States)

    Li, Tao; Lu, Zhe-Ming; Guo, Mei; Wu, Qin-Jiao; Chen, Ke-Neng; Xing, Hai-Ping; Mei, Qiang; Ke, Yang

    2002-12-15

    Human papillomavirus (HPV) plays an important role in the development of carcinomas at various body sites. It was found previously that the p53 codon 72 polymorphism (C/G) is a high-risk factor for the development HPV-associated cervical carcinoma. However, it still was considered controversial in several studies of cervical and esophageal carcinoma. In the current study, the authors used an allele specific polymerase chain reaction (PCR) method to analyze correlation between the p53 codon 72 (C/G) polymorphism and HPV-associated, noncancerous esophageal epithelium as well as esophageal, ovarian, and breast carcinoma in the Chinese population. Esophageal balloon cytology examination samples were obtained from high-incidence and low-incidence populations for esophageal carcinoma in Anyang (Henan Province). Thirty-six of 48 esophageal balloon samples from the high-incidence population were HPV positive, and 13 of 33 esophageal balloon samples from the low-incidence population were HPV positive. Thirty-nine of 62 esophageal carcinoma samples from Anyang Tumor Hospital were HPV positive. Twenty-six of 39 ovarian carcinoma samples from the Second Affiliated Hospital of Inner Mongolia Medical College were HPV positive. Nineteen of 82 breast carcinoma samples from Beijing Cancer Hospital were HPV positive. It is noteworthy that the distribution of the p53 codon 72 Arg homozygous genotype in HPV positive samples of esophageal epithelium, ovarian carcinoma, and breast carcinoma was significantly higher compared with HPV negative tumor samples. (P p53 codon 72 Arg homozygous genotype is one of the high-risk genetic factors for HPV-associated malignancies among the Chinese population. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.11008

  6. The IL-6 -634C/G polymorphism: a candidate genetic marker for the prediction of idiopathic recurrent pregnancy loss

    Directory of Open Access Journals (Sweden)

    Zarnegar Rasti

    2016-02-01

    Full Text Available Background: Recurrent pregnancy loss (RPL is defined as two or more miscarriages before the 20th week of gestation and its etiology is unknown in 50% of the cases. Interleukin 6 is an immune mediator, plays a regulatory role in embryo implantation and placental development. Objective: The purpose was to assess the association between IL-6 -634C/G polymorphism and, susceptibility to idiopathic RPL for the first time in Iran. Materials and Methods: In total 121 women with RPL and 121 healthy women as control group were enrolled in this case-control study. This study was performed from August 2013 to October 2014 in the Molecular Genetics Laboratory of Arsanjan University. Candidate polymorphism was evaluated by PCR-RFLP method on extracted genomic DNA. Data was analyzed using the statistical SPSS package. Results: Our results showed an increased risk of RPL in patients with GG + GC genotype (OR=5.1, 95%CI: 1.04-25.3, p=0.04 in comparison to CC genotype. The frequency of mutant allele G in patients and controls was 0.75 and 0.66 respectively. The mutant allele G predisposes women to miscarriage 1.5 times greater than controls (OR=1.5, 95%CI: 1.03-2.27, p=0.036. The mean number of live births in RPL women (1.3±2.3 was significantly lower compared to control women (4.8±2.3. Conclusion: This study indicated that the promoter polymorphism (-634C/G of the IL-6 gene has likely influence on individual susceptibility to RPL.

  7. Molecular characterization of the recombinant protein RmLTI-BmCG-LTB: Protective immunity against Rhipicephalus (Boophilus microplus.

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    Bárbara Guimarães Csordas

    Full Text Available The bovine tick Rhipicephalus (Boophilus microplus is found in several tropical and subtropical regions of the world. This parasite transmits pathogens that cause disease, such as babesiosis (Babesia bovis and B. bigemina and anaplasmosis (Anaplasma marginale. Tick infestations cause enormous livestock losses, and controlling tick infestations and the transmission of tick-borne diseases remains a challenge for the livestock industry. Because the currently available commercial vaccines offer only partial protection against R. (B. microplus, there is a need for more efficient vaccines. Several recombinant antigens have been evaluated using different immunization strategies, and they show great promise. This work describes the construction and immunological characterization of a multi-antigen chimera composed of two R. (B. microplus antigens (RmLTI and BmCG and one Escherichia coli antigen (B subunit, LTB. The immunogenic regions of each antigen were selected and combined to encode a single polypeptide. The gene was cloned and expressed in E. coli. For all of the experiments, two groups (treated and control of four Angus heifers (3-6 months old were used. The inoculation was performed via intramuscular injection with 200 μg of purified recombinant chimeric protein and adjuvated. The chimeric protein was recognized by specific antibodies against each subunit and by sera from cattle inoculated with the chimera. Immunization of RmLTI-BmCG-LTB cattle reduced the number of adult female ticks by 6.29% and vaccination of cattle with the chimeric antigen provided 55.6% efficacy against R. (B. microplus infestation. The results of this study indicate that the novel chimeric protein is a potential candidate for the future development of a more effective vaccine against R. (B. microplus.

  8. Molecular characterization of the recombinant protein RmLTI-BmCG-LTB: Protective immunity against Rhipicephalus (Boophilus) microplus.

    Science.gov (United States)

    Csordas, Bárbara Guimarães; Cunha, Rodrigo Casquero; Garcia, Marcos Valério; da Silva, Sérgio Silva; Leite, Fábio Leivas; Andreotti, Renato

    2018-01-01

    The bovine tick Rhipicephalus (Boophilus) microplus is found in several tropical and subtropical regions of the world. This parasite transmits pathogens that cause disease, such as babesiosis (Babesia bovis and B. bigemina) and anaplasmosis (Anaplasma marginale). Tick infestations cause enormous livestock losses, and controlling tick infestations and the transmission of tick-borne diseases remains a challenge for the livestock industry. Because the currently available commercial vaccines offer only partial protection against R. (B.) microplus, there is a need for more efficient vaccines. Several recombinant antigens have been evaluated using different immunization strategies, and they show great promise. This work describes the construction and immunological characterization of a multi-antigen chimera composed of two R. (B.) microplus antigens (RmLTI and BmCG) and one Escherichia coli antigen (B subunit, LTB). The immunogenic regions of each antigen were selected and combined to encode a single polypeptide. The gene was cloned and expressed in E. coli. For all of the experiments, two groups (treated and control) of four Angus heifers (3-6 months old) were used. The inoculation was performed via intramuscular injection with 200 μg of purified recombinant chimeric protein and adjuvated. The chimeric protein was recognized by specific antibodies against each subunit and by sera from cattle inoculated with the chimera. Immunization of RmLTI-BmCG-LTB cattle reduced the number of adult female ticks by 6.29% and vaccination of cattle with the chimeric antigen provided 55.6% efficacy against R. (B.) microplus infestation. The results of this study indicate that the novel chimeric protein is a potential candidate for the future development of a more effective vaccine against R. (B.) microplus.

  9. Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols

    DEFF Research Database (Denmark)

    Løssl, Kristine; Andersen, A N; Loft, A

    2006-01-01

    Temporary exposure of follicles to increased levels of androgens may enhance their sensitivity to FSH. The aim of this study was to increase the intraovarian androgen level using aromatase inhibitors and hCG before controlled ovarian stimulation (COH) and to test this concept clinically.......Temporary exposure of follicles to increased levels of androgens may enhance their sensitivity to FSH. The aim of this study was to increase the intraovarian androgen level using aromatase inhibitors and hCG before controlled ovarian stimulation (COH) and to test this concept clinically....

  10. Predictive value of serum progesterone level on β-hCG check day in women with previous repeated miscarriages after in vitro fertilization.

    Science.gov (United States)

    Kim, Yong Jin; Shin, Jung Ho; Hur, Jun Yong; Kim, Hoon; Ku, Seung-Yup; Suh, Chang Suk

    2017-01-01

    To evaluate the predictive value of the progesterone level at the beta-human chorionic gonadotropin (β-hCG) check day for ongoing pregnancy maintenance in in vitro fertilization (IVF) cycles in women with previous unexplained repeated miscarriages. One hundred and forty-eight women, with visible gestational sac after IVF, were recruited in this observational study. All subjects had unexplained recurrent miscarriages in more than two previous IVF cycles. The progesterone level at the β-hCG check day (i.e. 14 days after oocyte retrieval) was assessed. The area under the curve (AUC) of the progesterone level was evaluated to predict the ongoing pregnancy or miscarriage outcomes. The overall ongoing pregnancy rate was 60.8% (90/148). The cut-off value with β-hCG levels higher than 126.5 mIU/mL and with progesterone levels higher than 25.2 ng/mL could be the predictive factors for ongoing pregnancy maintenance (AUC = 0.788 and 0.826; sensitivity = 0.788 and 0.723; specificity = 0.689 and 0.833; P hCG > 126.5 mIU/mL and 13.0% (10/77) in those with > 25.2 ng/mL. In the comparison of the ROC curves between both values, a similar significance was found. The subjects with β-hCG > 126.5 mIU/mL and progesterone > 25.2 ng/mL showed higher ongoing pregnancy rates [98.0% (49/50) vs. 41.8% (41/98)] than those with β-hCG ≤ 126.5 mIU/mL or progesterone ≤ 25.2 ng/mL. The progesterone level at 14 days after oocyte retrieval can be a good predictive marker for ongoing pregnancy maintenance in women with repeated IVF failure with miscarriage, together with the β-hCG level. The combined cut-off value of progesterone > 25.2 ng/mL and β-hCG > 126.5 mIU/mL may suggest a good prognosis.

  11. USO DA eCG PARA FORMAÇÃO DO CORPO LÚTEO EQÜINO E PRODUÇÃO DE PROGESTERONA

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    Tiago Gomes RODRIGUES

    2015-12-01

    Full Text Available Este estudo foi conduzido com a finalidade de avaliar o uso da gonadotrofina coriônica eqüina (eCG logo após a ovulação de éguas com o objetivo avaliar a formação do corpo lúteo e produção de progesterona. Utilizou-se 50 éguas durante 2 estações de monta 2011/2012 e 2012/2013. Com auxílio da ultrassonografia as éguas foram monitoradas as características dos órgãos genitais durante o estro até o dia da ovulação (D0 e no diestro em D2, D4 e D8. O experimento foi dividido em 2 tratamentos: Tratamento I (n=25 – éguas com ovulação natural e tratamento II (n=25  – éguas com ovulação induzida. Verificada a ovulação, os tratamentos foram sub divididas em 5 grupos de 5 animais, obedecendo a administração do fármaco estudado (eCG, sendo GI: controle; GII: 250 UI eCG no DO; GIII: 250 UI eCG no DO + 250 UI eCG no D2; GIV: 500 UI no Do; e GV: 500 UI eCG no D0 + 500 UI no D2. Para a avaliação do efeito dose resposta do fármaco e influência do eCG sob a glândula luteínica, foram coletados os dados: tônus uterino, ecogenicidade e tamanho do corpo lúteo (CL e concentração de progesterona. Na análise estatística somente quando comparando o GV entre os dois tratamentos há diferença estatística para o D8 na concentração de progesterona. Portanto o uso da eCG no momento da ovulação, não produziu efeito significativo esperado, mas este trabalho inicial abre portas para novas investigações a respeito desta biomolécula, e que venha contribuir na biotecnologia reprodutiva equina.

  12. In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT.

    Science.gov (United States)

    Shen, Li-Fang; Zhao, Xin; Zhou, Shui-Hong; Lu, Zhong-Jie; Zhao, Kui; Fan, Jun; Zhou, Min-Li

    2017-05-23

    Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 × 107/mL × 0.2 mL) and Tu212 cells (2 × 107/mL × 0.2 mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μg) and GLUT-1 AS-ODNs (100 μg) on the radiosensitivity of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after treatment (p effect (necrosis, apoptosis). Simultaneous inhibition of HIF-1α and GLUT-1 expression might increase the radiosensitivity of laryngeal carcinoma, decreasing MVD

  13. Complementary and Alternative Medicine

    Science.gov (United States)

    ... for Educators Search English Español Complementary and Alternative Medicine KidsHealth / For Teens / Complementary and Alternative Medicine What's ... a replacement. How Is CAM Different From Conventional Medicine? Conventional medicine is based on scientific knowledge of ...

  14. Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders and induces a gene expression switch toward fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats.

    Science.gov (United States)

    Li, Linyi; Yoshitomi, Hisae; Wei, Ying; Qin, Lingling; Zhou, Jingxin; Xu, Tunhai; Wu, Xinli; Zhou, Tian; Sun, Wen; Guo, Xiangyu; Wu, Lili; Wang, Haiyan; Zhang, Yan; Li, Chunna; Liu, Tonghua; Gao, Ming

    2015-01-01

    Increased energy intake and reduced physical activity can lead to obesity, diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks has become a focus of current drug discovery research into the prevention and treatment of metabolic disorders associated with energy surplus and obesity. Tang-Nai-Kang (TNK), a mixture of five herbal plant extracts, has been shown to improve abnormal glucose metabolism in patients with pre-diabetes. Here, we report the metabolic phenotype of SHR.Cg-Leprcp/NDmcr (SHR/cp) rats treated with TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose (1.67 g/kg) and TNK high-dose (3.24 g/kg) groups. After high-dose treatment for 2 weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly reduced compared to controls. After 3 weeks of administration, the high dose of TNK significantly reduced the body weight and fat mass of SHR/cp rats without affecting food consumption. Serum fasting glucose and insulin levels in the TNK-treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated rats exhibited obvious improvements in glucose intolerance and insulin resistance. The improved glucose metabolism may be caused by the substantial reduction in serum lipids and body weight observed in SHR/cp rats starting at 3 weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin 1 (SIRT1) and genes related to fatty acid oxidation was markedly up-regulated in the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK promoted the deacetylation of two well-established SIRT1 targets, PPARγ coactivator 1α (PGC1α) and forkhead transcription factor 1 (FOXO1), and induced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in different tissues. These observations suggested that TNK may be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a gene expression switch toward fat

  15. Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison

    NARCIS (Netherlands)

    van Mello, N. M.; Mol, F.; Verhoeve, H. R.; van Wely, M.; Adriaanse, A. H.; Boss, E. A.; Dijkman, A. B.; Bayram, N.; Emanuel, M. H.; Friederich, J.; van der Leeuw-Harmsen, L.; Lips, J. P.; van Kessel, M. A.; Ankum, W. M.; van der Veen, F.; Mol, B. W.; Hajenius, P. J.

    2013-01-01

    What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and

  16. Temporal effects of maternal and pregnancy characteristics on serum PAPP-A and free β-hCG at 7-14 weeks' gestation

    DEFF Research Database (Denmark)

    Ball, Susan; Ekelund, Charlotte; Wright, Dave

    2013-01-01

    Objective: Investigate gestational age dependent effects of racial origin, smoking status and mode of conception on maternal serum levels of free ß-human chorionic gonadotropin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. Methods: Data arise from prospective...

  17. Ovulation and conception rates according intravaginal progesterone device and hCG or GnRH to induce ovulation in buffalo during the off breeding season

    Directory of Open Access Journals (Sweden)

    P.S. Baruselli

    2010-02-01

    Full Text Available The objective of this study was to evaluate the effect of intravaginal progesterone device (P4; first or second use of different ovulatory inductors on ovulation and conception rates in buffaloes during the off breeding season. Two hundred and forty two buffaloes were allocated in four groups and received P4 device of first or second use plus estradiol benzoate on Day 0 (D0. The P4 device was removed and a dose of PGF2α and eCG was administered on D9. On D11, buffaloes received hCG or GnRH and 16hs after the animals were inseminated. The ultrasound examination was performed on D0 to verify the ovarian status, from D9 to D14 to establish the moment of ovulation and on D40 for pregnancy diagnosis. Data were analyzed by ANOVA and Chi-square test. There was no effect of interaction. The ovulation and conception rate were similar for P4 device of first and second use, for hCG and GnRH. Results indicate that the use of P4 device for two times and the use of GnRH instead of hCG provide satisfactory ovulation and conception rate in buffalo during the off breeding season and might reduce the cost of the protocol for artificial insemination.

  18. Short-term androgen priming by use of aromatase inhibitor and hCG before controlled ovarian stimulation for IVF. A randomized controlled trial

    DEFF Research Database (Denmark)

    Lossl, K; Andersen, C Yding; Loft, A

    2008-01-01

    Temporary exposure of follicles to increased levels of androgens may augment follicular responsiveness. The present study tested whether short-term androgen priming by aromatase inhibitor and human chorionic gonadotrophin (hCG) before controlled ovarian stimulation (COS) increases the number of top......-quality embryos after IVF/ICSI....

  19. Identification of patients with persistent trophoblastic disease after complete hydatidiform mole by using a normal 24-hour urine hCG regression curve

    NARCIS (Netherlands)

    Cromvoirt, S.M. van; Thomas, C.M.G.; Quinn, M.A.; McNally, O.M.; Bekkers, R.L.M.

    2014-01-01

    OBJECTIVE: The aim of this study was to establish a reference 24-hour urine human chorionic gonadotropin (hCG) regression curve in patients with complete hydatidiform mole (CHM) as diagnostic tool in the prediction of persistent trophoblastic disease (PTD). METHODS: From 2004 to 2011, 312 cases

  20. Sowing Seeds on the Beautiful Journey in 10 Cities : Improving Corporate Governance Practices among Chinese Companies by Strengthening Local Capacity for CG Consulting Services

    OpenAIRE

    Liu, Min

    2010-01-01

    Corporate governance (CG) is a journey, not a destination. The International Finance Corporation (IFC) China Corporate Governance Program started its journey in ten cities of China in 2009 and sowed 'seeds' on the ground. Today, some of those seeds are germinating, blossoming, and bearing fruit. This smart lesson describes what steps we took, including selecting partners, mapping the journ...

  1. Higher fatty acids in Chlorella vulgaris (pyrenoidosa): Content of indivudual acids and use of the algae for the preparation of higher fatty acids - 14C(G)

    International Nuclear Information System (INIS)

    Matucha, M.

    1975-01-01

    A survey of data on the occurrence of higher fatty acids in the lipids of C h l o r e l l a v u l g a r i s (pyrenoidosa) is presented with a view to the biosynthetical preparation of fatty acids- 14 C(G). (author)

  2. Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols

    DEFF Research Database (Denmark)

    Løssl, Kristine; Andersen, A N; Loft, A

    2006-01-01

    Temporary exposure of follicles to increased levels of androgens may enhance their sensitivity to FSH. The aim of this study was to increase the intraovarian androgen level using aromatase inhibitors and hCG before controlled ovarian stimulation (COH) and to test this concept clinically....

  3. Mutations in the pfmdr1, cg2, and pfcrt genes in Plasmodium falciparum samples from endemic malaria areas in Rondonia and Pará State, Brazilian Amazon Region.

    Science.gov (United States)

    Viana, Giselle Maria Rachid; Machado, Ricardo Luís Dantas; Calvosa, Vanja Sueli Pachiano; Póvoa, Marinete Marins

    2006-12-01

    The objectives of this study were to investigate the molecular basis for Plasmodium falciparum resistance to chloroquine in isolates from the Brazilian Amazon and to identify polymorphisms in the pfmdr1 gene, codons 184, 1042, and 1246, the kappa and gamma regions of the cg2 gene, and the K76T mutation of the pfcrt gene, in order to calculate the distribution of polymorphism within each target gene, comparing samples from distinct geographic areas, using allele-specific polymerase chain reaction (PCR) for the pfmdr gene and PCR plus restriction fragment length polymorphism (RFLP) for the cg2 and pfcrt genes. The sample consisted of 40 human blood isolates, already collected and morphologically diagnosed as carriers of P. falciparum parasites, from four localities: Porto Velho in Rondonia State and Maraba, Itaituba, and Tailandia in Pará State. Distribution of P. falciparum in vitro chloroquine resistance in the isolates was 100% for pfmdr1, cg2 gamma region, and pfcrt, except for the polymorphism in the cg2 kappa region, which was not found.

  4. CG0009, a novel glycogen synthase kinase 3 inhibitor, induces cell death through cyclin D1 depletion in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Hyun Mi Kim

    Full Text Available Glycogen synthase kinase 3α/β (GSK3α/β is a constitutively active serine/threonine kinase involved in multiple physiological processes, such as protein synthesis, stem cell maintenance and apoptosis, and acts as a key suppressor of the Wnt-β-catenin pathway. In the present study, we examined the therapeutic potential of a novel GSK3 inhibitor, CG0009, in the breast cancer cell lines, BT549, HS578T, MDA-MB-231, NCI/ADR-RES, T47D, MCF7 and MDA-MB-435, from the NCI-60 cancer cell line panel. Assessment of cytotoxicity, apoptosis and changes in estrogen-signaling proteins was performed using cell viability assays, Western blotting and quantitative real-time PCR. CG0009 enhanced the inactivating phosphorylation of GSK3α at Ser21 and GSK3β at Ser9 and simultaneously decreased activating phosphorylation of GSK3β at Tyr216, and induced caspase-dependent apoptosis independently of estrogen receptor α (ERα expression status, which was not observed with the other GSK3 inhibitors examined, including SB216763, kenpaullone and LiCl. CG0009 treatment (1 µmol/L completely ablated cyclin D1 expression in a time-dependent manner in all the cell lines examined, except T47D. CG0009 alone significantly activated p53, leading to relocation of p53 and Bax to the mitochondria. GSK3 inhibition by CG0009 led to slight upregulation of the β-catenin target genes, c-Jun and c-Myc, but not cyclin D1, indicating that CG0009-mediated cyclin D1 depletion overwhelms the pro-survival signal of β-catenin, resulting in cell death. Our findings suggest that the novel GSK3 inhibitor, CG0009, inhibits breast cancer cell growth through cyclin D1 depletion and p53 activation, and may thus offer an innovative therapeutic approach for breast cancers resistant to hormone-based therapy.

  5. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

    Science.gov (United States)

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

    2015-10-01

    Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace

  6. hCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in Leydig cells of the testis

    Science.gov (United States)

    Park, Sun-Ji; Kim, Tae-Shin; Park, Choon-Keun; Lee, Sang-Hee; Kim, Jin-Man; Lee, Kyu-Sun; Lee, In-kyu; Park, Jeen-Woo; Lawson, Mark A; Lee, Dong-Seok

    2014-01-01

    Endoplasmic reticulum (ER) stress generally occurs in secretory cell types. It has been reported that Leydig cells, which produce testosterone in response to human chorionic gonadotropin (hCG), express key steroidogenic enzymes for the regulation of testosterone synthesis. In this study, we analyzed whether hCG induces ER stress via three unfolded protein response (UPR) pathways in mouse Leydig tumor (mLTC-1) cells and the testis. Treatment with hCG induced ER stress in mLTC-1 cells via the ATF6, IRE1a/XBP1, and eIF2α/GADD34/ATF4 UPR pathways, and transient expression of 50 kDa protein activating transcription factor 6 (p50ATF6) reduced the expression level of steroidogenic 3β-hydroxy-steroid dehydrogenase Δ5-Δ4-isomerase (3β-HSD) enzyme. In an in vivo model, high-level hCG treatment induced expression of p50ATF6 while that of steroidogenic enzymes, especially 3β-HSD, 17α-hydroxylase/C17–20 lyase (CYP17), and 17β-hydrozysteroid dehydrogenase (17β-HSD), was reduced. Expression levels of steroidogenic enzymes were restored by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Furthermore, lentivirus-mediated transient expression of p50ATF6 reduced the expression level of 3β-HSD in the testis. Protein expression levels of phospho-JNK, CHOP, and cleaved caspases-12 and -3 as markers of ER stress-mediated apoptosis markedly increased in response to high-level hCG treatment in mLTC-1 cells and the testis. Based on transmission electron microscopy and H&E staining of the testis, it was shown that abnormal ER morphology and destruction of testicular histology induced by high-level hCG treatment were reversed by the addition of TUDCA. These findings suggest that hCG-induced ER stress plays important roles in steroidogenic enzyme expression via modulation of the ATF6 pathway as well as ER stress-mediated apoptosis in Leydig cells. PMID:23256993

  7. The dual role of candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance

    Science.gov (United States)

    Costa, Catarina; Henriques, André; Pires, Carla; Nunes, Joana; Ohno, Michiyo; Chibana, Hiroji; Sá-Correia, Isabel; Teixeira, Miguel C.

    2013-01-01

    Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms. In this study, the drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g), from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a green fluorescent protein fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of 3H-flucytosine and, to a moderate extent, of 3H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of 14C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization and

  8. Depleted uranium management alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process.

  9. Cut-off value of initial serum β-hCG level predicting a successful MTX therapy in tubal ectopic pregnancy: a retrospective cohort study.

    Science.gov (United States)

    Helmy, S; Bader, Y; Pablik, E; Tiringer, D; Pils, S; Laml, T; Kölbl, H; Koch, M

    2014-08-01

    To determine the optimal serum β-hCG cut-off level to predict MTX treatment success in tubal ectopic pregnancy (EP). Data of 240 women, who presented between 2003 and 2011 at the Department of Gynecology and Obstetrics, Medical University of Vienna, with tubal EP and who received MTX as primary treatment, were retrieved from the hospital information system (KIS). 198 patients could be included for final evaluation. Statistical analysis included area under the ROC curve, maximal Euclidean and Youden index, chi-squared and a five-fold cross validation. The serum β-hCG level cut-off value was calculated at 2121mlU/ml with a specificity of 76.54% and sensitivity of 80.56% (AUC 0.789; ptreatment failure in 5.3% (n=7), compared to 43.3% (n=29) of patients with an initial serum β-hCG level equal to or above 2121mlU/ml (n=67). There was no statistically significant correlation between clinical symptoms and the MTX therapy outcome (p=0.580; likelihood quotient p=0.716). The correct decision of therapy in patients with tubal ectopic pregnancy still represents a challenge. In this study we can conclude that, according to our results there is no endpoint of initial serum β-hCG levels, which can be clearly used as cut-off value for the optimal management of tubal EP. However, an initial serum β-hCG level of less than 2121mlU/ml seems to be a good value to expect a successful MTX treatment. Limitations are the retrospective study design and the inability of classifying clinical symptoms like pain as an objective parameter. Wider implications of the findings may include more detailed patient information and more accurate selection of suitable patients for MTX therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

    Science.gov (United States)

    Roli, L; Santi, D; Belli, S; Tagliavini, S; Cavalieri, S; De Santis, M C; Baraldi, E; Fanelli, F; Mezzullo, M; Granata, A R; Pagotto, U; Pasquali, R; Rochira, V; Carani, C; Simoni, M; Trenti, T

    2017-08-01

    Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

  11. Estrogen Modulates Specific Life and Death Signals Induced by LH and hCG in Human Primary Granulosa Cells In Vitro.

    Science.gov (United States)

    Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Marino, Marco; Vecchi, Eugenia; Morini, Daria; Nicoli, Alessia; La Sala, Giovanni Battista; Simoni, Manuela

    2017-04-28

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17β-estradiol, in long-term, serum-starved human primary granulosa cells (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR). To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and procaspase 3 cleavage were evaluated over three days by Western blotting, along with the expression of target genes by real-time PCR and cell viability by colorimetric assay. We found that LH induced predominant pERK1/2 and pAKT activation STARD1 , CCND2 and anti-apoptotic XIAP gene expression, while hCG mediated more potent CREB phosphorylation, expression of CYP19A1 and procaspase 3 cleavage than LH. Cell treatment by LH is accompanied by increased (serum-starved) cell viability, while hCG decreased the number of viable cells. The hCG-specific, pro-apoptotic effect was blocked by a physiological dose of 17β-estradiol, resulting in pAKT activation, lack of procaspase 3 cleavage and increased cell viability. These results confirm that relatively high levels of steroidogenic pathway activation are linked to pro-apoptotic signals in vitro, which may be counteracted by other factors, i.e., estrogens.

  12. The value of delaying hCG administration to enable maturation of medium-sized follicles in patients undergoing superovulation for IVF/ICSI.

    Science.gov (United States)

    Awonuga, Awoniyi O; Wheeler, Karen; Thakur, Mili; Jeelani, Roohi; Diamond, Michael P; Puscheck, Elizabeth E

    2018-02-01

    The purpose of the study is to determine whether continued stimulation of mature follicles to allow "catch up" growth of medium-sized follicles in assisted reproductive technology compromises the clinical pregnancy (CPR) and live birth (LBR) rates in IVF/ICSI cycles. This retrospective cohort study reviewed 200 first IVF ± ICSI cycles out of a total of 340 cycles with complete data. Women underwent stimulation protocols with gonadotropins (Gn) and GnRH antagonist. Treatment cycles were divided into two groups (Gp): hCG administration delayed despite the presence of two mature follicles, defined as ≥ 18 mm [Gp1, n = 79] and hCG administration given when there were two mature follicles [Gp2, n = 121]. The patients in Gp1 were significantly younger than those in Gp2 [32.9 (4.5) vs. 34.3 (4.8), p = 0.04] and needed a median of one more day of superovulation before ovulation was triggered with hCG. The extra days was associated with the use of 450 [75-2025] more Gn, such that at the time the hCG was administered, patient's in group 1 had developed significantly greater number of follicles ≥ 18 mm [mean (SD), 4.9 (1.8) vs. 3.4 (1.7), p hCG administration to allow further growth of the medium-sized follicles added further days of superovulation and cost without improvement in CPR and LBR.

  13. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  14. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song; Chen, Hungwen

    2016-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Pre-hCG 3D and 3D power Doppler assessment of the follicle for improving pregnancy rates in intrauterine insemination cycles

    Directory of Open Access Journals (Sweden)

    Sonal Panchal

    2009-01-01

    Full Text Available Background: The assessment of follicular maturity at the time of human chorionic gonadotropin (hCG is one of the key factors for the success of all assisted reproductive techniques. Aim: To assess follicles by three dimensional (3D and 3D power Doppler (PD before giving hCG to improve pregnancy rates in intrauterine insemination (IUI cycles. Design: Prospective randomized study. Materials and Methods: Ultrasound for pre-hCG follicular assessment was performed over a period of 10 months for all 1000 cycles of IUI. Follicular assessment was performed using a transvaginal multifrequency volume probe. Follicles considered mature by 2D US and color Doppler were assessed by 3D and 3D PD. These values were independently evaluated for the conception and the non-conception groups. Results: Conception rates were 32.3 and 27% respectively and individually when the perifollicular resistance index was 11 cm/s 10-12 h before hCG. Conception rates of 32% were achieved with a follicular volume between 3 and 7 cc. The conception rate was 32.3% in the cumulus group. A perifollicular vascularity index of between six and 20 gave conception rates of 35% and perifollicular flow index of 27-43 gave conception rates of 33%. Conclusions: 3D ultrasound is much more accurate for volume assessment of the follicle. Presence of cumulus increases the surety of the presence of a mature ovum in the follicle. 3D and 3D PD when used with 2D US and color Doppler for pre-hCG follicular assessment would definitely improve pregnancy rates in IUI cycles.

  16. Chemokine (C-C motif) ligand 5 -28C>G is significantly associated with an increased risk of tuberculosis: a meta-analysis

    Science.gov (United States)

    Hu, Lelin; Zhang, Kaixian; Yao, Lihong; Wang, Junjie

    2015-01-01

    Objective: Chemokine (C-C motif) ligand 5 (CCL5) has been shown to play an important role in antimycobacterial immune responses. Previous studies have extensively reported that the CCL5 -28C>G gene polymorphism is associated with susceptibility to tuberculosis (TB). However, the results of these studies have been inconsistent. To investigate the relationship between the CCL5 -28C>G and the risk of TB, we performed a meta-analysis. Methods: We searched articles published before June 6, 2014 from PubMed, CNKI, and Wanfang databases. Data were extracted from all eligible publications independently by two investigators and statistically analyzed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the strength of the association between CCL5 polymorphism and TB. Results: Four case-control studies including 647 TB cases and 726 controls were involved in the meta-analysis. Our meta-analysis indicated the CCL5 -28C>G gene polymorphism was significantly associated with increased risk of TB (G vs. C: 3.75, 95% CI = 1.76-7.99; GG vs. CC: OR = 30.26, 95% CI = 14.28-64.12). Conclusion: Our results suggested that the -28C>G polymorphism is significantly associated with higher TB risk, which is opposite from previously published reports. However, the number of the study is limited, additional well-designed studies are required to elucidate the association between the CCL5 -28C>G gene polymorphism and TB. PMID:26550245

  17. Longer time-to-pregnancy in spontaneously conceived pregnancies is associated with lower PAPP-A and free β-hCG in first trimester screening for Down syndrome

    DEFF Research Database (Denmark)

    Kirkegaard, I; Uldbjerg, N; Tabor, A

    2014-01-01

    -hCG) and hence the risk estimates in Down syndrome screening. METHODS: The study included a cohort of 10 469 singleton pregnant women who underwent first trimester combined screening and responded to a questionnaire regarding TTP. PAPP-A and free β-hCG levels were measured between gestational week 8 + 0 and 13...

  18. Humidity effects on soluble core mechanical and thermal properties (polyvinyl alcohol/microballoon composite) type CG extendospheres, volume 2

    Science.gov (United States)

    1993-01-01

    This document constitutes the final report for the study of humidity effects and loading rate on soluble core (PVA/MB composite material) mechanical and thermal properties under Contract No. 100345. This report describes test results procedures employed, and any unusual occurrences or specific observations associated with this test program. The primary objective of this work was to determine if cured soluble core filler material regains its tensile and compressive strength after exposure to high humidity conditions and following a drying cycle. Secondary objectives include measurements of tensile and compressive modulus, and Poisson's ratio, and coefficient of thermal expansion (CTE) for various moisture exposure states. A third objective was to compare the mechanical and thermal properties of the composite using 'SG' and 'CG' type extendospheres. The proposed facility for the manufacture of soluble cores at the Yellow Creek site incorporates no capability for the control of humidity. Recent physical property tests performed with the soluble core filler material showed that prolonged exposure to high humidity significantly degradates in strength. The purpose of these tests is to determine if the product, process or facility designs require modification to avoid imparting a high risk condition to the ASRM.

  19. Community-acquired meningitis caused by a CG86 hypervirulent Klebsiella pneumoniae strain: first case report in the Caribbean.

    Science.gov (United States)

    Melot, Bénédicte; Brisse, Sylvain; Breurec, Sébastien; Passet, Virginie; Malpote, Edith; Lamaury, Isabelle; Thiery, Guillaume; Hoen, Bruno

    2016-12-07

    Community-acquired bacterial meningitis due to Klebsiella pneumoniae has mainly been described in Southeast Asia and has a poor prognosis. Severe invasive infections caused by K. pneumoniae, including meningitis, are often due to hypervirulent strains (hvKP), which are characterized by capsular serotypes K1 and K2, a gene responsible for hypermucoviscosity, and the cluster for synthesis of the siderophore aerobactin. A 55 year old man with a history of essential hypertension, benign prostate hyperplasia, hyperlipidemia, obstructive sleep apnea, and chronic alcoholism was admitted for meningitis due to Klebsiella pneumoniae with a wild-type susceptibility profile. Its genomic features were consistent with a capsular K2 strain belonging to clonal group 86 (CG86) displaying the large virulence of Klebsiella plasmid (pLVPK) with heavy metal resistance gene clusters, aerobactin, rmpA. This is the first case of community-acquired meningitis caused by a hypervirulent strain of hvKP ever reported in the Caribbean.

  20. Effect of recombinant-LH and hCG in the absence of FSH on in vitro maturation (IVM) fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.

    Science.gov (United States)

    Dinopoulou, Vasiliki; Drakakis, Peter; Kefala, Stella; Kiapekou, Erasmia; Bletsa, Ritsa; Anagnostou, Elli; Kallianidis, Konstantinos; Loutradis, Dimitrios

    2016-06-01

    During in vitro maturation (IVM), intrinsic and extrinsic factors must co-operate properly in order to ensure cytoplasmic and nuclear maturation. We examined the possible effect of LH/hCG in the process of oocyte maturation in mice with the addition of recombinant LH (r-LH) and hCG in our IVM cultures of mouse germinal vesicle (GV)-stage oocytes. Moreover, the effects of these hormones on fertilization, early embryonic development and the expression of LH/hCG receptor were examined. Nuclear maturation of GV-stage oocytes was evaluated after culture in the presence of r-LH or hCG. Fertilization rates and embryonic development were assessed after 24h. Total RNA was isolated from oocytes of different stages of maturation and from zygotes and embryos of different stages of development in order to examine the expression of LH/hCG receptor, using RT-PCR. The in vitro nuclear maturation rate of GV-stage oocytes that received hCG was significantly higher compared to the control group. Early embryonic development was increased in the hCG and LH cultures of GV oocytes when LH was further added. The LH/hCG receptor was expressed in all stages of in vitro matured mouse oocytes and in every stage of early embryonic development. Addition of hCG in IVM cultures of mouse GV oocytes increased maturation rates significantly. LH, however, was more beneficial to early embryonic development than hCG. This suggests a promising new technique in basic science research or in clinical reproductive medicine. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Alternative Auditing Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Kandt, Alicen J [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-15

    This presentation for the 2017 Energy Exchange in Tampa, Florida, offers information about advanced auditing technologies and techniques including alternative auditing approaches and considerations and caveats.

  2. A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

    Science.gov (United States)

    Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

    2017-05-01

    Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30

  3. Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

    Science.gov (United States)

    Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

    2016-11-01

    A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  4. Assessment of Serum Progesterone Level on the Day of hCG Injection in Infertile Polycystic Ovarian Syndrome Patients Referred to Women’s Hospital, Tehran, 2009

    Directory of Open Access Journals (Sweden)

    Forough Forghani

    2012-01-01

    Full Text Available Background: Polycystic ovarian syndrome (PCOS is one of the most common causes of endocrine disorders and main reasons for infertility due to unovulation and recurrent abortions. There is no consensus on effect of serum progesterone level on the day of human chorionic gonadotropin (hCG injection. This study aims to evaluate the effect of plasma levels of progesterone on the day of hCG injection on the rate of pregnancy in in vitro fertilization (IVF cycles of PCOS cases.Materials and Methods: A stratified cohort study was conducted over a period of one year (2009 on 38 infertile women with PCOS who were suitable candidates for the IVF program. Patients were evaluated for other causes of infertility with hysterosalpingography (HSG, laparoscopy and normal sperm analysis. Patients were placed on the long protocol, followed by oocyte pick up, and finally IVF-embryo transfer (ET. Study patients were grouped according to progesterone levels of greater or less than 1.2 ng/ml on the day of hCG injection. Pregnancy rates were defined in each group. Levels on day of hCG day clinical pregnancy outcome were assessed. Experimental data were then compared against Fisher’s exact test in SPSS version 18.Results: The overall pregnancy rate in this study was 26.3%. In the group with progesterone levels more than 1.2 ng/ml on the day of hCG injection, the clinical pregnancy rate was 4 (21.1% and chemical pregnancy rate was 3(15.8%. In the group with progesterone levels less than 1.2 ng/ml, the clinical pregnancy rate was 1(5.3% and chemical pregnancy rate was 2(10. 5%.Conclusion: This study showed that PCOS patients with progesterone levels more than 1.2 ng/ml on the day of hCG injection resulted in higher chemical and clinical pregnancy rates. However, no significant statistical differences were found between the two groups. For further verification, we recommend additional studies with larger numbers of subjects.

  5. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

    2017-03-07

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  6. Serum angiopoietin-2 and β-hCG as predictors of prolonged uterine bleeding after medical abortion in the first trimester.

    Directory of Open Access Journals (Sweden)

    Maofeng Wang

    Full Text Available OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We evaluate serum Angiopoietin-2 (Ang-2 and β human chorionic gonadotropin (β-hCG in women who had undergone a medical abortion as markers of prolonged uterine bleeding (PUB. METHODS: Prospective trial involving 2843 women attending an gynecology outpatient clinic who following a medical abortion with mifepristone and misoprostol, the study cohort was divided into women with duration of uterine bleeding >14 days (PUB and women with duration of uterine bleeding ≤14 days (normal uterine bleeding, NUB. Serum determinations of Ang-2 levels by ELISA and β-hCG levels by electrochemiluminiscence immunoassay. Receiver Operating Characteristics (ROC analyses were calculated and plotted for the diagnostic accuracy of serum β-hCG and Ang-2 concentration to discriminate PUB and NUB. RESULTS: Baseline characteristics for both groups were similar, Only duration of bleeding showed a significant difference between the PUB group and NUB group. Ang-2 serum levels moderately correlated with serum β-hCG levels with statistically significant correlation coefficients of 0.536. Serum β-hCG and Ang-2 levels on day 7 and on day 14 after medical abortion were signifcantly higher in PUB group than in NUB group. Plotted as ROC curves, β-hCG area under curve (AUC was 0.65 (95% CI, 0.53-0.76 on day 7, rising to AUC = 0.83 (95% CI, 0.75-0.92 on day 14. Using Ang-2 on day 7 and day 14 as predictive parameter resulted in an analogous AUC (AUC = 0.61 on day 7, AUC = 0.78 on day 14. CONCLUSIONS: Both parameters are clinically useful as a diagnostic test in predicting PUB after medical abortion, and can be helpful in uncertain clinical situations, but should be considered as supplementary to a general clinical evaluation.

  7. Alternative health insurance schemes

    DEFF Research Database (Denmark)

    Keiding, Hans; Hansen, Bodil O.

    2002-01-01

    In this paper, we present a simple model of health insurance with asymmetric information, where we compare two alternative ways of organizing the insurance market. Either as a competitive insurance market, where some risks remain uninsured, or as a compulsory scheme, where however, the level...... competitive insurance; this situation turns out to be at least as good as either of the alternatives...

  8. The RpfCG two-component system negatively regulates the colonization of sugar cane stalks by Xanthomonas albilineans.

    Science.gov (United States)

    Rott, Philippe; Fleites, Laura A; Mensi, Imène; Sheppard, Lauren; Daugrois, Jean-Heinrich; Dow, J Maxwell; Gabriel, Dean W

    2013-06-01

    The genome of Xanthomonas albilineans, the causal agent of sugar cane leaf scald, carries a gene cluster encoding a predicted quorum sensing system that is highly related to the diffusible signalling factor (DSF) systems of the plant pathogens Xylella fastidiosa and Xanthomonas campestris. In these latter pathogens, a cluster of regulation of pathogenicity factors (rpf) genes encodes the DSF system and is involved in control of various cellular processes. Mutation of Xanthomonas albilineans rpfF, encoding a predicted DSF synthase, in Florida strain XaFL07-1 resulted in a small reduction of disease severity (DS). Single-knockout mutations of rpfC and rpfG (encoding a predicted DSF sensor and regulator, respectively) had no effect on DS or swimming motility of the pathogen. However, capacity of the pathogen to cause disease was slightly reduced and swimming motility was severely affected when rpfG and rpfC were both deleted. Similar results were obtained when the entire rpfGCF region was deleted. Surprisingly, when the pathogen was mutated in rpfG or rpfC (single or double mutations) it was able to colonize sugar cane spatially more efficiently than the wild-type. Mutation in rpfF alone did not affect the degree of spatial invasion. We conclude that the DSF signal contributes to symptom expression but not to invasion of sugar cane stalks by Xanthomonas albilineans strain XaFL07-1, which is mainly controlled by the RpfCG two-component system.

  9. Functional analysis of the glycogen binding subunit CG9238/Gbs-70E of protein phosphatase 1 in Drosophila melanogaster.

    Science.gov (United States)

    Kerekes, Éva; Kókai, Endre; Páldy, Ferenc Sándor; Dombrádi, Viktor

    2014-06-01

    The product of the CG9238 gene that we termed glycogen binding subunit 70E (Gbs-70E) was characterized by biochemical and molecular genetics methods. The interaction between Gbs-70E and all catalytic subunits of protein phosphatase 1 (Pp1-87B, Pp1-9C, Pp1-96A and Pp1-13C) of Drosophila melanogaster was confirmed by pairwise yeast two-hybrid tests, co-immunoprecipitation and pull down experiments. The binding of Gbs-70E to glycogen was demonstrated by sedimentation analysis. With RT-PCR we found that the mRNAs coding for the longer Gbs-70E PB/PC protein were expressed in all developmental stages of the fruit flies while the mRNA for the shorter Gbs-70E PA was restricted to the eggs and the ovaries of the adult females. The development specific expression of the shorter splice variant was not conserved in different Drosophila species. The expression level of the gene was manipulated by P-element insertions and gene deletion to analyze the functions of the gene product. A small or moderate reduction in the gene expression resulted in no significant changes, however, a deletion mutant expressing very low level of the transcript lived shorter and exhibited reduced glycogen content in the imagos. In addition, the gene deletion decreased the fertility of the fruit flies. Our results prove that Gbs-70E functions as the glycogen binding subunit of protein phosphatase 1 that regulates glycogen content and plays a role in the development of eggs in D. melanogaster. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Influence of cholesterol and its esters on [125I] hCG binding to rat testicular membranes and their ordering effect on membranes and liposomes

    International Nuclear Information System (INIS)

    Horkovics-Kovats, S.; Kolena, J.

    1986-01-01

    The influence of cholesterol, cholesterol acetate and cholesterol hemisuccinate on specific binding of [ 125 I] hCG to rat testicular membranes was studied. The increase of specific binding of [ 125 I] hCG only in the presence of cholesterol hemisuccinate in the membranes was observed. The influence of sterols on the ordering of membranes and liposomes prepared from egg phosphatidylcholine was further studied at three depths of the membranes by means of ESR spectroscopy in the temperature range 5-30 0 C. A different effect of cholesterol was observed when compared with its two above-mentioned esters in biological and artificial membranes in the hydrophilic part of the membrane as detected by the CAT 16 spin probe. (author)

  11. Crystallization and preliminary X-ray diffraction studies of Drosophila melanogaster Gαo-subunit of heterotrimeric G protein in complex with the RGS domain of CG5036

    International Nuclear Information System (INIS)

    Tishchenko, Svetlana; Gabdulkhakov, Azat; Tin, Uliana; Kostareva, Olga; Lin, Chen; Katanaev, Vladimir L.

    2012-01-01

    D. melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization and preliminary X-ray crystallographic analysis of the complex of the two proteins are reported. Regulator of G-protein signalling (RGS) proteins negatively regulate heterotrimeric G-protein signalling through their conserved RGS domains. RGS domains act as GTPase-activating proteins, accelerating the GTP hydrolysis rate of the activated form of Gα-subunits. Although omnipresent in eukaryotes, RGS proteins have not been adequately analysed in non-mammalian organisms. The Drosophila melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization of the complex of the two proteins using PEG 4000 as a crystallizing agent and preliminary X-ray crystallographic analysis are reported. Diffraction data were collected to 2.0 Å resolution using a synchrotron-radiation source

  12. Design criteria -- Reactor plant modifications for increased production and 100-C Area Alterations (Sections A and B) CG-558. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Russ, M.H.

    1954-08-10

    This document defines the basic criteria to be used in the preparation of detailed design for Project CG-558, Reactor Plant Modification for Increased Production and for Project CG-600, 100-C Area Alterations. It has been determined that the most economical method of increasing plutonium production within the next five years is by the modernization and improvement of the 100-B, 100-C, 100-D, 100-DR, 100-F, and 100-H reactor plants. These reactors are currently incapable of operating at their maximum potential power levels because of a limited availability of process cooling water. As a result of this programs, it is estimated that 1650-2350 megawatts of total additional production will be achieved. The purpose of this document is to set forth the design for certain modifications and additions to Hanford reactors and their supporting facilities as required to obtain higher power levels and improve the safety of reactor operation.

  13. Ultrasensitive colorimetric immunoassay for hCG detection based on dual catalysis of Au@Pt core-shell nanoparticle functionalized by horseradish peroxidase

    Science.gov (United States)

    Wang, Weiguo; Zou, Yake; Yan, Jinwu; Liu, Jing; Chen, Huixiong; Li, Shan; Zhang, Lei

    2018-03-01

    In this paper, an ultrasensitive colorimetric biosensor for human chorionic gonadotrophin (hCG) detection was designed from bottom-up method based on the dual catalysis of the horseradish peroxidase (HRP) and Au@Pt nanoparticles (NPs) relative to H2O2-TEM system. HRP and monoclonal mouse anti-hCG antibody (β-submit, mAb1) were co-immobilized onto the Au@Pt NP surface to improve catalytic efficiency and specificity, which formed a dual functionalized Au@Pt-HRP probe with the mean size of 42.8 nm (D50). The colorimetric immunoassay was developed for the hCG detection, and the Au@Pt-HRP probe featured a higher sensitivity in the concentration range of 0.4-12.8 IU L- 1 with a low limit of detection (LOD) of 0.1 IU L- 1 compared with the LODs of 0.8 IU L- 1 for BA-ELISA and of 2.0 IU L- 1 for Au@Pt, which indicated that the Au@Pt-HRP probe possessed higher catalytic efficiency with 2.8-fold increase over Au@Pt and 33.8-fold increase over HRP. Also, the Au@Pt-HRP probe exhibited good precision and reproducibility, high specificity and acceptable accuracy with CV being less than 15%. The dual functionalized Au@Pt-HRP probe as a type of signal amplified method was firstly applied in the colorimetric immunoassay for the hCG detection.

  14. Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

    OpenAIRE

    Hashimoto Michio; Katakura Masanori; Nabika Toru; Tanabe Yoko; Hossain Shahdat; Tsuchikura Satoru; Shido Osamu

    2011-01-01

    Abstract Background Hydrogen (H2), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. Therefore, we investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in the metabolic syndrome rat model, SHR.Cg-Leprcp/NDmcr (SHR-cp). Methods Male SHR-cp rats (5...

  15. A Quantitative Risk Assessment of the Skin Sensitization Induction Potential of the Kathon CG Preservative in Rinse-off and Leave-on Personal Care and Cosmetic Products.

    Science.gov (United States)

    Towle, Kevin M; Drechsel, Derek A; Warshaw, Erin M; Fung, Ernest S; Novick, Rachel M; Paustenbach, Dennis J; Monnot, Andrew D

    2018-03-22

    Kathon CG is a commonly used cosmetic-grade preservative that contains active ingredients methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). The aim of the study was to perform a skin sensitization induction risk assessment of daily exposure to Kathon CG after use of various personal care and cosmetic products. We calculated an estimated daily consumer exposure level for rinse-off and leave-on products using the amount of product applied per application, number of applications per day, a retention factor, the MCI/MI concentration, and body surface area values. We assumed that the products contained the maximum recommended safe concentration of MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We compared estimated consumer exposure levels with the no expected sensitization induction level for MCI/MI and applied sensitization assessment factors to calculate product-specific margins of safety (MOSs). The MOSs for rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave-on products containing the maximum recommended safe concentration of Kathon CG may increase the risk of sensitization induction due to exposure to MCI/MI. In contrast, rinse-off products were not associated with a potential increased risk of skin sensitization induction.

  16. Impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in Murrah buffalo (Bubalus bubalis).

    Science.gov (United States)

    Pandey, A K; Dhaliwal, G S; Ghuman, S P S; Agarwal, S K

    2015-11-01

    The present study aimed to establish the impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in buffalo. The buffalo (n=45) were subjected to an estrous synchronization protocol (synthetic analog of PGF2α administered, through intramuscular route, 11 days apart), followed by artificial insemination (AI) during mid to late estrus. On day 5 post-ovulation, buffalo were administered (i.m.) normal saline (Control, n=14), buserelin acetate (20μg, d5-BA, n=14) or human chorionic gonadotropin (3000IU, d5-hCG, n=17). Ovarian ultrasonography was conducted on the day of induced estrus and on days 0, 5, 12, 16 and 21 post-ovulation to assess preovulatory follicle or corpus luteum (CL) diameter. Also, on these days, jugular vein blood sampling was conducted for the estimation of plasma progesterone. First service conception rate was greater (χ(2)=5.18, P>0.05) in d5-BA and d5-hCG groups (71.4% and 47.1%, respectively) as compared to control (28.6%). Both treatment groups had a greater (Pconception rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit

    2015-01-01

    -luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome......STUDY QUESTION: Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER: Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support...... with exogenous progesterone. WHAT IS KNOWN ALREADY: A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. STUDY DESIGN, SIZE, DURATION: This is a proof-of-concept study conducted...

  18. Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter.

    Science.gov (United States)

    Al-Faisal, A H M; Al-Ramahi, I J; Abudl-Hassan, I A; Hamdan, A T; Barusrux, S

    2014-01-01

    Sixty-three Arabic patients (16 males and 47 females) with thyroid toxic and nontoxic goiter who attended the endocrinologist in Nuclear Medicine Hospital and Al Yarmok Nuclear Medicine Department in Baghdad, Iraq were examined for thyroid peroxidase (TPO) gene mutations. A total of ten heterozygous mutations have been identified in the human TPO gene associated with thyroid toxic and nontoxic goiter. These mutations involved transition or transversion of cysteine either by thymine or guanine at the position 1708 of the exon 10 (c.1708C>T) and the position 1978 of the exon 11 (c.1978C>G). From a total of ten detected mutations, two c.1978C>G mutations were detected in nontoxic goiter patients and eight (two c.1708C>T and six c.1978C>G mutations) were detected in toxic goiter. In conclusion, this study identified ten TPO mutations associated with toxic and nontoxic goiter that have not been yet reported in Iraq, and most of them are detected among females (90 %) and adults age between 30 and 50 years old (80 %).

  19. First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.

    Science.gov (United States)

    Shiefa, S; Amargandhi, M; Bhupendra, J; Moulali, S; Kristine, T

    2013-01-01

    The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free β-hCG is increased whereas in trisomies 18 and 13 free β-hCG is decreased.

  20. HL-LHC alternatives

    CERN Document Server

    Tomás, R; White, S

    2014-01-01

    The HL-LHC parameters assume unexplored regimes for hadron colliders in various aspects of accelerator beam dynamics and technology. This paper reviews three alternatives that could potentially improve the LHC performance: (i) the alternative filling scheme 8b+4e, (ii) the use of a 200 MHz RF system in the LHC and (iii) the use of proton cooling methods to reduce the beam emittance (at top energy and at injection). The alternatives are assessed in terms of feasibility, pros and cons, risks versus benefits and the impact on beam availability.

  1. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  2. Alternative medicine: Soul healers

    Directory of Open Access Journals (Sweden)

    Stojanović Marko

    2005-01-01

    Full Text Available The wars and subsequent crisis in the former Yugoslavia have brought about a different, distressed value system to the populations in Serbia. One of its reflections is seen in an establishment of the so-called alternative healing systems. The contemporary, modern medicine holds that illnesses are caused by various psycho-somatic agents, therefore, I take contemporary healers to be alternative psychiatrists and therapists which balance and cure individual distresses. Crisis in societies are psycho-physical triggers that initiate structural disturbances in personalities of active and passive participants, and initiate a search for psycho-therapeutic methods which include transcendental. The processes of globalization and urbanization have helped clear up the fact that the official/established and alternative/traditional medicines have structural determination and corresponding status with the prevailing value system and religious affiliation of the population. Cultural-historic processes are often established in the alternative, and the opposite.

  3. Alternative disinfectant water treatments

    Science.gov (United States)

    Alternative disinfestant water treatments are disinfestants not as commonly used by the horticultural industry. Chlorine products that produce hypochlorous acid are the main disinfestants used for treating irrigation water. Chlorine dioxide will be the primary disinfestant discussed as an alternativ...

  4. Alternative gravity theories

    International Nuclear Information System (INIS)

    Francaviglia, M.

    1990-01-01

    Although general relativity is a well-established discipline the theory deserves efforts aimed at producing alternative or more general frameworks for investigating the classical properties of gravity. These are either devoted to producing alternative viewpoints or interpretations of standard general relativity, or at constructing, discussing and proposing experimental tests for alternative descriptions of the dynamics of the gravitational field and its interaction (or unification) with external matter fields. Classical alternative theories of gravitation can roughly classified as follows; theories based on a still 4-dimensional picture, under the assumption that the dynamics of the gravitational field is more complicated than Einstein's and theories based on higher-dimensional pictures. This leads to supergravity and strings which are not included here. Theories based on higher-dimensional pictures on the assumption that space-time is replaced by a higher-dimensional manifold. Papers on these classifications are reviewed. (author)

  5. Seal design alternatives study

    International Nuclear Information System (INIS)

    Van Sambeek, L.L.; Luo, D.D.; Lin, M.S.; Ostrowski, W.; Oyenuga, D.

    1993-06-01

    This report presents the results from a study of various sealing alternatives for the WIPP sealing system. Overall, the sealing system has the purpose of reducing to the extent possible the potential for fluids (either gas or liquid) from entering or leaving the repository. The sealing system is divided into three subsystems: drift and panel seals within the repository horizon, shaft seals in each of the four shafts, and borehole seals. Alternatives to the baseline configuration for the WIPP seal system design included evaluating different geometries and schedules for seal component installations and the use of different materials for seal components. Order-of-magnitude costs for the various alternatives were prepared as part of the study. Firm recommendations are not presented, but the advantages and disadvantages of the alternatives are discussed. Technical information deficiencies are identified and studies are outlined which can provide required information

  6. Alternative and Integrative Medicine

    Science.gov (United States)

    ... government and regulatory agencies. In conventional medicine, effective cancer treatment is defined as one that causes a tumor to reduce in size or remain stable. Description Many alternative therapies seek to treat illness by helping the body ...

  7. Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

    Directory of Open Access Journals (Sweden)

    De la Cruz-Mosso Ulises

    2012-03-01

    Full Text Available Abstract Background Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children. Methods This study included 100 children with an age range between 6-11 years divided in two groups: a 48 children diagnosed with metabolic syndrome and b 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol th percentile, systolic blood pressure (SBP and diastolic blood pressure (DBP ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP. Results For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015 and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015 were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02, decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03 and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01. The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02 in comparison with C/C genotype. Conclusions The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the

  8. Análise comparativa da acurácia in vitro de testes de detecção de hCG urinário Comparative analysis of the accuracy of urinary hCG tests in vitro

    Directory of Open Access Journals (Sweden)

    Gisele Silva de Moraes

    2011-10-01

    Full Text Available OBJETIVO: Identificar se os pontos de corte de sensibilidade anunciados por três testes de gravidez na urina são compatíveis com os anunciados pelo fabricante e descrever os seus desempenhos diagnósticos. MÉTODOS: A urina de um voluntário masculino foi usada para diluir β-hCG recombinante em concentrações definidas de 0; 6,25; 12,5; 25; 50; e 100 mUI/mL. As amostras foram codificadas e cegamente analisadas para a positividade em três diferentes lotes dos testes hCG Strip Test Plus®, BioEasy® e Visitect Pregnancy®. O tamanho da amostra foi calculado para um erro alfa de 5%, com um poder de 99%. RESULTADOS: As três marcas apresentaram sensibilidade de 100% na detecção do β-hCG nos três lotes analisados, com 100% de valor preditivo negativo, usando somente controles negativos e amostras com concentrações iguais ou superiores ao limite do teste (n = 180/marca. A acurácia dos testes foi 83% (BioEasy®, 84% (Visitect® e 91% (Strip Test Plus®. O Strip Test Plus® apresentou o melhor desempenho para a razão de probabilidade positiva (52,5, enquanto que o produto Visitect® teve a melhor razão de probabilidade negativa (zero. CONCLUSÃO: Os três produtos analisados têm a sensibilidade dos pontos de corte anunciados. O produto Strip Test Plus® tem o melhor desempenho para identificar concentrações urinárias de β-hCG > 12,5 mUI/mL, consequentemente, confirmando gravidez, enquanto que o Visitect® tem o melhor desempenho para descartar a presença de β-hCG na urina (probabilidade pós-teste negativo: zero.OBJECTIVE: To identify whether cutoff for sensitivity advertised by three pregnancy tests in urine are compatible to those reported by the manufacturer and to describe their diagnostic performance. METHODS: The urine of a male volunteer was used to dilute recombinant β-hCG at defined concentrations of 0, 6.25, 12.5, 25, 50, and 100 mIU/mL. The tubes containing each of the concentrations were coded and blindly assessed for

  9. Alternative fuel cycles

    International Nuclear Information System (INIS)

    Penn, W.J.

    1979-05-01

    Uranium resource utilization and economic considerations provide incentives to study alternative fuel cycles as future options to the PHWR natural uranium cycle. Preliminary studies to define the most favourable alternatives and their possible introduction dates are discussed. The important and uncertain components which influence option selection are reviewed, including nuclear capacity growth, uranium availability and demand, economic potential, and required technological developments. Finally, a summary of Ontario Hydro's program to further assess cycle selection and define development needs is given. (auth)

  10. Alternative drugs of abuse.

    Science.gov (United States)

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  11. Alternative fuels for vehicles; Alternative drivmidler

    Energy Technology Data Exchange (ETDEWEB)

    2012-02-15

    Up until 2020 and onwards the analysis indicates that especially electricity, biogas and natural gas as propellants is economically attractive compared to conventional gasoline and diesel while other fuels have the same or higher costs for petrol and diesel. Especially biogas and electricity will also offer significant reductions in CO{sub 2} emissions, but also hydrogen, methanol, DME and to a lesser extent the second generation bioethanol and most of the other alternative fuels reduce CO{sub 2} emissions. Use of the traditional food-based first generation biofuels involves, at best, only modest climate benefits if land use changes are counted, and at worst, significant negative climate effects. Natural gas as a propellant involves a moderate climate gain, but may play a role for building infrastructure and market for gaseous fuels in large fleets, thereby contributing to the phasing in of biogas for transport. The electric-based automotive fuels are the most effective due to a high efficiency of the engine and an increasing proportion of wind energy in the electricity supply. The methanol track also has a relatively high efficiency. Among the others, the track based on diesel engines (biodiesel) is more effective than the track based on gasoline/Otto engines (gas and ethanol) as a result of the diesel engine's better efficiency. For the heavy vehicles all the selected alternative fuels to varying degrees reduce emissions of CO{sub 2}, particularly DME based on wood. The only exception to this is - as for passenger cars - the propellant synthetic diesel based on coal. (LN).

  12. FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques.

    Science.gov (United States)

    Martins, Wellington P; Vieira, Andrea D D; Figueiredo, Jaqueline B P; Nastri, Carolina O

    2013-03-28

    During controlled ovarian hyperstimulation (COH) follicle-stimulating hormone (FSH) is frequently used for several days to achieve follicular development. FSH is a relatively expensive drug, substantially contributing to the total expenses of assisted reproductive techniques (ART). When follicles achieve a diameter greater than 10 mm they start expressing luteinising hormone (LH) receptors. At this point, FSH might be replaced by low-dose human chorionic gonadotropin (hCG), which is less expensive. In addition to cost reduction, replacing FSH by low-dose hCG has a theoretical potential to reduce the incidence of ovarian hyperstimulation syndrome (OHSS). To evaluate the effectiveness and safety of using low-dose hCG to replace FSH during the late follicular phase in women undergoing COH for assisted reproduction, compared to the use of a conventional COH protocol. We searched for randomised controlled trials (RCT) in electronic databases (Menstrual Disorders and Subfertility Group Specialized Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); additionally we handsearched the reference list of included studies and similar reviews. The last electronic search was performed in February 2013.. Only true RCTs comparing the replacement of FSH by low-dose hCG during late follicular phase of COH were considered eligible; quasi or pseudo-randomised trials were not included. Cross-over trials would be included only if data regarding the first treatment of each participant were available; trials that included the same participant more than once would be included only if each participant was always allocated to the same intervention and follow-up periods were the same in both/all arms, or if data regarding the first treatment of each participant were

  13. Catalysis for alternative energy generation

    CERN Document Server

    2012-01-01

    Summarizes recent problems in using catalysts in alternative energy generation and proposes novel solutions  Reconsiders the role of catalysis in alternative energy generation  Contributors include catalysis and alternative energy experts from across the globe

  14. Alternative pricing methodologies

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    With the increased interest in competitive market forces and growing recognition of the deficiencies in current practices, FERC and others are exploring alternatives to embedded cost pricing. A number of these alternatives are discussed in this chapter. Marketplace pricing, discussed briefly here, is the subject of the next chapter. Obviously, the pricing formula may combine several of these methodologies. One utility of which the authors are aware is seeking a price equal to the sum of embedded costs, opportunity costs, line losses, value of service, FERC's percentage adder formula and a contract service charge

  15. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.

    Science.gov (United States)

    Venetis, Christos A; Kolibianakis, Efstratios M; Bosdou, Julia K; Lainas, George T; Sfontouris, Ioannis A; Tarlatzis, Basil C; Lainas, Tryfon G

    2015-03-01

    What is the proper way of assessing the effect of progesterone elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo transfer after in vitro fertilization (IVF) using GnRH analogues and gonadotrophins? This study indicates that a multivariable approach, where the effect of the most important confounders is controlled for, can lead to markedly different results regarding the association between PE on the day of hCG and live birth rates after IVF when compared with the bivariate analysis that has been typically used in the relevant literature up to date. PE on the day of hCG is associated with decreased pregnancy rates in fresh IVF cycles. Evidence for this comes from observational studies that mostly failed to control for potential confounders. This is a retrospective analysis of a cohort of fresh IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF centre during the period 2001-2013. Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH analogues. Natural cycles and cycles where stimulation involved the administration of clomiphene were excluded. In order to reflect routine clinical practice, no other exclusion criteria were imposed on this dataset. The primary outcome measure for this study was live birth defined as the delivery of a live infant after 24 weeks of gestation. We compared the association between PE on the day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple bivariate analyses with that derived from multivariable logistic regression. The multivariable analysis controlled for female age, number of oocytes retrieved, number of embryos transferred, developmental stage of embryos at transfer (cleavage versus blastocyst), whether at least one good-quality embryo was transferred, the woman's body mass index, the total dose of FSH administered during ovarian stimulation and the type of GnRH analogues used (agonists versus antagonists) during ovarian

  16. Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Ding, Nan; Liu, Xingchen; Jian, Qiliang; Liang, Zhongzhen; Wang, Fang

    2017-11-01

    Increasing evidence indicates that a dual trigger (a gonadotrophin-releasing hormone agonist [GnRH-a] with a human chorionic gonadotrophin [hCG] trigger) is the best choice for final oocyte maturation in the GnRH antagonist (GnRH-ant) cycle. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of a GnRH-a combined with a standard hCG trigger in comparison with hCG alone for final oocyte maturation in the GnRH-ant cycle for in vitro fertilization. Complete electronic databases, including PubMed, Embase, The Cochrane Library, and Web of Science, were searched for relevant randomized controlled trials (RCT). The search was not restricted by language or publication time. Two reviewers selected trials and assessed trial quality independently by using the Cochrane Handbook 5.1.0. Four eligible RCT studies involving 527 women were included. The results of this meta-analysis indicated that the dual trigger group had a significantly higher pregnancy rate (relative risk [RR], 1.55; 95% confidence interval [CI], 1.17-2.06) than the hCG-only trigger group. No significant differences were found in the number of oocytes retrieved (weighted mean difference [WMD], 0.47; 95% CI, -0.42 to 1.37), number of mature oocytes retrieved (WMD, 0.41; 95% CI, -0.48 to 1.30), number of fertilized oocytes (WMD, 0.47; 95% CI, -0.32 to 1.26), number of good-quality embryos (WMD, 0.17; 95% CI, -0.29 to 0.64), or implantation rate (RR, 1.17; 95% CI, 0.69-2.00) between the two groups. GnRH-a and hCG as dual trigger was equivalent to hCG in triggering oocyte maturation and may be beneficial in improving reproductive outcomes. Further intensive randomized-controlled studies should be conducted to investigate the efficacy of the dual trigger. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. miR-146a C/G polymorphism increased the risk of head and neck cancer, but overall cancer risk: an analysis of 89 studies.

    Science.gov (United States)

    Sun, Dezhong; Zhang, Xiaoyan; Zhang, Xiaolei

    2018-02-28

    Several studies have evaluated the association of miR-146a C/G with head and neck cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive outcomes. To drive a more precise estimation, we carried out this meta-analysis. The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane Library, and Google Scholar databases to identify eligible studies. A total of 89 studies were included. The results showed that miR-146a C/G was significantly associated with increased HNC risk in dominant model ( I 2 =15.6%, P heterogeneity =0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002-1.182, P =0.044). However, no cancer risk was detected under all genetic models. By further stratified analysis, we found that rs4919510 mutation contributed to the risk of HNC amongst Asians under homozygote model ( I 2 =0, P heterogeneity =0.541, OR =1.189, 95% CI =1.025-1.378, P =0.022), and dominant model ( I 2 =0, P heterogeneity =0.959, OR =1.155, 95% CI =1.016-1.312, P =0.028). Simultaneously, in the stratified analysis by source of controls, a significantly increased cancer risk amongst population-based studies was found under homozygote model, dominant model, recessive model, and allele comparison model. However, no significant association was found in the stratified analysis by ethnicity and source of control. The results indicated that miR-146a C/G polymorphism may contribute to the increased HNC susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, no significant association was found in subgroup analysis by ethnicity and source of control. To further confirm these results, well-designed large-scale case-control studies are needed in the future. © 2018 The Author(s).

  18. Arabidopsis ANAC069 binds to C[A/G]CG[T/G] sequences to negatively regulate salt and osmotic stress tolerance.

    Science.gov (United States)

    He, Lin; Shi, Xinxin; Wang, Yanmin; Guo, Yong; Yang, Kejun; Wang, Yucheng

    2017-03-01

    ANAC069 binds to the DNA sequence of C[A/G]CG[T/G] to regulate the expression of genes, resulting in decreased ROS scavenging capability and proline biosynthesis, which contribute to increased sensitivity to salt and osmotic stress. NAM-ATAF1/2 and CUC2 (NAC) proteins are plant-specific transcription factors that play important roles in abiotic stress responses. In the present study, we characterized the physiological and regulatory roles of Arabidopsis thaliana ANAC069 in response to abiotic stresses. Arabidopsis plants overexpressing ANAC069 displayed increased sensitivity to abscisic acid, salt, and osmotic stress. Conversely, ANAC069 knockdown plants showed enhanced tolerance to salt and osmotic stress, but no change in ABA sensitivity. Further studies showed that ANAC069 inhibits the expression of SOD, POD, GST, and P5CS genes. Consequently, the transcript level of ANAC069 correlated negatively with the reactive oxygen species (ROS) scavenging ability and the proline level. The genes regulated by ANAC069 were further studied using a gene chip on a genome-wide scale, and 339 and 226 genes up- and downregulated by ANAC069 were identified. Analysis of the promoters of the genes affected by ANAC069 suggested that ANAC069 regulates the expression of genes mainly through interacting with the DNA sequence C[A/G]CG[T/G] in response to abiotic stresses. Collectively, our data suggest that ANAC069 could recognize C[A/G]CG[T/G] sequences to regulate the expression of genes that negatively regulates salt and osmotic stress tolerance by decreasing ROS scavenging capability and proline biosynthesis.

  19. Reproductive performance of dairy cows with ovarian cysts after synchronizing ovulation using GnRH or hCG during the warm or cool period of the year.

    Science.gov (United States)

    De Rensis, F; Bottarelli, E; Battioni, F; Capelli, T; Techakumphu, M; García-Ispierto, I; López-Gatius, F

    2008-03-01

    This study was designed to compare the reproductive response to timed AI of lactating dairy cows with cystic ovarian follicles treated with GnRH or hCG to synchronize ovulation. The effectiveness of treatment during the warm or cool period of the year was also compared. Cows were given 12 microg GnRH-agonist i.m. on day 0 of the protocol, 15 mg PGF(2alpha) i.m. on day 7, and either GnRH-agonist (GPG treatment) or 3000 IU hCG i.m. (GPH treatment) on day 9, followed by timed AI. The cows were randomly chronologically assigned to GPG (n=130) or GPH (n=136) group. All cows were inseminated at fixed time 16-22 h after the end of treatment. During the warm period the pregnancy rate to first AI was 12% (7/60) and 21% (14/68) for the GPG and GPH groups, respectively, there being no significant differences between groups; the cumulative pregnancy rate was 22% (13/60) and 21% (14/68) for the GPG and GPH groups, respectively, again with no significant intergroup differences. During the cool period pregnancy rate to first AI was not different between groups: 29% (20/70) for GPG and 32% (22/68) for GPH, respectively; whereas the cumulative pregnancy rate was significantly higher (Pwarm period, the pregnancy rates of the cystic cows were similar whether they received GPG or GPH treatment, during the cool period, there is a beneficial effect to use hCG at day 9 of the ovsynch protocol compared GnRH on cumulative pregnancy rate.

  20. Basal follicle stimulating hormone and leptin on the day of hCG administration predict successful fertilization in in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Andon Hestiantoro

    2016-04-01

    Full Text Available Background: Successful pregnancy in in vitro fertilization (IVF program depends on multiple factors. This study aimed to determine whether age, body mass index (BMI, basal follicle stimulating hormone (FSH, estradiol, and leptin on the day of trigger ovulation with human chorionic gonadotropin (hCG might be used as predictor for successful oocyte fertilization in in vitro fertilization (IVF program.Methods: This is a cross sectional study conducted in Yasmin Fertility Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Forty participating patients underwent IVF program, excluding smokers, patients with diabetic, morbid obesity, and severe oligospermia or azoospermia. Age, BMI, basal FSH, estradiol, leptin on the day of hCG administration, oocyte count on oocyte retrieval, the number of mature oocyte, and fertility rate were analyzed using bivariate and multivariate analysis to determine which eligible factors play role in predicting the successful of fertilization.Results: Significant correlation was found between basal FSH level and serum leptin/oocyte ratio on the day of hCG administration with successful fertilization. We found probability formula as follows: 1/(1+exp –(6.2 - 0.4(leptin serum/oocyte ratio - 0.8(basal FSH, with 77.8% sensitivity, 77.8% specificity, and AUC levels of 85.6% indicating strong predictability. Probability of successful fertilization related to basal FSH level of 5.90 mIU/mL and leptin serum/oocyte ratio of 3.98.Conclusion: The formula consisting of basal FSH and leptin serum/oocyte ratio on the day of trigger ovulation was capable in predicting the probability of successful fertilization in IVF procedure.

  1. Alternate energy sources

    International Nuclear Information System (INIS)

    Stevens-Guille, P.D.

    1975-01-01

    The author highlights the interesting points made by the speeches during the conference on Energy and its Future in Southern Africa. He also draws attention to potential alternate energy sources such as power from tides, ocean waves, ocean temperature differences and geothermal power

  2. Energy conversion alternatives study

    Science.gov (United States)

    Shure, L. T.

    1979-01-01

    Comparison of coal based energy systems is given. Study identifies and compares various advanced energy conversion systems using coal or coal derived fuels for baselaoad electric power generation. Energy Conversion Alternatives Study (ECAS) reports provede government, industry, and general public with technically consistent basis for comparison of system's options of interest for fossilfired electric-utility application.

  3. Alternatives in solar energy

    Science.gov (United States)

    Schueler, D. G.

    1978-01-01

    Although solar energy has the potential of providing a significant source of clean and renewable energy for a variety of applications, it is expected to penetrate the nation's energy economy very slowly. The alternative solar energy technologies which employ direct collection and conversion of solar radiation as briefly described.

  4. TWTF design alternates

    International Nuclear Information System (INIS)

    Ayers, A.L. Sr.

    1982-03-01

    The Transuranic Waste Treatment Facility (TWTF) will process transuranic (TRU) waste in retrievable storage at the Idaho National Engineering Laboratory (INEL). The costs for a TWTF concept using a slagging pyrolysis incinerator were excessive. Alternate concepts using a slow speed shredder, a rotary kiln incinerator, and concrete immobilization should result in significant cost reductions. These will be included in future TWTF considerations

  5. Alternative Break Service Trips

    Science.gov (United States)

    DuPre, Carrie

    2010-01-01

    Even as educators understand how their millennial students learn in such different ways than previous generations (watching how-to videos downloaded from YouTube or engaging in experiential learning adventures), colleges still rely heavily on in-the-classroom learning. The author can't offer an alternative to this classroom format, but she…

  6. Alternative Energy Busing

    Science.gov (United States)

    LaFee, Scott

    2012-01-01

    In recent years, school districts have converted portions of their bus fleets to cleaner-burning, sometimes cheaper, alternative fossil fuels, such as compressed natural gas or propane. Others have adopted biodiesel, which combines regular diesel with fuel derived from organic sources, usually vegetable oils or animal fats. The number of biodiesel…

  7. A promoter polymorphism -945C>G in the connective tissue growth factor in heart failure patients with mechanical circulatory support: a new marker for bridge to recovery?

    Science.gov (United States)

    Posch, Maximilian G; Schmidt, Gunther; Steinhoff, Laura; Perrot, Andreas; Drews, Thorsten; Dandel, Michael; Krabatsch, Thomas; Hetzer, Roland; Potapov, Evgenij V

    2015-01-01

    Mechanical circulatory support (MCS) creates improvement of cardiac function in a small portion of patients with idiopathic dilated cardiomyopathy (iDCM). Among other factors, cardiomyocyte hypertrophy seems to represent an important prerequisite for MCS-related cardiac recovery. We have previously shown that connective tissue growth factor (CTGF) leads to adaptive cardiomyocyte hypertrophy associated with a protective cardiac function in transgenic mice. To test whether a functional genetic variant in the CTGF promoter impacts MCS-related cardiac recovery, three groups of iDCM patients with and without cardiac recovery on MCS were genotyped. The CTGF promoter variant (c.-945C>G) was analysed in 314 patients with iDCM receiving medical treatment only (Group I). Forty-nine iDCM patients who were either weaned from MCS for more than 6 months (Group II; n=20) or bridged to cardiac transplantation (Group III: n=29) were also genotyped. Patients on MCS were followed up for at least 12 months. Clinical characteristics and outcome on MCS were correlated with the respective genotypes. The c.-945C>G allele frequencies in 314 iDCM patients (Group I) were similar to controls deposited in the HapMap database or those published in a recent study. There were no differences in allele prevalence between patients with mild to moderate iDCM (Group I) compared with patients with severe iDCM requiring MCS (Groups II and III). Intriguingly, 50% of patients who were weaned from MCS (Group II) were homozygous for the G allele compared with only 17.2% of patients included in Group III, which is a significant difference (P=0.03). Homozygosity of the promoter-activating G allele in the CTGF_c.-945C>G variant is overrepresented in patients with cardiac recovery on MCS when compared with iDCM patients without cardiac recovery. Further studies are needed to evaluate c.-945C>G as a genetic predictor for clinical outcome on MCS. © The Author 2014. Published by Oxford University Press on behalf

  8. Chromosomal localisation of the CD4cre transgene in B6·Cg-Tg(Cd4-cre)1Cwi mice.

    Science.gov (United States)

    Westendorf, Kerstin; Durek, Pawel; Ayew, Samia; Mashreghi, Mir-Farzin; Radbruch, Andreas

    2016-09-01

    The B6·Cg-Tg(Cd4-cre)1Cwi line expresses CRE recombinase under the control of the promoter and regulatory elements of the Cd4 gene. Here we show that CRE recombinase expression reduces the number and frequencies of CD4 positive subsets in a dose-dependent manner and localize the integration site of the transgenic construct to position 60335693-60341285 (qD) of chromosome 3. The insert contains at least 15 complete sequential copies of the transgenic construct. Based on this information we describe a novel PCR assay for genetic typing of transgenic mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects.

    Science.gov (United States)

    Tribble, David R; Baqar, Shahida; Carmolli, Marya P; Porter, Chad; Pierce, Kristen K; Sadigh, Katrin; Guerry, Patricia; Larsson, Catherine J; Rockabrand, David; Ventone, Cassandra H; Poly, Frederic; Lyon, Caroline E; Dakdouk, Sandra; Fingar, Ann; Gilliland, Theron; Daunais, Patrick; Jones, Erika; Rymarchyk, Stacia; Huston, Christopher; Darsley, Michael; Kirkpatrick, Beth D

    2009-11-15

    A robust human challenge model for Campylobacter jejuni is an important tool for the evaluation of candidate vaccines. The previously established model conveys a potential risk of Guillain-Barré syndrome attributable to lipooligosaccharide ganglioside mimicry. This work establishes a new C. jejuni human challenge model that uses a strain (CG8421) without ganglioside mimicry and that applies Campylobacter-specific cellular immunity screening to achieve high attack rates at lower inoculum doses. Healthy Campylobacter-naive adults participated in an open-label challenge trial. Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern of illness, bacterial shedding, and immunologic responses were determined. Following screening, 23 subjects received 1 X 10(6) or 1 X 10(5) colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1 X 10(6) colony-forming units) or 93% (1 X 10(5) colony-forming units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%), nausea (65%), and fever (39%). No major safety concerns occurred, including bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent infection occurred in 2 subjects (1 subject without Campylobacter-specific adaptive immune responses and 1 with azithromycin resistance acquired in vivo); both infections cleared after receipt of additional antibiotics. Cumulative Campylobacter-specific immune responses were as follows: serologic response occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro interferon-gamma production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. The C. jejuni CG8421 challenge model provides a safe and effective tool, without the risk of Guillain-Barré syndrome. The model demonstrates high attack rates after lower doses of challenge

  10. Reflectance spectroscopy of natural organic solids, iron sulfides and their mixtures as refractory analogues for Rosetta/VIRTIS' surface composition analysis of 67P/CG

    Science.gov (United States)

    Moroz, Lyuba V.; Markus, Kathrin; Arnold, Gabriele; Henckel, Daniela; Kappel, David; Schade, Ulrich; Rousseau, Batiste; Quirico, Eric; Schmitt, Bernard; Capaccioni, Fabrizio; Bockelee-Morvan, Dominique; Filacchione, Gianrico; Érard, Stéphane; Leyrat, Cedric; VIRTIS Team

    2016-10-01

    Analysis of 0.25-5 µm reflectance spectra provided by the Visible and InfraRed Thermal Imaging Spectrometer (VIRTIS) onboard Rosetta orbiter revealed that the surface of 67P/CG is dark from the near-UV to the IR and is enriched in refractory phases such as organic and opaque components. The broadness and complexity of the ubiquitous absorption feature around 3.2 µm suggest a variety of cometary organic constituents. For example, complex hydrocarbons (aliphatic and polycyclic aromatic) can contribute to the feature between 3.3 and 3.5 µm and to the low reflectance of the surface in the visible. Here we present the 0.25-5 µm reflectance spectra of well-characterized terrestrial hydrocarbon materials (solid oil bitumens, coals) and discuss their relevance as spectral analogues for a hydrocarbon part of 67P/CG's complex organics. However, the expected low degree of thermal processing of cometary hydrocarbons (high (H+O+N+S)/C ratios and low carbon aromaticities) suggests high IR reflectance, intense 3.3-3.5 µm absorption bands and steep red IR slopes that are not observed in the VIRTIS spectra. Fine-grained opaque refractory phases (e.g., iron sulfides, Fe-Ni alloys) intimately mixed with other surface components are likely responsible for the low IR reflectance and low intensities of absorption bands in the VIRTIS spectra of the 67P/CG surface. In particular, iron sulfides are common constituents of cometary dust, "cometary" chondritic IDPs, and efficient darkening agents in primitive carbonaceous chondrites. Their effect on reflectance spectra of an intimate mixture is strongly affected by grain size. We report and discuss the 0.25-5 µm reflectance spectra of iron sulfides (meteoritic troilite and several terrestrial pyrrhotites) ground and sieved to various particle sizes. In addition, we present reflectance spectra of several intimate mixtures of powdered iron sulfides and solid oil bitumens. Based on the reported laboratory data, we discuss the ability of

  11. Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

    Directory of Open Access Journals (Sweden)

    Chambers Anne E

    2012-12-01

    Full Text Available Abstract Background Soluble LH/hCG receptor (sLHCGR released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS, preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL, and high (equal to or greater than 170 pmol/mL concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21% which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL compared to controls (median 16.15 pmol/mL, n = 390. The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy.

  12. Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

    Science.gov (United States)

    2012-01-01

    Background Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy. PMID:23245345

  13. Radioactive waste management alternatives

    International Nuclear Information System (INIS)

    Baranowski, F.P.

    1976-01-01

    The information in the US ERDA ''Technical Alternatives Document'' is summarized. The first two points show that waste treatment, interim storage and transportation technologies for all wastes are currently available. Third, an assessment of integrated waste management systems is needed. One such assessment will be provided in our expanded waste management environmental statement currently planned for release in about one year. Fourth, geologies expected to be suitable for final geologic storage are known. Fifth, repository system assessment methods, that is a means to determine and assess the acceptability of a terminal storage facility for nonretrievable storage, must and will be prepared. Sixth, alternatives to geologic storage are not now available. Seventh, waste quantities and characteristics are sensitive to technologies and fuel-cycle modes, and therefore an assessment of these technologies and modes is important. Eighth, and most important, it is felt that the LWR fuel cycle can be closed with current technologies

  14. Alternative propulsion for automobiles

    CERN Document Server

    Stan, Cornel

    2017-01-01

    The book presents – based on the most recent research and development results worldwide - the perspectives of new propulsion concepts such as electric cars with batteries and fuel cells, and furthermore plug in hybrids with conventional and alternative fuels. The propulsion concepts are evaluated based on specific power, torque characteristic, acceleration behaviour, specific fuel consumption and pollutant emissions. The alternative fuels are discussed in terms of availability, production, technical complexity of the storage on board, costs, safety and infrastructure. The book presents summarized data about vehicles with electric and hybrid propulsion. The propulsion of future cars will be marked by diversity – from compact electric city cars and range extender vehicles for suburban and rural areas up to hybrid or plug in SUV´s, Pick up´s and luxury class automobiles.

  15. [Alternatives to animal testing].

    Science.gov (United States)

    Fabre, Isabelle

    2009-11-01

    The use of alternative methods to animal testing are an integral part of the 3Rs concept (refine, reduce, replace) defined by Russel & Burch in 1959. These approaches include in silico methods (databases and computer models), in vitro physicochemical analysis, biological methods using bacteria or isolated cells, reconstructed enzyme systems, and reconstructed tissues. Emerging "omic" methods used in integrated approaches further help to reduce animal use, while stem cells offer promising approaches to toxicologic and pathophysiologic studies, along with organotypic cultures and bio-artificial organs. Only a few alternative methods can so far be used in stand-alone tests as substitutes for animal testing. The best way to use these methods is to integrate them in tiered testing strategies (ITS), in which animals are only used as a last resort.

  16. The effects of GnRH analogue (buserelin) or hCG (Chorulon) on Day 12 of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth and placentation in ewes and ewe lambs.

    Science.gov (United States)

    Khan, T H; Beck, N F G; Khalid, M

    2007-12-01

    The objectives of this study were to determine the effect of GnRH analogue (buserelin) or human chorionic gonadotrophin (hCG, Chorulon) treatment on Day 12 of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth and placentation in ewes and ewe lambs. After oestrus synchronization with progestagen sponges and eCG, all the animals were mated with fertile rams. Both ewes and ewe lambs (20 per treatment group) were given either normal saline or 4 microg GnRH or 200 IU hCG on Day 12 post-mating. Pre- and post-treatment plasma hormone concentrations were determined in seven pregnant animals per treatment group in samples collected 1h before and 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment. Overall mean progesterone concentrations were higher (Pewes as compared with ewe lambs in saline-treated controls. GnRH or hCG treatment increased (Pewes than in ewe lambs. Oestradiol concentrations were similar in the two control groups. In ewes, but not in ewe lambs, both GnRH and hCG treatments significantly (Pewes than in ewe lambs, whereas FSH release in ewes was less (Pewe lambs. The effects of GnRH or hCG on conceptus growth and placentation was determined at slaughter on Day 25. In ewes, GnRH treatment increased (Pewe lambs. In ewes, hCG treatment also enhanced (Pewe lambs, there was no difference (Pewes. However, these treatments were less effective in ewe lambs.

  17. Faillure in the effect of the analogue (hCG of luteinizing hormone on the luteal angiogenesis in rats (Rattus novergicus

    Directory of Open Access Journals (Sweden)

    Diego Gonçalves Silva

    2013-04-01

    Full Text Available The knowledge of the mechanisms that affect the control of the ovarian activity is essential for the success of reproduction biotechnologies. Although a number of studies have been carried out in which the luteinizing hormone (LH was used to control the ovarian activity, little is known about its influence in the morphology and vascular formation of the corpus luteum, aiming to increase the local blood flow. Thus, the objective of the present experiment was the quantification of the vascular density of corpora lutea (Cls in animals treated with human chorionic gonadotropin (hCG just after ovulation. Therefore, eighteen wistar rats were used in this experiment. Eight rats in the treated group and ten rats in the control group. Corpora lutea were divided into two groups: group (A treated with hCG in the following morning after copulation, and group (B control animals which received an injection of 0.9% sodium chloride solution. Ovaries from each group were used for preparation of histological sections for vascular density qualification. No statistical significance was found between the two groups tested.

  18. Endometrial carcinoma with yolk sac tumor-like differentiation and elevated serum ß-hCG: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Ji M

    2013-10-01

    Full Text Available Mingliang Ji,1 Yan Lu,1 Lina Guo,2 Fengzhi Feng,1 Xirun Wan,1 Yang Xiang1 1Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Beijing, People's Republic of China Abstract: Endometrial carcinoma with a germ cell tumor component is a rare event. Here we report a uterine neoplasm with a unique combination of endometrioid adenocarcinoma and mixed germ cell malignant elements. A 28-year-old woman with abnormal vaginal bleeding, an abdominal mass, and elevated alfa-fetoprotein and beta-human chorionic gonadotropin (ß-hCG levels had a history of biopsy of an omental mass and chemotherapy in another hospital one month before her referral to our department. Histologic examination of the mass removed from the omentum revealed an endometrioid adenocarcinoma with yolk sac tumor-like differentiation. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and removal of metastatic disease were then undertaken at our hospital. Postoperative chemotherapy was given. Eight months postoperatively, serum alfa-fetoprotein and ß-hCG rose again. Cases with primary yolk sac tumors of the endometrium or endometrial carcinoma with trophoblastic differentiation in the literature were reviewed. Keywords: endometrial carcinoma, yolk sac tumor, trophoblastic differentiation

  19. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

    Directory of Open Access Journals (Sweden)

    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

  20. Extracto etéreo de frutos de Bromelia pinguin L. (piña de ratón por el sistema acoplado CG-EM

    Directory of Open Access Journals (Sweden)

    Juan Abreu Payrol

    2001-04-01

    Full Text Available Se realizó el estudio del extracto etéreo de frutos de Bromelia pinguin L. (piña de ratón mediante el sistema acoplado CG-EM. Se detectó la presencia de los ácidos 2-pentenodioico, octanodioico, ftálico, cítrico, nonanodioico, 12-metiltetradecanoico, palmítico, oleico, linolénico, esteárico, 11,14,17-eicosatrienoico y 11,14-eicosadienoico. La identificación fue realizada sobre la base de los tiempos de retención y fue confirmada por comparación de los espectros de masas con los de patrones. Por primera vez es informada la presencia de estos compuestos en los frutos de B. pinguin L.The study of the ethereal extract from fruits of Bromelia pinguin L. ("piña de ratón" was conducted by the CG-EM coupled system. The following acids were detected: 2-pentanedioic, octanedioic, phthalic, citric, nonanodioic, 12-methyltetradecanoic, palmitic, oleic, linoleic, stearic, 11,14,17-eicosatrie-noic and 11,14-eicosadienoic. Their identification was based on the times of retention and it was confirmed by comparing the spectra of masses with those of patterns. The presence of these compounds in the fruits of B. pinguin L. is reported for the first time.

  1. Alternative REST Splicing Underappreciated

    OpenAIRE

    Chen, Guo-Lin; Miller, Gregory

    2017-01-01

    As a major orchestrator of the cellular epigenome, the repressor element-1 silencing transcription factor (REST) can either repress or activate thousands of genes depending on cellular context, suggesting a highly context-dependent REST function tuned by environmental cues. While REST shows cell-type non-selective active transcription, an N-terminal REST4 isoform caused by alternative splicing - inclusion of an extra exon (N3c) which introduces a pre-mature stop codon - has been implicated in...

  2. Metamaterials critique and alternatives

    CERN Document Server

    Munk, Ben A

    2009-01-01

    A Convincing and Controversial Alternative Explanation of Metamaterials with a Negative Index of Refraction In a book that will generate both support and controversy, one of the world's foremost authorities on periodic structures addresses several of the current fashions in antenna design-most specifically, the popular subject of double negative metamaterials. Professor Munk provides a comprehensive theoretical electromagnetic investigation of the issues and concludes that many of the phenomena claimed by researchers may be impossible. While denying the existence of negative refractio

  3. The renewable alternative

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This chapter discusses renewable energy sources as an alternative to a fossil fuel based economy. The topics discussed in the chapter include the historic aspects and current status of use of renewable energy, status of the renewable energy industry, market barriers to renewable energy, research and development and commercialization of renewable energy, the environmental and social costs associated with renewable energy, valuing future costs and benefits of energy use, and the potential market of renewable energy

  4. Alternative Energy Sources

    CERN Document Server

    Michaelides, Efstathios E (Stathis)

    2012-01-01

    Alternative Energy Sources is designed to give the reader, a clear view of the role each form of alternative energy may play in supplying the energy needs of the human society in the near and intermediate future (20-50 years).   The two first chapters on energy demand and supply and environmental effects, set the tone as to why the widespread use of alternative energy is essential for the future of human society. The third chapter exposes the reader to the laws of energy conversion processes, as well as the limitations of converting one energy form to another. The sections on exergy give a succinct, quantitative background on the capability/potential of each energy source to produce power on a global scale. The fourth, fifth and sixth chapters are expositions of fission and fusion nuclear energy. The following five chapters (seventh to eleventh) include detailed descriptions of the most common renewable energy sources – wind, solar, geothermal, biomass, hydroelectric – and some of the less common sources...

  5. Alternative Respiratory Pathway

    Science.gov (United States)

    Siedow, James N.; Girvin, Mark E.

    1980-01-01

    Oxygen uptake during the first hours of imbibition in intact soybean and mung bean seeds showed a marked sensitivity to potassium cyanide but was unaffected by addition of either salicylhydroxamic acid or propyl gallate. However O2 uptake by finely ground seed particles was very sensitive to the addition of either compound. The results indicated that O2 uptake in intact, imbibing seeds was associated with a cyanide-sensitive process, most probably mitochondrial mediated respiration, and not the result of the cyanide-insensitive lipoxygenase activity which was readily detectable in ground seed particles. The antioxidant propyl gallate was found to inhibit specifically alternative pathway electron transfer in isolated mung bean mitochondria. Half-maximal inhibition occurred with 2 to 5 micromolar propyl gallate. Kinetic analysis indicated that propyl gallate inhibition of the alternative pathway occurred at, or very near, the site of inhibition of the alternative pathway by salicylhydroxamic acid. A high level of lipoxygenase activity was found to be associated with washed mitochondria isolated from a variety of etiolated plant tissues. Most of this lipoxygenase activity could be eliminated from mung bean mitochondria if the mitochondria were purified on a discontinuous sucrose gradient. This indicated that the mitochondrial-associated activity was probably the result of nonspecific adsorption of lipoxygenase onto the mitochondrial membranes during isolation. PMID:16661259

  6. Is garlic alternative medicine?

    Science.gov (United States)

    Rivlin, Richard S

    2006-03-01

    Garlic has been used medicinally since antiquity. In virtually every early civilization known, such as ancient India, Egypt, Rome, China, and Japan, garlic was part of the therapeutic regimen for a variety of maladies. Therefore, the ancient medicinal tradition of garlic use would qualify it as a folk medicine or as an alternative or complementary medicine. But is garlic an alternative to established methods of disease prevention or treatment? Scientists from around the world have identified a number of bioactive substances in garlic that are water soluble (e.g., S-allyl methylcysteine), and fat soluble (e.g., diallyldisulfide). Mechanisms of action are being elucidated by modern technology. The validity of ancient medicine is now being evaluated critically in cell-free systems, animal models, and human populations. Preventive and therapeutic trials of garlic are still in early stages. There are many promising lines of research suggesting the potential effects of garlic. The current state of knowledge does not recognize garlic as a true alternative, but it will likely find a place for garlic as a complement to established methods of disease prevention and treatment. Our goal should be to examine garlic together with other agents to evaluate its possible efficacy and toxicity under conditions of actual use in humans.

  7. State alternative route designations

    International Nuclear Information System (INIS)

    1989-07-01

    Pursuant to the Hazardous Materials Transportation Act (HMTA), the Department of Transportation (DOT) has promulgated a comprehensive set of regulations regarding the highway transportation of high-level radioactive materials. These regulations, under HM-164 and HM-164A, establish interstate highways as the preferred routes for the transportation of radioactive materials within and through the states. The regulations also provide a methodology by which a state may select alternative routes. First,the state must establish a ''state routing agency,'' defined as an entity authorized to use the state legal process to impose routing requirements on carriers of radioactive material (49 CFR 171.8). Once identified, the state routing agency must select routes in accordance with Large Quantity Shipments of Radioactive Materials or an equivalent routing analysis. Adjoining states and localities should be consulted on the impact of proposed alternative routes as a prerequisite of final route selection. Lastly, the states must provide written notice of DOT of any alternative route designation before the routes are deemed effective

  8. Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptability of a multi-level pregnancy test (MLPT) for home monitoring of hCG trends after assisted reproduction.

    Science.gov (United States)

    Shochet, Tara; Comstock, Ioanna A; Ngoc, Nguyen Thi Nhu; Westphal, Lynn M; Sheldon, Wendy R; Loc, Ly Thai; Blum, Jennifer; Winikoff, Beverly; Blumenthal, Paul D

    2017-08-22

    To evaluate the utility and acceptability of using multi-level pregnancy tests (MLPTs) at home to monitor hCG trends following assisted reproductive technology (ART). One hundred and four women presenting for ART at either Stanford Medicine Fertility and Reproductive Health Clinic (Stanford, CA) or Hung Vuong Hospital (Ho Chi Minh City, Vietnam) participated in this pilot study. Women were asked to perform the MLPT at home, primarily on days when they were also scheduled to receive standard clinic-based serum hCG testing. These tests were administered up to 6 times over the 6-week period following embryo transfer or intrauterine insemination (IUI). Concordance of serial hCG readings for each time point was assessed by comparing trends in urine MLPT results with trends in serum hCG. Stable or increasing hCG level was interpreted as an indication of a progressing pregnancy, while a declining hCG was interpreted as a lack of established or progressing pregnancy. At study end, all participants were asked about the acceptability and convenience of using the MLPT at home for monitoring hCG trends following ART. Data from both urine and serum testing are available for 156 of 179 clinic visits (87.2%). There was high concordance of serial trend results between the two types of tests: among the 156 sets of serum and urine hCG data points, 150 (96.2%) showed a matching trend in hCG pattern and 6 (3.8%) resulted in a discordant trend. Seventy-three percent of women reported being satisfied or very satisfied with using the MLPTs at home. Almost all (96.6%) said that the MLPT was easy or very easy to use. The MLPT offers women and health care providers a client-friendly diagnostic tool to detect very early pregnancy and monitor its progress. This study was registered on clinicaltrials.gov as NCT01846403 (May 1, 2013), and NCT01919502 (August 5, 2013).

  9. Sincronização da onda folicular com hCG prévia à indução da luteólise com cloprostenol em bovinos Follicular wave synchronization with hCG prior the luteolisis induction with cloprostenol in cattle

    Directory of Open Access Journals (Sweden)

    Deiler Sampaio Costa

    1999-08-01

    Full Text Available O efeito da aplicação de diferentes doses de hCG sobre a emergência de nova onda de crescimento folicular e o número de folículos recrutados dessa onda, a formação de corpo lúteo acessório, o diâmetro do folículo dominante e do corpo lúteo espontâneo no dia da aplicação do luteolítico, a subseqüente taxa de sincronização e o intervalo da aplicação de PGF2α à manifestação do estro foram avaliados. Vinte fêmeas bovinas mestiças em diestro, divididas em quatro tratamentos, contendo cinco animais cada, foram usadas. No tratamento 1, os animais receberam 500 UI I.M. hCG no dia 0, dia em que se iniciou o tratamento, e 150 μg D(+ cloprostenol no dia 6; já nos tratamentos 2, 3 e 4, receberam, respectivamente, 1000, 2000 e 3000 UI hCG, pela mesma via de aplicação, e 150 μg D(+ cloprostenol no dia 6. A atividade ovariana foi monitorada diariamente, com auxílio do aparelho de ultra-sonografia, do dia 0 ao estro, ou até o dia 11 após o tratamento, nos animais que não responderam à prostaglandina. Não houve diferença entre os efeitos de 500, 1000, 2000 e 3000 UI hCG sobre a dinâmica folicular, a taxa de sincronização e o intervalo da aplicação de PGF2α ao estro. Houve, no entanto, tendência de as dosagens de 2000 e 3000 UI induzirem à emergência de nova onda de crescimento folicular mais rapidamente que 500 ou 1000 UI destes hormônios.The effect of different doses of hCG administration on the emergence of a new follicular growth wave and the number of recruited follicles from this wave, the accessory corpus luteum formation, the diameter of the dominant follicle and of the spontaneous corpus luteum on the day of a luteolitic administration and subsequent synchronization rate and the interval between the PGF2α administration and the estrus manifestation were evaluated. Twenty crossbred female cattle in diestrus, divided in four treatments containing five animals each were used. In treatment 1, the animals

  10. Alternative energy options

    International Nuclear Information System (INIS)

    Bennett, K.F.

    1983-01-01

    It is accepted that coal will continue to play the major role in the supply of energy to the country for the remainder of the century. In this paper, however, emphasis has been directed to those options which could supplement coal in an economic and technically sound manner. The general conclusion is that certain forms of solar energy hold the most promise and it is in this direction that research, development and implementation programmes should be directed. Tidal energy, fusion energy, geothermal energy, hydrogen energy and fuel cells are also discussed as alternative energy options

  11. Dounreay: an alternative development

    International Nuclear Information System (INIS)

    Low, K.

    1990-01-01

    With the Government decision to phase out the Fast Reactor at Dounreay there is a need to find alternative employment in the area. Traditionally Caithness is an area of farming, fishing and tourism which could be damaged if Dounreay were to be made a nuclear waste repository. The suggestion is that Dounreay should become a centre for research, development and subsequent manufacture of renewable energy sources and devices to harness renewable energy. The Scottish coastline has potential for wind and wave power developments and this could lead to a whole industry in the future. (UK)

  12. Alternative energy sources

    International Nuclear Information System (INIS)

    Chapman, P.

    1978-01-01

    It is suggested that the development of alternative energy sources has made them more attractive than nuclear power, due to their characteristics, such as small scale and short lead times, moderate costs and minimal environmental impact. The objectives of energy policy are discussed in relation to forecasts of energy demand. Tables show (a) projected useful energy demands UK; (b) patterns of end-use of energy; (c) costs of heating fuels; (d) net present value of gas purchases; (e) useful-energy by end-use analysis; and (f) primary fuel summary 2025. The contributions of hydro, nuclear, waves, solar, oil, gas and coal are estimated to 2025. (U.K.)

  13. Alternate fuels; Combustibles alternos

    Energy Technology Data Exchange (ETDEWEB)

    Romero Paredes R, Hernando; Ambriz G, Juan Jose [Universidad Autonoma Metropolitana. Iztapalapa (Mexico)

    2003-07-01

    In the definition and description of alternate fuels we must center ourselves in those technological alternatives that allow to obtain compounds that differ from the traditional ones, in their forms to be obtained. In this article it is tried to give an overview of alternate fuels to the conventional derivatives of petroleum and that allow to have a clear idea on the tendencies of modern investigation and the technological developments that can be implemented in the short term. It is not pretended to include all the tendencies and developments of the present world, but those that can hit in a relatively short term, in accordance with agreed with the average life of conventional fuels. Nevertheless, most of the conversion principles are applicable to the spectrum of carbonaceous or cellulosic materials which are in nature, are cultivated or wastes of organic origin. Thus one will approach them in a successive way, the physical, chemical and biological conversions that can take place in a production process of an alternate fuel or the same direct use of the fuel such as burning the sweepings derived from the forests. [Spanish] En la definicion y descripcion de combustibles alternos nos debemos centrar en aquellas alternativas tecnologicas que permitan obtener compuestos que difieren de los tradicionales, al menos en sus formas de ser obtenidos. En este articulo se pretende dar un panorama de los combustibles alternos a los convencionales derivados del petroleo y que permita tener una idea clara sobre las tendencias de la investigacion moderna y los desarrollos tecnologicos que puedan ser implementados en el corto plazo. No se pretende abarcar todas las tendencias y desarrollos del mundo actual, sino aquellas que pueden impactar en un plazo relativamente corto, acordes con la vida media de los combustibles convencionales. Sin embargo, la mayor parte de los principios de conversion son aplicables al espectro de materiales carbonaceos o celulosicos los cuales se

  14. Alternatives to eigenstate thermalization.

    Science.gov (United States)

    Rigol, Marcos; Srednicki, Mark

    2012-03-16

    An isolated quantum many-body system in an initial pure state will come to thermal equilibrium if it satisfies the eigenstate thermalization hypothesis (ETH). We consider alternatives to ETH that have been proposed. We first show that von Neumann's quantum ergodic theorem relies on an assumption that is essentially equivalent to ETH. We also investigate whether, following a sudden quench, special classes of pure states can lead to thermal behavior in systems that do not obey ETH, namely, integrable systems. We find examples of this, but only for initial states that obeyed ETH before the quench.

  15. Alternatives to Seesaw

    International Nuclear Information System (INIS)

    Murayama, Hitoshi

    2004-01-01

    The seesaw mechanism is attractive not only because it 'explains' small neutrino mass, but also because of its packaging with the SUSY-GUT, leptogenesis, Dark Matter, and electroweak symmetry breaking. However, this package has the flavor, CP, and gravitino problems. I discuss two alternatives to the seesaw mechanism. In one of them, the anomaly-mediated supersymmetry breaking solves these problems, while predicts naturally light Dirac neutrinos. In the other, the light Majorana neutrinos arise from supersymmetry breaking with right-handed neutrinos below TeV, and the Dark Matter and collider phenomenology are significantly different.

  16. on some properties of the alternating sylvester series and alternating ...

    African Journals Online (AJOL)

    DJFLEX

    We investigate some properties connected with the alternating Sylvester series and alternating Engel Series representation for real numbers, in terms of the integer digits involved. In particular, we look at an algorithm that leads to a general alternating series expansion for real numbers in terms of rationals and deduce the ...

  17. Alternative fuels. Daitai nenryo

    Energy Technology Data Exchange (ETDEWEB)

    Kim, E. (Japan Automobile Research Inst. Inc., Tsukuba (Japan))

    1992-05-05

    Evaluation of alternative fuels has been conducted by various agencies since the first oil crisis in 1973 and at that time, the development of coal, oil shale, tar sand and such synthetic fuels as coal liquefaction oil etc. was pursued in several countries like Japan and the U.S.A. as national projects. However, since the second oil crisis, due to the progress of energy saving and other measures, demand and supply of petrolium has been relaxed and synthetic oil development projects have greatly been reduced in Japan as well as other countries. At the present, because of the environmental problems, the stress has been shifted to natural gas whose cost is lower than that of coal and whose exhaust gas is expected to be cleaner than that of coal. In this article, with regard to methanol and compressible natural gas which are most expected domestically as well as overseas as alternative fuels, evaluation from the viewpoint of character, evaluation from the viewpoint 'of utilization technique and evaluation from the viewpoint of production and supply are discussed respectively. 3 refs.

  18. Alternative Therapies for PKU

    Directory of