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Sample records for binding protein-3 luteinizing

  1. Lutein

    Science.gov (United States)

    ... this eye disease. Eye problems in premature infants (retinopathy of prematurity). Early research suggests that lutein does not decrease the risk or severity of retinopathy of prematurity. Other conditions. More evidence is needed to rate ...

  2. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein.

    Science.gov (United States)

    Horvath, Martin P; George, Evan W; Tran, Quang T; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S

    2016-08-01

    A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ℇ-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings. PMID:27487925

  3. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    International Nuclear Information System (INIS)

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final 125I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. 125I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors

  4. Binding of progesterone to cell surfaces of human granulosa-lutein cells.

    Science.gov (United States)

    Younglai, Edward V; Wu, Yanjing; Foster, Warren G; Lobb, Derek K; Price, Thomas M

    2006-09-01

    Progesterone is produced by granulosa cells under the influence of luteinizing hormone. Nuclear progesterone receptors have been found in rat granulosa cells. Human granulosa-lutein cells rapidly respond to progesterone with an increase in intracellular calcium suggesting the existence of a nongenomic mechanism. This study was conducted to determine whether binding of progesterone to granulosa cells could occur at the membrane. Granulosa cells were obtained from an in vitro fertilization program and examined immunohistochemically with an antiserum to membrane progesterone receptors. Approximately 14-70% of freshly harvested or cultured granulosa cells of six patients showed a positive reaction to the antiserum, limited to the cell membrane. Western blot analysis of homogenates of granulosa cells and a granulosa cell tumour confirmed the presence of progesterone receptors A, B and C and low amounts of a putative membrane receptor. These results demonstrate that the plasma membranes of human granulosa cells possess binding components for progesterone which may be involved in its nongenomic mechanism of action. PMID:16905308

  5. Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein.

    Science.gov (United States)

    2003-01-01

    Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of osteoporosis; diseases associated with protein wasting including chronic renal failure, cachexia and severe trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe burn trauma. Combined therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of SomatoKine and its components, IGF-1 and binding protein-3. CGMP clinical production of SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of SomatoKine is

  6. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit;

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed as...... production or to increased cleavage by proteases other than MMP-9....

  7. Insulin-like growth factor binding protein-3 in preterm infants with retinopathy of prematurity

    OpenAIRE

    Manizheh Mostafa Gharehbaghi; Ali Peirovifar; Karim Sadeghi; Haleh Mostafidi

    2012-01-01

    Background: Retinopathy of prematurity (ROP) is the main cause of visual impairment in preterm newborn infants. Objective: This study was conducted to determine whether insulin-like growth factor binding protein -3 (IGFBP-3) is associated with proliferative ROP and has a role in pathogenesis of the disease in premature infants. Materials and Methods: A total of 71 preterm infants born at or before 32 weeks of gestation participated in this study. Studied patients consisted of 41 neonates with...

  8. Functional modulation of insulin-like growth factor binding protein-3 expression in melanoma

    OpenAIRE

    Dar, Altaf A.; Majid, Shahana; Nosrati, Mehdi; deSemir, David; Federman, Scot; Kashani-Sabet, Mohammed

    2010-01-01

    Insulin-like growth factor binding protein-3 (IGFBP3) is a member of the IGFBP family, which regulates mitogenic and anti-apoptotic effects of insulin-like growth factors. In this report we evaluated the role of IGFBP3 in melanoma. Quantitative real-time PCR (qRT-PCR), western and ELISA analysis indicated a significant downregulation of IGFBP3 expression in melanoma cell lines as compared to a normal melanocyte cell line. Melanoma cell lines treated with the demethylating agent 5-AZA-2′ deoxy...

  9. Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells

    Institute of Scientific and Technical Information of China (English)

    Shou-Liang Gong; Gang Zhao; Hong-Guang Zhao; Wen-Tian Lü; Guang-Wei Liu; Ping Zhu

    2004-01-01

    AIM: To explore the ability of recombinant toxin luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) anH binding to LHRH receptor(LHRHR) on the membrane surfa ogf hman liver cancer HEPG cells.METHODS: LHRH was beled by using 125I with enzymatic reaction. The affinity and receptor volume of LHRH-PE40and LHRH binding to LHRHR on the membrane surface of human liver cancer cells were measured with radioligand receptor assay.RESULTS:The specific activity of LHRH labeled with 125I was 2.7×104 kBq/μL, and its radiochemical purity reached to 99.2-99.7%. The binding of 125I to LHRH was maximal for 240 min in the warm cultivation, and this binding was stabilized. The inhibiting rates of 125I-LHRH and LHRH on the proliferation of human liver cancer HEPG cells were not significantly different. On the basis of the saturation curve of 125I-LHRH binding to the membrane LHRHR of HEPG cells, 125I-LHRH of 1×105 cpm was selected for radioligand receptor assay. The affinity constants (Kd) of LHRH-PE40and LHRH bively,and their receptor volumes were 0.37±0.15 μmol/g and0.42±0.13 μmol/g, respectively. The binding of LHRH-PE40to the membrane proteinof normal liver cells was not observed.CONCLUSION: The recombinant toxin LHRH-PE40 binding to the membrane surface of LHRHR of human liver cancer HEPG cells was very strong, while the specific binding of it to normal liver cells was not observed. The results provide an important experimental basis for the clinical application of LHRH-PE.

  10. Characterization of milk proteins-lutein complexes and the impact on lutein chemical stability.

    Science.gov (United States)

    Yi, Jiang; Fan, Yuting; Yokoyama, Wallace; Zhang, Yuzhu; Zhao, Liqing

    2016-06-01

    In this study, the interaction of WPI (whey protein isolate) and SC (sodium caseinate) with hydrophobic lutein was investigated through UV-vis spectroscopy and circular dichroism (CD) as well as fluorescence. The effects on lutein's chemical stability were also examined. The decrease of turbidity of lutein suggested that lutein's aqueous solubility was improved after binding with milk proteins. CD analysis indicated lutein had little impact on the secondary structures of both proteins. Different preparation methods have significant impacts on the binding constant. Fluorescence results indicated that WPI and SC interact with lutein by hydrophobic contacts. Milk proteins have protective effects on lutein against oxidation and decomposition, and SC showed better capability in protecting lutein from oxidation than WPI during 16days storage. The lutein's chemical stability was increased with increasing of proteins concentration. The results indicated that milk proteins may act as effective carriers for lipophilic nutraceuticals. PMID:26830565

  11. Insulin-like growth factor binding protein-3 in preterm infants with retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Manizheh Mostafa Gharehbaghi

    2012-01-01

    Full Text Available Background: Retinopathy of prematurity (ROP is the main cause of visual impairment in preterm newborn infants. Objective: This study was conducted to determine whether insulin-like growth factor binding protein -3 (IGFBP-3 is associated with proliferative ROP and has a role in pathogenesis of the disease in premature infants. Materials and Methods: A total of 71 preterm infants born at or before 32 weeks of gestation participated in this study. Studied patients consisted of 41 neonates without vaso-proliferative findings of ROP as the control group and 30 preterm infants with evidence of severe ROP in follow up eye examination as the case group. Blood samples obtained from these infants 6-8 weeks after birth and blood levels of IGFBP-3 were measured using enzyme-linked immunosorbent assay (ELISA. Results: The mean gestation age and birth weight of the studied patients were 28.2±1.6 weeks and 1120.7±197 gram in the case group and 28.4±1.6 weeks and 1189.4±454 gram in the control group (P=0.25 and P=0.44 respectively. The infants in the case group had significantly lower Apgar score at first and 5 min after birth. Insulin-like growth factor binding protein -3 (IGFBP-3 was significantly lower in the patients with proliferative ROP than the patients without ROP [592.5±472.9 vs. 995.5±422.2 ng/ml (P=0.009]. Using a cut-off point 770.45 ng/ml for the plasma IGFBP-3, we obtained a sensitivity of 65.9% and a specificity of 66.7% in the preterm infants with vasoproliferative ROP. Conclusion: Our data demonstrated that the blood levels IGFBP-3 was significantly lower in the patients with ROP and it is suspected that IGFBP-3 deficiency in the premature infants may have a pathogenetic role in proliferative ROP.

  12. Nuclear actions of insulin-like growth factor binding protein-3.

    Science.gov (United States)

    Baxter, Robert C

    2015-09-10

    In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ). These interactions modulate the functions of these receptors, for example inhibiting VDR-dependent transcription in osteoblasts and PPARγ-dependent transcription in adipocytes. Nuclear IGFBP-3 can be detected by immunohistochemistry in cancer and other tissues, and its presence in the nucleus has been shown in many cell culture studies to be necessary for its pro-apoptotic effect, which may also involve interaction with the nuclear receptor Nur77, and export from the nucleus. IGFBP-3 is p53-inducible and in response to DNA damage, forms a complex with the epidermal growth factor receptor (EGFR), translocating to the nucleus to interact with DNA-dependent protein kinase. Inhibition of EGFR kinase activity or downregulation of IGFBP-3 can inhibit DNA double strand-break repair by nonhomologous end joining. IGFBP-3 thus has the ability to influence many cell functions through its interactions with intranuclear pathways, but the importance of these interactions in vivo, and their potential to be targeted for therapeutic benefit, require further investigation. PMID:26074086

  13. Identification of StARD3 as a Lutein-binding Protein in the Macula of the Primate Retina†

    OpenAIRE

    Li, Binxing; Vachali, Preejith; Frederick, Jeanne M.; Bernstein, Paul S

    2011-01-01

    Lutein, zeaxanthin and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum and macula are associated with decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provi...

  14. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    OpenAIRE

    Lu Zhou; Hyoung-Won Koh; Ui-Jin Bae; Byung-Hyun Park

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R in...

  15. Differential expression of the RNA-binding motif protein 3 in human astrocytoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-tao; ZHANG Zhi-wen; XUE Jing-hui; KONG Hai-bo; LIU Ai-jun; LI Shou-chun; LIU Yu-xiao

    2013-01-01

    Background The RNA-binding motif protein 3 (RBM3),which is transcriptionally induced by low temperature and hypoxia,has recently been found to be upregulated in human tumors.However,its expression status in human astrocytoma is not well defined.This article focuses on the differential expression of RBM3 in human astrocytomas of different grades and normal brain tissues.Methods RBM3 was detected in astrocytomas and normal brain tissues by quantitative real-time PCR,immunohistochemistry,and Western blotting.Analysis of variance was performed on the data from quantitative real-time PCR.The Fisher's exact test was used to analyze the immunohistochemistry results.A P-value of less than 0.05 indicates a statistically significant difference.Results On one hand,the mRNA expression levels of three X-chromosome-related RBM genes (RBMX,RBM3,and RBM10) were detected by quantitative real-time PCR.The results showed that there were no significant differences in RBMX and RBM10 mRNA expression levels in human astrocytomas of different grades and normal brain tissues.However,RBM3 mRNA expression levels were elevated in high-grade (World Health Organization (WHO) Grade Ⅲ-Ⅳ) astrocytomas versus low-grade (WHO Grade Ⅰ-Ⅱ) astrocytomas (5.06±0.66 vs.1.60±0.58; P <0.05) or normal controls (5.06±0.66 vs.1.03±0.22; P <0.05) as determined by quantitative real-time PCR analysis.On the other hand,immunohistochemistry showed an increased RBM3 labeling index in astrocytomas of different grades and normal brain tissues (positive staining rate:astrocytoma Grade Ⅳ,92.9%; astrocytoma Grade Ⅲ,81.8%; astrocytoma Grade Ⅰ-Ⅱ,50%;normal brain tissues,37.5%; high-grade astrocytoma versus normal brain tissues,P <0.05; high-grade astrocytoma versus low-grade astrocytoma,P <0.05).The higher protein levels of RBM3 were also validated in high-grade astrocytomas and low-grade astrocytomas compared with normal brain tissues by Western blotting.Conclusions These

  16. Interaction of Insulin-like Growth Factor-binding Protein-3 and BAX in Mitochondria Promotes Male Germ Cell Apoptosis

    OpenAIRE

    Jia, Yue; Lee, Kuk-Wha; Swerdloff, Ronald; Hwang, David; Cobb, Laura J.; Sinha Hikim, Amiya; Lue, Yan He; Cohen, Pinchas; Wang, Christina

    2009-01-01

    Germ cell apoptosis is crucial for spermatogenesis and can be triggered by various stimuli, including intratesticular hormone deprivation. This study proposes a role for insulin-like growth factor binding protein-3 (IGFBP-3) in male germ cell apoptosis. Groups of adult Sprague-Dawley male rats received one of the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of the gonadotropin-releasing hormone antagonis...

  17. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    OpenAIRE

    Kim, Ho-Seong

    2013-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFB...

  18. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    Science.gov (United States)

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  19. FOXA1 promotes tumor progression in prostate cancer via the insulin-like growth factor binding protein 3 pathway.

    Directory of Open Access Journals (Sweden)

    Yusuke Imamura

    Full Text Available Fork-head box protein A1 (FOXA1 is a "pioneer factor" that is known to bind to the androgen receptor (AR and regulate the transcription of AR-specific genes. However, the precise role of FOXA1 in prostate cancer (PC remains unknown. In this study, we report that FOXA1 plays a critical role in PC cell proliferation. The expression of FOXA1 was higher in PC than in normal prostate tissues (P = 0.0002, and, using immunohistochemical analysis, we found that FOXA1 was localized in the nucleus. FOXA1 expression levels were significantly correlated with both PSA and Gleason scores (P = 0.016 and P = 0.031, respectively. Moreover, FOXA1 up-regulation was a significant factor in PSA failure (P = 0.011. Depletion of FOXA1 in a prostate cancer cell line (LNCaP using small interfering RNA (siRNA significantly inhibited AR activity, led to cell-growth suppression, and induced G0/G1 arrest. The anti-proliferative effect of FOXA1 siRNA was mediated through insulin-like growth factor binding protein 3 (IGFBP-3. An increase in IGFBP-3, mediated by depletion of FOXA1, inhibited phosphorylation of MAPK and Akt, and increased expression of the cell cycle regulators p21 and p27. We also found that the anti-proliferative effect of FOXA1 depletion was significantly reversed by simultaneous siRNA depletion of IGFBP-3. These findings provide direct physiological and molecular evidence for a role of FOXA1 in controlling cell proliferation through the regulation of IGFBP-3 expression in PC.

  20. Interaction between acid-labile subunit and insulin-like growth factor binding protein 3 expressed in Xenopus oocytes.

    Science.gov (United States)

    Choi, Kyung-Yi; Lee, Dong-Hee

    2002-03-31

    The acid-labile subunit (ALS) associates with the insulinlike growth factor (IGF)-I or II, and the IGF binding protein-3 (IGFBP-3) in order to form a 150-kD complex in the circulation. This complex may regulate the serum IGFs by restricting them in the vascular system and promoting their endocrine actions. Little is known about how ALS binds to IGFBP3, which connects the IGFs to ALS. Xenopus oocyte was utilized to study the function of ALS in assembling IGFs into the ternary complexes. Xenopus oocyte was shown to correctly translate in vitro transcribed mRNAs of ALS and IGFBP3. IGFBP3 and ALS mRNAs were injected in a mixture, and their products were immunoprecipitated by antisera against ALS and IGFBP3. Contrary to traditional reports that ALS interacts only with IGF-bound IGFBP3, this study shows that ALS is capable of forming a binary complex with IGFBP3 in the absence of IGF. When cross-linked by disuccinimidyl suberate, the band that represents the ALSIGFBP3 complex was evident on the PAGE. IGFBP3 movement was monitored according to the distribution between the hemispheres. Following a localized translation in the vegetal hemisphere, IGFBP3 remained in the vegetal half in the presence of ALS. However, the mutant IGFBP3 freely diffused into the animal half, despite the presence of ALS, which is different from the wild type IGFBP3. This study, therefore, suggests that ALS may play an important role in sequestering IGFBP3 polypeptides via the intermolecular aggregation. Studies using this heterologous model will lead to a better understanding of the IGFBP3 and ALS that assemble into the ternary structure and circulate the IGF system. PMID:12297028

  1. Serum insulin-like growth factor-I, IGF binding protein-3 and IGFBP-3 protease activity after cranial irradiation.

    Science.gov (United States)

    Tillmann, V; Shalet, S M; Price, D A; Wales, J K; Pennells, L; Soden, J; Gill, M S; Whatmore, A J; Clayton, P E

    1998-01-01

    The relationship between peak growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3) and IGFBP-3 protease activity was studied in 28 children and adolescents undergoing investigation of pituitary function 0.4-14.2 years after cranial or craniospinal irradiation for the treatment of CNS tumours distant from the hypothalamic-pituitary axis (n = 16) or prophylaxis against CNS leukaemia (n = 12). Seven out of 15 patients with GH deficiency (GHD) (defined as a peak GH concentration Western ligand blot (WLB) (r = 0.71; p < 0.0001). IGFBP-3 protease activity was negatively correlated to IGFBP-3 by RIA (r = -0.55; p < 0.01) and to IGFBP-3 by WLB (r = -0.51; p < 0.01). Twenty-two patients had normal IGFBP-3 protease activity (<30% of the activity in pregnancy serum) indicating that serum IGFBP-3 protease activity does not account for the normal levels of IGFBP-3 in RIA. Low serum IGF-I but normal IGFBP-3 concentrations and in the majority normal IGFBP-3 protease activity was found in patients in the years after CNS irradiation. Neither serum IGF-I nor IGFBP-3 can be used as a reliable index of the development of radiation-induced GHD. PMID:9701699

  2. DIAGNOSTIC VALUE OF SERUM INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

    Institute of Scientific and Technical Information of China (English)

    覃舒文; 史轶蘩; 邓洁英

    2002-01-01

    Objective. To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). Methods. To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. Results. Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6± 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six -month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3± 0.7 mg/L to 2.7± 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3± 2.2 mg/L, which was not significantly different from that in normal group. Conclusion. Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

  3. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

    Energy Technology Data Exchange (ETDEWEB)

    Bhattarai, Govinda; Lee, Young-Hee [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lee, Min-Ho [Department of Dental Materials, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Park, Il-Song [Division of Advanced Materials Engineering, Research Center for Advanced Materials, Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Yi, Ho-Keun, E-mail: yihokn@chonbuk.ac.kr [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

    2015-10-01

    Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology.

  4. IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer

    International Nuclear Information System (INIS)

    The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated. Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed. Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001). IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer

  5. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

    International Nuclear Information System (INIS)

    Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology.

  6. Excessive gestational weight gain and obesity contribute to altered expression of maternal insulin-like growth factor binding protein-3

    Directory of Open Access Journals (Sweden)

    Ferraro ZM

    2013-10-01

    0.01. However, serum IGFBP-3 expression in the EXCEED mothers was greater than that in the ADHERE group (P ≤ 0.05. Conclusion: These findings provide preliminary evidence suggesting that small deviations in IGFBP-regulated IGF bioavailability arising from excessive GWG/positive energy balance may affect adipocyte differentiation through subclinical insulin resistance. Keywords: gestational weight gain, insulin-like growth factors, insulin-like growth factor binding protein-3, pregnancy, insulin sensitivity

  7. Radioimmunoassay of human insulin-like growth factor binding protein-3 in serum and its clinical application

    International Nuclear Information System (INIS)

    Objective: To establish a specific radioimmunoassay (RIA) for serum level of human insulin-like growth factor binding protein-3 (IGFBP-3) and study serum IGFBP-3 levels in normal adults and some pathophysiological states. Methods: IGFBP-3 antibody was raised and iodinated IGFBP-3 was made with lactoperoxidase as a tracer, then set up the RIA for human serum IGFBP-3. Serum levels of normal adults, patients suffered from acromegaly, growth hormone deficiency (GHD), liver cirrhosis and chronic renal failure (CRF) were tested. Results: The minimal detectable range of this IGFBP-3 RIA was (16.9 +- 2.4) μg/L. The affinity constant is 7.9 x 1010 L/mol, without cross-reactivity with IGFBP-1, IGFBP-2, insulin-like growth factor-1 (IGF-1) and human growth hormone (hGH). The mean rate of recovery was 98.7%, and the mean coefficients of variation for intra- and inter batch-assay were (7.8 +- 3.5)% and (10.8 +- 3.1)% respectively. The mean serum levels of IGFBP-3 in 88 normal adults were (3.1+- 0.5) mg/L (range 2.0-4.0 mg/L), while that in 49 active acromegalics were (16.8 +- 9.9) mg/L (range 5.6-42.8 mg/L) and in 19 CRF were (13.2 +- 3.6) mg/L (range 9.8-25.0 mg/L), none of them was overlapping the normal adult levels. The mean serum IGFBP-3 levels of 129 GHD and 18 liver cirrhosis were (1.6 +-0.9) mg/L (range 0.4-3.7 mg/L) and (2.4+-0.7) mg/L (range 1.2-3.7 mg/L) respectively, all of them were overlapping the lower level of serum IGFBP-3 of normal adults. Conclusions: This RIA is easy to use, can detect wide range of serum IGFBP-3, has high specificity and good reproducibility. Serum IGFBP-3 assay is very useful in diagnosis of the hyper-, normal and hypo-secretory state of hGH

  8. Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

    OpenAIRE

    Steiger-Luther, Nicole C; Darwiche, Houda; Oh, Seh-Hoon; Williams, Jennifer M.; PETERSEN, BRYON E.

    2010-01-01

    Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as “oval cells”, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3) during this process of oval cell activation is of particular...

  9. The Association between Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Levels and Clinical Prognosis in Patients with Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Hasan Yaşar

    2015-04-01

    Full Text Available OBJECTIVE: Recent studies report that the insulin-like growth factor system may be involved in stroke pathogenesis, and is reported to increase myelination, maturation, cell proliferation and neuronal sprouting of the central nervous system. The aim of the present study is to demonstrate the role of insulin-like growth factor system in ischemic stroke pathogenesis and its association with the prognosis by investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels in patients diagnosed with acute ischemic stroke. METHODS: : Sixty-eight patients and 20 healthy individuals were included to this study. Clinical evaluation of the patients was performed according to National Institute of Health Stroke Scale and functional outcomes were graded according to Modified Rankin Scale. Bamford classification was used for the clinical classification of ischemic strokes, and the TOAST system for etiological classification. Each patient's levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured on the first, fifth and thirtieth day of ischemic stroke. RESULTS: Only the levels of insulin-like growth factor binding protein-3 on the day of 5 were significantly decreased compared to the control group. The decrease in IGF-1 values was associated with an increased risk of death and was accompanied by clinical worsening and decreased functionality. CONCLUSION: It has been concluded that the levels of investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 may affect mortality risk, clinical condition and functionality outcomes in patients presenting with ischemic stroke, and further studies are needed for the investigation of different effects of insulin-like growth factor-1 in future.

  10. Enhancing the Apoptotic Potential of Insulin-Like Growth Factor-Binding Protein-3 in Prostate Cancer by Modulation of CK2 Phosphorylation

    OpenAIRE

    Cobb, Laura J.; Mehta, Hemal; Cohen, Pinchas

    2009-01-01

    IGF-binding protein 3 (IGFBP-3) promotes apoptosis by both IGF-dependent and -independent mechanisms. We have previously reported that phosphorylation of IGFBP-3 (S156) by DNA-dependent protein kinase enhances its nuclear accumulation and is essential for its ability to interact with retinoid X receptor-α and induce apoptosis in cultured prostate cancer cells. Using specific chemical inhibitors and small interfering RNA, we demonstrate that preventing casein kinase 2 (CK2) activation enhanced...

  11. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    OpenAIRE

    Vestey, Sarah B; Perks, Claire M.; Sen, Chandan; Calder, Caroline J; Holly, Jeff MP; Winters, Zoe E

    2004-01-01

    Introduction Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In v...

  12. Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells

    OpenAIRE

    Laich, A; Matscheski, A.; Mück, C.; Ferrando-May, E.; H. Pircher; Ebner, H L; Micutkova, L.; Huber, L A; M. Hermann; Offerdinger, M.; Hess, M. W.; Jansen-Dürr, P; Zwerschke, W.

    2010-01-01

    Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an important regulator of cell proliferation and survival, which plays an important role in a variety of epithelial cancers, including prostate cancer, cervical cancer and breast cancer. IGFBP-3 was described as a tumor suppressor in the prostate and identified as a functional cellular target for the E7 oncoprotein of human papillomaviruses. IGFBP-3 interacts with IGF-I outside the cell; however, IGF-independent actions of IGFBP...

  13. Effects of Hibiscus sabdariffa Linn. on insulin-like growth factor binding protein 3 (IGFBP-3) to prevent overtraining syndrome

    OpenAIRE

    Ermita I.I. Ilyas; Neng T. Kartinah; Trinovita Andraini; Roman A. Goenarjo; Donna N. Kahandjak

    2015-01-01

    Background: Excessive physical exercises (overtraining) can increase the production of reactive oxygen species (ROS). One of the indicators of overtraining syndrome is a decrease in insulin-like growth factor binding protein 3 (IGFBP-3). Administration of Hibiscus sabdariffa Linn., a powerful antioxidant, is expected to boost endogenous antioxidants, and thus prevents overtraining. The aim of this study is to determine the effect of H. sabdariffa on IGFBP-3 levels in rats under ”overtraining ...

  14. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

    OpenAIRE

    Ikonen, Maaria; LIU, BINGRONG; Hashimoto, Yuichi; Ma, Liqun; Lee, Kuk-Wha; Niikura, Takako; Nishimoto, Ikuo; Cohen, Pinchas

    2003-01-01

    Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell growth and survival. By using a yeast two-hybrid screen to identify IGFBP-3-interacting proteins, we cloned humanin (HN) as an IGFBP-3-binding partner. HN is a 24-aa peptide that has been shown to specifically inhibit neuronal cell death induced by familial Alzheimer's disease mutant genes and amyloid-β (Aβ). The physical interaction of HN with IGFBP-3 was determined to be of...

  15. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    Energy Technology Data Exchange (ETDEWEB)

    Liwei Chen

    2003-05-31

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic {sup 13}C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic {sup 13}C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of {sup 13}C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The {sup 13}C/{sup 12}C ratio in the TTR extract was measured by GCC-IRMS. There was no {sup 13}C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  16. Potentiation of Growth Factor Signaling by Insulin-like Growth Factor-binding Protein-3 in Breast Epithelial Cells Requires Sphingosine Kinase Activity*

    OpenAIRE

    Martin, Janet L; Mike Z. Lin; Eileen M. McGowan; Baxter, Robert C.

    2009-01-01

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1...

  17. Effect of sigma factor S (sigmaS) on the stability of penicillin-binding protein 3 (PBP3) of Escherichia colt K12

    OpenAIRE

    Rosane S. Machado; Douglas C. Camelo; de Almeida, Darcy F.; Ferreira, Luis C. S.

    1996-01-01

    The stability of penicillin-binding protein 3 (PBP3), a cell septum synthesizing protein, was analyzed at different incubation temperatures in three Escherichia coli K12 strains carrying a PBP3-overproducing plasmid. The stability of PBP3 was significantly reduced in stationary phase cells shifted to 42°C for 4 h, compared to samples incubated at 28 or 37°C. The half-life of PBP3 in the C600 strain was 60 min at 42°C, while samples incubated at 28 or 37°C had PBP3 half-lives greater than 4 h....

  18. Changes in the level of growth hormone, insulin like growth factor-1 and insulin like growth factor binding proteine-3 in young males 24 hours after submaximaltraining

    OpenAIRE

    ÇOKNAZ, Hakkı

    2011-01-01

    The study was accomplished as a control study, under the question whether 6-weeks endurance training affects the growth hormone (GH), insulin like growth factor-1 (IGF-1) and the IGF bindings protein-3 (IGFBP-3) levels. Sixty male subjects participated in the study. The subjects were separated into 2 groups as control (n=30; mean age=21,13±1,16 years) and study (n=30; mean age=21,53±1,61 years) randomly, prior to the runtest. Blood samples were drawn before breakfast and analyzed in the labor...

  19. Isolation of complexes formed between insulin-like growth factor-binding protein-3 and transferrin from the human serum

    Directory of Open Access Journals (Sweden)

    Miljuš Goran

    2012-01-01

    Full Text Available Insulin-like growth factors (IGFs play an important role in the regulation of cell growth, differentiation and metabolism. The amount of free, biologically active IGFs is regulated by the IGF-binding proteins (IGFBPs. IGFBP-3 is the most abundant binding protein and it is known to interact with other circulating proteins, including transferrin (Tf. In order to elucidate the possible role of IGF/IGFBP-3 in the iron metabolism, it is necessary to isolate IGFBP-3/Tf complexes. Several affinity-based techniques were employed. Results have shown that only double immunoprecipitation method with anti-Tf and anti-IGFBP-3 antibodies selectively separated complexes from other molecular forms, such as monomers, oligomers or fragments of IGFBP-3 and Tf. Isolated complexes can now be used to investigate the relationship between IGF/IGFBP-3 and iron, both in structural and metabolic tеrms.

  20. Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

    OpenAIRE

    TAKAOKA, MUNENORI; Harada, Hideki; Andl, Claudia D; Oyama, Kenji; Naomoto, Yoshio; Dempsey, Kelly L.; Klein-Szanto, Andres J.; El-Deiry, Wafik S; GRIMBERG, ADDA; Nakagawa, Hiroshi

    2004-01-01

    Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell proliferation through both insulin-like growth factor-dependent and independent mechanisms. We found that IGF...

  1. Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Atsushi [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan); Ogawa, Masahiro [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yanai, Hideyuki [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan); Naka, Daiji [ZOEGENE Corp., 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033 (Japan); Goto, Ayana; Ao, Tomoka [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Tanno, Yuji [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Takeda, Kiyoshi [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Watanabe, Yoshinori [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Honda, Kenya [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Taniguchi, Tadatsugu, E-mail: tada@m.u-tokyo.ac.jp [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan)

    2011-07-22

    Highlights: {yields} We identified RNA-binding motif protein 3 (RBM3) as CpG-B DNA-binding protein. {yields} RBM3 translocates from the nucleus to the cytoplasm and co-localized with CpG-B DNA. {yields} We newly generated Rbm3-deficient (Rbm3{sup -/-}) mice. {yields} DNA-mediated cytokine gene induction was normally occured in Rbm3{sup -/-} cells. {yields}Rbm3{sup -/-} MEFs showed poorer proliferation rate and increased number of G2-phase cells. -- Abstract: The activation of innate immune responses is critical to host defense against microbial infections, wherein nucleic acid-sensing pattern recognition receptors recognize DNA or RNA from viruses or bacteria and activate downstream signaling pathways. In a search for new DNA-sensing molecules that regulate innate immune responses, we identified RNA-binding motif protein 3 (RBM3), whose role has been implicated in the regulation of cell growth. In this study, we generated Rbm3-deficient (Rbm3{sup -/-}) mice to study the role of RBM3 in immune responses and cell growth. Despite evidence for its interaction with immunogenic DNA in a cell, no overt phenotypic abnormalities were found in cells from Rbm3{sup -/-} mice for the DNA-mediated induction of cytokine genes. Interestingly, however, Rbm3{sup -/-} mouse embryonic fibroblasts (MEFs) showed poorer proliferation rates as compared to control MEFs. Further cell cycle analysis revealed that Rbm3{sup -/-} MEFs have markedly increased number of G2-phase cells, suggesting a hitherto unknown role of RBM3 in the G2-phase control. Thus, these mutant mice and cells may provide new tools with which to study the mechanisms underlying the regulation of cell cycle and oncogenesis.

  2. Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth

    International Nuclear Information System (INIS)

    Highlights: → We identified RNA-binding motif protein 3 (RBM3) as CpG-B DNA-binding protein. → RBM3 translocates from the nucleus to the cytoplasm and co-localized with CpG-B DNA. → We newly generated Rbm3-deficient (Rbm3-/-) mice. → DNA-mediated cytokine gene induction was normally occured in Rbm3-/- cells. →Rbm3-/- MEFs showed poorer proliferation rate and increased number of G2-phase cells. -- Abstract: The activation of innate immune responses is critical to host defense against microbial infections, wherein nucleic acid-sensing pattern recognition receptors recognize DNA or RNA from viruses or bacteria and activate downstream signaling pathways. In a search for new DNA-sensing molecules that regulate innate immune responses, we identified RNA-binding motif protein 3 (RBM3), whose role has been implicated in the regulation of cell growth. In this study, we generated Rbm3-deficient (Rbm3-/-) mice to study the role of RBM3 in immune responses and cell growth. Despite evidence for its interaction with immunogenic DNA in a cell, no overt phenotypic abnormalities were found in cells from Rbm3-/- mice for the DNA-mediated induction of cytokine genes. Interestingly, however, Rbm3-/- mouse embryonic fibroblasts (MEFs) showed poorer proliferation rates as compared to control MEFs. Further cell cycle analysis revealed that Rbm3-/- MEFs have markedly increased number of G2-phase cells, suggesting a hitherto unknown role of RBM3 in the G2-phase control. Thus, these mutant mice and cells may provide new tools with which to study the mechanisms underlying the regulation of cell cycle and oncogenesis.

  3. Stability of lutein in wholegrain bakery products naturally high in lutein or fortified with free lutein.

    Science.gov (United States)

    Abdel-Aal, El-Sayed M; Young, J Christopher; Akhtar, Humayoun; Rabalski, Iwona

    2010-09-22

    Lutein is a yellow pigment found in common foods that promotes the health of eyes and skin and is associated with reduced risk of age-related macular degeneration and cataracts. In the present study, selected high-lutein wheat and corn were milled into wholegrain flours by two mills to improve flour uniformity. The high-lutein and lutein-fortified wholegrain flours were processed into breads, cookies, and muffins to study lutein stability during baking and subsequent storage. Lutein and its isomers were separated, identified, and quantified by LC-UV/vis and LC-MS following extraction with water-saturated 1-butanol. Baking resulted in a significant reduction in all-trans-lutein and the formation of cis-lutein and cis-zeaxanthin isomers. Subsequent storage at ambient temperature had a slight impact on the content of all-trans-lutein. Effects of processing were more pronounced in lutein-fortified products, and the degradation rate of lutein was influenced by concentration and baking recipe. Fortified cookies and muffins showed greater lutein reduction compared with bread. Despite the significant reduction in lutein, the fortified bakery products still possessed reasonable amounts per serving that would enhance daily intake and consumption of wholegrain foods. PMID:20734986

  4. Characterization of the transcripts and protein isoforms for cytoplasmic polyadenylation element binding protein-3 (CPEB3 in the mouse retina

    Directory of Open Access Journals (Sweden)

    Cooper Nigel GF

    2009-12-01

    Full Text Available Abstract Background Cytoplasmic polyadenylation element binding proteins (CPEBs regulate translation by binding to regulatory motifs of defined mRNA targets. This translational mechanism has been shown to play a critical role in oocyte maturation, early development, and memory formation in the hippocampus. Little is known about the presence or functions of CPEBs in the retina. The purpose of the current study is to investigate the alternative splicing isoforms of a particular CPEB, CPEB3, based on current databases, and to characterize the expression of CPEB3 in the retina. Results In this study, we have characterized CPEB3, whose putative role is to regulate the translation of GluR2 mRNA. We identify the presence of multiple alternative splicing isoforms of CPEB3 transcripts and proteins in the current databases. We report the presence of eight alternative splicing patterns of CPEB3, including a novel one, in the mouse retina. All but one of the patterns appear to be ubiquitous in 13 types of tissue examined. The relative abundance of the patterns in the retina is demonstrated. Experimentally, we show that CPEB3 expression is increased in a time-dependent manner during the course of postnatal development, and CPEB3 is localized mostly in the inner retina, including retinal ganglion cells. Conclusion The level of CPEB3 was up-regulated in the retina during development. The presence of multiple CPEB3 isoforms indicates remarkable complexity in the regulation and function of CPEB3.

  5. PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.Y. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, M.S.; Lee, M.K. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, J.S.; Yi, H.K. [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Nam, S.Y. [Department of Alternative Therapy, Jeonju University, Jeonju (Korea, Republic of); Lee, D.Y.; Hwang, P.H. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2015-01-13

    Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

  6. PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

    International Nuclear Information System (INIS)

    Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor

  7. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T;

    1995-01-01

    Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...... treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with...

  8. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T; Breum, Leif; Christiansen, J S; Hilsted, J

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated by...... anthropometric computed tomography (CT)-calibrated equations. In females, IGF-1 was inversely associated with the abdominal sagittal diameter (SagD) and with the visceral AT (r = -.41, P = .006). No significant correlations were found between IGF-1 and BMI or other indices of adiposity. Weight loss caused a...

  9. Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly

    DEFF Research Database (Denmark)

    Sneppen, S B; Lange, Merete Wolder; Pedersen, L M;

    2001-01-01

    insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease...... activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients....

  10. Lutein and brain function

    Science.gov (United States)

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated in macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Rece...

  11. The Effects of Combined Antioxidant Supplementation on Antioxidant Capacity, DNA Single-Strand Breaks and Regulation of Insulin Growth Factor-1/IGF-Binding Protein 3 in the Ferret Model of Lung Cancer

    Science.gov (United States)

    Purpose: Insulin-like growth factor 1 (IGF-1) and its major binding protein, IGF binding protein 3 (IGFBP-3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (...

  12. NKX3.1 activates expression of insulin-like growth factor binding protein-3 to mediate insulin-like growth factor-I signaling and cell proliferation.

    Science.gov (United States)

    Muhlbradt, Erin; Asatiani, Ekaterina; Ortner, Elizabeth; Wang, Antai; Gelmann, Edward P

    2009-03-15

    NKX3.1 is a homeobox gene that codes for a haploinsufficient prostate cancer tumor suppressor. NKX3.1 protein levels are down-regulated in the majority of primary prostate cancer tissues. NKX3.1 expression in PC-3 cells increased insulin-like growth factor binding protein-3 (IGFBP-3) mRNA expression 10-fold as determined by expression microarray analysis. In both stably and transiently transfected PC-3 cells and in LNCaP cells, NKX3.1 expression increased IGFBP-3 mRNA and protein expression. In prostates of Nkx3.1 gene-targeted mice Igfbp-3 mRNA levels correlated with Nkx3.1 copy number. NKX3.1 expression in PC-3 cells attenuated the ability of insulin-like growth factor-I (IGF-I) to induce phosphorylation of type I IGF receptor (IGF-IR), insulin receptor substrate 1, phosphatidylinositol 3-kinase, and AKT. The effect of NKX3.1 on IGF-I signaling was not seen when cells were exposed to long-R3-IGF-I, an IGF-I variant peptide that does not bind to IGFBP-3. Additionally, small interfering RNA-induced knockdown of IGFBP-3 expression partially reversed the attenuation of IGF-IR signaling by NKX3.1 and abrogated NKX3.1 suppression of PC-3 cell proliferation. Thus, there is a close relationship in vitro and in vivo between NKX3.1 and IGFBP-3. The growth-suppressive effects of NKX3.1 in prostate cells are mediated, in part, by activation of IGFBP-3 expression. PMID:19258508

  13. Effects of quercetin on insulin-like growth factors (IGFs and their binding protein-3 (IGFBP-3 secretion and induction of apoptosis in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vijayababu Marati R

    2006-04-01

    Full Text Available Abstract Background Quercetin, the predominant flavonoid, has been reported to lower the risk of several cancers. This flavonoid found in onion, grapes, green vegetables, etc. has been shown to possess potent antiproliferative effects against various malignant cells. This study was designed to investigate its effects on insulin-like growth factors (IGFs and their binding protein-3 (IGFBP-3 proteins secretion and also apoptosis induction in the human prostate cancer cell line, PC-3. Methods We evaluated the secretion of IGF-I, -II and IGFBP-3 in quercetin treated cells by immunoradiometric (IRMA method. Apoptosis was studied in quercetin treated cells by TUNEL and DNA fragmentation. Protein expressions of Bcl-2, Bcl-xL, Bax and caspase-3 were studied by western blot. Results At a dose of 100 μM concentration, we observed increased IGFBP-3 accumulation in PC-3 cells conditioned medium with a dose dependent increase with 2 fold over a base line, and significantly reduced the both IGF-I and IGF-II levels. Apoptosis induction was also confirmed by TUNEL assay. Bcl-2 and Bcl-xL protein expressions were significantly decreased and Bax and caspase-3 were increased. Conclusion These results suggest that the decreased level of IGFs could be due to the increased levels of IGFBP-3, because of the high binding affinity towards IGFs, thereby decreasing the cell proliferation. The increased level of IGFBP-3 was associated with increased pro-apoptotic proteins and apoptosis in response to quercetin, suggesting it may be a p53-independent effector of apoptosis in prostate cancer cells.

  14. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival

    International Nuclear Information System (INIS)

    Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin). We evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression. IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8). Our data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer

  15. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T;

    1995-01-01

    , stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...... cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P <0.0001, respectively) compared to those in normal age-matched prepubertal...... levels after 2 yr of treatment (P <0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio...

  16. Identification of polymorphism in fatty acid binding protein 3 (FABP3) gene and its association with milk fat traits in riverine buffalo (Bubalus bubalis).

    Science.gov (United States)

    Dubey, Praveen Kumar; Goyal, Shubham; Mishra, Shailendra Kumar; Arora, Reena; Mukesh, Manishi; Niranjan, Saket Kumar; Kathiravan, Periasamy; Kataria, Ranjit Singh

    2016-04-01

    The fatty acid binding protein 3 (FABP3) gene, known to be associated with fat percentage of milk and meat in bovines, was screened among swamp and riverine buffaloes for polymorphism detection and further association with milk fat contents. An SNP g.307C > T was identified in the intron 2 (+53 exon 2) region of FABP3 gene of Indian buffaloes. The SNP identified was genotyped in 692 animals belonging to 15 riverine, swamp and hybrid (riverine × swamp) buffalo populations of diverse phenotypes and utilities, by PCR-RFLP. A marked contrast was observed between the C and T allele frequencies in three types of buffaloes. The frequency of C allele ranged from 0.67 to 0.96 in pure swamp buffalo populations, with the highest in Mizoram (0.96). Whereas the frequency of T allele was high across all the Indian riverine buffalo breeds, ranging from 0.57 to 0.96. None of the genotypes at FABP3 g.307C > T locus was found to have significant association with milk fat and other production traits in Mehsana dairy buffalo breed. Our study revealed marked differences in the allele frequencies between riverine and swamp buffaloes at FABP3 g.307C > T locus, without any significant association with different milk traits in riverine buffaloes. PMID:26894500

  17. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    Science.gov (United States)

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. PMID:26943480

  18. Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly

    DEFF Research Database (Denmark)

    Sneppen, S B; Lange, Merete Wolder; Pedersen, L M; Kristensen L, L Ø; Main, K M; Juul, A; Skakkebaek, N E; Feldt-Rasmussen, U

    2001-01-01

    insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease...... the inactive and the active groups, we found that positive and negative predictive values (PV(pos), PV(neg)) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to...... activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients....

  19. Effect of sigma factor S (sigmaS on the stability of penicillin-binding protein 3 (PBP3 of Escherichia colt K12

    Directory of Open Access Journals (Sweden)

    Rosane S. Machado

    1996-01-01

    Full Text Available The stability of penicillin-binding protein 3 (PBP3, a cell septum synthesizing protein, was analyzed at different incubation temperatures in three Escherichia coli K12 strains carrying a PBP3-overproducing plasmid. The stability of PBP3 was significantly reduced in stationary phase cells shifted to 42°C for 4 h, compared to samples incubated at 28 or 37°C. The half-life of PBP3 in the C600 strain was 60 min at 42°C, while samples incubated at 28 or 37°C had PBP3 half-lives greater than 4 h. Analysis of the PBP3 content in mutants deficient in rpoS (coding for the stationary phase sigma factor, sigmaS and rpoH (coding for the heat shock sigma factor, sigma32 genes after shift to 42°C showed that stability of the protein was controlled by sigmaS but not by sigma32. These results suggest that control of the PBP3 levels in E. coli K12 is through a post-transcriptional mechanism regulated by the stationary phase regulon. We demonstrated that stability of PBP3 in E. coli K12 involves degradation of the protein. Moreover, we observed that incubation of cells at 42°C significantly reduces the stability of PBP3 in early stationary phase cells in a process controlled by sigmaS.

  20. Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores

    International Nuclear Information System (INIS)

    The oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell-migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. To our knowledge, IMP3 expression has not been investigated in prostate carcinomas so far. Immunohistochemical stainings for IMP3 were performed on tissue microarray (TMA) organized samples from 507 patients: 31 normal prostate tissues, 425 primary carcinomas and 51 prostate cancer metastases or castration-resistant prostate cancers (CRPC). IMP3 immunoreactivity was semiquantitatively scored and correlated with clinical-pathologic parameters including survival. IMP3 is significantly stronger expressed in prostate carcinomas compared to normal prostate tissues (p < 0.0001), but did not show significant correlation with the pT-stage, the proliferation index (MIB1), preoperative serum PSA level and the margin status. Only a weak and slightly significant correlation was found with the Gleason score and IMP3 expression failed to show prognostic significance in clinico-pathological correlation-analyses. Although IMP3 is overexpressed in a significant proportion of prostate cancer cases, which might be of importance for novel therapeutic approaches, it does not appear to possess any immediate diagnostic or prognostic value, limiting its potential as a tissue biomarker for prostate cancer. These results might be corroborated by the fact, that two independent tumor cohorts were separately reviewed

  1. Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.

    Science.gov (United States)

    Hattori, Yukinori; Yoshida, Akihiko; Yoshida, Masayuki; Takahashi, Masahide; Tsuta, Koji

    2015-06-01

    Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas. PMID:25727644

  2. Associations of serum carotenoid concentrations and fruit or vegetable consumption with serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 concentrations in the Third National Health and Nutrition Examination Survey (NHANES III).

    Science.gov (United States)

    Diener, Anja; Rohrmann, Sabine

    2016-01-01

    Dietary intervention may alter the insulin-like growth factor (IGF) system and thereby cancer risk. In a qualitative review, eleven of twenty studies showed a link between one or more carotenoids, vegetable or fruit intake and the IGF system, however, with partly contrary findings, such that no firm conclusion can be drawn. Therefore, we evaluated associations between serum carotenoid concentrations or the intake of fruits and vegetables with IGF-1, IGF binding protein (BP)-3 and their molar ratio (IGF-1:IGFBP-3) within the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). In our analysis, we included 6061 NHANES III participants and used multivariable-adjusted linear regression models. IGF-1 concentrations were significantly positively associated with serum concentrations of lycopene, β-carotene, α-carotene, β-cryptoxanthin and lutein/zeaxanthin in men and women. Statistically significant positive associations were observed for serum concentrations of α-carotene and lutein/zeaxanthin and intake of fruits with serum IGFBP-3 concentrations in women, but not in men. The IGF-1:IGFBP-3 molar ratio was significantly positively associated with serum concentrations of lycopene, β-carotene and α-carotene in men and with β-carotene in women. In conclusion, dietary interventions with carotenoids, fruits and vegetables may affect the IGF system, although the direction of these effects is currently unclear. PMID:27313849

  3. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S; Winkler, K; Jørgensen, J O; Christiansen, J S; Skakkebaek, N E

    1994-01-01

    for 4 months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms...

  4. Potentiation of growth factor signaling by insulin-like growth factor-binding protein-3 in breast epithelial cells requires sphingosine kinase activity.

    Science.gov (United States)

    Martin, Janet L; Lin, Mike Z; McGowan, Eileen M; Baxter, Robert C

    2009-09-18

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1, but not SphK2, expression. Similarly, IGFR1 phosphorylation and DNA synthesis stimulated by LR3-IGF-I (an IGF-I analog not bound by IGFBP-3), were enhanced by IGFBP-3, and this was blocked by SphK1 silencing. SphK1 expression and activity were stimulated by IGFBP-3 approximately 2-fold over 24 h. Silencing of sphingosine 1-phosphate receptor 1 (S1P1) or S1P3, but not S1P2, abolished the effect of IGFBP-3 on EGF-stimulated EGFR activation. The effects of IGFBP-3 could be reproduced with exogenous S1P or medium conditioned by cells treated with IGFBP-3, and this was also blocked by inhibition of S1P1 and S1P3. These data indicate that potentiation of growth factor signaling by IGFBP-3 in MCF-10A cells requires SphK1 activity and S1P1/S1P3, suggesting that S1P, the product of SphK activity and ligand for S1P1 and S1P3, is the "missing link" mediating IGF and EGFR transactivation and cell growth stimulation by IGFBP-3. PMID:19633297

  5. Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

    International Nuclear Information System (INIS)

    Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  6. Association between serum insulin-like growth factor I or IGF-binding protein 3 and estimated glomerular filtration rate: results of a population-based sample

    Directory of Open Access Journals (Sweden)

    Dittmann Kathleen

    2012-12-01

    Full Text Available Abstract Background Insulin-like growth factor I (IGF-I, which is mostly carried in blood by IGF-binding protein 3 (IGFBP-3, was associated to the glomerular filtration rate and chronic kidney disease in a multiethnic study among US adults. The aim of the present study was to investigate whether serum IGF-I or IGFBP-3 are associated with estimated glomerular filtration rate (eGFR in a population-based study of Caucasian adults. Methods Data from 4028 subjects (2048 women aged 20 to 81 years from the Study of Health in Pomerania (SHIP were analyzed. Total serum IGF-I and IGFBP-3 concentrations were determined by chemiluminescence immunoassays and categorized into sex- and age-specific quartiles. Results After adjusting for age, waist circumference and type 2 diabetes mellitus, analysis of variance (ANOVA revealed inverse associations between serum IGF-I concentrations and eGFR in men as well as between serum IGFBP-3 concentrations and eGFR in men and women. Logistic regression analyses confirmed these findings and showed that high IGF-I or IGFBP-3 concentrations were associated with an increased risk of decreased eGFR (2 in men or women. These relations became stronger when lower eGFR cut-offs were used for the analyses. Conclusion Our data revealed associations of increased serum IGF-I concentrations and decreased eGFR in men but not in women and an association of increased serum IGFBP-3 concentrations and decreased eGFR in both sexes.

  7. Changes in the level of growth hormone, insulin like growth factor-1 and insulin like growth factor binding proteine-3 in young males 24 hours after submaximaltraining

    Directory of Open Access Journals (Sweden)

    Hakkı Çoknaz

    2011-04-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 The study was accomplished as a control study, under the question whether 6-weeks endurance training affects the growth hormone (GH, insulin like growth factor-1 (IGF-1 and the IGF bindings protein-3 (IGFBP-3 levels. Sixty male subjects participated in the study. The subjects were separated into 2 groups as control (n=30; mean age=21,13±1,16 years and study (n=30; mean age=21,53±1,61 years randomly, prior to the runtest. Blood samples were drawn before breakfast and analyzed in the laboratory of the medical faculty of Abant Izzet Baysal University concerning GH, IGF-1and IGFBP-3. VO2max was measured in all individuals. The individuals experimental group trained 3 times a week (Monday, Wednesday, and Friday for 6 weeks, on the other hand the control group had rest/rested for 6 weeks. Trainings included 30-40 minutes submaximal run on the treadmill, per day. After the last session of training, blood samples were drawn from all subjects following day before breakfast, and were analyzed similar to the first measurements. Then, all subjects (experimental and control groups were subjected to VO2max measurement again. There were no differences within groups and between the groups in GH, IGF-1, IGFBP-3levels before (p>0.05 and after the test (p>0.05. VO2max was found to be significantly higher in the study group compare to controls (p<0.05. We conclude that submaximal training does not affect the production of growth hormones, although it may increase oxygen consumption. 

  8. The joint effects of arsenic and risk diplotypes of insulin-like growth factor binding protein-3 in renal cell carcinoma.

    Science.gov (United States)

    Huang, Chao-Yuan; Huang, Ya-Li; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Chen, Wei-Jen; Chen, Shih-Shan; Lin, Ying-Chin; Su, Chien-Tien; Hsueh, Yu-Mei

    2016-07-01

    The association between renal cell carcinoma (RCC) and diabetes mellitus (DM), alcohol consumption, insulin-like growth factor binding protein-3 (IGFBP-3) gene, and arsenic exposure, has been the subject of independent studies. However, few studies have examined the combined effect of these factors on RCC risk. The aim of this study was to examine the association between these risk factors and the odds ratio (OR) of RCC. A hospital-based case-control study was conducted in 398 RCC patients and 756 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of IRS-1 (Gly972Arg), PI3-K (Met362Ile), IGFBP-3 (A[-202]C), and IGFBP-3 (C[-1590]A) by PCR-RFLP. Profiles of urinary arsenic were measured by high performance liquid chromatography linked with hydride generator and atomic absorption spectrometry. Participants who had never consumed alcohol and who had high total levels of urinary arsenic and DM had a high OR of RCC. IGFBP-3 (A[-202]C) and IGFBP-3 (C[-1590]A) were in linkage disequilibrium. Participants carrying high-risk IGFBP-3 diplotypes A-C/C-C, A-A/A-C, and C-A/C-A had a significantly higher odds ratio (OR) and 95% confidence interval (2.80, 1.91-4.12) of RCC compared to those carrying other IGFBP-3 diplotypes. This is the first study to show that borderline significant interaction of high total levels of urinary arsenic and IGFBP-3 high-risk diplotypes significantly enhanced the OR of RCC. Our data also provide evidence that subjects with more risk factors (e.g., high total levels of urinary arsenic, never consumed alcohol, IGFBP-3 high-risk diplotypes) may experience a higher OR of RCC. PMID:27038904

  9. Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

    Science.gov (United States)

    Archontogeorgis, Kostas; Nena, Evangelia; Papanas, Nikolaos; Xanthoudaki, Maria; Hatzizisi, Olga; Kyriazis, Georgios; Tsara, Venetia; Maltezos, Efstratios; Froudarakis, Marios; Steiropoulos, Paschalis

    2015-01-01

    Background and Aim: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. Materials and Methods: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. Results: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 μg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). Conclusion: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy. PMID:27006717

  10. Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive.

    Science.gov (United States)

    Frost, R A; Nachman, S A; Lang, C H; Gelato, M C

    1996-08-01

    Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children. PMID:8768858

  11. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.

    Science.gov (United States)

    2005-01-01

    Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate

  12. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    International Nuclear Information System (INIS)

    Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach

  13. Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma.

    Science.gov (United States)

    Kanzaki, Akiko; Kudo, Mitsuhiro; Ansai, Shin-Ichi; Peng, Wei-Xia; Ishino, Kousuke; Yamamoto, Tetsushi; Wada, Ryuichi; Fujii, Takenori; Teduka, Kiyoshi; Kawahara, Kiyoko; Kawamoto, Yoko; Kitamura, Taeko; Kawana, Seiji; Saeki, Hidehisa; Naito, Zenya

    2016-03-01

    In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC. PMID:26782292

  14. Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

    Directory of Open Access Journals (Sweden)

    Nicole C Steiger-Luther

    2010-02-01

    Full Text Available Nicole C Steiger-Luther1, Houda Darwiche1, Seh-Hoon Oh1, Jennifer M Williams1, Bryon E Petersen1,21Department of Pathology, Immunology and Laboratory Medicine, 2Program in Stem Cell Biology and Regenerative Medicine, College of Medicine, University of Florida, Gainesville, FL, USAAbstract: Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as “oval cells”, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3 during this process of oval cell activation is of particular interest because it is produced in liver and has been shown to induce migration and differentiation of other stem cell populations both in vitro and in vivo. Additionally, IGFBP-3 production has been linked to the transforming growth factor-β (TGF-β superfamily, a pathway known to be induced during oval cell proliferation. In this study, we set out to determine whether IGFBP-3 plays a role in oval cell proliferation, migration and differentiation during this specific type of regeneration. Through activation of the oval cell-mediated liver regeneration in a rat model, we found that IGFBP-3 is elevated in the liver and serum of animals during peak days of oval cell activation and proliferation. Furthermore, in vitro assays found that WB-344 cells, a liver stem cell line similar to oval cells, were induced to migrate in the presence of IGFBP-3. When expression of IGFBP-3 was knocked down during oval cell activation in vivo, we found that oval cell proliferation was increased and observed the appearance of numerous atypical ductular structures, which were OV-6 and Ki67-positive. Finally, quantitative realtime PCR analysis of liver tissue from IGFBP-3 small interfering

  15. Genetic variants in insulin-like growth factor binding protein-3 are associated with prostate cancer susceptibility in Eastern Chinese Han men

    Directory of Open Access Journals (Sweden)

    Zhang G

    2015-12-01

    Full Text Available Guiming Zhang,1–3 Yao Zhu,1,2 Fang Liu,4,5 Chengyuan Gu,1,2 Haitao Chen,4,5 Jianfeng Xu,4–6 Dingwei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3Department of Urology, The Affiliated Hospital of Qingdao University, Shandong, 4Fudan Institute of Urology, Huashan Hospital, Fudan University, 5State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 6Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Growing evidence has indicated that insulin-like growth factor binding protein-3 (IGFBP-3 polymorphisms are associated with altered risk of prostate cancer (PCa. However, few studies have been conducted in Chinese population to validate this association. Materials and methods: Herein, we examined the association between genetic variants in the IGFBP-3 gene and PCa risk in the Chinese Han population based on a genome-wide association study (1,417 cases and 1,008 controls, and replicated three genetic variants loci in an independent case-control study (1,755 cases and 1,523 controls using Sequenom platform. Logistic regression analyses were performed to estimate odds ratios (ORs and 95% confidence intervals (95% CIs. Results: We found that in the discovery stage, rs9691259 (OR =0.691, 95% CI: 0.587–0.814, P<0.001 and rs6950179 (OR =1.420, 95% CI: 1.201–1.677, P<0.001 were significantly associated with PCa risk, whereas rs2854744 showed a marginal association with PCa risk. In the replication stage, the association between rs9691259 and rs6950179 and PCa risk was not replicated, whereas rs2854744 conferred a significant association with PCa risk (OR =1.399, 95% CI: 1.010–1.937, P=0.043. After combining the two stages, we found that rs9691259, rs6950179, and rs2854744 were all significantly associated with PCa risk. Conclusion

  16. Emergence of clonally related multidrug resistant Haemophilus influenzae with penicillin-binding protein 3-mediated resistance to extended-spectrum cephalosporins, Norway, 2006 to 2013.

    Science.gov (United States)

    Skaare, D; Anthonisen, I L; Kahlmeter, G; Matuschek, E; Natås, O B; Steinbakk, M; Sundsfjord, A; Kristiansen, B E

    2014-01-01

    Resistance to cephalosporins in Haemophilus influenzae is usually caused by characteristic alterations in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene. Resistance to extended-spectrum cephalosporins is associated with high-level PBP3-mediated resistance (high-rPBP3), defined by the second stage S385T substitution in addition to a first stage substitution (R517H or N526K). The third stage L389F substitution is present in some high-rPBP3 strains. High-rPBP3 H. influenzae are considered rare outside Japan and Korea. In this study, 30 high-rPBP3 isolates from Norway, collected between 2006 and 2013, were examined by serotyping, multilocus sequence typing (MLST), ftsI sequencing, detection of beta-lactamase genes and minimum inhibitory concentration (MIC) determination. MICs were interpreted according to clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Respiratory isolates predominated (proportion: 24/30). The 30 isolates included one serotype f isolate, while the remaining 29 lacked polysaccharide capsule genes. Resistance to extended-spectrum cephalosporins (cefixime, 29 isolates/30 isolates; cefepime, 28/30; cefotaxime, 26 /30; ceftaroline, 26/30; ceftriaxone, 14/30), beta-lactamase production (11/30) and co-resistance to non-beta-lactams (trimethoprim-sulfamethoxazole, 13/30; tetracycline, 4/30; chloramphenicol, 4/30; ciprofloxacin, 3/30) was frequent. The N526K substitution in PBP3 was present in 23 of 30 isolates; these included a blood isolate which represents the first invasive S385T + N526K isolate reported from Europe. The L389F substitution, present in 16 of 30 isolates, coincided with higher beta-lactam MICs. Non-susceptibility to meropenem was frequent in S385T + L389F + N526K isolates (8/12). All 11 beta-lactamase positive isolates were TEM-1. Five clonal groups of two to 10 isolates with identical MLST-ftsI allelic profiles were observed, including the first reported high-rPBP3

  17. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  18. Der Zusammenhang zwischen den Blutplasmakonzentrationen des zirkulierenden Insulin-like-Growth-Factor-1 sowie des Insulin-like-Growth-Factor-Binding-Protein-3 und dem funktionell-neurologischen Outcome nach ischämischem Schlaganfall

    OpenAIRE

    Armbrust, Moritz

    2016-01-01

    Background: Potential neuroprotective effects of both Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) on hypoxically-ischemically injured brain tissue have been contradictorily described elsewhere. The aim of this study was to determine if plasma levels of IGF-1 and IGFBP-3 assessed in stroke patients within the acute phase are indicative of three months functional outcome. Methods: IGF-1 and IGFBP-3 plasma levels were measured using a chemil...

  19. Insulin-like Growth Factor-binding Protein-3 (IGFBP-3) Blocks the Effects of Asthma by Negatively Regulating NF-κB Signaling through IGFBP-3R-mediated Activation of Caspases*♦

    OpenAIRE

    Lee, Yong-Chul; Jogie-Brahim, Sherryline; Lee, Dae-Yeol; Han, Jinfeng; Harada, Aki; Murphy, Liam J.; Oh, Youngman

    2011-01-01

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein known for modulating mitogenic and metabolic actions of IGFs as well as exerting a variety of biological actions not involving IGFs. Here, we show that IGFBP-3 blocks specific physiological consequences of asthma in an IGF-independent manner in vitro and in vivo. IGFBP-3 treatment effectively reduced all physiological manifestations of asthma examined in vivo (airway hyper-responsiveness, cellular and patholog...

  20. Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Recent studies have found that insulin-like growth factors (IGFs) and insulin-like growth factor binding protein-3 (IGFBP-3) have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear.OBJECTIVE: To explore the changes of insulin-like growth factor-Ⅱ (IGF-Ⅱ ) and IGFBP-3 in cerebrospinal fluid (CSF) of children with tuberculous meningitis and the significance of the changes.DESIGN: A non-randomized concurrent controlled study.SETTING: Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College.PARTICIPANTS: Thirty children with tuberculous meningitis (14 males and 16 females) were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children (13 males and 17 females) with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children (13 males and 17 females) without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children.METHODS: ① The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid (3 mL). The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined

  1. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Mika; Sugiyama, Shigeru, E-mail: sugiyama@chem.eng.osaka-u.ac.jp [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Ishida, Hanako; Niiyama, Mayumi [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Daisuke; Hara, Toshiaki [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Mizohata, Eiichi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Murakami, Satoshi [Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Kanagaw 226-8501 (Japan); Inoue, Tsuyoshi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Shigeru; Murata, Michio [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan)

    2013-11-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.

  2. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    International Nuclear Information System (INIS)

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS

  3. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte Rønde;

    2004-01-01

    Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV......-lipodystrophy. These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin...

  4. Bioavailability and biodistribution of nanodelivered lutein.

    Science.gov (United States)

    Kamil, Alison; Smith, Donald E; Blumberg, Jeffrey B; Astete, Carlos; Sabliov, Cristina; Oliver Chen, C-Y

    2016-02-01

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the maximal plasma concentration (Cmax) and area under the time-concentration curve in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ⩾ 3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to improve the bioavailability of lutein in vivo. PMID:26304429

  5. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    International Nuclear Information System (INIS)

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 ± 9.0 ng/mL, 1.1 ± 0.2 μg/mL, and 7.6 ± 3.3% of radioactivity as compared to time 0 values: 139 ± 15 ng/mL, 2.2 ± 0.2 μg/mL, and 20.0 ± 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab

  6. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nivot, S.; Adan, L.; Souberbielle, J.; Rappaport, R.; Brauner, R.; Benelli, C.; Clot, J.P.; Saucet, C. [Hopital des Enfants-Malades, Paris (France); Zucker, J.M. [Institut Curie, Paris (France)

    1994-03-01

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 {+-} 9.0 ng/mL, 1.1 {+-} 0.2 {mu}g/mL, and 7.6 {+-} 3.3% of radioactivity as compared to time 0 values: 139 {+-} 15 ng/mL, 2.2 {+-} 0.2 {mu}g/mL, and 20.0 {+-} 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab.

  7. Analysis of Serum Levels of Anti-Müllerian Hormone, Inhibin B, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Binding Protein-3, and Follicle-Stimulating Hormone with Respect to Age and Menopausal Status

    OpenAIRE

    Shin, Sun Young; Lee, Jung Ryeol; Noh, Gyung Woon; Kim, Hyun Joo; Kang, Won Jun; Kim, Seok Hyun; Chung, June-Key

    2008-01-01

    This study was undertaken to investigate age-dependent and postmenopausal changes in the serum levels of anti-Müllerian hormone (AMH), inhibin B, insulin-like growth factor (IGF)-I, IGF-binding protein-3 (IGFBP-3), and follicle-stimulating hormone (FSH), and to determine which of these markers best reflects the aging process in women. A total of 144 women aged 20-59 yr were enrolled in this cross-sectional study. Blood samples were obtained on cycle day 3 of regularly menstruating women (n=11...

  8. Lutein and lutein esters in marigold flowers by high performance chromatography

    Institute of Scientific and Technical Information of China (English)

    JIANG Xin-yu; CHEN Long-sheng; ZHOU Chun-shan

    2005-01-01

    Lutein and lutein esters in marigold flowers was quantitatively determined by high performance chromatography (HPLC) with ODS-C18 column. A mixture of CH3CN - CH3OH - CH3COOCH2CH3 with volume ratio of 55: 1: 44 was used as mobile phase at a flow rate of 1.0 mL/min and detection was carried out at 460 nm. The column temperature was about 20 ℃. The contents of lutein and lutein esters were determined by analytical curve of lutein since lutein and lutein esters have the same spectral characteristics. Determination results of hexane extracts and saponified samples of lutein show that the saponification transforms the esters into free lutein. The increase of the content of dipalmitate and palmitate stearate reveals that the reaction includes transesterifications.

  9. Cloning and expression of full-length human insulin-like growth factor binding protein 3 (IGFBP3) in the Escherichia coli

    OpenAIRE

    Emad Khodadadi; Mojtaba Panjepour; Mahdi Abbasian; Zahra Khalili Broujeni; Mohammad Reza Mofid

    2015-01-01

    Background: The effect of the growth hormone on target cells is mediated by the insulin-like growth factor 1 (IGF-1). IGF-1 binds to the insulin-like growth factor binding proteins (IGFBPs) in blood and biological fluids. Considering the important application of IGBP3 as a drug component, in this research we cloned and expressed the full-length IGFBP3 in the pET-11a vector and BL21 (DE3) expression host. Materials and Methods: First the sequence encoding of IGFBP3 was designed based on th...

  10. Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

    NARCIS (Netherlands)

    Wilczak, N; Ramsaransing, GSM; Mostert, J; Chesik, D; De Keyser, J

    2005-01-01

    Using radioimmunoassay we measured serum levels of insulin- like growth factor ( IGF)- 1 and IGF binding protein ( IGFBP)- 3 in patients with relapsing multiple sclerosis ( MS) and a benign course ( Expanded Disability Status Scale ( EDSS) less than or equal to 3 despite > 10 years disease duration)

  11. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a northern european family population

    OpenAIRE

    Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; ALI Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A.; Kissebah, Ahmed H.

    2013-01-01

    Background Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated w...

  12. Histone Deacetylase Inhibitors Enhance the Apoptotic Activity of Insulin-Like Growth Factor Binding Protein-3 by Blocking PKC-Induced IGFBP-3 Degradation

    OpenAIRE

    Oh, Seung Hyun; Whang, Young Mi; Min, Hye-Young; Han, Seung Ho; Kang, Ju-Hee; Song, Ki-Hoon; Glisson, Bonnie S.; Kim, Yeul Hong; Lee, Ho-Young

    2012-01-01

    Overexpression of insulin-like growth factor binding protein (IGFBP)-3 induces apoptosis of cancer cells. However, preexisting resistance to IGFBP-3 could limit its antitumor activities. This study characterizes the efficacy and mechanism of the combination of recombinant IGFBP-3 (rIGFBP-3) and HDAC inhibitors to overcome IGFBP-3 resistance in a subset of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cells. The effects of the combination of rIGFBP-3 and ...

  13. Targeting insulin-like growth factor-I and insulin-like growth factor-binding protein-3 signaling pathways. A novel therapeutic approach for asthma.

    Science.gov (United States)

    Lee, Hyun; Kim, So Ri; Oh, Youngman; Cho, Seong Ho; Schleimer, Robert P; Lee, Yong Chul

    2014-04-01

    Insulin-like growth factor (IGF)-I has been recognized to play critical roles in the pathogenesis of asthma, whereas IGF-binding protein (IGFBP)-3 blocks crucial physiologic manifestations of asthma. IGF-I enhances subepithelial fibrosis, airway inflammation, airway hyperresponsiveness, and airway smooth muscle hyperplasia by interacting with various inflammatory mediators and complex signaling pathways, such as intercellular adhesion molecule-1, and the hypoxia-inducible factor/vascular endothelial growth factor axis. On the other hand, IGFBP-3 decreases airway inflammation and airway hyperresponsiveness through IGFBP-3 receptor-mediated activation of caspases, which subsequently inhibits NF-κB signaling pathway. It also inhibits the IGF-I/hypoxia-inducible factor/vascular endothelial growth factor axis via IGF-I-dependent and/or IGF-I-independent mechanisms. This Translational Review summarizes the role of IGF-I and IGFBP-3 in the context of allergic airway disease, and discusses the therapeutic potential of various strategies targeting the IGF-I and IGFBP-3 signaling pathways for the management of asthma. PMID:24219511

  14. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A; Skakkebaek, N E

    1997-01-01

    Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some...... controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and...... determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should...

  15. Effect of recombinant porcine IGF-binding protein-3 on proliferation of embryonic porcine myogenic cell cultures in the presence and absence of IGF-I.

    Science.gov (United States)

    Pampusch, M S; Kamanga-Sollo, E; White, M E; Hathaway, M R; Dayton, W R

    2003-02-01

    IGF-binding protein (IGFBP)-3 is produced by cultured porcine embryonic myogenic cell (PEMC) cultures and is secreted into the medium. Levels of secreted IGFBP-3 and IGFBP-3 mRNA are significantly reduced during differentiation and increase after differentiation is complete, suggesting that IGFBP-3 may play some role in myogenesis and/or in changes in myogenic cell proliferation that accompany differentiation. IGFBP-3 reportedly may either suppress or stimulate proliferation of cultured cells depending on cell type. Additionally, IGFBP-3 has been shown to affect proliferation via both IGF-dependent and IGF-independent mechanisms in some cell types but not all. Currently, the effect, if any, of IGFBP-3 on myogenic cell proliferation is not known. Consequently, the goal of this study was to assess the IGF-I-dependent and IGF-I-independent actions of recombinant porcine IGFBP-3 on proliferation of cultured porcine myogenic cells. To facilitate these investigations, we have expressed porcine IGFBP-3 in the baculovirus system, purified and characterized the expressed recombinant porcine IGFBP-3 (rpIGFBP-3), and produced and characterized an anti-porcine IGFBP-3 antibody that neutralizes the biological activity of porcine IGFBP-3. rpIGFBP-3 suppressed IGF-I-stimulated proliferation of PEMCs in a concentration-dependent manner with equimolar concentrations of IGF-I and rpIGFBP-3, resulting in complete suppression of IGF-I-stimulated proliferation. rpIGFBP-3 also suppressed Long-R3-IGF-I-stimulated proliferation of PEMC, indicating that rpIGFBP-3 possesses IGF-independent activity in this cell system. These data have established that IGFBP-3 has the potential to affect proliferation of PEMCs during critical periods of muscle development that may impact ultimate muscle mass achievable postnatally. PMID:12553871

  16. Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.

    Science.gov (United States)

    Díaz, Paula; Harris, Jessica; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-12-15

    Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver. PMID:26491104

  17. Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study

    Science.gov (United States)

    Diorio, Caroline; Brisson, Jacques; Bérubé, Sylvie; Pollak, Michael

    2008-01-01

    Introduction Levels of insulin-like growth factor (IGF)-I and its main binding protein (IGFBP-3) have been associated with breast cancer risk among premenopausal women. However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Here, we examine the association of breast cancer risk factors with intact and total IGFBP-3 levels. Methods This cross-sectional study includes 737 premenopausal women recruited at screening mammography. Plasma intact and total IGFBP-3 and IGF-I levels were measured by enzyme-linked immunosorbent assay methods. Percent and absolute breast density were estimated using a computer-assisted method. The associations were evaluated using generalized linear models and Pearson (r) or Spearman (rs) partial correlation coefficients. Results Means ± standard deviations of intact and total IGFBP-3 levels (ng/mL) were 1,044 ± 234 and 4,806 ± 910, respectively. Intact and total IGFBP-3 levels were correlated with age and smoking. Levels of intact IGFBP-3 were negatively correlated with waist-to-hip ratio (WHR) (r = -0.128; P = 0.0005), parity (rs = -0.078; P = 0.04), and alcohol intake (r = -0.137; P = 0.0002) and positively correlated with energy intake (r = 0.075; P = 0.04). In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115; P = 0.002), parity (rs = 0.089; P = 0.02), body mass index (BMI) (r = 0.115; P = 0.002), physical activity (r = 0.118; P = 0.002), and IGF-I levels (r = 0.588; P total (intact and fragmented) IGFBP-3 levels. These findings suggest that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk. PMID:18471292

  18. Insulin-like growth factor-independent insulin-like growth factor binding protein 3 promotes cell migration and lymph node metastasis of oral squamous cell carcinoma cells by requirement of integrin β1.

    Science.gov (United States)

    Yen, Yi-Chen; Hsiao, Jenn-Ren; Jiang, Shih Sheng; Chang, Jeffrey S; Wang, Ssu-Han; Shen, Ying-Ying; Chen, Chung-Hsing; Chang, I-Shou; Chang, Jang-Yang; Chen, Ya-Wen

    2015-12-01

    Frequent metastasis to the cervical lymph nodes leads to poor survival of patients with oral squamous cell carcinoma (OSCC). To understand the underlying mechanisms of lymph node metastasis, two sublines were successfully isolated from cervical lymph nodes of nude mice through in vivo selection, and identified as originating from poorly metastatic parental cells. These two sublines specifically metastasized to cervical lymph nodes in 83% of mice, whereas OEC-M1 cells did not metastasize after injection into the oral cavity. After gene expression analysis, we identified insulin-like growth factor binding protein 3 (IGFBP3) as one of the significantly up-regulated genes in the sublines in comparison with their parental cells. Consistently, meta-analysis of the public microarray datasets and IGFBP3 immunohistochemical analysis revealed increased both levels of IGFBP3 mRNA and protein in human OSCC tissues when compared to normal oral or adjacent nontumorous tissues. Interestingly, the up-regulated IGFBP3 mRNA expression was significantly associated with OSCC patients with lymph node metastasis. IGFBP3 knockdown in the sublines impaired and ectopic IGFBP3 expression in the parental cells promoted migration, transendothelial migration and lymph node metastasis of orthotopic transplantation. Additionally, ectopic expression of IGFBP3 with an IGF-binding defect sustained the IGFBP3-enhanced biological functions. Results indicated that IGFBP3 regulates metastasis-related functions of OSCC cells through an IGF-independent mechanism. Furthermore, exogenous IGFBP3 was sufficient to induce cell motility and extracellular signal-regulated kinase (ERK) activation. The silencing of integrin β1 was able to impair exogenous IGFBP3-mediated migration and ERK phosphorylation, suggesting a critical role of integrin β1 in IGFBP3-enchanced functions. PMID:26540630

  19. Stimulation of the 150-kilodalton insulin-like growth factor-binding protein-3 ternary complex by continuous and pulsatile patterns of growth hormone (GH) administration in GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Flyvbjerg, Allan; Jørgensen, Jens Otto Lunde;

    2000-01-01

    Abstract In the circulation insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS) form a 150-kDa ternary complex that is of importance for the regulation of IGF-I bioactivity. GH administration is known to increase each of the single components of...... GH dose (2 IU/m2-24 h) was administered iv randomly as 1) continuous infusion or 2) eight bolus injections to five GH-deficient patients over a period of 24 h. GH administration significantly increased serum IGF-I and IGFBP-3 levels and the IGF-I/IGFBP-3 ratio. IGF-I levels increased most......, formation of the ternary complex was unaffected by the pattern of GH delivery. In conclusion, short-term GH administration increased all components of the 150-kDa ternary complex. Higher levels of IGF-I after constant GH exposure could indicate an increased bound fraction. However, the GH pattern did not...

  20. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A;

    1997-01-01

    Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some...... controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and...... IGFBP-3 levels were compared to those in 1237 healthy controls (312 controls > 18 yr) as well as to peak GH levels. Seventy-nine patients had peak GH values below a cut-off value of 7.5 micrograms/L (34 with isolated GHD), whereas 29 patients had a normal GH response (28 with previous isolated GHD), i...

  1. Absorption and ocular deposition of dietary lutein in marine mammals.

    Science.gov (United States)

    Koutsos, Elizabeth A; Schmitt, Todd; Colitz, Carmen M H; Mazzaro, Lisa

    2013-01-01

    Cataracts and ocular disease are common lesions of marine mammals in zoological collections. Lutein, an oxygenated carotenoid, may have therapeutic or prophylactic effects on ocular disorder. Therefore, this study examined the ability of marine mammals to absorb dietary lutein. Two preliminary trials examined lutein in two forms (beadlet or ester) in a small sample size of marine mammals representing pinnipeds and cetaceans. Lutein was fed daily in tablets providing 0.89-3.6 mg lutein/kg body weight(0.75) per day for 15 days to 2 years. A third study was conducted using lutein beadlet fed at 3.6 mg lutein/kg body weight(0.75) per day for 15-21 days. Blood was analyzed for lutein pre- and postsupplementation. In the preliminary trials, lutein beadlet was observed to result in greater blood lutein levels than lutein esters, and cetaceans had more noticeable responses than pinnipeds. In Study 3, serum lutein and zeaxanthin increased postsupplementation in beluga whales (P harp seals. The lutein levels in dolphins after supplementation are similar to those reported in free-ranging animals. Ocular lutein in harp seals demonstrates that ocular deposition occurs despite low circulating lutein levels. PMID:22753123

  2. Lutein and cataract: from bench to bedside.

    Science.gov (United States)

    Manayi, Azadeh; Abdollahi, Mohammad; Raman, Thiagarajan; Nabavi, Seyed Fazel; Habtemariam, Solomon; Daglia, Maria; Nabavi, Seyed Mohammad

    2016-10-01

    Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein. PMID:26042352

  3. Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3.

    Directory of Open Access Journals (Sweden)

    Stanley C K Cheung

    Full Text Available BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3 is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I to form a complex (IGF-I/IGFBP-3 that can treat growth hormone insensitivity syndrome (GHIS and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3 in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively when compared with wild type rice. CONCLUSION/SIGNIFICANCE: These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.

  4. Inhibition of Human MCF-7 Breast Cancer Cells and HT-29 Colon Cancer Cells by Rice-Produced Recombinant Human Insulin-Like Growth Binding Protein-3 (rhIGFBP-3)

    Science.gov (United States)

    Liu, Lizhong; Liu, Qiaoquan; Lan, Linlin; Tong, Peter C. Y.; Sun, Samuel S. M.

    2013-01-01

    Background Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. Methodology/Principal Findings We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ±3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice. Conclusion/Significance These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future. PMID:24143239

  5. Association of sterol regulatory element binding protein 2 and insulin-like growth factor binding protein 3 genetic polymorphisms with avascular necrosis of the femoral head in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    SONG Yang; DU Zhen-wu; LI Qiu-ju; ZHANG Gui-zhen; WANG Ling-ling; WU Ning; WANG Jin-cheng; GAO Zhong-li

    2012-01-01

    Background Sterol regulatory element binding protein(SREBP)-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways.The insulin-like growth factor binding protein(IGFBP)family regulates growth and metabolism,especially bone cell metabolism,and correlates with osteonecrosis.However,association of their gene polymorphisms with risk of avascular necrosis of the femoral head(ANFH)has rarely been reported.We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population.Methods Two single nucleotide polymorphisms of SREBP2 gene,rs2267439 and rs2267443,and one of IGFBP-3 gene,rs2453839,were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay.Results The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies(against normal control group),respectively.Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genctypes of SREBF-2 in ANFH patients was significantly higher than in the control group(P<0.05).Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT+CC carriers(P<0.01).CT+CC genotype frequency in patients with stage Ⅲ/Ⅳ?bilateral hip lesions was significantly higher than in those with stage Ⅲ/Ⅳ?unilateral lesions and stage Ⅱ/Ⅲ?bilateral lesions(P<0.05-0.02).Conclusions Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population.The most significant finding was that the CT+CC genotype carriers of IGFBP-3 rs2453839 were highly associated with the

  6. Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3.

    Science.gov (United States)

    Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

    2011-06-01

    The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH. PMID:21536469

  7. An Open-Label Trial of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-1/rhIGFBP-3) in Myotonic Dystrophy Type 1

    Science.gov (United States)

    Heatwole, Chad R.; Eichinger, Katy J.; Friedman, Deborah I.; Hilbert, James E.; Jackson, Carlayne E.; Logigian, Eric L.; Martens, William B.; McDermott, Michael P.; Pandya, Shree K.; Quinn, Christine; Smirnow, Alexis M.; Thornton, Charles A.; Moxley, Richard T.

    2012-01-01

    Objective To evaluate the safety and tolerability of recombinant human insulin-like growth factor-1 (rhIGF-1) complexed with IGF binding protein-3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1). Design Open-label dose-escalation clinical trial. Setting University medical center. Participants Fifteen moderately affected ambulatory participants with genetically-proven DM1. Intervention Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 over 24 weeks followed by a 16 week washout period. Outcome Measures Serial assessments of safety, muscle mass, muscle function, and metabolic state were performed. The primary outcome variable was the ability of participants to complete 24 weeks on rhIGF-1/rhIGFBP-3 treatment. Results All participants tolerated rhIGF-1/rhIGFBP-3. There were no significant changes in muscle strength or functional outcomes measures. Lean body muscle mass measured by dual energy x-ray absorptiometry increased by 1.95 kg (p=0.0007) after treatment. Participants also experienced a mean reduction in triglyceride levels of 47 mg/dL (p=0.002), a mean increase in HDL levels of 5.0 mg/dL (p=0.03), a mean reduction in HbA1c of 0.15% (p=0.03), and a mean increase in testosterone level (in men) of 203 ng/dL (p=0.002) while on rhIGF-1/rhIGFBP-3. Mild reactions at the injection site occurred (n=9 participants), as did mild transient hypoglycemia (n=3), lightheadedness (n=2), and transient papilledema (n=1). Conclusions rhIGF-1/rhIGFBP-3 treatment was generally well tolerated in DM1. rhIGF-1/rhIGFBP-3 was associated with increased lean body mass and improvements in metabolism, but not with increased muscle strength or function. Larger randomized controlled trials would be needed to further evaluate the efficacy and safety of this medication in patients with neuromuscular disease. PMID:20837825

  8. 胰岛素样生长因子结合蛋白3和特发性肺纤维化%Insulin-like growth factor binding protein-3 and idiopathic pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    叶琳; 赵洪文

    2008-01-01

    Idiopathic pulmonary fibrosis(IPF)is a fibrous degeneration disease whose etiopathogenisis is unclear,but incidence and case fatality is prominent.During the fibrous degeneration,a lot of cytokines take part in cell regulation.Insulin-like growth factor binding Protein-3(IGFBP-3)is discovered to be related with IPF.But its concrete mechanism of action is unclear.Many scholars have discovered IGFBP-3 can bind with IGF by dependent or non-dependent mode,but the concrete IGFBP-3 signal transduction pathway has not been elucidated completely.More and more studies have shown IGFBP-3 exerts very important role in many body organs and scholars put emphasis on the pulmonary fibrosis study in recent years.But the concrete mechanism of this action is not so clear,according to relative reports,maybe it iS relative to aspects below:①growth inhibiting of IGFBP-3 and apoptosis;②IGFBP-3 and IGF-1;③IGFBP-3 and TGF-β1;④IGF-1 and TGF-β1;⑤IGFBP-3 and extracellular matrix.So potential and inevitable association exists between IGFBP-3 and IPF,IGFBP-3 has important role in pulmonary fibrosis.%特发性肺纤维化(IPF)是原因不明但发病率和病死率明显的纤维变性疾病,在肺纤维化过程中,众多细胞因子参与了细胞调控,其中胰岛素样生长因子结合蛋白3(IGFBP-3)被发现与IPF有关,但其具体作用机制还不明了.许多学者发现IGFBP-3可以通过依赖性和非依赖性地方式结合IGF,但具体的IGFBP-3信号传导通路还没完全阐明.越来越多的研究显示出IGFBP-3这种蛋白在人体多器官中的重要作用,近年来研究者们把目光聚焦在肺上,而且有关纤维化的相关研究逐渐浮出水面.但其作用机制尚不清楚,阅览国内外有关报道,可能与以下内容相关:①IGFBP-3的生长抑制和细胞凋亡作用;②IGFBP-3与IGF-1;③IGFBP-3与TGF-β1;④IGF-1与TGF-β1;⑤IGFBP-3与细胞外基质.由此可见,IGFBP-3与IPF有着潜在的必然关系,IGFBP-3在促IPF的形成扮演着重要角色.

  9. Bioavailability of lutein from a lutein-enriched egg-yolk beverage and its dried re-suspended versions

    NARCIS (Netherlands)

    Bunger, M.; Quataert, M.C.J.; Kamps, L.M.; Versloot, P.; Hulshof, P.J.M.; Togtema, K.A.; Amerongen, van A.; Mensink, M.R.

    2014-01-01

    Drying a fresh lutein-enriched egg-yolk beverage would extend its shelf life, however, functional properties should not be affected. It was investigated whether consumption of a dried beverage containing lutein-enriched egg-yolk significantly increases serum lutein. One-hundred healthy young subject

  10. The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein

    Science.gov (United States)

    Kamil, Alison

    Lutein, a fat-soluble xanthophyll, contributes partially to the health benefits from consuming plant foods. Like all dietary carotenoids, lutein has a low bioavailability. In addition to increasing the intake of lutein-rich foods to enhance lutein status, delivery of lutein in polymeric nanoparticles (NP) presents a novel approach to enhancing lutein bioavailability. The overall research objective of this project was to investigate, in rats, the impact of nanoencapsulation using poly(lactic-co-glycolic acid) (PLGA) on the pharmacokinetics of lutein. We also used an in vitro cell culture approach utilizing human epithelial colorectal adenocarcinoma (Caco-2) cells grown in both conventional (CONV) and permeable support (PS) systems to investigate the impact of PLGA-NP on the absorption of lutein in intestinal cells. In chapter one, we compared the efficacy of lutein absorption in vitro using Caco-2 cells grown in both CONV and PS systems. We further examined the role of the micelle, the physiological vehicle for lutein within the small intestine, on its intestinal absorption in vitro compared to an organic solvent, ethanol, which is safe and consumed by humans. The finding from this study demonstrated that the CONV system displayed a larger efficacy of lutein uptake by Caco-2 cells. Further, in the PS system, micelle components appeared to facilitate more effective intestinal secretion of lutein. These findings suggest that lutein uptake by Caco-2 cells is subject to the influence of culturing system (CONV vs. PS) and delivery vehicle (ethanol vs. micelle). Chapter two examined the impact of PLGA-NP in rats on lutein pharmacokinetics in plasma and distribution in selected tissues as compared to free lutein. We also investigated the effect of nanoencapsulation on the absorption of lutein in intestinal cells compared to a more physiological vehicle, the micelle, using the PS method. In addition, we explored the need of additional micelles for the ultimate absorption of

  11. Luteinized fat in Krukenberg tumor: MR findings

    International Nuclear Information System (INIS)

    To our knowledge, there is no description of the fat-containing Krukenberg tumor. We report on a case of Krukenberg tumor associated with luteinized fat, which showed hyperintensity on T1-weighted MR image. The diagnosis was surgically confirmed. Hyperintense portion of the Krukenberg tumor on T1-weighted image showed diminished signal intensity on fat-saturated, T1-weighted images. Krukenberg tumor should be considered in the differential diagnosis of ovarian masses when fat signal is seen. (orig.)

  12. Characterization of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) interaction with the Bovine Aortic Endothelial (BAE) cell surface : Examination of the Role of Heparan Sulfate Proteoglycans (HSPG).

    OpenAIRE

    Parghi, Nirav

    1998-01-01

    Insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the insulin-like growth factor (IGF-I). However, their precise role is as yet unclear. Further, recent studies have indicated that IGFBP-3 has a receptor mediated growth inhibitory response of its own. In the present study, we quantified the binding characteristics of IGFBP-3 to bovine aortic endothelial (BAE) cells. Binding studies at 4 oC were conducted and a specific binding curve for IGFB...

  13. The Photobiology of Lutein and Zeaxanthin in the Eye

    OpenAIRE

    Roberts, Joan E.; Jessica Dennison

    2015-01-01

    Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and o...

  14. Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis

    DEFF Research Database (Denmark)

    Støving, R K; Flyvbjerg, A; Frystyk, J;

    1999-01-01

    Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3...

  15. Possible degradation/biotransformation of lutein in vitro and in vivo: isolation and structural elucidation of lutein metabolites by HPLC and LC-MS (atmospheric pressure chemical ionization).

    Science.gov (United States)

    Lakshminarayana, Rangaswamy; Aruna, Gorusupudi; Sangeetha, Ravi Kumar; Bhaskar, Narayan; Divakar, Sounder; Baskaran, Vallikannan

    2008-10-01

    Metabolites of lutein are highly concentrated in the human macula and are known to provide protection against age-related macular degeneration. The aim of this investigation was to characterize the in vitro oxidation products of lutein obtained through photo-oxidation and to compare them with biologically transformed dietary lutein in intestine, plasma, liver, and eyes of rats. In vivo studies involved feeding rats a diet devoid of lutein for 2 weeks to induce deficiency. Rats were divided into two equal groups (n=6/group) and received either micellar lutein by gavage for 10 days or diet supplemented with fenugreek leaves as a lutein source for 4 weeks. Lutein metabolites/oxidation products obtained from in vivo and in vitro studies were characterized by HPLC and LC-MS (APCI) techniques to elucidate their structure. The characteristic fragmented ions resulting from photo-oxidation of lutein were identified as 523 (M(+)+H(+)-3CH(3)), 476 (M(+)+H(+)-6CH(3)), and 551 (M(+)+H(+)-H(2)O). In the eyes, the fragmented molecules resulting from lutein were 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein. Epoxycarotenoids were identified in liver and plasma, whereas anhydrolutein was identified in intestine. This study emphasizes the essentiality of dietary lutein to maintain its status in the retina. PMID:18640265

  16. Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome (SRY)-positive 46,XX karyotypes

    DEFF Research Database (Denmark)

    Aksglaede, L.; Skakkebaek, N.E.; Juul, A.

    2008-01-01

    sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured. RESULTS: In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy...... girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and...... elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal. CONCLUSION: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in...

  17. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F;

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

  18. Insulin-like growth factor-binding protein-3 promotes transforming growth factor-β1-mediated epithelial-to-mesenchymal transition and motility in transformed human esophageal cells

    OpenAIRE

    Natsuizaka, Mitsuteru; Ohashi, Shinya; Wong, Gabrielle S; Ahmadi, Azal; Kalman, Ross A.; Budo, Daniela; Klein-Szanto, Andres J.; Herlyn, Meenhard; Diehl, J. Alan; Nakagawa, Hiroshi

    2010-01-01

    Insulin-like growth factor-binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma. Yet, the role of IGFBP3 in esophageal tumor biology remains to be elucidated. We find that IGFBP3 facilitates transforming growth factor (TGF)-β1-mediated epithelial-to-mesenchymal transition (EMT) in transformed human esophageal epithelial cells, EPC2–hTERT–EGFR–p53R175H. In organotypic 3D culture, a form of human tissue engineering, laser-capture microdissection revealed c...

  19. Protective effect of silk lutein on ultraviolet B-irradiated human keratinocytes

    Directory of Open Access Journals (Sweden)

    Sutatip Pongcharoen

    2013-01-01

    Full Text Available Carotenoids are efficient antioxidants that are of great importance for human health. Lutein and zeaxanthin are carotinoids present in high concentrations in the human retina which are involved in the photoprotection of the human eye. Lutein may also protect the skin from ultraviolet (UV-induced damage. The present study investigated the protective effect of lutein extracted from yellow silk cocoons of Bombyx mori on human keratinocytes against UVB irradiation. A human keratinocyte cell line and primary human keratinocytes were used to investigate the UVB protection effects of silk lutein and plant lutein. Silk lutein showed no cytotoxicity to keratinocytes. Treatment with silk lutein prior to UVB irradiation enhanced cell viability and cell proliferation, and reduced cell apoptosis. The protective effects of silk lutein may be superior to those of plant lutein. Silk lutein may have a benefit for protection of keratinocytes against UVB-irradiation.

  20. Lutein and lutein esters in whole grain flours made from 75 genotypes of 5 triticum species grown at multiple sites.

    Science.gov (United States)

    Ziegler, Jochen U; Wahl, Sabine; Würschum, Tobias; Longin, C Friedrich H; Carle, Reinhold; Schweiggert, Ralf M

    2015-05-27

    Concentrations of lutein and lutein esters were determined in an ample collection of 75 wheat genotypes comprising bread wheat (Triticum aestivum L.), durum (Triticum durum Desf.), spelt (Triticum spelta L.), emmer (Triticum dicoccum Schrank), and einkorn (Triticum monococcum L.) grown in five different environments. Einkorn genotypes showed the highest total amounts of lutein (4.5-7.8 μg/g dry matter), followed by durum (2.0-4.6 μg/g), spelt (0.9-2.0 μg/g), emmer (0.8-1.9 μg/g), and bread wheat (0.7-2.0 μg/g). Due to the observed highly significant genetic variance and high heritability, lutein contents of wheat genotypes may be increased by future plant breeding. Detailed HPLC-DAD-APCI(±)-MS(n) data allowing the identification of six lutein monoesters and nine diesters are presented. Linoleic, palmitic, and oleic acids were the most abundant fatty acids in both the lutein esters and total free lipid fractions. Lutein esters were virtually absent in the tetraploid durum and emmer species, whereas their concentrations considerably differed among the genotypes belonging to the other species. PMID:25946219

  1. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function.

    OpenAIRE

    Nagayama, Y; Wadsworth, H L; Chazenbalk, G D; Russo, D.; Seto, P; Rapoport, B

    1991-01-01

    To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction we constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese ...

  2. Nutritional and clinical relevance of lutein in human health.

    Science.gov (United States)

    Granado, F; Olmedilla, B; Blanco, I

    2003-09-01

    Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine. PMID:14513828

  3. Lutein as protective agent against neonatal oxidative stress

    Directory of Open Access Journals (Sweden)

    Giuseppe Buonocore

    2014-06-01

    Full Text Available Free radicals (FR are important for a correct development of neonatal organs and tissues. However, newborn and fetus have profoundly impaired antioxidant system. In these subjects, oxidative stress (OS may be detrimental by activating deleterious cellular processes. Decreasing FR and restoring oxidative imbalance certainly appear to be beneficial in perinatal period. Among the therapeutic antioxidant approaches in newborns, lutein, a compound belonging to the xanthophyll family of carotenoids, is one of the emerging strategies. Humans cannot synthesize lutein, hence the intake primarily depends on diet. In the neonatal period, fresh, non-processed human milk is the main dietary source of lutein, while infant formula is lacking it. Lutein has antioxidant and anti-inflammatory properties. Lutein supplementation in human newborns during the first days of life has been demonstrated to decrease plasma biomarkers of OS and increase antioxidant capacities. Numerous experimental study have demonstrated that lutein effectively neutralizes oxidants and modulates inflammatory processes, showing particular protective effects on macula and photoreceptors against phototoxicity and oxidative injury. Only few clinical studies evaluated the effectiveness of lutein in reducing preterm and term infant morbidity, reporting no definitive results. The challenge for the future is to better clarify the timing, the optimal dose and the duration of lutein intervention in perinatal period and to verify its impact on infants’ health. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  4. Lutein Inhibits the Migration of Retinal Pigment Epithelial Cells via Cytosolic and Mitochondrial Akt Pathways (Lutein Inhibits RPE Cells Migration

    Directory of Open Access Journals (Sweden)

    Ching-Chieh Su

    2014-08-01

    Full Text Available During the course of proliferative vitreoretinopathy (PVR, the retinal pigment epithelium (RPE cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

  5. Lutein is needed for efficient chlorophyll triplet quenching in the major LHCII antenna complex of higher plants and effective photoprotection in vivo under strong light

    Directory of Open Access Journals (Sweden)

    Havaux Michel

    2006-12-01

    Full Text Available Abstract Background Lutein is the most abundant xanthophyll in the photosynthetic apparatus of higher plants. It binds to site L1 of all Lhc proteins, whose occupancy is indispensable for protein folding and quenching chlorophyll triplets. Thus, the lack of a visible phenotype in mutants lacking lutein has been surprising. Results We have re-assessed the lut2.1 phenotypes through biochemical and spectroscopic methods. Lhc proteins from the lut2.1 mutant compensate the lack of lutein by binding violaxanthin in sites L1 and L2. This substitution reduces the capacity for regulatory mechanisms such as NPQ, reduces antenna size, induces the compensatory synthesis of Antheraxanthin + Zeaxanthin, and prevents the trimerization of LHCII complexes. In vitro reconstitution shows that the lack of lutein per se is sufficient to prevent trimerization. lut2.1 showed a reduced capacity for state I – state II transitions, a selective degradation of Lhcb1 and 2, and a higher level of photodamage in high light and/or low temperature, suggesting that violaxanthin cannot fully restore chlorophyll triplet quenching. In vitro photobleaching experiments and time-resolved spectroscopy of carotenoid triplet formation confirmed this hypothesis. The npq1lut2.1 double mutant, lacking both zeaxanthin and lutein, is highly susceptible to light stress. Conclusion Lutein has the specific property of quenching harmful 3Chl* by binding at site L1 of the major LHCII complex and of other Lhc proteins of plants, thus preventing ROS formation. Substitution of lutein by violaxanthin decreases the efficiency of 3Chl* quenching and causes higher ROS yield. The phenotype of lut2.1 mutant in low light is weak only because rescuing mechanisms of photoprotection, namely zeaxanthin synthesis, compensate for the ROS production. We conclude that zeaxanthin is effective in photoprotection of plants lacking lutein due to the multiple effects of zeaxanthin in photoprotection, including ROS

  6. The Photobiology of Lutein and Zeaxanthin in the Eye.

    Science.gov (United States)

    Roberts, Joan E; Dennison, Jessica

    2015-01-01

    Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s) produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage. PMID:26798505

  7. The Photobiology of Lutein and Zeaxanthin in the Eye

    Directory of Open Access Journals (Sweden)

    Joan E. Roberts

    2015-01-01

    Full Text Available Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage.

  8. Lutein and Zeaxanthin Isomers in Eye Health and Disease.

    Science.gov (United States)

    Mares, Julie

    2016-07-17

    Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status. PMID:27431371

  9. Several insulin-like growth factor-I analogues and complexes of insulin-like growth factors-I and -II with insulin-like growth factor-binding protein-3 fail to mimic the effect of growth hormone upon lactation in the rat.

    Science.gov (United States)

    Flint, D J; Tonner, E; Beattie, J; Gardner, M

    1994-02-01

    Lactation was suppressed in rats using a combined treatment of bromocriptine (to reduce prolactin concentrations) and a specific antiserum to rat GH administered twice daily for 2 days. When milk production had ceased, as determined by litter weight loss and the absence of milk in the stomachs of pups, attempts were made to reinitiate lactation using prolactin, GH, insulin-like growth factor-I (IGF-I) precomplexed to recombinant human IGF-binding protein-3 (hIGFBP-3) or IGF-I plus IGF-II precomplexed to hIGFBP-3. Despite the fact that all treatments except prolactin led to increases in serum IGFs and IGFBP-3, only prolactin and GH provoked the reinitiation of milk production as determined by increased litter weight gain, milk in the stomach of pups and a significant increase in the weight of the mammary glands. Since the mammary gland has been shown to produce IGFBPs which may inhibit IGF action we also tested three IGF-I analogues, R3-IGF-I, Long-IGF-I and Long-R3-IGF-I. R3-IGF-I has a single amino acid substitution (Glu to Arg) at position 3 whereas Long-IGF-I has a 13 amino acid N-terminal extension. These modifications dramatically reduce the ability of these analogues to bind to IGFBPs although they remain active at the IGF-I receptor. Such IGF analogues would therefore be expected to be active irrespective of the production of inhibitory IGFBPs. However, none was effective in reinitiating lactation, even at doses which have been shown to be biologically effective in terms of nitrogen retention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7513341

  10. Effect of ultrasonic waves on the stability of all-trans lutein and its degradation kinetics.

    Science.gov (United States)

    Song, Jiang-Feng; Li, Da-Jing; Pang, Hui-Li; Liu, Chun-Quan

    2015-11-01

    Ultrasound treatment has been widely applied in the extraction of biologically active compounds including carotenoids. However, there are few reports on their effects on the stability of these compounds. In the present study, the stability of all-trans lutein, one of the carotenoids, was investigated under the action of ultrasound. Results showed that ultrasound induced the isomerization of all-trans lutein to its isomers, namely to 13-cis lutein, 13'-cis lutein, 9-cis lutein and 9'-cis lutein as analyzed by HPLC coupled with DAD and LC-MS; and the percentage of the isomerization increased with increasing both ultrasonic frequency and power. The stability of all-trans lutein in dichloromethane was worst among multiple kinds of solvents. Interestingly, the retention rate of all-trans lutein improved as the temperature increased, which runs counter to the Arrhenius law. Under ultrasound irradiation, the degradation mechanism might be different with various temperatures, the degradation of all-trans lutein followed first-order kinetics at 20°C, while second-order kinetics was followed at 30-50°C. As the ultrasonic reaction time prolonged, lutein epoxidation nearly occurred. Those results presented here emphasized that UAE techniques should be carefully used in the extraction of all-trans lutein. PMID:25934130

  11. Serum free and total insulin-like growth factor-1, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 levels in healthy elderly individuals - Relation to self-reported duality of health and disability

    NARCIS (Netherlands)

    Janssen, JAMJL; Stolk, RP; Pols, HAP; Grobbee, DE; Lamberts, SWJ

    1998-01-01

    Background: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. Design: In a cross-sectional population based study of 218 healthy elderly su

  12. Expression and Localization of Uncoupling Protein 3 and Heart Fatty Acid-binding Protein in Skeletal Muscle Cells of Nuogu Pig%糯谷猪解耦联蛋白3和心脏型脂肪酸结合蛋白在骨骼肌中的表达和定位

    Institute of Scientific and Technical Information of China (English)

    王阳; 冉雪琴; 王嘉福; 冯诚诚; 胡倩

    2011-01-01

    Uncoupling protein 3 (UCP3) and heart fatty acid-binding protein (H-FABP) are pivotal in the regulation of fat metabolism in skeletal muscle cells. Taking binary crossbreed pig of Large White pig and Landrace as control, the expression and localization of UCP3 and H-FABP genes and proteins are detected in the skeletal muscle cells by reverse transcription polymerase chain reaction (RT-PCR) and histological and immunohistochemistry methods. The results show that both of UCP3 and H-FABP are detected in the cytoplasm of muscle cells from Nuogu pig and crossbreed pig. Compared with crossbreed pig,however, the expressions of UCP3 and H-FABP in Nuogu pig breed are significantly lower based on the scan results of mean optical density (mOD) of positive pellets in the muscle cells. And the content of serum free fatty acids and intramuscular fat (IMF) of skeletal muscle are much higher in Nuogu pig breeds together with larger muscle cells and intracellular spaces. It sounds that the absorption of fatty acids from blood is less because of the lower H-FABP in muscle cells of Nuogu pig. And the production of adenosine triphosphate (ATP) is much more effective in Nuogu pig due to the lower expression of UCP3, which seems to be compensation to the less intake of fatty acids for energy supply in muscle cells of Nuogu pig.As a result, the excessive fatty acids would turn to synthesize triglyceride deposited in fat cells inside of muscle and fat tissue, which results in higher intramuscular fat (IMF) and backfat in Nuogu pig breed.It suggests that both of UCP3 and H-FABP genes and the expression in the muscle cells are contributed to the meat quality and backfat traits in Nuogu pig breed.%为了探索解耦联蛋白3(uncoupling protein 3,UCP3)和心脏型脂肪酸结合蛋白(heart fatty acid-binding protein,H.FABP)对骨骼肌细胞中脂肪代谢的调节作用,采用RT-PCR和免疫组织化学方法,研究了地方猪品种糯谷猪骨骼肌细胞中UCP3和H.FABP基因的表达

  13. Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis.

    Science.gov (United States)

    Fratianni, Alessandra; Mignogna, Rossella; Niro, Serena; Panfili, Gianfranco

    2015-12-01

    A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein. PMID:26540023

  14. *602044 UNCOUPLING PROTEIN 3; UCP3 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 602044 FIELD TI 602044 UNCOUPLING PROTEIN 3; UCP3 FIELD TX CLONING Boss et al. (1997) a ... 3 is expressed as a 2.3-kb message in skeletal muscle an d heart. In rat tissue, UCP3 transcripts were foun ... n the levels of UCP2 and UCP3 mRNA in skeletal muscle an d adipose tissue from both lean ... and obese individu ...

  15. Lutein acts via multiple antioxidant pathways in the photo-stressed retina.

    Science.gov (United States)

    Kamoshita, Mamoru; Toda, Eriko; Osada, Hideto; Narimatsu, Toshio; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein's effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes. PMID:27444056

  16. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese

    Directory of Open Access Journals (Sweden)

    Mirian Tiaki Kaneiwa Kubo

    2013-02-01

    Full Text Available The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine the transference of the lutein (dye, added to the milk, in the whey, and cheese, to evaluate the effect of the lutein addition, light exposure, and storage time on the cheese color, and to verify the sensory acceptance of Prato cheese with addition of lutein. The lutein recovery of cheese was 95.25%. Color saturation (chrome increased during storage time resulting in a cheese with more intense color, but there were no changes in the hue of the cheese. Adjusting the amount of lutein added to Prato cheese may lead to greater acceptance. The high recovery of lutein in the cheese and the fact that the hue remained unchanged during storage under light showed that the incorporation of lutein into Prato cheese is feasible from a technical point of view.

  17. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Seiji [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Kobayashi, Saori [Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Tsubota, Kazuo [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ozawa, Yoko, E-mail: ozawa@a5.keio.jp [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2014-04-04

    Highlights: • Lutein reduced ROS levels in a PC12D neuronal cell line. • Lutein induced mRNAs of phase II antioxidative enzymes in PC12D neuronal cells. • Lutein increased protein levels of HO-1, SOD2, and NQO-1 in PC12D neuronal cells. • Lutein had no effect on intranuclear Nrf2 levels in PC12D neuronal cells. • Lutein did not activate potential upstream Nrf2 nuclear translocation pathways. - Abstract: The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  18. Differentiation between lutein monoester regioisomers and detection of lutein diesters from marigold flowers (Tagetes erecta L.) and several fruits by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Breithaupt, Dietmar E; Wirt, Ursula; Bamedi, Ameneh

    2002-01-01

    Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCIMS) was employed for the identification of eight lutein monoesters, formed by incomplete enzymatic saponification of lutein diesters of marigold (Tagetes erecta L.) by Candida rugosa lipase. Additionally, the main lutein diesters naturally occurring in marigold oleoresin were chromatographically separated and identified. The LC-MS method allows for characterization of lutein diesters occurring as minor components in several fruits; this was demonstrated by analysis of extracts of cape gooseberry (Physalis peruviana L.), kiwano (Cucumis metuliferus E. Mey. ex Naud.), and pumpkin (Cucurbita pepo L.). The assignment of the regioisomers of lutein monoesters is based on the characteristic fragmentation pattern: the most intense daughter ion generally results from the loss of the substituent (fatty acid or hydroxyl group) bound to the epsilon-ionone ring, yielding an allylic cation. The limit of detection was estimated at 0.5 microg/mL with lutein dimyristate as reference compound. This method provides a useful tool to obtain further insight into the biochemical reactions leading to lutein ester formation in plants. PMID:11754543

  19. Radioimmunological and clinical studies with luteinizing hormone releasing hormone (LRH)

    International Nuclear Information System (INIS)

    Radioimmunoassay for Luteinizing Hormone Releasing Hormone (LRH) has been established, tested and applied. Optimal conditions for the performance with regards to incubation time, incubation temperature, concentration of antiserum and radiolabelled LRH have been established. The specificity of the LRH immunoassay was investigated. Problems with direct measurement of LRH in plasmas of radioimmunoassay are encountered. The LRH distribution in various tissues of the rat are investigated. By means of a system for continuous monitoring of LH and FSH in women the lowest effective dose of LRH causing a significant release of LH and FSH could be established. (Auth.)

  20. The Relationship between Lutein and Zeaxanthin Status and Body Fat

    OpenAIRE

    Hammond, Billy R.; Lewis, Richard D.; Emily R. Bovier

    2013-01-01

    The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L) and zeaxanthin (Z) status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2) were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A). Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment ...

  1. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Science.gov (United States)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

  2. Distribution of lutein, zeaxanthin, and related geometrical isomers in fruit, vegetables, wheat, and pasta products.

    Science.gov (United States)

    Humphries, Julia M; Khachik, Frederick

    2003-02-26

    Quantitative data with regard to dietary (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, and their (E/Z)-geometrical isomers are scarce, and in most cases, only the combined concentrations of these two carotenoids in foods are reported. Lutein and zeaxanthin accumulate in the human macula and have been implicated in the prevention of age-related macular degeneration (AMD). The qualitative and quantitative distributions of lutein, zeaxanthin, and their (E/Z)-isomers in the extracts from some of the most commonly consumed fruits, vegetables, and pasta products were determined by HPLC employing a silica-based nitrile-bonded column. Green vegetables had the highest concentration of lutein (L) and zeaxanthin (Z), and the ratios of these carotenoids (L/Z) were in the range 12-63. The yellow-orange fruits and vegetables, with the exception of squash (butternut variety), had much lower levels of lutein in comparison to greens but contained a higher concentration of zeaxanthin. The ratio of lutein to zeaxanthin (L/Z) in two North American bread varieties of wheat (Pioneer, Catoctin) was 11 and 7.6, respectively, while in a green-harvested wheat (Freekeh) imported from Australia, the ratio was 2.5. Between the two pasta products examined, lasagne and egg noodles, the latter had a much higher concentration of lutein and zeaxanthin. The levels of the (E/Z)-geometrical isomers of lutein and zeaxanthin in these foods were also determined. PMID:12590476

  3. Lutein acts via multiple antioxidant pathways in the photo-stressed retina

    Science.gov (United States)

    Kamoshita, Mamoru; Toda, Eriko; Osada, Hideto; Narimatsu, Toshio; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein’s effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes. PMID:27444056

  4. 非霍奇金淋巴瘤患者血清胰岛素样生长因子-1及其结合蛋白-3表达水平的初步观察%Observation on the expressions of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in non-Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    李康保; 刘国龙; 朱志刚; 朱园; 朱国栋

    2012-01-01

    To investigate the expressions of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with non-Hodgkin's lymphoma (NHL) and its clinical significance. Methods:Twenty-eight cases with newly diagnosed NHL and 28 cases of healthy volunteers were involved in the study. Serum levels of IGF-1 and IGFBP-3 were determined by the method of chemical luminescence,and ratio of IGF-l/IGFBP-3 was counted. The differences were compared between two groups. Results: Serum levels of IGF-1 and IGFBP-3 were significantly lower in NHL group than those in control group (P 0.05); and there were no differences in serum levels of IGF-1, IGFBP-3 and the ratio of IGF-l/IGFBP-3 among different (ypes of non-Hodgkin's lymphoma ( P > 0. 05 ). Conclusions ; Serum levels of IGF-1 and IGFBP-3 significantly decreased in patients with NHL,and might relate with NHL. The ratio of IGF-l/IGFBP-3 has no obvious correlation with NHL. Serum levels of IGF-1 and IGFBP-3 have no obvious correlation with types of NHL.%目的:探讨非霍奇金淋巴瘤(NHL)患者血清胰岛素样生长因子-1(IGF-1)及其结合蛋白-3(IGFBP-3)表达水平及其临床意义.方法:选择28例诊断初发NHL患者(淋巴瘤组)及28例健康志愿者(对照组),化学发光法测定血清IGF-1及IGFBP-3水平并计算IGF- 1/IGFBP-3值,分析组间的差异.结果:血清IGF-1及IGFBP-3水平淋巴瘤组显著低于正常对照组(均P<0.01);IGF-1/IGFBP-3淋巴瘤组与正常对照组差异无统计学意义(P>0.05);不同亚型的淋巴瘤组的血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值的差异均未达到统计学意义(P>0.05).结论:N HL患者血清IGF-I及IGFBP-3水平明显降低,可能与NHL相关.IGF-1/IGFBP-3比值与NHL无明显相关性,IGF-1及IGFBP-3水平与NHL的分型无明显相关.

  5. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  6. Biological role of lutein in the light-induced retinal degeneration.

    Science.gov (United States)

    Sasaki, Mariko; Yuki, Kenya; Kurihara, Toshihide; Miyake, Seiji; Noda, Kosuke; Kobayashi, Saori; Ishida, Susumu; Tsubota, Kazuo; Ozawa, Yoko

    2012-05-01

    Lutein, a xanthophyll of a carotenoid, is anticipated as a therapeutic product to prevent human eye diseases. However, its biological mechanism is still unclear. Here, we show the molecular mechanism of lutein's effect to reduce photodamage of the retina. We analyzed the light-exposed retinas of Balb/c mice given lutein-supplemented or normal diet. Visual function was measured by electroretinogram, and histological changes were observed. Immunohistochemical and immunoblot analyses were performed to analyze molecular mechanism. The reactive oxygen species induced in the retina was evaluated by fluorescent probes. In the mice after light exposure, reduction of a-wave and b-wave amplitudes in electroretinogram, indicating visual impairment, and thinning of the photoreceptor cell layer owing to apoptosis were both attenuated by lutein diet. Interestingly, γ-H2AX, a marker for double-strand breaks (DSBs) in DNA, was up-regulated in the photoreceptor cells after light exposure, but this increase was attenuated by lutein diet, suggesting that DSBs caused by photodamage contributed to the photoreceptor cell death and that this change was suppressed by lutein. Moreover, the expression of eyes absent (EYA), which promotes DNA repair and cell survival, was significantly up-regulated with lutein diet in the light-exposed retina. Therefore, lutein induced EYA for DNA repair, which could suppress DNA damage and photoreceptor cell apoptosis. Lutein reduced light-induced oxidative stress in the retina, which might contribute to promote DNA repair. The lutein-supplemented diet attenuated light-induced visual impairment by protecting the photoreceptor cells' DNA. PMID:21658930

  7. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.

    Science.gov (United States)

    Bernstein, Paul S; Li, Binxing; Vachali, Preejith P; Gorusupudi, Aruna; Shyam, Rajalekshmy; Henriksen, Bradley S; Nolan, John M

    2016-01-01

    The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age. PMID:26541886

  8. Enhancement of Lutein Production in Chlorella sorokiniana (Chorophyta by Improvement of Culture Conditions and Random Mutagenesis

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vargas

    2011-09-01

    Full Text Available Chlorella sorokiniana has been selected for lutein production, after a screening of thirteen species of microalgae, since it showed both a high content in this carotenoid and a high growth rate. The effects of several nutritional and environmental factors on cell growth and lutein accumulation have been studied. Maximal specific growth rate and lutein content were attained at 690 µmol photons m−2 s−1, 28 °C, 2 mM NaCl, 40 mM nitrate and under mixotrophic conditions. In general, optimal conditions for the growth of this strain also lead to maximal lutein productivity. High lutein yielding mutants of C. sorokiniana have been obtained by random mutagenesis, using N-methyl-N′-nitro-nitrosoguanidine (MNNG as a mutagen and selecting mutants by their resistance to the inhibitors of the carotenogenic pathway nicotine and norflurazon. Among the mutants resistant to the herbicides, those exhibiting both high content in lutein and high growth rate were chosen. Several mutants exhibited higher contents in this carotenoid than the wild type, showing, in addition, either a similar or higher growth rate than the latter strain. The mutant MR-16 exhibited a 2.0-fold higher volumetric lutein content than that of the wild type, attaining values of 42.0 mg L−1 and mutants DMR-5 and DMR-8 attained a lutein cellular content of 7.0 mg g−1 dry weight. The high lutein yield exhibited by C. sorokiniana makes this microalga an excellent candidate for the production of this commercially interesting pigment.

  9. Elevation of lutein content in tomato: a biochemical tug-of-war between lycopene cyclases.

    Science.gov (United States)

    Giorio, Giovanni; Yildirim, Arzu; Stigliani, Adriana Lucia; D'Ambrosio, Caterina

    2013-11-01

    Lutein is becoming increasingly important in preventive medicine due to its possible role in maintaining good vision and in preventing age-related maculopathy. Average daily lutein intake in developed countries is often below suggested daily consumption levels, and lutein supplementation could be beneficial. Lutein is also valuable in the food and feed industries and is emerging in nutraceutical and pharmaceutical markets. Currently, lutein is obtained at high cost from marigold petals, and synthesis alternatives are thus desirable. Tomato constitutes a promising starting system for production as it naturally accumulates high levels of lycopene. To develop tomato for lutein synthesis, the tomato Red Setter cultivar was transformed with the tomato lycopene ε-cyclase-encoding gene under the control of a constitutive promoter, and the HighDelta (HD) line, characterised by elevated lutein and δ-carotene content in ripe fruits, was selected. HD was crossed to the transgenic HC line and to RS(B) with the aim of converting all residual fruit δ-carotene to lutein. Fruits of both crosses were enriched in lutein and presented unusual carotenoid profiles. The unique genetic background of the crosses used in this study permitted an unprecedented analysis of the role and regulation of the lycopene cyclase enzymes in tomato. A new defined biochemical index, the relative cyclase activity ratio, was used to discern post-transcriptional regulation of cyclases, and will help in the study of carotenoid biosynthesis in photosynthetic plant species and particularly in those, like tomato, that have been domesticated for the production of food, feed or useful by-products. PMID:24141052

  10. Relationship between insulin-like growth factor binding protein-3 and intelligence development of children with congenital hypothyroidism%IGFBP-3与先天性甲状腺功能减低症儿童智力发育的关系

    Institute of Scientific and Technical Information of China (English)

    蒋新液; 古桂雄; 裴晶晶; 于亮; 朱敏敏; 许飞; 陶晓红

    2011-01-01

    Objective: To explore the relationship between insulin - like growth factor binding protein - 3 ( IGFBP - 3 ) and intelligence development of children with congenital hypothyroidism (CH).Methods: Immunoradiometric assay was used to detect the expression level of IGFBP - 3, CDCC and C - WYCSI we re used to determine the levels of intelligence of children aged 2 ~ years old and 3 ~ 7 years old.Results: The intelligence quotients of the two groups were within normal range, but the intelligence quotient in case group was lower than that in control group (P < 0.05).Among the children aged 2 ~ years old, there was no significant difference in expression level of IGFBP - 3 between case group and control group ( P > 0.05 ); among the children aged 3 ~ 7 years old, the expression level of IGFBP - 3 in case group was lower than that in control group (P < 0.05 ).Among the children aged 2 ~ years old, there was no correlation between IGFBP - 3 and intelligence quotient (P > 0.05 ); among the children aged 3 ~ 7 years old, there was a positive correlation between IGFBP - 3 and linguistic IQ, Verbal intelligence quotient (P < 0.05).IGFBP - 3 level was selected as dependent variable, the scores of various tests in C - WYCSI were selected as independent variable, multivariate regression analysis was carried out, among intelligent factors, the first six effect factors of IGFBP -3 level were picture vocabulary, understanding, memory inverse order, maze, visual analysis and reciting orderly.Conclusion: For the children with CH, early diagnosis and timely treatment can avoid disorder of intelligence development, but injury of cognition exists; after early treatment, the serum level of IGFBP - 3 in the children with CH is still lower than that in normal children; the level of IGFBP - 3 is related to development of linguistic IQ in children; CH may induce low expression of IGFBP - 3 and affect the development of intelligence in children.%目的:探讨胰岛

  11. Radioimmunoassay of bovine, ovine and porcine luteinizing hormone with a monoclonal antibody and a human tracer

    International Nuclear Information System (INIS)

    A radioimmunoassay for bovine (bLH), ovine (oLH) and porcine (pLH) luteinizing hormone was developed using a human 125ILH tracer from a commercial kit and a monoclonal antibody (518B7) specific for LH but with low species specificity. Standard curves demonstrated similar binding kinetics when bLH, oLH and pLH were incubated with tracer and antibody for 2 h at room temperature. A 30-min delay in the addition of the tracer gave sufficient sensitivity when analysing pLH. Separation of antibody-bound LH from free hormone was achieved by using second antibody-coated micro Sepharose beads. The assay was validated and the performance compared with that of an RIA currently in use for determination of bLH (coefficient of correlation: 0.99 and 0.98). Regardless of the standards used, intra-assay coefficients of variation were <10% for LH concentrations exceeding 1 μg/L. The inter-assay coefficients of variation were <15%. The assay was used for clinical evaluation demonstrating the pre-ovulatory LH surge in two cyclic cows, LH pulsatility in an oophorectomized ewe and LH response to GnRH injection in a boar. (au) (7 refs.)

  12. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  13. Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?

    Directory of Open Access Journals (Sweden)

    Chunyan Xue

    2015-01-01

    Full Text Available Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases.

  14. Silk lutein extract and its combination with vitamin E reduce UVB-mediated oxidative damage to retinal pigment epithelial cells.

    Science.gov (United States)

    Aimjongjun, Sathid; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip

    2013-07-01

    Increased exposure to solar ultraviolet B (UVB) radiation may promote age related macular degeneration (AMD). Lutein can protect retinal pigment epithelial (RPE) cells from various oxidative insults but its direct protection against UVB has not been reported. This study aimed to demonstrate protective effects of silk lutein extract against UVB-induced oxidative damage to RPE cells and compared with standard lutein and Trolox, a vitamin E analog. ARPE-19 cells were treated with luteins with and without Trolox prior to UVB exposure. Cell viability and apoptosis were determined by trypan blue staining and caspase-3 activity, respectively. Oxidative damage was evaluated by measuring intracellular reactive oxygen species (ROS), lipid peroxidation, and activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Levels of lutein remained in culture medium was determined by HPLC. Both luteins reduced cellular ROS levels and lipid peroxidation mediated by UVB, and subsequently increased cell viability and reduced apoptosis. They also restored activities of most tested antioxidant enzymes. Enhancement of lutein antioxidant efficacy was observed in the presence of Trolox. In all these effects, the two lutein preparations had similar effectivenesses. In cell free media, Trolox enhanced the protective effect of lutein probably by reducing its degradation and repairing the oxidized derivatives. Yellow silk cocoon is a potential candidate of lutein for further development as dietary supplement for the prevention of AMD. PMID:23651647

  15. Enhanced production of lutein in heterotrophic Chlorella protothecoides by oxidative stress

    Institute of Scientific and Technical Information of China (English)

    WEI Dong; CHEN Feng; CHEN Gu; ZHANG XueWu; LIU LongJun; ZHANG Hao

    2008-01-01

    The fast growing unicellular green microalgae Chlorella protothecoides has attracted interest as a promising organism for commercial production of a high-value carotenoid, lutein, by heterotrophic fermentation. Effects of two oxidant-forming reactive oxygen species (ROS) on the biomass concentration, and yield and content of lutein in batch culture of heterotrophic Chlorella protothecoides were investigated in this study. The addition of 0.1 mmol/L H2O2 and 0.01 mmol/L NaClO plus 0.5 mmol/L Fe2+ to the culture led to the generation of OH and enhanced the lutein content from 1.75 to 1.90 and 1.95 mg/g, respectively. The lutein content further increased to 1.98 mg/g when 0.01 mmol/L H2O2 and 0.5 mmol/L NaClO were added to generate 1O2. The maximum yield of lutein (28.5, 29.8 and 31.4 mg/L) and a high biomass concentration (15.0, 15.3 and 15.9 g/L) were also achieved through the above treatments. The results indicated that 1O2 could promote lutein formation and enhance lutein production in heterotrophic Chlorella protothecoides. Moreover, 1O2 produced from the reaction of H2O2 and NaClO was more effective in enhancing lutein production and reducing biomass loss than OH from the reaction of H2O2 or NaClO plus Fe2+.

  16. Extraction of lutein from Marigold flower petals - Experimental kinetics and modelling

    OpenAIRE

    Hojnik, Maša; Škerget, Mojca; Knez, Željko

    2012-01-01

    The extraction kinetics behaviour of lutein from Marigold flower petals and simultaneous alkali hydrolysis has been studied. Extraction was carried out by varying following operating conditions: type of organic solvent, temperature, ratio liquid: material, concentration of alkali solution, and particle size of plant material. Experimental extraction curves were analysed with a mathematical model derived from Fick's second law. The extraction of lutein appeared to be governed by slow and fast ...

  17. Solitary luteinized follicle cyst of pregnancy complicated with persistent postpartum vaginal bleeding: case report

    Institute of Scientific and Technical Information of China (English)

    ZHANG Song-ying; HUANG He-feng; TONG Xiao-mei

    2007-01-01

    @@ Solitary luteinized follicle cyst, a rare cause of ovarian enlargement during pregnancy and puerperium, is a self-limited disease that can regress spontaneously after labor. The complications of the disease include ovarian torsion, intracystic hemorrhage, and rupture; endocrine disturbances have not been reported.1-4 Here we report a case of solitary luteinized follicle cyst of pregnancy,which required surgical intervention owing to persistent postpartum vaginal bleeding.

  18. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese

    OpenAIRE

    Mirian Tiaki Kaneiwa Kubo; Diogo Maus; Ana Augusta Odorissi Xavier; Adriana Zerlotti Mercadante; Walkiria Hanada Viotto

    2013-01-01

    The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine...

  19. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  20. Lutein Leads to a Decrease of Factor D Secretion by Cultured Mature Human Adipocytes

    Science.gov (United States)

    Tian, Yuan; Kijlstra, Aize; Renes, Johan; Wabitsch, Martin; Webers, Carroll A. B.; Berendschot, Tos T. J. M.

    2015-01-01

    Purpose. Complement plays an important role in the pathogenesis of age related macular degeneration (AMD) and trials are currently being conducted to investigate the effect of complement inhibition on AMD progression. We previously found that the plasma level of factor D (FD), which is the rate limiting enzyme of the complement alternative pathway, was significantly decreased following lutein supplementation. FD is synthesized by adipose tissue, which is also the main storage site of lutein. In view of these findings we tested the hypothesis whether lutein could affect FD synthesis by adipocytes. Methods. A cell line of mature human adipocytes was incubated with 50 μg/mL lutein for 24 and 48 h, whereafter FD mRNA and protein expression were measured. Results. Lutein significantly inhibited adipocyte FD mRNA expression and FD protein release into adipocyte culture supernatants. Conclusions. Our earlier observations showing that a daily lutein supplement in individuals with early signs of AMD lowered the level of circulating FD might be caused by blocking adipocyte FD production. PMID:26504594

  1. The Relationship between Lutein and Zeaxanthin Status and Body Fat

    Directory of Open Access Journals (Sweden)

    Billy R. Hammond

    2013-03-01

    Full Text Available The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L and zeaxanthin (Z status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2 were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A. Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment optical density; MPOD was measured using heterochromatic flicker photometry. Body fat percentage (total and regional was inversely related to MPOD (p < 0.01 but no significant relationship was found for serum LZ. Higher body fat percentage, even within relatively healthy limits, is associated with lower tissue LZ status. The results indicate that adiposity may affect the nutritional state of the retina. Such links may be one of the reasons that obesity promotes age-related degenerative conditions of the retina.

  2. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  3. Dietary Sources of Lutein and Zeaxanthin Carotenoids and Their Role in Eye Health

    Directory of Open Access Journals (Sweden)

    Rashida Ali

    2013-04-01

    Full Text Available The eye is a major sensory organ that requires special care for a healthy and productive lifestyle. Numerous studies have identified lutein and zeaxanthin to be essential components for eye health. Lutein and zeaxanthin are carotenoid pigments that impart yellow or orange color to various common foods such as cantaloupe, pasta, corn, carrots, orange/yellow peppers, fish, salmon and eggs. Their role in human health, in particular the health of the eye, is well established from epidemiological, clinical and interventional studies. They constitute the main pigments found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration (AMD and cataracts. Research over the past decade has focused on the development of carotenoid-rich foods to boost their intake especially in the elderly population. The aim of this article is to review recent scientific evidences supporting the benefits of lutein and zexanthin in preventing the onset of two major age-related eye diseases with diets rich in these carotenoids. The review also lists major dietary sources of lutein and zeaxanthin and refers to newly developed foods, daily intake, bioavailability and physiological effects in relation to eye health. Examples of the newly developed high-lutein functional foods are also underlined.

  4. Optimization by response surface methodology of lutein recovery from paprika leaves using accelerated solvent extraction.

    Science.gov (United States)

    Kang, Jae-Hyun; Kim, Suna; Moon, BoKyung

    2016-08-15

    In this study, we used response surface methodology (RSM) to optimize the extraction conditions for recovering lutein from paprika leaves using accelerated solvent extraction (ASE). The lutein content was quantitatively analyzed using a UPLC equipped with a BEH C18 column. A central composite design (CCD) was employed for experimental design to obtain the optimized combination of extraction temperature (°C), static time (min), and solvent (EtOH, %). The experimental data obtained from a twenty sample set were fitted to a second-order polynomial equation using multiple regression analysis. The adjusted coefficient of determination (R(2)) for the lutein extraction model was 0.9518, and the probability value (p=0.0000) demonstrated a high significance for the regression model. The optimum extraction conditions for lutein were temperature: 93.26°C, static time: 5 min, and solvent: 79.63% EtOH. Under these conditions, the predicted extraction yield of lutein was 232.60 μg/g. PMID:27006224

  5. A review of luteinizing hormone and its role in ovarian reserve testing

    Directory of Open Access Journals (Sweden)

    Vinayak Smith

    2014-02-01

    Findings: The evidence is equivocal in the use of luteinizing hormone as an independent predictor of ovarian reserve. However, there is much stronger evidence to suggest that the follicle stimulating hormone/luteinizing hormone ratio is a useful marker of ovarian reserve- in particular when it is ≥2 and approaching 3. The evidence base for this ratio at present however is sparse. In addition, ovarian reserve tests are fraught with issues over reliability, accuracy, definition and the implications of testing itself. In order to overcome these issues, more quality research needs to be carried out to test this relationship between luteinizing hormone and follicle stimulating hormone. [Int J Reprod Contracept Obstet Gynecol 2014; 3(1.000: 11-18

  6. Interfacial properties of Quillaja saponins and its use for micellisation of lutein esters.

    Science.gov (United States)

    Tippel, Janine; Lehmann, Maren; von Klitzing, Regine; Drusch, Stephan

    2016-12-01

    Natural food colourants, colouring foods and bioactive food ingredients need to be solubilised for their incorporation in food. Aim of the present study was to investigate the micelle-forming properties of saponins from Quillaja saponaria Mollina (QS) in order to solubilise a lutein ester extract for its incorporation in food matrices. QS showed a high surface activity and functionality with respect to micellisation as derived from interfacial tension measurements and subsequent data fitting to the classical Frumkin model. The composition of the aqueous phase affected the lutein ester incorporation as revealed by particle size, zeta potential and colour measurements. In terms of morphology of lutein ester loaded saponin micelles (LMS), cryo-TEM micrographs showed depending on the composition of the medium both, spherical and elongated branched micelles. PMID:27374503

  7. THE EFFECT OF LUTEIN ADDITIVES ON BIOCHEMICAL PARAMETERS IN BLOOD OF LAYING HENS

    Directory of Open Access Journals (Sweden)

    Manuela Grčević

    2016-06-01

    Full Text Available The aim of this study was to present the performance and some biochemical parameters in the blood of hens fed feed mixtures with different levels of lutein. The study involved a total of 291 Tetra SL hybrid laying hens, divided into 3 groups (O0 with 0 mg/kg lutein added, O200 with 200 mg/kg lutein added and O400 with 400 mg/kg lutein added, and lasted for 5 weeks. The O0 group included 93 hens, whereas experimental groups 98 and 100 hens, respectively. The highest egg production and the best feed consumption per egg were recorded in O400 group with a total of 3367 pieces of eggs produced and 128.60 g of feed consumed. The best laying intensity (96.68% and number of eggs per laying hen (34.19 as well as the highest feed consumption per day (129.01 g, was recorded in O200 group. Lutein added to feed mixtures for laying hens did not significantly affect the values of biochemical parameters in blood (P>0.05. An increase in total cholesterol (CHOL and HDL cholesterol content as well as the decrease of total protein (PROT and albumin (ALB content in the experimental groups can be observed. The content of glucose (GUK and urea was similar between the experimental groups, while the highest content of triglycerides (TGC was recorded in O200 group. It can be concluded that different levels of lutein added to the feed mixtures for laying hens did not have negative effect on the performance and blood biochemical parameters of laying hens.

  8. Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin

    NARCIS (Netherlands)

    Broekmans, WMR; Berendschot, TTJM; Klopping-Ketelaars, IAA; de Vries, AJ; Goldbohm, RA; Tijburg, LBM; Kardinaal, AFM; van Poppel, G

    2002-01-01

    Background: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxant

  9. 重组人生长激素对特发性矮小患儿症血清胰岛素样生长因子1与胰岛素样生长因子结合蛋白3水平的影响%Effect of recombinant human growth hormone on serum levels of insulin like growth factor 1 and insulin-like growth factor binding protein 3 in children with idiopathic short stature

    Institute of Scientific and Technical Information of China (English)

    干冬梅; 石小军

    2015-01-01

    目的:探讨重组人生长激素对特发性矮小症患儿血清胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)与胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein-3,IGFBP-3)水平的影响。方法收集宁波市妇女儿童医院儿5科收治的特发性矮小症患儿48例,随机分为对照组和实验组,每组各24例,对照组患儿给予营养治疗,实验组在对照组基础上给予重组人生长激素治疗,均治疗12个月。治疗结束后,对所有患儿的血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平及身高进行检测。结果与对照组治疗后比较,实验组患儿的血清IGF-1水平较高( P<0.05);实验组患儿的血清IGFBP-3水平较高( P<0.05);实验组患儿的身高较高(P<0.05)。结论重组人生长激素能够显著提高特发性矮小症患儿血清IGF-1、IGFBP-3水平,促进患儿生长,对临床有指导意义。%Objective To investigate the effect of recombinant human growth hormone on serum levels of insulin like growth factor 1(IGF-1) and insulin-like growth factor binding protein 3(IGFBP-3)in children with short stature.Methods 48 children were diagnosed with idiopathic short stature were collected.All children were randomly divided into control group and experimental group ,24 cases in each group.Children in control group received nutritional therapy, children in experimental group were given recombinant human growth hormone on the basis of control group treatment, both group were treated for 12 month.After the treatment, the serum levels of IGF-1,IGFBP-3 and the height were detected in all children.Results Compared with control group post-treatment,,the serum level of IGF-1 was higher in experimental group ( P<0.05 );the serum level of IGFBP-3 was higher in experimental group ( P<0.05 );the height was higher in experimental group ( P<0.05 ) .Conclusion

  10. Clearance of yellow pigments lutein and zeathanxin in channel catfish reared at different water temperatures

    Science.gov (United States)

    A study was conducted to determine clearance time of yellow pigments lutein and zeaxanthin in channel catfish at various temperatures. Fish of initial weight of 13.4 g were stocked into flow-through aquaria and fed once daily with a yellow pigment enhanced diet for 11 weeks when the yellow color be...

  11. Structural and spectroscopic features of lutein/butanoyl-β-cyclodextrin nanoassemblies

    DEFF Research Database (Denmark)

    Stancanelli, R.; Løjkner, L.D.; Larsen, Kim Lambertsen; Guardo, M.; Cannavà, C.; Tommasini, S.; Ventura, C.A.; Calabrò, M.L.; Micali, N.; Villari, V.; Mazzaglia, A.

    2012-01-01

    ) represent a drawback for bioavailability. To circumvent these unfavorable characteristics, in this work lutein (Lut) have been encapsulated in amphiphilic cyclodextrin (ACyD) by following the well-established strategy of entrapping a lipophilic drug in CyD carriers. Primary face butyrate modified β-cyclodextrins...

  12. Enhanced Productivity of a Lutein-Enriched Novel Acidophile Microalga Grown on Urea

    NARCIS (Netherlands)

    Casal, C.; Cuaresma, M.; Vega, J.M.; Vilchez, C.

    2011-01-01

    Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of b-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related i

  13. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study.

    Science.gov (United States)

    Koh, Hui-Hiang; Murray, Ian J; Nolan, Daniel; Carden, Dave; Feather, Jim; Beatty, Stephen

    2004-07-01

    There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM. PMID:15183097

  14. Localization and synthesis of the hormone-binding regions of the human thyrotropin receptor.

    OpenAIRE

    Atassi, M Z; Manshouri, T; Sakata, S.

    1991-01-01

    Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) (residues 12-44 and 308-364) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364) were studied for their ability to bind 125I-labeled human TSH (hTSH), its isolated alpha and beta subunits, bovine TSH, ovine TSH, human luteinizing hormone, and human follicle-...

  15. PGR: A Graph Repository of Protein 3D-Structures

    OpenAIRE

    Dhifli, Wajdi; Diallo, Abdoulaye Baniré

    2016-01-01

    Graph theory and graph mining constitute rich fields of computational techniques to study the structures, topologies and properties of graphs. These techniques constitute a good asset in bioinformatics if there exist efficient methods for transforming biological data into graphs. In this paper, we present Protein Graph Repository (PGR), a novel database of protein 3D-structures transformed into graphs allowing the use of the large repertoire of graph theory techniques in protein mining. This ...

  16. Development and validation of a dissolution test for lutein tablets and evaluation of intestinal permeability.

    Science.gov (United States)

    Anselmo, Carina de Souza; Mendes, Thamara de Carvalho; Honorio, Thiago da Silva; do Carmo, Flávia Almada; Cabral, Lucio Mendes; de Sousa, Valeria Pereira

    2016-11-01

    Lutein is a carotenoid with antioxidant activity that is present in various dosage forms. The bioavailability of carotenoid from oral dosage formulations depends on their release, dissolution and its permeability through the gastrointestinal tract. Here, a dissolution test was developed for evaluating formulations and the bioavailability was assessed. The test utilized a USP-apparatus II with rotations of 50, 75 and 100rpm in water with P80 at 1, 2 and 5% (w/v). A non-everted rat intestinal sac model was used in conjunction to assess the intestinal permeability. The most discriminative conditions were 100rpm in water with 2% polysorbate 80, which showed profile differences between two formulations. The intestinal permeation studies showed a lag-time and apparent permeability coefficient that were characteristic of highly permeable drugs. We suggest that a dissolution test can be an essential quality control tool for formulations containing compounds as lutein, although not mandatory by the regulation agencies. PMID:27211621

  17. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3

    DEFF Research Database (Denmark)

    Shi, Z; Xu, Wei; Loechel, F;

    2000-01-01

    yet the pregnancy-specific protease, or proteases, have not been identified. We utilized a yeast two-hybrid assay and a human placental cDNA library to investigate IGFBP-3-interacting proteins. A disintegrin and metalloprotease-12 (ADAM 12), a member of a family of metalloprotease disintegrins that is...... highly expressed in placental tissue, was identified as interacting with IGFBP-3. This interaction involved the cysteine-rich domain of ADAM 12. Unlike other members of this family of disintegrin metalloproteases that are membrane proteins, ADAM 12 exists as an alternatively spliced soluble secreted...... protein. To verify the interaction between ADAM 12 and IGFBP-3, an expression construct containing an ADAM 12-S cDNA was transfected into COS-1 cells. Co-precipitation was observed when conditioned medium was analyzed by immunoprecipitation with an antibody against either ADAM 12 or IGFBP-3 followed by...

  18. Single nucleotide polymorphism in Egyptian cattle insulin-like growth factor binding protein-3 gene

    Directory of Open Access Journals (Sweden)

    Othman E. Othman

    2014-12-01

    It is concluded that the IGFBP-3/HaeIII polymorphism may be utilized as a good marker for genetic differentiation between cattle animals for different body functions such as growth, metabolism, reproduction, immunity and energy balance. The nucleotide sequences of Egyptian cattle IGFBP-3 A and C alleles were submitted to GenBank with the accession numbers KF899893 and KF899894, respectively.

  19. Electrical and synaptic properties of embryonic luteinizing hormone-releasing hormone neurons in explant cultures.

    OpenAIRE

    Kusano, K.; Fueshko, S; Gainer, H; Wray, S

    1995-01-01

    Voltage- and ligand-activated channels in embryonic neurons containing luteinizing hormone-releasing hormone (LHRH) were studied by patch-pipette, whole-cell current and voltage clamp techniques. LHRH neurons were maintained in explant cultures derived from olfactory pit regions of embryonic mice. Cells were marked intracellularly with Lucifer yellow following recording. Sixty-two cells were unequivocally identified as LHRH neurons by Lucifer yellow and LHRH immunocytochemistry. The cultured ...

  20. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin

    OpenAIRE

    BEATTY, S; Nolan, John; Kavanagh, H.; O'Donovan, O. M.

    2004-01-01

    Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxycarotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate...

  1. Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

    Directory of Open Access Journals (Sweden)

    M. Naviliat

    2005-12-01

    Full Text Available Nitric oxide (·NO is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ·NO and oxidants leads to the generation of nitrogen dioxide (·NO2, a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2 group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ·NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ·NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ·NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ·NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ·NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

  2. Mutations in a novel, cryptic exon of the luteinizing hormone/chorionic gonadotropin receptor gene cause male pseudohermaphroditism.

    Directory of Open Access Journals (Sweden)

    Nina Kossack

    2008-04-01

    Full Text Available BACKGROUND: Male pseudohermaphroditism, or Leydig cell hypoplasia (LCH, is an autosomal recessive disorder in individuals with a 46,XY karyotype, characterized by a predominantly female phenotype, a blind-ending vagina, absence of breast development, primary amenorrhea, and the presence of testicular structures. It is caused by mutations in the luteinizing hormone/chorionic gonadotropin receptor gene (LHCGR, which impair either LH/CG binding or signal transduction. However, molecular analysis has revealed that the LHCGR is apparently normal in about 50% of patients with the full clinical phenotype of LCH. We therefore searched the LHCGR for novel genomic elements causative for LCH. METHODS AND FINDINGS: In the present study we have identified a novel, primate-specific bona fide exon (exon 6A within the LHCGR gene. It displays composite characteristics of an internal/terminal exon and possesses stop codons triggering nonsense-mediated mRNA decay (NMD in LHCGR. Transcripts including exon 6A are physiologically highly expressed in human testes and granulosa cells, and result in an intracellular, truncated LHCGR protein of 209 amino acids. We sequenced exon 6A in 16 patients with unexplained LCH and detected mutations in three patients. Functional studies revealed a dramatic increase in the expression of the mutated internal exon 6A transcripts, indicating aberrant NMD. These altered ratios of LHCGR transcripts result in the generation of predominantly nonfunctional LHCGR isoforms, thereby preventing proper expression and functioning. CONCLUSIONS: The identification and characterization of this novel exon not only identifies a new regulatory element within the genomic organization of LHCGR, but also points toward a complex network of receptor regulation, including events at the transcriptional level. These findings add to the molecular diagnostic tools for LCH and extend our understanding of the endocrine regulation of sexual differentiation.

  3. Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo ( Bubalus bubalis)

    Science.gov (United States)

    Perera, K. S.; Gwazdauskas, F. C.; Akers, R. M.; McGilliard, M. L.

    1989-06-01

    Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months ( n=24, 24 months) were randomly assigned to groups subject to either natural daylight +4h supplemental light ( n=25) or natural day light ( n=25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were >27° C and buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body wieght during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.

  4. The clinical evaluation of the radioimmunoassay of luteinizing hormone in urine

    International Nuclear Information System (INIS)

    The studies comprised 177 persons: 39 healthy males, 20 women in the reproductive age, 35 postmenopausal women and 83 patients with different types of gonadal insufficiency (gonadal dysgenesis; premature ovarian failure, male hypogonadism, pituitary dwarfism). The luteinizing hormone was determined in acetone extracts of the urine by radioimmunnoassay using double antibody technique. The results of urinary LH assays allowed to differentiate the concentration of this hormone in healthy males from postmenopausal women. In a group of patients with primary ganadal deficiency urinary LH was elevated while there was a lack urinary LH in cases of secondary gonadal insufficiency. (author)

  5. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    Science.gov (United States)

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  6. Local Production of Luteinizing Hormone Antisera to Be Used In Radioimmunoassay Technique

    International Nuclear Information System (INIS)

    Luteinizing hormone (LH) is a glycoprotein hormone. It is one of the coordinate pituitary regulators of gonadal function (2). Serum LH concentration increase in polycystic ovary syndrome (PCOS) which is the most common cause of infertility among infertile women. (3). The expensive imported LH kits lead us to think seriously to develop our local reagents. The antibody is a backbone of RIA reagents and this study is describing how to raise LH antibody and how to use it for a local LH kit production. Human LH was emulsified to Freunds adjuvant and acted as an immunogen Local Sudanese sheep was used to raise anti-LH antisera. The obtained antisera were adsorbed physically onto polystyrene beads with a dilution of 1/100.000 in order to develop an RIA kit. Optimization of LH assay conditions including incubation temperature and reaction time were performed. Assay validation tests including specificity, sensitivity, linearity, recovery, reproducibility and comparability for the local kit were performed. The polystyrene beads RIA LH system showed a minimum detectable dose of 0.04 m U/L. For the linearity and recovery tests, the regression coefficients were found to be 0.99, 0.997 respectively. The assay was found to be reproducible where the coefficients of variation within and between assays were less than 10%. Comparison between local and Chinese reagents for Luteinizing hormone determination in serum showed high correlation where r=0.96. (Authors)

  7. Local production of luteinizing hormone antisera to be used in radioimmunoassay technique

    International Nuclear Information System (INIS)

    Luteinizing hormone (LH) is a glycoprotein hormone. It is one of the coordinate pituitary regulators of gonadal function (2). Serum LH concentration increase in polycystic ovary syndrome (PCOS) which is the most common cause of infertility among infertile women (3). The expensive imported LH kits lead us to think seriously to develop our local reagents. The antibody is a backbone of RIA reagents and this study is describing how to raise LH antibody and how to use it for a local LH kit production. Human LH was emulsified to Freunds adjuvant and acted as an immunogen local Sudanese sheep was used to raise anti-LH antisera. The obtained antisera were adsorbed physically onto polystyrene beads with a dilution of 1/100.000 in order to develop an RIA kit. Optimization of LH assay conditions including incubation temperature and reaction time were performed. Assay validation tests including specificity, sensitivity, linearity, recovery, reproducibility and comparability for the local kit were performed. The polystyrene beads RIA LH system showed a minimum detectable dose of 0.04 m U/L. For the linearity and recovery tests, the regression coefficients were found to be 0.99, 0.997 respectively. The assay was found to be reproducible where the coefficients of variation within and between assays were less than 10%. Comparison between local and Chinese reagents for luteinizing hormone determination in serum showed high correlation where r=0.96. (Author)

  8. Lutein in selected Canadian crops and agri-food processing by-products and purification by high-speed counter-current chromatography.

    Science.gov (United States)

    Tsao, Rong; Yang, Raymond

    2006-04-21

    This study mainly focused on lutein content in several selected crops grown in southern Ontario, Canada. Marigold flower, a good rotation crop for the control of nematodes in tobacco fields was found to contain 0.77% lutein (after saponification, on dry basis). A high-speed counter-current chromatography (HSCCC) method using a two-phase solvent system consisting of hexane-ethanol-water (6:4.5:1.5, v/v/v) was developed for the purification of lutein from the saponification mixture of marigold flower extract. The purity of lutein prepared using this HSCCC method was 97%. Free lutein was found to be the predominant form in three squash varieties, and it was mostly found in the peel rather than the commonly consumed flesh. Sweet Mamma, Buttercup and Pepper squash varieties contained 25.4, 18.4 and 30.1mg/100g fresh weigh (FW) of lutein in the peels, respectively. These concentrations were significantly higher than that in spinach and kale (3.7 and 12.3 mg/100 g FW). beta-Carotene was found most in the peel of Sweet Mamma squash at 13.6 mg/100g FW, whereas it was below 2mg/100g FW in all other samples. Cooking increased extractable free lutein by 22-65% in squash peels. Lutein in Yukon Gold potato was at ca. 0.4 mg/100 g FW. Certain Yukon Gold was also found to contain violaxanthin (0.35 mg/100 g FW). Structures of lutein, beta-carotene and violaxanthin were identified by LC-atmospheric pressure chemical ionization MS in positive ion mode, and by comparing the retention time and UV-vis spectral data with standards. Results from this study suggest the selected crops and agri-food industrial processing by-products of these can be a good source of free lutein. PMID:16242702

  9. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    Directory of Open Access Journals (Sweden)

    Carmen Herrero-Barbudo

    Full Text Available Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.

  10. Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation

    DEFF Research Database (Denmark)

    Chu, Adrienne; Zhu, Lei; Blum, Ian D;

    2013-01-01

    While there is evidence for a circadian regulation of the preovulatory luteinizing hormone (LH) surge, the contributions of individual tissue clocks to this process remain unclear. We studied female mice deficient in the Bmal1 gene (Bmal1(-/-)), which is essential for circadian clock function, an...

  11. Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido

    Science.gov (United States)

    The objective was to determine the effects of naloxone, an opioid peptide receptor antagonist on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n = 8) or low libido (n = 8) based on the willingness to mount an artificial sow and allow s...

  12. Effects of Lutein on Hyperosmoticity-Induced Upregulation of IL-6 in Cultured Corneal Epithelial Cells and Its Relevant Signal Pathways

    Science.gov (United States)

    Chao, Shih-Chun; Nien, Chan-Wei; Iacob, Codrin; Hu, Dan-Ning; Huang, Sheng-Chieh

    2016-01-01

    Dry eye is a common disorder characterized by deficiency of tear. Hyperosmoticity of tear stimulates inflammation and damage of ocular surface tissues and plays an essential role in the pathogenesis of dry eye. Cultured human corneal epithelial (CE) cells were used for the study of effects of lutein and hyperosmoticity on the secretion of IL-6 by CE cells. Cell viability of CE cells was not affected by lutein at 1–10 μM as determined by MTT assay. Hyperosmoticity significantly elevated the secretion of IL-6 by CE cells as measured by ELISA analysis. The constitutive secretion of IL-6 was not affected by lutein. Lutein significantly and dose-dependently inhibited hyperosmoticity-induced secretion of IL-6. Phosphorylated- (p)- p38 MAPK, p-JNK levels in cell lysates and NF-κB levels in cell nuclear extracts were increased by being exposed to hyperosmotic medium. JNK, p38, and NF-κB inhibitors decreased hyperosmoticity-induced secretion of IL-6. Lutein significantly inhibited hyperosmoticity-induced elevation of NF-κB, p38, and p-JNK levels. We demonstrated that lutein inhibited hyperosmoticity-induced secretion of IL-6 in CE cells through the deactivation of p38, JNK, and NF-κB pathways. Lutein may be a promising agent to be explored for the treatment of dry eye. PMID:27047687

  13. Physicochemical stability, microrheological properties and microstructure of lutein emulsions stabilized by multilayer membranes consisting of whey protein isolate, flaxseed gum and chitosan.

    Science.gov (United States)

    Xu, Duoxia; Aihemaiti, Zulipiya; Cao, Yanping; Teng, Chao; Li, Xiuting

    2016-07-01

    The impact of chitosan (CTS) on the physicochemical stability, microrheological property and microstructure of whey protein isolate (WPI)-flaxseed gum (FG) stabilized lutein emulsions at pH 3.0 was studied. A layer-by-layer electrostatic deposition method was used to prepare multilayered lutein emulsions. Droplet size, zeta-potential, instability index, microstructure and microrheological behavior of lutein emulsions were measured. The influences of interfacial layer, metal chelator and free radical scavenger on the chemical stability of lutein emulsions were also investigated. It was found that multilayer emulsions had better physical stability showing the pronounced effect of 1wt% CTS. The mean square displacement analysis demonstrated that CTS led to increases of macroscopic viscosity and elasticity index for WPI-FG stabilized lutein emulsions due to CTS embedding in the network. CTS also helped to chemically stabilize the lutein emulsions against degradation. The combination of interfacial membrane and prooxidative metal chelator or free radical scavenger was an effective method to control lutein degradation. PMID:26920280

  14. Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells

    Directory of Open Access Journals (Sweden)

    Jueun Oh

    2013-01-01

    Full Text Available Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic, antiangiogenic, photoprotective, hepatoprotective, and neuroprotective properties. Although the anti-inflammatory effects of lutein have previously been described, the mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, in the present study, we aimed to investigate the regulatory activity of lutein in the inflammatory responses of skin-derived keratinocytes or macrophages and to elucidate the mechanism of its inhibitory action. Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL- 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX- 2 from interferon-γ/tumor necrosis-factor-(TNF- α-treated HaCaT cells, and the enhancement of matrix-metallopeptidase-(MMP- 9 level in UV-irradiated keratinocytes. By evaluating the intracellular signaling pathway and the nuclear transcription factor levels, we determined that lutein inhibited the activation of redox-sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal kinase (JNK. Evaluation of the radical and ROS scavenging activities further revealed that lutein was able to act as a strong anti-oxidant. Taken together, our findings strongly suggest that lutein-mediated AP-1 suppression and anti-inflammatory activity are the result of its strong antioxidative and p38/JNK inhibitory activities. These findings can be applied for the preparation of anti-inflammatory and cosmetic remedies for inflammatory diseases of the skin.

  15. Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors.

    Science.gov (United States)

    Hanke-Gogokhia, Christin; Wu, Zhijian; Gerstner, Cecilia D; Frederick, Jeanne M; Zhang, Houbin; Baehr, Wolfgang

    2016-03-25

    Arf-like protein 3 (ARL3) is a ubiquitous small GTPase expressed in ciliated cells of plants and animals. Germline deletion ofArl3in mice causes multiorgan ciliopathy reminiscent of Bardet-Biedl or Joubert syndromes. As photoreceptors are elegantly compartmentalized and have cilia, we probed the function of ARL3 (ADP-ribosylation factor (Arf)-like 3 protein) by generating rod photoreceptor-specific (prefix(rod)) and retina-specific (prefix(ret))Arl3deletions. In predegenerate(rod)Arl3(-/-)mice, lipidated phototransduction proteins showed trafficking deficiencies, consistent with the role of ARL3 as a cargo displacement factor for lipid-binding proteins. By contrast,(ret)Arl3(-/-)rods and cones expressing Cre recombinase during embryonic development formed neither connecting cilia nor outer segments and degenerated rapidly. Absence of cilia infers participation of ARL3 in ciliogenesis and axoneme formation. Ciliogenesis was rescued, and degeneration was reversed in part by subretinal injection of adeno-associated virus particles expressing ARL3-EGFP. The conditional knock-out phenotypes permitted identification of two ARL3 functions, both in the GTP-bound form as follows: one as a regulator of intraflagellar transport participating in photoreceptor ciliogenesis and the other as a cargo displacement factor transporting lipidated protein to the outer segment. Surprisingly, a farnesylated inositol polyphosphate phosphatase only trafficked from the endoplasmic reticulum to the Golgi, thereby excluding it from a role in photoreceptor cilia physiology. PMID:26814127

  16. High affinity human antibody fragments to dengue virus non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Nicole J Moreland

    Full Text Available BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein 3 (NS3 are essential for virus replication. They are distributed between the N-terminal protease domain in the first one-third and the C-terminal ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a flexible linker, was used as bait in biopanning with a naïve human Fab phage-display library. Using a range of truncated constructs spanning the NS2B cofactor region and the full-length NS3, 10 unique Fab were identified and characterized. Of these, monoclonal Fab 3F8 was shown to bind α3″ (residues 526 through 531 within subdomain III of the helicase domain. The antibody inhibits the ATPase and helicase activites of NS3 in biochemical assays and reduces DENV replication in HEK293 cells that were previously transfected with Fab 3F8 compared with mock transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable tools for studying the molecular mechanisms of flaviviral replication and for the monospecific detection of replicating dengue virus in vivo.

  17. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  18. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    Science.gov (United States)

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  19. Immunoreactive luteinizing hormone-releasing hormone in the seminal plasma and human semen parameters

    International Nuclear Information System (INIS)

    A luteinizing hormone-releasing hormone (LH-RH)-like substance has been detected in human seminal plasma by a radioimmunoassay (RIA) with a highly specific anti-LH-RH antiserum. The seminal samples - not only the plasma itself but also the sample extracted by an acid/alcohol method - showed satisfactory displacement curves in our RIA system. The relationship between fertility and the LH-RH values in the seminal plasma was studied by comparing the peptide levels with sperm concentration and motility. By these two parameters, 103 samples were divided into four groups. In the low-concentration groups (oligozoospermic patients), the hormonal concentrations differed significantly between those specimens demonstrating good and poor motility. These data suggest that this immunoreactive LH-RH may play a role in human spermatogenesis

  20. Effect of luteinizing hormone on the concentration of cyclic GMP in rabbit ovaries

    International Nuclear Information System (INIS)

    It has been shown that luteinizing hormone (LH) causes a rapid increase in cyclic AMP in the ovarian tissue of rabbits which precedes the LH-induced increase in steroidogenesis. Investigations have been made to ascertain the effect of LH on cyclic GMP, using radioimmunoassay techniques. It was found that the concentration of cyclic GMP remained unaffected up to four hours after LH stimulation, but between 4 and 8 hours it was significantly reduced and then returned to the control level. It is suggested that cyclic GMP may have no role in ovarian events in the first few hours after LH treatment. The diminished levels in the later periods may conceivably be related to later effects of LH, such as stimulation of prostaglandin biosynthesis. (U.K.)

  1. Luteinizing hormone-releasing hormone: radioimmunoassay and extraction from human serum

    International Nuclear Information System (INIS)

    Luteinizing hormone-releasing hormone (LRH) is a decapeptide which releases both LH and FSH in man. Its chemical synthesis allowed sufficient amounts to become available for clinical studies and for the generation of specific antibodies. Radioimmunoassay techniques have advantages over bioassays in relation to sensitivity and specificity. Radioimmunoassays have been applied to quantify exogenously administered LRH but data on the endogenous LRH levels of unextracted serum samples are still conflicting. The low concentrations of various polypeptide hormones make extraction procedures almost essential for their assay, in particular for improvement of specificity and for removal of interfering substances. The present paper concerns the extraction of LRH from biological fluids and the development of radioimmunoassay for testing the extracted samples

  2. Active Immunization and Evaluation Against Luteinizing Hormone for Radioimmunoassay Technique in Human Serum

    International Nuclear Information System (INIS)

    This study evaluated the antigenicity of luteinizing hormone conjugate with Bovine Serum Albumin (LH-BSA). The conjugation of LH- BSA was carried out by 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide HCl (ECDI). Three rabbits were immunized against LH-BSA. Two rabbits were immunized against nonconjugated LH and two rabbits against BSA only. Immunization was carried out through primary injection and 4 boosters. The preparation of the radioiodinated 125 I-LH was carried out using N- Bromo-Succinimide as oxidizing agent. The preparation of LH standards was carried out. The obtained LH antisera were characterized of titer, immuno response and displacement profile formulation, optimization and validation of the local liquid phase LH- Radioimmunoassay (RIA) system was carried out. The results provide a highly sensitive and accurate RIA system of LH-BSA. This technique could be used in measuring LH in human serum to investigate fertility especially disorders of the hypothalamic / pituitary / gonadal axis

  3. Chemical, Lutein and Zeaxanthin Composition of Wheat-yellow Maize Bread for the Prevention of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ngozi Innocentia Olaitan

    2015-04-01

    Full Text Available The study examined the effect of substitution of wheat flour with yellow maize flour on the Lutein, Zeaxanthin and proximate composition as well as sensory properties of their bread samples. Standard procedures were used in the production of yellow maize flour. The blend ratios of wheat-yellow maize composite flour used in the production of the bread samples were 100:0 (control, 90:10, 80:20, 70:30, 60:40 and 50:50%, respectively. Results revealed that there were significant (p≤0.05 increases in the lutein 92.4 µg (100:0% to 132.4 µg (50:50% and zeaxanthin 225.0 &mug (100:0% to 580.3 &mug (50:50% content of the bread samples. The proximate composition of the bread samples however, revealed that the carbohydrate, protein and ash content of the bread samples decreased with increase in yellow maize flour. The increase in yellow maize flour however, significantly (p≤0.05 increased the fiber, fat and moisture content of the bread samples. Bread sample B (90:10 was generally the most accepted with an organoleptic score of 8.11, however, sample F (50:50 was the most preferred on the basis of color (7.78, flavor (7.78 and texture (7.58. It would be concluded that substitution of wheat flour with yellow maize flour could be employed to improve on the carotenoids composition of bread, increase their intake and confer protection on consumers against atherosclerosis. The low carbohydrate content of the bread samples could be employed to control spike in blood glucose levels, weight gain and in the management of diabetes. The high fibre content could be harnessed in the prevention and management of obesity and hyperlipideamia.

  4. Enhanced Productivity of a Lutein-Enriched Novel Acidophile Microalga Grown on Urea

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    Carlos Vilchez

    2010-12-01

    Full Text Available Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of b-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related industries. The acidic culture medium (pH < 2.5 that prevents outdoor cultivation from non-desired microorganism growth is one of the main advantages of acidophile microalgae production. Conversely, acidophile microalgae growth rates are usually very low compared to common microalgae growth rates. In this work, we show that mixotrophic cultivation on urea efficiently enhances growth and productivity of an acidophile microalga up to typical values for common microalgae, therefore approaching acidophile algal production towards suitable conditions for feasible outdoor production. Algal productivity and potential for carotenoid accumulation were analyzed as a function of the nitrogen source supplied. Several nitrogen conditions were assayed: nitrogen starvation, nitrate and/or nitrite, ammonia and urea. Among them, urea clearly led to the best cell growth (~4 ´ 108 cells/mL at the end of log phase. Ammonium led to the maximum chlorophyll and carotenoid content per volume unit (220 mg·mL-1 and 35 mg·mL-1, respectively. Interestingly, no significant differences in growth rates were found in cultures grown on urea as C and N source, with respect to those cultures grown on nitrate and CO2 as nitrogen and carbon sources (control cultures. Lutein accumulated up to 3.55 mg·g-1 in the mixotrophic cultures grown on urea. In addition, algal growth in a shaded culture revealed the first evidence for an active xanthophylls cycle operative in acidophile microalgae.

  5. Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin

    Directory of Open Access Journals (Sweden)

    Howard Alan N

    2007-05-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects. Methods A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student's t-test. Results During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 ± 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group (9 subjects for whom the average rate was -0.17 ± 0.42 milli-absorbance units/day. Conclusion We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and

  6. effect of luteinizing hormone-releasing hormone analogue on the sexual behavior of sacalia quadriocellata

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    luteinizing hormone-releasing hormone (lhrh) is known to influence sexual behavior in many vertebrate taxa,but there have been no systematic studies on the role of lhrh in sexual behavior of turtles.we tested the hypotheses that exogenous lhrh analogues would induce sexual behavior of male four-eyed turtle,sacalia quadriocellata.we examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue (lhrh-a),human chorionic gonadotropin (hcg),or a combination of the two,and subsequently exposing them to sexually receptive females for behavioral observation.our data show that the injection of only hcg could not,while that of only lhrh-a could,facilitate sexual behavior along with testicular recrudescence and spermatogenesis in s.quadriocellata.the injection of both lhrh-a and hcg would induce more drastic sexual behavior of the animals than that of lhrh-a alone,indicating hcg enhances the effects of lhrh-a induced sexual behavior.however,different pharmacological dosages of lhrh-a (0.5 μg,1 μg,2 μg per 100 g bodyweight) did not correspond to different activity levels.though the mechanism of lhrh effect was not determined,this study may support that the sexual behavior ofs.quadriocellata which occurs at the beginning of the injection despite regression of the gonads.this is the first report on the exogenous lhrh-a induced sexual behavior for this species.

  7. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    OpenAIRE

    Sun, Hongfan

    2010-01-01

    Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH) receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposome...

  8. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants

    International Nuclear Information System (INIS)

    The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P2 and PI(3,4,5)P3. A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of ORP3. The endoplasmic reticulum (ER) targeting of ORP3 is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of ORP3 with the ER and the nuclear membrane. Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3. Notably, over-expression of ORP3 together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid starvation promotes formation of dilated peripheral ER (DPER) structures dependent on the ORP3 protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of ORP3 in the membrane targeting of the protein

  9. Lutein sequestration and furanocoumarin metabolism in parsnip webworms under different ultraviolet light regimes in the montane west.

    Science.gov (United States)

    Carroll, Mark J; Berenbaum, May R

    2006-02-01

    Both biotic and abiotic selection pressures can contribute to geographic variation in allelochemical production in plants. We examined furanocoumarin production in western North American populations of Heracleum lanatum and Pastinaca sativa that, at different latitudes and altitudes, experience different ultraviolet (UV) light regimes. Total furanocoumarins and linear furanocoumarins of fruits were negatively correlated with UV irradiance, whereas amounts of angular furanocoumarins, which are generally less phototoxic, were not. Another factor potentially influencing furanocoumarin production is the presence of the parsnip webworm Depressaria pastinacella, (Lepidoptera: Oecophoridae), an herbivore that feeds on reproductive structures of both plant species. These insects sequester lutein from their host plants; this carotenoid acts to ameliorate furanocoumarin toxicity. Although the concentration of lutein in fruits did not vary with UV irradiance, lutein sequestration by sixth instars was positively correlated with UV irradiance. Webworm populations are variably infested with the polyembryonic webworm parasitoid Copidosoma sosares Walker (Hymenoptera: Encyrtidae). H. lanatum fruits from populations with webworms parasitized by C. sosares had lower concentrations of furanocoumarins, with the exception of sphondin, than fruits from plants infested with webworms free from parasitism. Lower levels of these furanocoumarins may reduce negative effects on the fitness of this parasitoid. In contrast with the variation in furanocoumarin content, the ability of webworms to metabolize furanocoumarins by cytochrome P450 did not differ significantly among populations from New Mexico to Alberta. PMID:16555136

  10. Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma

    DEFF Research Database (Denmark)

    Udby, Lene; Sørensen, Ole E; Pass, Jesper;

    2004-01-01

    -like substances found in lizard saliva or snake venom. Human CRISP-3 is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity. On the basis of the relatively high content of CRISP-3 in human plasma and the small size of the protein...... (28 kDa), we hypothesized that CRISP-3 in plasma was bound to another component. This was supported by size-exclusion chromatography and immunoprecipitation of plasma proteins. The binding partner was identified by mass spectrometry as alpha(1)B-glycoprotein (A1BG), which is a known plasma protein of......Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to a family of closely related proteins found in mammals and reptiles. Some mammalian CRISPs are known to be involved in the process of reproduction, whereas some of the CRISPs from reptiles are neurotoxin...

  11. The effect of ovarian steroid feedback upon radioimmunoreactive luteinizing hormone releasing hormone in the hypothalamus

    International Nuclear Information System (INIS)

    A radioimmunoassay (RIA) method for luteinizing hormone (LH) releasing hormone (RH) utilizing rabbit antiserum against synthetic (Glu1)-LH-RH coupled with human serum albumin at the N-terminus, is described. This assay system for LH-RH also cross-reacted with several LH-RH analogues or fragments, but not with pituitary trophic hormones. The assay was performed on the hypothalamic extracts of adult ovariectomized rats and female immature rats which had been treated with estradiol. The FSH and LH levels in the pituitary gland and serum of the same animals were determined by RIA. The radioimmunoreactive LH-RH content of the stalk median eminence markedly increased seven days after ovariectomy. The serum levels and the pituitary contents of FSH and LH of the same rats were also significantly augmented. In immature rats, the hypothalamic content of LH-RH, as measured by RIA, was significantly increased one hour after the injection of estradiol. The FSH and LH levels in the pituitary showed a significant rise after 7 hours. (auth.)

  12. Plasma levels of luteinizing hormone and gonadal maturation of lambari females under different photoperiods

    Directory of Open Access Journals (Sweden)

    Fernanda Keley Silva Pereira Navarro

    2013-08-01

    Full Text Available The objective of this work was to evaluate the effect of photoperiod on luteinizing hormone (LH plasma levels and gonadal maturation of lambari females. One hundred and twenty adult lambaris, distributed into 12 aquaria of 20 L each, were randomly subjected to three different treatments, in a completely randomized design, and four replicates. Treatments were photoperiods in hours of light (L and darkness (D: T1, 0 L:24 D; T2, 12 L:12 D; T3, 24 L:0 D. After 40 days, fish were subjected to fasting for 24 hours and, then, anesthetized. Immediately after slaughter, fish were weighed, and their gonads and livers were removed and weighed. Ovaries were weighed and immersed in Bouin's fixative solution for 24 hours and, then, kept in 70% alcohol until processing the material. Subsequently, the oocyte developmental stage was determined. No significant differences were observed between treatments for final weight, ovary weight, gonadosomatic index (GSI, hepatosomatic index (HSI and LH levels. In all treatments, lambari females showed maturing ovaries with prevalence of vitellogenic oocytes. Photoperiod does not affect the LH levels and ovarian maturation in lambari females.

  13. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    Science.gov (United States)

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. PMID:26952754

  14. Synthesis and release of luteinizing hormone in vitro: manipulations of Ca2+ environment

    International Nuclear Information System (INIS)

    The authors determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. They monitored LH synthesis when LH release was stimulated either by specific [gonadotropin-releasing hormone (GnRH)] or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of [3H]glucosamine (glycosylation) and [14C]alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and [14C]alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus, glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined

  15. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    Science.gov (United States)

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  16. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin.

    Science.gov (United States)

    Beatty, Stephen; Nolan, John; Kavanagh, Heather; O'Donovan, Orla

    2004-10-01

    Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxy-carotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate. However, the nature of the relationships between L and Z in foodstuffs, blood, and macula is confounded by many variables including processes which influence digestion, absorption, and transport of the compounds in question, and accumulation and stabilization of the carotenoids in the tissues. If macular pigment is protective for age-related maculopathy, a clear understanding of the mechanisms whereby L and Z arrive at the target tissue (retina) from their source (foodstuff) is essential. In this paper, we review the literature germane to this growing area of interest. PMID:15325913

  17. The effect of dietary supplementation with the natural carotenoids curcumin and lutein on broiler pigmentation and immunity.

    Science.gov (United States)

    Rajput, N; Naeem, M; Ali, S; Zhang, J F; Zhang, L; Wang, T

    2013-05-01

    The objective of this study was to compare the effects of supplementation with 2 carotenoids, curcumin and lutein, on pigmentation and immunity in lipopolysaccharide (LPS)-stimulated broiler chicks. Two hundred forty 1-d-old Arbor Acres broilers were randomly distributed into 3 dietary treatment groups: a basal diet without carotenoid supplementation (control), a basal diet supplemented with 200 mg/kg of curcumin (CRM), or a basal diet supplemented with 200 mg/kg of lutein (LTN) for 42 d. The birds were vaccinated against Newcastle disease (ND) and avian influenza on d 10. At 16, 18, and 20 d of age, half of the chicks in each group were injected in the abdominal region with either LPS (250 mg/kg of BW) or an equal volume of 0.9% NaCl. The intensity of the shank skin color (Roche color fan score) and the b* (yellow) values of the breasts and thighs were highest in lutein-supplemented broilers, followed by curcumin-supplemented and control broilers, whereas the a* (red) value of the thigh muscle was highest in curcumin-supplemented LPS-induced birds. At 42 d, the relative weight of the abdominal fat was lowest in the CRM-supplemented group, followed by the LTN-supplemented and control groups; the spleen weight was lower in the non-LPS-induced LTN-supplemented group than the LPS-induced control group. The ND and avian influenza titers were significantly higher in the CRM-supplemented group than in the other groups at 20 d; at 30 d, the ND titer was significantly higher in the LPS-induced LTN group. Supplementation with curcumin significantly promoted B and T lymphocyte proliferation in both LPS- and non-LPS-induced birds at 21 d. Curcumin also promoted B lymphocyte proliferation in non-LPS-induced birds at 42 d. Curcumin significantly reduced alanine aminotransferase and aspartate aminotransferase activities at 42 d in non-LPS-treated birds, whereas lutein significantly increased the activities of these enzymes in LPS-induced birds. Both carotenoids significantly

  18. Expression of Leptin Long-form Receptor mRNA in Luteinized Granulosa Cells of Obese Women with Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    YIN Jie; LIU Yi; LV Liqun; WANG Donghua; GONG Cheng; XIAO Wei; SHENG Hui

    2007-01-01

    To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa cells of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added (0, 10, 100 and 1000 ng/mL). After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLmRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control (P<0.05). In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation (P<0.01), and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak. It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

  19. Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

    Science.gov (United States)

    Goh, H H; Chew, P C; Karim, S M; Ratnam, S S

    1980-02-01

    Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH. PMID:6772356

  20. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  1. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    International Nuclear Information System (INIS)

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement

  2. MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone.

    Directory of Open Access Journals (Sweden)

    Juan Cui

    Full Text Available BACKGROUND: MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH contributions to LH receptor (LHR-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. METHODS: Human ovarian cancer cells (SKOV3 were chosen as negative control (LHR- and stably transfected to express functional LHR (LHR+, followed by incubation with LH (0-20 h. At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™, which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs. FINDINGS: In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. CONCLUSION: The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles.

  3. Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

    Directory of Open Access Journals (Sweden)

    S. Malaivijitnond

    2010-09-01

    Full Text Available To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group: distilled water, Butea superba (BS-10, BS-50, BS-250, and testosterone propionate (TP. They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH, follicle-stimulating hormone (FSH and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

  4. Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

    Science.gov (United States)

    Lafuente, A; Márquez, N; Piquero, S; Esquifino, A I

    1999-01-11

    Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent. PMID:10048746

  5. Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

    Science.gov (United States)

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

    2015-03-01

    Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches. PMID:25687742

  6. Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262

    Directory of Open Access Journals (Sweden)

    Kline Lawrence E

    2006-05-01

    Full Text Available Abstract Background In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH. Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. Results Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation is suggested. Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men. Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile.

  7. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Energy Technology Data Exchange (ETDEWEB)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.

  8. A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on neural processing speed and efficiency.

    Directory of Open Access Journals (Sweden)

    Emily R Bovier

    Full Text Available Lutein and zeaxanthin are major carotenoids in the eye but are also found in post-receptoral visual pathways. It has been hypothesized that these pigments influence the processing of visual signals within and post-retina, and that increasing lutein and zeaxanthin levels within the visual system will lead to increased visual processing speeds. To test this, we measured macular pigment density (as a biomarker of lutein and zeaxanthin levels in brain, critical flicker fusion (CFF thresholds, and visual motor reaction time in young healthy subjects (n = 92. Changes in these outcome variables were also assessed after four months of supplementation with either placebo (n = 10, zeaxanthin only (20 mg/day; n = 29 or a mixed formulation containing 26 mg/day zeaxanthin, 8 mg/day lutein, and 190 mg/day mixed omega-3 fatty acids (n = 25. Significant correlations were found between retinal lutein and zeaxanthin (macular pigment and CFF thresholds (p<0.01 and visual motor performance (overall p<0.01. Supplementation with zeaxanthin and the mixed formulation (considered together produced significant (p<0.01 increases in CFF thresholds (∼12% and visual motor reaction time (∼10% compared to placebo. In general, increasing macular pigment density through supplementation (average increase of about 0.09 log units resulted in significant improvements in visual processing speed, even when testing young, healthy individuals who tend to be at peak efficiency.

  9. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

    Science.gov (United States)

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K.; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B.; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-01-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder. PMID:25669657

  10. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  11. Human chorionic ganodotropin binding sites in the human endometrium

    International Nuclear Information System (INIS)

    The existence of high-affinity and low-capacity specific binding sites for luteinizing hormone/human chorionic gonadotropin (hCG) has been reported in porcine, rabbit and rat uteri. The authors have identified the hCG binding sites in the human endometrium collected from 35-42-year-old ovulatory and anovulatory women. The binding characteristics of hCG to endometrial tissue preparations from ovulatory and anovulatory women showed saturability with high affinity and low capacity. Scatchard plot analysis showed the dissociation constant of specific binding sites in the ovulatory women to be 3.5x10-10 mol/l and in anovulatory women to be 3.1x10-10 mol/l. The maximum binding capacity varied considerably between ovulatory and anovulatory endometrium. Among the divalent metal ions tested Zn2+ effected a remarkable increase in [125I]hCG binding to the endometrium, whereas Mn2+ showed a marginal increase and other metal ions did not have any effect. Data obtained with human endometrium indicate an influence of the functional state of the ovary on [125I]hCG binding to endometrium. 14 refs., 3 figs

  12. Significance of monoclonal antibodies against the conserved epitopes within non-structural protein 3 helicase of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Yixin Bian

    Full Text Available Nonstructural protein 3 (NS3 of hepatitis C virus (HCV, codes for protease and helicase carrying NTPase enzymatic activities, plays a crucial role in viral replication and an ideal target for diagnosis, antiviral therapy and vaccine development. In this study, monoclonal antibodies (mAbs to NS3 helicase were characterized by epitope mapping and biological function test. A total of 29 monoclonal antibodies were produced to the truncated NS3 helicase of HCV-1b (T1b-rNS3, aa1192-1459. Six mAbs recognized 8/29 16mer peptides, which contributed to identify 5 linear and 1 discontinuous putative epitope sequences. Seven mAbs reacted with HCV-2a JFH-1 infected Huh-7.5.1 cells by immunofluorescent staining, of which 2E12 and 3E5 strongly bound to the exposed linear epitope (1231PTGSGKSTK(1239 (EP05 or core motif (1373IPFYGKAI(1380 (EP21, respectively. Five other mAbs recognized semi-conformational or conformational epitopes of HCV helicase. MAb 2E12 binds to epitope EP05 at the ATP binding site of motif I in domain 1, while mAb 3E5 reacts with epitope EP21 close to helicase nucleotide binding region of domain 2. Epitope EP05 is totally conserved and EP21 highly conserved across HCV genotypes. These two epitope peptides reacted strongly with 59-79% chronic and weakly with 30-58% resolved HCV infected blood donors, suggesting that these epitopes were dominant in HCV infection. MAb 2E12 inhibited 50% of unwinding activity of NS3 helicase in vitro. Novel monoclonal antibodies recognize highly conserved epitopes at crucial functional sites within NS3 helicase, which may become important antibodies for diagnosis and antiviral therapy in chronic HCV infection.

  13. Determination of beta-carotene and lutein available from green leafy vegetables by an in vitro digestion and colonic fermentation method.

    Science.gov (United States)

    Serrano, José; Goñi, Isabel; Saura-Calixto, Fulgencio

    2005-04-20

    Green leafy vegetables (Spinacea oleracea, Cnidoscolus aconitifolius, and Solanum americanum) contain a high amount of beta-carotene (27-52 mg/100 g of dry sample) and lutein (140-193 mg/100 g of dry sample). The amount of beta-carotene and lutein released from the food matrix by the action of digestive enzymes ranged from 22 to 67% and from 27 to 77%, respectively. There was a significant correlation between the enzymatic release of carotenoids (lutein + beta-carotene) and the content of Klason lignin, nonstarch polysaccharides, and resistant protein. The carotenoids released by the in vitro colonic fermentation ranged from 2 to 11%, and part of them (0.251-4.03 mg/100 g of original dry sample) remained intact in the fermentation media and could be potentially absorbed in the colon. A significant part of carotenoids seems to be unavailable in the intestinal tract (16% in S. oleracea to 58% in C. aconitifolius). PMID:15826042

  14. Secondary Analyses of the Effects of Lutein/Zeaxanthin on Age-Related Macular Degeneration Progression AREDS2 Report No.3

    OpenAIRE

    Emily Y Chew; Clemons, Traci E.; SanGiovanni, John Paul; Danis, Ronald P; Ferris, Frederick L.; Elman, Michael J.; Antoszyk, Andrew; Ruby, Alan; Orth, David; Bressler, Susan B.; Fish, Gary; Hubbard, Baker; Klein, Michael; Chandra, Suresh; Blodi, Barbara

    2014-01-01

    The Age-Related Eye Disease Study (AREDS) formulation for treatment of age-related macular degeneration contains vitamins C, E, beta-carotene and zinc with copper. Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk of lung cancer from beta-carotene in smokers and former smokers. As previously reported in a secondary analysis, AREDS2 participants taking lutein/zeaxanthin with or without omega-3...

  15. Seasonal variation in plasma testosterone, luteinizing hormone concentrations and LH-RH responsiveness in mature, male rusa deer (Cervus rusa timorensis).

    Science.gov (United States)

    van Mourik, S; Stelmasiak, T; Outch, K H

    1986-01-01

    Plasma testosterone and luteinizing hormone (LH) concentrations in immobilized or yarded rusa stags (Cervus rusa timorensis) were investigated over a two-year period. Testosterone concentrations showed a minor elevation in autumn (May) and reached maximal levels in late winter-early spring (August) coinciding with the rut. Luteinizing hormone in plasma was only detectable from January to May. Maximal responsiveness of the pituitary-gonadal axis to LH-RH stimulation was recorded in August. The combination of Fentaz (fentanylcitrate and azaperone) and Rompun (xylazine hydrochloride) for immobilizing deer influences hypothalamic function. PMID:2869876

  16. Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation

    International Nuclear Information System (INIS)

    Since a substantial percentage of ovarian cancers express gonadotropin receptors and are responsive to the relatively high concentrations of pituitary gonadotropins during the postmenopausal years, it has been suggested that receptor activation may contribute to the etiology and/or progression of the neoplasm. The goal of the present study was to develop a cell model to determine the impact of luteinizing hormone (LH) receptor (LHR) expression and LH-mediated LHR activation on gene expression and thus obtain insights into the mechanism of gonadotropin action on ovarian surface epithelial (OSE) carcinoma cells. The human ovarian cancer cell line, SKOV-3, was stably transfected to express functional LHR and incubated with LH for various periods of time (0-20 hours). Transcriptomic profiling was performed on these cells to identify LHR expression/activation-dependent changes in gene expression levels and pathways by microarray and qRT-PCR analyses. Through comparative analysis on the LHR-transfected SKOV-3 cells exposed to LH, we observed the differential expression of 1,783 genes in response to LH treatment, among which five significant families were enriched, including those of growth factors, translation regulators, transporters, G-protein coupled receptors, and ligand-dependent nuclear receptors. The most highly induced early and intermediate responses were found to occupy a network impacting transcriptional regulation, cell growth, apoptosis, and multiple signaling transductions, giving indications of LH-induced apoptosis and cell growth inhibition through the significant changes in, for example, tumor necrosis factor, Jun and many others, supportive of the observed cell growth reduction in in vitro assays. However, other observations, e.g. the substantial up-regulation of the genes encoding the endothelin-1 subtype A receptor, stromal cell-derived factor 1, and insulin-like growth factor II, all of which are potential therapeutic targets, may reflect a positive

  17. The mare as a model for luteinized unruptured follicle syndrome: intrafollicular endocrine milieu.

    Science.gov (United States)

    Bashir, S T; Gastal, M O; Tazawa, S P; Tarso, S G S; Hales, D B; Cuervo-Arango, J; Baerwald, A R; Gastal, E L

    2016-03-01

    Luteinized unruptured follicle (LUF) syndrome is a recurrent anovulatory dysfunction that affects up to 23% of women with normal menstrual cycles and up to 73% with endometriosis. Mechanisms underlying the development of LUF syndrome in mares were studied to provide a potential model for human anovulation. The effect of extended increase in circulating LH achieved by administration of recombinant equine LH (reLH) or a short surge of LH and decrease in progesterone induced by prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), identification of an optimal dose of COX-2 inhibitor (flunixin meglumine, FM; to block the effect of prostaglandins) for inducing LUFs (Experiment 2), and evaluation of intrafollicular endocrine milieu in LUFs (Experiment 3) were investigated. In Experiment 1, mares were treated with reLH from Day 7 to Day 15 (Day 0=ovulation), PGF2α on Day 7, or in combination. In Experiment 2, FM at doses of 2.0 or 3.0 mg/kg every 12 h and human chorionic gonadotropin (hCG) (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3, FM at a dose of 2.0 mg/kg every 12 h plus hCG was used to induce LUFs and investigate the intrafollicular endocrine milieu. No LUFs were induced by reLH or PGF2α treatment; however, LUFs were induced in 100% of mares using FM. Intrafollicular PGF2α metabolite, PGF2α, and PGE2 were lower and the ratio of PGE2:PGF2α was higher in the induced LUF group. Higher levels of intrafollicular E2 and total primary sex steroids were observed in the induced LUF group along with a tendency for higher levels of GH, cortisol, and T; however, LH, PRL, VEGF-A, and NO did not differ between groups. In conclusion, this study reveals part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation, and indicates that the mare might be an appropriate model for studying the poorly understood LUF syndrome. PMID:26647418

  18. Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla.

    Science.gov (United States)

    Rather, Mohd Ashraf; Bhat, Irfan Ahmad; Sharma, Rupam

    2016-07-01

    Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. The coding region of lhb gene encoded a peptide of 148 amino acids. The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. PMID:26980432

  19. Stability evaluation of lutein nanodispersions prepared via solvent displacement method: The effect of emulsifiers with different stabilizing mechanisms.

    Science.gov (United States)

    Tan, Tai Boon; Yussof, Nor Shariffa; Abas, Faridah; Mirhosseini, Hamed; Nehdi, Imededdine Arbi; Tan, Chin Ping

    2016-08-15

    The stability of lutein nanodispersions was evaluated during storage and when exposed to different environmental conditions. Lutein nanodispersions were prepared using Tween 80, sodium dodecyl sulfate (SDS), sodium caseinate (SC) and SDS-Tween 80 as the emulsifiers. During eight weeks of storage, all samples showed remarkable physical stability. However, only the SC-stabilized nanodispersion showed excellent chemical stability. Under different environmental conditions, the nanodispersions exhibited a varied degree of stability. All nanodispersions showed constant particle sizes at temperatures between 30 and 60°C. However, at pH 2-8, only the SC-stabilized nanodispersion was physically unstable. The addition of NaCl (300-400mM) only caused flocculation in nanodispersion stabilized by SDS-Tween 80. All nanodispersions were physically stable when subjected to different centrifugation speeds. Only Tween 80-stabilized nanodispersion was stable against the effect of freeze-thaw cycles (no phase separation observed). In this study, there was no particular emulsifier that was effective against all of the environmental conditions tested. PMID:27006226

  20. Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens.

    Science.gov (United States)

    Otaka, Junnosuke; Seo, Shigemi; Nishimura, Marie

    2016-01-01

    α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting that plant factors might induce its production in fungi. Through immunofluorescence observations of fungal cell walls, we found that carrot (Daucus carota) extract induced the accumulation of α-1,3-glucan on germlings in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes anthracnose disease in various dicot plants. Bioassay-guided fractionation of carrot leaf extract successfully identified two active substances that caused α-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely distributed in plants, and stigmasterol, a plant-specific membrane component. Lutein, which had a greater effect on C. fioriniae, also induced α-1,3-glucan accumulation in other Colletotrichum species and in the phylogenetically distant rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results suggested that fungal plant pathogens reorganize their cell wall components in response to specific plant-derived compounds, which these pathogens may encounter during infection. PMID:27483218

  1. Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone

    International Nuclear Information System (INIS)

    Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period

  2. Bilateral vanished testes diagnosed with a single blood sample showing very high gonadotropins (follicle-stimulating hormone and luteinizing hormone) and very low inhibin B

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Petersen, Bodil Laub; Kvist, Kolja;

    2011-01-01

    Objective. In boys with cryptorchidism median serum values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are higher and median serum values of inhibin B lower than in normal controls. Serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes....

  3. AGE-RELATED ALTERATIONS IN THE STIMULATED RELEASE IN VITRO OF CATECHOLAMINES AND LUTEINIZING HORMONE-RELEASING HORMONE FROM THE MALE RAT HYPOTHALAMUS

    Science.gov (United States)

    Using an in vitro perifusion system, the present study investigated the possibility that alterations in catecholamine and luteinizing hormone-releasing hormone (LHRH) secretion from the male rat mediobasal hypothalamus are present during the period of middle-age. The results indi...

  4. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    DEFF Research Database (Denmark)

    Gräs, S; Ovesen, P; Andersen, A N;

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular...

  5. Hepatitis C virus non-structural protein 3 interacts with cytosolic 5'(3'-deoxyribonucleotidase and partially inhibits its activity.

    Directory of Open Access Journals (Sweden)

    Chiu-Ping Fang

    Full Text Available Infection with hepatitis C virus (HCV is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been demonstrated previously that HCV non-structural protein 3 (NS3 is involved in cell transformation. In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein. Cytosolic 5'(3'-deoxyribonucleotidase (cdN, dNT-1 was found to interact with HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system. Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells. The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems. Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions. Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles. Control of DNA precursor concentration is essential for the maintenance of genetic stability. Reduction of cdN activity would result in the imbalance of DNA precursor concentrations. Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.

  6. Generation of Monoclonal Antibodies against Non-structural Protein 3AB of Foot-and-Mouth Disease Virus

    Institute of Scientific and Technical Information of China (English)

    Tong Lin; Junjun Shao; Huiyun Chang; Shandian Gao; Guozheng Cong; Junzheng Du

    2012-01-01

    To identify linear epitopes on the non-structural protein 3AB of foot-and-mouth disease virus (FMDV),BABL/c mice were immunized with the 3AB protein and splenocytes of BALB/c mice were fused with myeloma Sp2/0 cells.Two hybridoma monoclonal antibodies (mAbs) cell lines against the 3AB protein of foot-and-mouth disease virus (FMDV) were obtained,named C6 and E7 respectively.The microneutralization titer was 1∶1024 for mAb C6,and 1∶512 for E7.Both mAbs contain kappa light chains,and were of subclass IgG2b.In order to define the mAbs binding epitopes,the reactivity of these mAbs against FMDV were examined by indirect ELISA.The results showed that both mAbs can react with FMDV,but had no cross-reactivity with Swine Vesicular Disease (SVD) antigens.The titers in abdomen liquor were 1∶5×106 for C6 and 1∶2×106 for E7.In conclusion,the mAbs obtained from this study are specific for the detection of FMDV,can be used for etiological and immunological researches on FMDV,and have potential use in diagnosis and future vaccine designs.

  7. Determination Of Estradiol (E2) And Luteinizing Hormone (LH) Of Petaurus Breviceps Papuanus (MARSUPIALIA) During One Estrus Cycle

    International Nuclear Information System (INIS)

    Concentration of plasma estradiol (E2)and luteinizing hormone during one estrus cycle of adult female Petaurus breviceps papuanus, a marsupialia living in Irian Jaya and Aru islands, has been determined. Data on the reproductive biology of this animal is very rare. Plasma estradiol and LH during the estrus cycle phases was determined using RIA method, The results revealed i that estradiol and LH concentration changes significantly along with the phases of the' estrus cycle, the highest concentration was at estrus and the lowest was at diestrus. A surge of LH concentration occurred at estrus, which means that during this period ovulation could occur. However, timing of ovulation in this experiment could not be determined. It could be concluded that the highest concentration of E2 and LH of adult female Petaurus breviceps papuanus during one estrus cycle was at estrus and the lowest one was at diestrus

  8. Quick method for the determination of the luteinizing hormone (LH). Eine schnelle Methode der radioimmunologischen Bestimmung des luteinisierenden Hormons (LH)

    Energy Technology Data Exchange (ETDEWEB)

    Koch, R.

    1985-01-17

    A radioimmunological determination method for luteinizing hormone (LH) was developed, whose time requirement could be reduced from 2 days down to 2 hours. All of the parameters influenced by the test were studied and for the test correspondingly optimized. The biggest advantages of this method are the accuracy in the nanogram area, the non-dependence on the cooperation and discipline of the patients (immunological LH-measurements in urine), and the lack of time-consuming preparations and increasing costs in large treatment centers, where, for example, a large number of patients for insemination or in vitro fertilization would need to be observed at the same time. The results were tested for correctness against clinical and clinical-chemical criteria and compared with results of recently used methods. (TRV).

  9. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    Directory of Open Access Journals (Sweden)

    Yingna He

    2010-09-01

    Full Text Available Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposomes were prepared by lipid film hydration and an ultrasound dispersion process. Thiolated gonadorelin with affinity for the LHRH receptor was chemically coupled to N-[(3-maleimide-1-oxopropyl aminopropyl polyethylene glycol-carbamyl] distearoyl-l-phosphatidyl-ethanolamine via a thioether bond and subsequently inserted into polyethylene glycol-grafted liposomes. The liposome was characterized in terms of its size, ligand density, drug loading, and leakage properties. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured MCF-7 breast cancer cells. A protein assay of ligand coupling to the liposomal surface indicated that more than 60% of the LHRH peptides were inserted into the liposome bilayer. Up to 1.0 mg/mL of stable liposomal mitoxantrone loading was achieved, with approximately 98% of this being entrapped within the liposomes. In vitro cell culture studies revealed that the gonadorelin-modified liposomes bound to their target cells had significantly higher affinity and better antitumor efficiency than generic drug-loaded liposomes. These events were presumed to occur through specific interactions of the LHRH with its cognate receptors on the cell surface. It was concluded that the targeting properties of the delivery system would potentially improve the therapeutic benefits of mitoxantrone, as compared with nontargeted liposomes.Keywords: mitoxantrone, liposome, luteinizing hormone-releasing hormone receptor

  10. Recombinant Group B Streptococcus Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein▿

    OpenAIRE

    Yang, Hsiao-Hui; Mascuch, Samantha J.; Madoff, Lawrence C.; Paoletti, Lawrence C.

    2008-01-01

    Conjugate vaccines against pathogens of multiple serotypes are optimized when all components induce functional antibody, resulting in broadened coverage. While most clinical studies of vaccines against group B Streptococcus (GBS) have evaluated conjugates composed of capsular polysaccharide (CPS) coupled to tetanus toxoid, conjugates prepared with GBS proteins as carriers have also been efficacious in animals. Here, we report that recombinant GBS alpha-like protein 3 (rAlp3) is both a strong ...

  11. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

    OpenAIRE

    Hesselink, M.K.C.; Greenhaff, P L; Constantin-Teodosu, D.; Hultman, E; Saris, W. H. M.; Nieuwlaat, R.; Schaart, G.; Kornips, C.F.P.; P. Schrauwen

    2003-01-01

    Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (L...

  12. Clinical implications and characteristics of factor forkhead box protein 3 in gastric cancer

    OpenAIRE

    Jiang, Changli; WANG, WEIHUA; Yan, Wei; Zhang, Yuhai; Yang, Jiangtao; Zhang, Song; Zhang, Cun; Zhang, Wei; Han, Wei; Wang, Junzhi; Zhang, Ying-qi

    2011-01-01

    Transcription factor forkhead box protein 3 (FOXP3) is a specific marker of naturally occurring regulatory T cells (Tregs). Recently, various reports have suggested that FOXP3 may represent a tumor escape mechanism in cancer cells apart from its roles in Tregs. In the present study, the clinical and biological characteristics of FOXP3 were evaluated in human gastric cancer. The expression and localization of FOXP3 in gastric cancer cell lines was analyzed to evaluate its cellular biological f...

  13. Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone

    International Nuclear Information System (INIS)

    The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence following systemic injection 125I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of 125I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine growth hormone, competitively blocked 125I-human growth hormone binding to the external median eminence. These observations provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effects of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus. (orig.)

  14. Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo: efficacy in ovulation induction and corpus luteum support

    International Nuclear Information System (INIS)

    The present data are the first, to the authors knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate

  15. Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: A rare co-existence with therapeutic dilemma

    Directory of Open Access Journals (Sweden)

    Murthy S Anand

    2012-01-01

    Full Text Available A 21 year old female presented with amenorrhea, hirsutism and change in voice along with an elevated serum β-HCG (human chorionic gonadotrophin level and normal CA-125 level. Laparotomy revealed an enlarged right ovary measuring 6 × 5 × 1 cms with presence of an ovarian hemangioma along with stromal luteinization and HCG producing mononucleate as well as multinucleate cells of uncertain histogenesis on histopathological examination. Immunohistochemistry for inhibin and calretinin were positive in the luteinized component whereas β-HCG and Ki-67 were positive in the multinucleate cell component. The diagnostic rarity and therapeutic dilemma of such a rare mixed tumor within a single ovary has proven to be an exceptional case and an excellent investigative opportunity.

  16. Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing.

    Science.gov (United States)

    Blair, Jeffrey A; Palm, Russell; Chang, Jaewon; McGee, Henry; Zhu, Xiongwei; Wang, Xinglong; Casadesus, Gemma

    2016-02-01

    Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss. PMID:26497249

  17. Membrane-association properties of avian encephalomyelitis virus protein 3A

    International Nuclear Information System (INIS)

    Avian encephalomyelitis virus (AEV) protein 3A is a membrane-interacting protein containing a stretch of 21 hydrophobic amino acid residues. Membrane-association property was assayed using chick embryo brain (CEB) cells transfected with the fusion GFP-3A and its various deletion mutants demonstrate that 3A is integrally interacted with membranes by its hydrophobic domain and further defines that the motif of amino acid residues 45-51, the most C-terminal hydrophobic domain essential for this feature. Expression of 3A in transfected CEB cells results in membrane permeability modifications through association of the third motif with membranes, which can be demonstrated by release of lactate dehydrogenase (LDH) into the medium. Furthermore, the localization of the protein 3A in transfected CEB and Cos-7 cells exhibited an overlapping staining pattern with an endoplasmic reticulum (ER) and involved in the disassembly of the Golgi apparatus under double-staining and confocal microscopic observations, whereas the 3A mutants lacking amino acids 45-51 could not localize to the ER and display an intact Golgi morphology as seen in the mutant devoid of the complete hydrophobic domain after transfection. Taken together, our results demonstrate that the motif (aa 45-51) of the transmembrane domain might be fundamental for the stable interaction of the protein 3A with the ER membrane regardless of the cell types. Although this motif was deleted, the resultant protein did not localize to the ER, which directly results in the loss of the ability to block the ER-to-Golgi transport by 3A protein and hence makes the morphology of the Golgi apparatus return to normal

  18. Cold Shock Domain Protein 3 Regulates Freezing Tolerance in Arabidopsis thaliana*

    OpenAIRE

    Kim, Myung-Hee; Sasaki, Kentaro; Imai, Ryozo

    2009-01-01

    In response to cold, Escherichia coli produces cold shock proteins (CSPs) that have essential roles in cold adaptation as RNA chaperones. Here, we demonstrate that Arabidopsis cold shock domain protein 3 (AtCSP3), which shares a cold shock domain with bacterial CSPs, is involved in the acquisition of freezing tolerance in plants. AtCSP3 complemented a cold-sensitive phenotype of the E. coli CSP quadruple mutant and displayed nucleic acid duplex melting activity, suggesting that AtCSP3 also fu...

  19. Genetic analysis on 3'-terminal flanking region of uncoupling protein 3 in different pig breeds

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 3′-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicatedthat Erhualian had extraordinary gene frequency, presented most significant difference by χ2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results canbe concluded that Taihu pigs have special genetic characteristics among pig breeds.

  20. Selective induction of apoptosis by the cytotoxic analog AN-207 in cells expressing recombinant receptor for luteinizing hormone-releasing hormone

    OpenAIRE

    Danila, Daniel C; Schally, Andrew V.; Nagy, Attila; Alexander, Joseph M

    1999-01-01

    The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells. Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubicin (AN-201) conjugated to [d-Lys6] luteinizing hormone-releasing hormone (LH-RH) (AN-207), was demonstrated to be less toxic than the nonconjugate...

  1. Rheological characterization of coloured oil-in-water food emulsions with lutein and phycocyanin added to the oil and aqueous phases

    OpenAIRE

    Sousa, Isabel; Batista, Ana Paula; Raymundo, Anabela; Empis, José

    2006-01-01

    The use of natural colourings in food products presents nutritional advantages, and certain pigments are associated with functional properties, e.g. antioxidant effects. This can be very advantageous in food products with high fat contents like mayonnaises. The aim of this work was to study the effect of adding natural pigments, lutein and phycocyanin, to the water and oil phases, respectively, of oil-in-water pea protein-stabilized emulsions, beyond the desirable and expected develo...

  2. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study.

    OpenAIRE

    Delcourt, Cécile; Carrière, Isabelle; Delage, Martine; Barberger-Gateau, Pascale; Schalch, Wolfgang

    2006-01-01

    PURPOSE: To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Li? ?'Age (POLA) Study. METHODS: Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125 microm) associated with pigme...

  3. Hubungan Kadar βHCG Praevakuasi, Gambaran Histopatologi, dan Kista Lutein dengan Performa βHCG pada Penderita Mola Hidatidosa yang Berkembang Menjadi PTG dan Kembali Normal

    Directory of Open Access Journals (Sweden)

    Yudi Mulyana Hidayat

    2014-12-01

    Full Text Available The incidence of trophoblastic diseases in Indonesia and developing countries is relatively high compared to the developed countries. The incidence of gestational trophoblast tumors (GTT after the evacuation of a hydatidiform mole ranges from 10% to 20%. Several clinical variables have been studied as the risk factors for malignancy, including the pre-evacuation level of beta human chorionic gonadotropin (βHCG, histopathological appearance, and the presence of lutein cysts. The purpose of this study was to determine the relationship between βHCG decline and pre-evacuation βHCG levels, histopathological features, and the lutein cysts status in patients with moles. This study was a case control study of patients with complete hydatidiform mole in Dr. Hasan Sadikin General Hospital during the period of 2007-2011. The results revealed that there was a significant correlation between the level of βHCG ≥100,000 mIU/mL and post-molar malignancy (p<0.05. There was also a significant relationship between the histopathologic feature of excessive post-molar cell proliferation and malignancy (p<0.05 and between the presence of lutein cyst and post-molar malignancy (p<0.05. This study concludes that the pre-evacuation βHCG level ≥100.000 mIU/mL, excessive proliferation, and the presence of lutein cysts are correlated with malignancy after molar evacuation. These risk factors are useful to differentiate whether a complete hydatidiform mole will become malignant or remain benign.

  4. Estradiol feedback effects on the alpha-subunit mRNA in the sheep pituitary gland: correlation with serum and pituitary luteinizing hormone concentrations.

    OpenAIRE

    Landefeld, T; Kepa, J.; Karsch, F.

    1984-01-01

    The effects of estradiol feedback on pituitary luteinizing hormone (LH) content, serum LH concentration, and in vitro-translated alpha subunit was examined in the ewe. Three animal models were used representing positive, negative, and no estradiol feedback. Two experiments were carried out: (i) anestrous ewes were treated acutely with five Silastic estradiol implants to induce a LH surge (positive feedback) and (ii) ovariectomized ewes were treated chronically with an estradiol implant (negat...

  5. Cultivation of two thermotolerant microalgae under tropical conditions: Influences of carbon sources and light duration on biomass and lutein productivity in four seasons.

    Science.gov (United States)

    Chiu, Pai-Ho; Soong, Keryea; Chen, Ching-Nen Nathan

    2016-07-01

    Biomass and lutein productivities of two thermotolerant microalgae were assessed in tropical outdoor conditions in all four seasons. Generally, addition of bicarbonate at 0.2g/L every two days or 2% CO2 did not enhance the productivities compared to the controls, and the productivities in the spring were higher than in the fall. Durations of effective irradiance positively correlated to the productivity of Coelastrella sp. F50 well, but not for Desmodesmus sp. F2. The ineffective light intensity was below 5000 lux (about 106μmol/m(2)s). The productivities produced in the 17cm diameter bottles were 1.5- to 1.9-fold higher than that in the 27cm ones. Lutein content, about 0.5% in biomass on average, did not change significantly grown in different carbon sources or seasons. The annual productivities of the microalgal biomass and lutein in one hectare were estimated to be 33tons and 180kg, respectively, using the non-optimized photobioreactor cultivation. PMID:27099944

  6. Localization of luteinizing hormone-releasing hormone in the preoptic area and hypothalamus of the rat using radioimmunoassay

    International Nuclear Information System (INIS)

    To determine the localization of luteinizing hormone-releasing hormone (LHRH), five brains from adult male rats were serially sectioned in a cryostat at -100C in either the frontal, horizontal, or sagittal planes. Acetic acid-ethanol extracts of each section were assayed for LHRH using radioimmunoassay (RIA) and in some cases using bioassay as well. Approximately 0.2 ng LHRH was concentrated in medial basal preoptic (MB-PO) tissue overlying the rostral portion of the optic chiasm. This LHRH appears to be associated with the organum vasculosum of the lamina terminalis and/or adjacent neural tissue. Uniform, low levels of LHRH were detected in hypothalamic tissue between the preoptic area (POA) and arcuate-median eminence (ARC-ME) region. In the ARC-ME region, 2.7 ng of LHRH were concentrated primarily in the median eminence. The lateral distribution of LHRH in the ARC-ME region extended beyond the median eminence into tissue corresponding to the lateral aspect of the ventromedial nucleus. Concomitant bioassay and RIA determinations of LHRH were highly correlated. Of the sections bioassayed, only those sections containing LHRH released FSH. These results confirm the presence of LHRH in the POA and in the rostral hypothalamus of the rat brain. The possible significance of LHRH in the POA for the regulation of LH release is discussed. (U.S.)

  7. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    International Nuclear Information System (INIS)

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an αβ heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the αβ heterodimer, the ββ homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the αβ heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ββ homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops

  8. Evaluation of testicular function in prepubertal boys by means of the luteinizing hormone-releasing hormone test.

    Science.gov (United States)

    Dickerman, Z; Landman, J; Prager-Lewin, R; Laron, Z

    1978-06-01

    Luteinizing hormone (LH)-releasing hormone (LH-RH) tests (50 microgram/sq m intravenously) were performed in 112 prepubertal boys ages 13/12 to 11 years (mean +/- standard deviation, 75/12 +/- 16/12 years) suspected of having a testicular disorder because of improperly located testes (77 boys) or hypogonadism (35 boys). Four of the patients were retested within a period ranging from 6 to 16 months. Of the 112 boys tested, 17% were found to have high basal levels of follicle-stimulating hormone (FSH) and 23% were found to have an abnormally high release of FSH after LH-RH administration. Only three patients had abnormally high basal levels of LH and/or elevated LH responses to LH-RH. The basal plasma testosterone levels were found to be normal in all 112 bosy. The fact that plasma FSH levels were elevated more often than LH levels suggests that the tubular elements are damaged more frequently than are the Leydig cells. The surprisingly high incidence of an abnormal response of plasma FSH to LH-RH in boys with mobile testes calls for an increased awareness of the importance of regular examination of these patients until full puberty has been achieved. It is concluded that determination of basal plasma FSH levels and the response to LH-RH stimulation is a useful diagnostic tool for evaluating testicular function in prepubertal boys with suspected pathology of the testes. PMID:26609

  9. Disposition of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in rats and rhesus monkeys

    International Nuclear Information System (INIS)

    Nafarelin acetate, [6-(3-(2-naphthyl)-D-Ala)]-luteinizing hormone-releasing hormone (LHRH), is a synthetic LHRH agonist. In the suppression of estrus in female rats, nafarelin acetate was about 200 times as potent as LHRH. The authors have studied the distribution and excretion of radiolabeled nafarelin acetate administered iv to rats and rhesus monkeys and have also compared the pharmacokinetics of nafarelin acetate to LHRH in these two species. Distribution of a single 100-micrograms dose [14C]nafarelin acetate into tissues in male rats was rapid and of the 13 tissues assayed, highest concentrations of radioactivity were observed in the kidneys, liver, and intestines. The urine to feces ratio of nafarelin-associated 14C was 4:1 in rhesus monkeys and 1:3 in rats. Nafarelin acetate and LHRH given iv to female rhesus monkeys in approximately equimolar doses had terminal plasma t1/2 values of 120 min and 33 min, and systemic clearance values of 2.7 ml/min/kg and 31.4 ml/min/kg, respectively. In female rats, the plasma t1/2 was 33.6 min for nafarelin acetate and 6.7 min for LHRH, and the systemic clearance values for nafarelin acetate and LHRH were 12.0 ml/min/kg and 57.6 ml/min/kg, respectively, after approximately equimolar doses

  10. Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Luciana Tock

    2014-01-01

    Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

  11. A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

    Science.gov (United States)

    Martinez, A R; Bernadus, R E; Voorhorst, F J; Vermeiden, J P; Schoemaker, J

    1991-10-01

    Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur. PMID:1752926

  12. Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat.

    Science.gov (United States)

    Zhang, F P; Rannikko, A; Huhtaniemi, I

    1995-05-25

    To study further the unexpected expression of the luteinizing hormone (LH) beta-subunit in the rat testis, we identified in a rat testicular cDNA library three LH beta clones with lengths of 3.2, 2.4 and 0.86 kb (TLH beta 1, TLH beta 2 and TLH beta 3). The clones were identified using a 32P-labeled cDNA probe complimentary to the known rat pituitary LH beta mRNA. Clone TLH beta 2 corresponds in size to the main LH beta mRNA species (2.7 kb) detected by Northern hybridization in the rat testis. Sequence analysis indicated that the different sizes of the three clones are due to alternative RNA splicing and differences at the 5' ends of transcripts. The sequence of one open reading frame deduced from TLH beta 1 is almost identical with the pituitary LH beta peptide, differing only in three amino acids in the putative signal peptide. It might encode a functional testis-specific LH beta peptide. Shorter transcripts from clones TLH beta 2 and TLH beta 3 may correspond to short testicular LH beta peptides. The present findings provide further evidence in the rat for expression of testis-specific mRNA variants of the LH beta gene. Their translation products may form a novel class of testicular para/autocrine factors. PMID:7763258

  13. Protective role of ginger on lead induced derangement in plasma testosterone and luteinizing hormone levels of male sprague dawley rats

    International Nuclear Information System (INIS)

    Background: Lead is one of the most serious environmental threats to human health especially in developing countries. It damages multiple body systems including the reproductive system. Ginger's antioxidant and androgenic activity is reported in multiple animal studies. The aim of this study was to investigate the ameliorative effect of Zingiber officinale (ginger) on lead induced derangement in plasma testosterone and luteinizing hormone (LH) levels of male rats. Methods: Sixty adult male Sprague Dawley rats were used in this study in four groups. Group A served as normal control, Group B received 0.3% lead acetate in drinking water, Group C and group D received supplementary 0.5 and 1 gm/Kg bodyweight of ginger respectively along with lead acetate in drinking water. Five rats from each group were sacrificed at the end of 2nd, 4th and 6th weeks. Serum testosterone and LH levels were analysed using ELISA technique. Results: After co administration with different doses of ginger, serum testosterone level which was significantly decreased in lead treated group, showed a significant rise as compared to lead treated group. LH levels which had exhibited no significant change by lead treatment, after co administration with different doses of ginger, again showed no significant change. Conclusion: Oral administration of ginger ameliorated lead induced testicular toxicity in male rats by increasing serum testosterone level at all durations which might be a product of both its androgenic and antioxidant properties. (author)

  14. Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells.

    Science.gov (United States)

    Fang, Ying; Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K; Yang, Xiaokui

    2016-09-01

    Lysyl oxidase (LOX), a key enzyme in the formation and stabilization of the extracellular matrix, is expressed in granulosa cells and plays a critical role in the regulation of granulosa cell differentiation, oocyte maturation and ovulation. To date, the regulation of LOX expression in human granulosa cells remains largely unknown. In this study, using primary and immortalized human granulosa lutein cells, we demonstrated that transforming growth factor (TGF)-β1 (TGFB1) upregulated LOX expression and downregulated microRNA-29a (MIR29A) expression via a TGF-β type I receptor-mediated signaling pathway. Additionally, we showed that MIR29A downregulated the expression of LOX in both types of cells. Furthermore, the downregulation of MIR29A contributed to the TGFB1-induced increase in LOX expression because the inhibition of MIR29A with a MIR29A inhibitor not only reversed the MIR29A-induced downregulation of LOX but also enhanced the TGFB1-induced upregulation of LOX. Our findings suggest that TGFB1 and MIR29A may play essential roles in the regulation of extracellular matrix remodeling during the periovulatory phase. PMID:27335131

  15. Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls

    DEFF Research Database (Denmark)

    Chellakooty, M; Schmidt, I M; Haavisto, A M;

    2003-01-01

    The early postnatal regulation of reproductive hormones seems to be more complex in girls than in boys. The aim of this study was to describe inhibins A and B, FSH, LH, estradiol, and SHBG in a large prospective cohort of 473 unselected, healthy, 3-month-old girls. In full term, appropriate...

  16. Quantitative and qualitative changes in serum luteinizing hormone after injectable testosterone undecanoate treatment in hypogonadal men

    Institute of Scientific and Technical Information of China (English)

    Yi-QunGU; Zheng-YanGE; Gui-YuanZHANG; WilliamJ.Bremner

    2000-01-01

    Aim: To clarify the immuno-active LH (i-LH) and bioactive LH (b-LH) responses and qualitative changes in the circulating LH to testosterone undecanoate (TU) injection. Methods: Eight men with Klinefelter's syndrome were recruited for the study. They received crossover injections of TU at doses of 500 and 1000 mg. Serum i-LH and b-LH levels before and at various time intervals after TU injection were measured and the serum i-LH, b-LH, b-LH/i-LH (B/I) and testosterone/sex hormone-binding globulin (T/SHBG) ratio in LH-responders and LH non-responders were compared. Results: A parallel suppression of serum i-LH and b-LH was consistent with their overall high correlation between each other (r = 0.84, P < 0. 001). Mean serum i-FSH levels were decreased by TU injection at both doses without dose-response effects. LH-responders had lower baseline serum i-LH and b-LH, and higher E2 levels and T/SHBG ratio. There was a quantitative change in serum LH as induced by TU without qualitative change within LH-responders os LH-non-responders. Conclusion: A high loading dose (1000 mg) of TU is important for the initial suppression of LH. With the lower dose (500 mg), repeated injections will be required to attain such LH suppression for the purpose of fertility regulation. The lower baseline serum i-LH level may be an intrinsic characteristic of LH-responders. ( Asian J Androl 2000 ; 2 : 65 - 71 )

  17. Sushi Domain-Containing Protein 3: A Potential Target for Breast Cancer.

    Science.gov (United States)

    Yu, Zhenghong; Jiang, Enze; Wang, Xinxing; Shi, Yaqin; Shangguan, Anna Junjie; Zhang, Luo; Li, Jie

    2015-06-01

    Aromatase inhibitors (AIs) are the most effective endocrine treatment for estrogen receptor α-positive (ERα+) postmenopausal breast cancer. Identification of biomarkers that are able to predict AIs responsiveness of patients is a key for successful treatment. The currently used biomarkers for tamoxifen responsiveness, which including ERα as well as progesterone receptor can only predict part of the potential responders to AIs treatment. Sushi domain-containing protein 3 (SUSD3) is a potential novel biomarker of AIs responsiveness. The lack of SUSD3 expression in breast cancer tissue can be an important predictor for non-responsiveness to AI. Here we reviewed the property and function of SUSD3, its usage as a biomarker and the practicability for SUSD3 to become a target for immune therapy. We suggest this protein can be potentially measured or targeted for prevention, diagnostic, and therapeutic purposes for estrogen or progesterone-dependent disorders including breast cancer in women. PMID:25556073

  18. Expression of Nonfusion Extracellular Porcine Zona Pellucida Protein 3β in E. coli

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To obtain the recombinant nonfusion extracellular porcine zona pellucida protein 3β (pZP3β ) in E. coliMethods By modificated the transition initiation region (TIR) in primers, synthetic nucleotide was gained by PCR. Such gene was cloned into pET-3c vector and trans-formed into E. coli BL21(DE3)pLysS.Results The recombinant nonfusion extracellular pZP3β was expressed in E. coli to 10% of total cellular proteins, and identified by the Western blot method.Conclusion Modification of nucleotide without changing amino acid sequences is an effective means to increase non fusion expression rate of recombinant proteins, such as pZP3β in E. coli.

  19. β-Microseminoprotein binds CRISP-3 in human seminal plasma

    OpenAIRE

    Udby, Lene; Lundwall, Åke; Johnsen, Anders H.; Fernlund, Per; Valtonen-André, Camilla; Blom, Anna M.; Lilja, Hans; Borregaard, Niels; Kjeldsen, Lars; Bjartell, Anders

    2005-01-01

    β -Microseminoprotein (MSP) and cysteine-rich secretory protein 3 (CRISP-3) are abundant constituents of human seminal plasma. Immunoprecipitation and gel filtration of seminal plasma proteins combined with examination of the proteins in their pure form showed that MSP and CRISP-3 form stable, non-covalent complexes. CRISP-3 binds MSP with very high affinity, as evidenced by surface plasmon resonance. Due to far higher abundance of MSP in prostatic fluid, it manifests large overcapacity for C...

  20. First attempt to monitor luteinizing hormone and reproductive steroids in urine samples of the Amazonian manatee (Trichechus inunguis).

    Science.gov (United States)

    Amaral, Rodrigo S; Rosas, Fernando C W; Graham, Laura H; da Silva, Vera M F; Oliveira, Claudio A

    2014-12-01

    The aims of this study were to validate an enzyme immunoassay (EIA) for the measurement of luteinizing hormone (LH) in urine samples of Amazonian manatees (Trichechus inunguis; Mammalia: Sirenia) and to monitor urinary LH and reproductive steroids during the ovarian cycle in this species. Urine samples were collected from two captive males following a hormonal challenge with a gonadotropin-releasing hormone (GnRH) analogue. The urinary LH results from hormonal challenge were compared with urinary androgens for the purpose of EIA validation. Furthermore, urine samples were collected daily, over a 12-wk period, from two captive adult females, for 2 consecutive yr. The urinary LH pattern from females was compared with the patterns of urinary progestagens and estrogen conjugates throughout the ovarian cycle. An LH peak was observed in both male Amazonian manatees after the hormonal challenge, occurring prior to or together with peak androgen levels. In the females, the ovarian cycle ranged from 40 to 48 days (mean of 43.7 days). Two distinct peaks of estrogen conjugates were observed across all cycles analyzed, and the urinary LH peaks observed were accompanied by peaks of urinary estrogen conjugates. The EIA was validated as a method for the quantification of urinary LH from Amazonian manatees, as it was able to detect variations in the levels of LH in urine samples. These results suggest that T. inunguis exhibits a peculiar hormonal pattern during the ovarian cycle. Therefore, further studies are desirable and necessary to clarify the relationship between this hormonal pattern and morphological changes, as well as mating behavior, in Amazonian manatee. PMID:25632672

  1. Intracerebroventricular Infusion of Vasoactive Intestinal Peptide (VIP Rescues the Luteinizing Hormone Surge in Middle-Aged Female Rats

    Directory of Open Access Journals (Sweden)

    Yan eSun

    2012-02-01

    Full Text Available Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP originating from the SCN excites gonadotropin-releasing hormone (GnRH neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.

  2. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

    International Nuclear Information System (INIS)

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells

  3. Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

    Science.gov (United States)

    Smyth, Hugh D C; Becket, Gordon; Mehta, Samir

    2002-05-01

    A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in

  4. 木糖醇叶黄素固体饮料的研制%Preparation of Xylitol-Lutein Solid Beverage

    Institute of Scientific and Technical Information of China (English)

    王成福

    2014-01-01

    以木糖醇、叶黄素为主要原料,经粉碎混合、造粒、整粒、干燥包袋等工艺制成木糖醇叶黄素固体饮料,确定产品的最佳工艺配方为木糖醇的添加量为76%,叶黄素的添加量为10%,甜菊糖的添加量为1%,维生素C的添加量为10%,香精的添加量为0.5%,粘合剂麦芽糖醇浆的添加量为2.5%。其产品的外观呈松散颗粒状,大小均匀一致,溶化后溶液呈透明的黄色,即冲即饮,具有携带、运输方便的优点,具有非常好的市场发展前景。%Xylitol-lutein solid beverage was made through crushing,mixing,granulating,drying processes,and packaging with xylitol and lutein as the main raw materials. The optimum formula as follows: xylitol is 76%;lutein is 10%;stevioside is 1%;vitamin C is 10%;essence is 0.5%;and adhesive maltitol syrup is 2.5%;The product has the appearance of a loose granular and of uniform size.The aqueous solution is bright yellow. It is a kind of instant drink with the advantages of convenient carrying and transportation and it has the very good market prospects.

  5. 万寿菊中叶黄素的提取皂化工艺研究%Extraction and Saponification Technology of Lutein from Marigold

    Institute of Scientific and Technical Information of China (English)

    赵洁; 尹俊涛; 郭亚可; 李超鹏; 陈文

    2011-01-01

    In this paper, Extraction and Saponification technology of Lutein esters in Tagetes erecta L.particle were investigated systemically.The mixed solvent of THF and Alc is main extraction solvent.The affecting factors such as the ratio of THF and Alc, reaction time , the ratio of reaction solution to material(mL/g), the addition of water, the addition of KOH in reaction solution and reaction temperature were investigate in singe factor experiments.An orthogonal test table L9 (34 ) was used to optimized the affecting factors on the base of singe factor experiments.The content of free Lutein in the end product was determined by HPLC.The results showed that the optimal Extraction and Saponification parameter was: 1.6g KOH, 4h, the ratio of 1∶20 (mL/g) ,ratio of THF and Alc is 2∶8.Under this condition,the yield of Free Lutein reach 1.14% and the content of Free Lutein reach 10.32 % in extracta sicca.%该文以四氢呋喃和乙醇的二元混合溶剂为主要提取剂,对万寿菊颗粒中叶黄素的提取皂化工艺进行了研究.实验分别考察了加入四氢呋喃与乙醇的比例、反应时间、料液比、加水体积、加碱量、反应温度对叶黄素得率的影响.在单因素试验的基础上,选取影响较大的4个因素采用L9(34)正交试验考察对叶黄素得率的影响,以得率为指标,确定最佳工艺条件为A1 B2 C2 D3,即料液比为1∶20,加碱质量1.6 g,反应时间4 h,THF∶乙醇=2∶8.由此可知:此条件下叶黄素得率为1.14%,所得浸膏中叶黄素的含量达到10.32%.

  6. D-Tryptophan-6 analog of luteinizing hormone-releasing hormone as a protective agent against testicular damage caused by cyclophosphamide in baboons.

    OpenAIRE

    Lewis, R W; Dowling, K J; Schally, A V

    1985-01-01

    Possible protective effects of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) against testicular damage caused by cyclophosphamide (Cytoxan) were investigated in subhuman primates. Three adult male baboons (Papio anubis) were first subjected to normal semen evaluation by using electroejaculation. The average baseline count for the animals ranged from 95.7 X 10(6) to 585.7 X 10(6) sperm per ml with 90% normal forms and 85% motility with excellent...

  7. Anti-Oxidative, Anti-Tumor-Promoting, and Anti-Carcinogensis Activities of Nitroastaxanthin and Nitrolutein, the Reaction Products of Astaxanthin and Lutein with Peroxynitrite

    Directory of Open Access Journals (Sweden)

    Hideo Etoh

    2012-06-01

    Full Text Available Astaxanthin captured peroxynitrite to form nitroastaxanthins. 15-Nitroastaxanthin was a major reaction product of astaxanthin with peroxynitrite. Here, the anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of 15-nitroastaxanthin were investigated. In addition to astaxanthin, 15-nitroastaxanthin showed excellent singlet oxygen quenching activity. Furthermore, 15-nitroastaxanthin showed inhibitory effects of in vitro Epstein-Barr virus early antigen activation and two-stage carcinogensis on mouse skin papillomas. These activities were slightly higher than those of astaxanthin. Similar results were obtained for the 15-nitrolutein, a major reaction product of lutein with peroxynitrite.

  8. Effect of foliar calcium chloride treatment on the level of chlorogenic acid, β-carotene, lutein and tocopherols in lettuce (Lactuca sativa L.)

    OpenAIRE

    Irena Perucka; Katarzyna Olszówka

    2012-01-01

    The aim of the presented study was to determine the effect of foliar application of CaCl2 on the level of β-carotene, lutein, tocopherols and phenolic compounds in the leaves of lettuce cv. Omega (Lactuca sativa L.). The experiments were conducted in the greenhouse of the Faculty of Cultivation and Fertilisation of Horticultural Plants, University of Life Sciences in Lublin. During the growing period, 7 and 14 days before harvest, the plants were treated with a solution of CaCl2 with concentr...

  9. THE RELATIONSHIP BETWEEN LUTEINIZING HORMONE LEVELS AND RECURRENT MISCARRIAGE%促黄体生成素水平与复发性流产的关系

    Institute of Scientific and Technical Information of China (English)

    商微; 王蔼明; 舒明明; 汤晓蓉; 李敏; 闫玲

    2012-01-01

    目的 测定复发性流产患者黄体期促黄体生成素的水平,探讨促黄体生成素与复发性流产的关系.方法 选择有复发性流产史患者43例为试验组,选择有正常生育史组妇女30例为对照组.监测卵泡发育,于排卵后第3天和第5天测定血清中促黄体生成素水平并进行比较.结果 对照组排卵后第3天和第5天促黄体生成素水平均明显高于试验组,差异有统计学意义(P<0.05).结论 黄体早期低促黄体生成素水平与复发性流产直接相关,改善黄体早期低促黄体生成素水平可降低复发性流产的发生.%Objective To discuss the relationship between luteinizing hormone ( LH ) level and recurrent miscarriage by measuring the luteinizing hormone levels of patients with recurrent miscarriage in luteal phase. Methods : Forty - three patients with recurrent miscarriage were selected as experimental group and thirty patients without recurrent miscarriage history and with secondary infertility of pure oviduct factors at the same time as control group. Results The LH concentrations of control group on the third day and the fifth day after ovulation were higher than those of the experimental group, which had statistical significance ( P <0. 05 ). Conclusion In early luteal phase,low luteinizing hormone level has close relationship with recurrent miscarriage. Timely increasing luteinizing hormone level in early luteal phase may decrease the occurrence of recurrent miscarriage.

  10. Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis

  11. Study on technologies of extracting and saponifying lutein ester from marigold%万寿菊花中叶黄素酯的提取及皂化工艺

    Institute of Scientific and Technical Information of China (English)

    刘洪海; 杜平; 梁红兵; 张希波; 张晓丽

    2009-01-01

    Lutein can be used to improve human immune system and prevent cataract and senile maculutea degeneration.It can be obtained by saponification of lutein ester,which is the major extracts from Marigold.Lutein is widely used in food,food additive,drugs and feed industries.In this paper,extraction of lutein ester from marigold is conducted with n-hexane as extractant.The best condition for saponifying lutein ester was chosen by the orthogonal experiments of L9 (34).It is found that using 20% KOH methanol as the extracting solution,with saponification reaction time of 40 minutes,at a temperature of 50℃,Lutein ester can be thoroughly sponified.Lutein can then be recrystallized in the solvent of acetone and methanol(v : v 1 : 1).The purity of lutein crystal is 97.2%.%叶黄素具有调节人体的免疫能力、防治老年性视黄斑退化和白内障等作用,目前天然叶黄素的提取原料主要为万寿菊花,万寿菊花的有机溶剂提取物含有大量叶黄素酯,经皂化后可转变为叶黄素,广泛用于食品、食品添加剂、药品及饲料等工业.本文采用甲醇处理万寿菊鲜花后直接用正己烷提取叶黄素酯,并通过L9 (34)正交实验选择了叶黄素酯皂化的最佳条件,即KOH/甲醇浓度为20%,提取液﹕KOH为4 : 1,时间为40min,温度为50℃时,叶黄素酯皂化进行的比较完全.皂化得到的叶黄素在丙酮﹕甲醇(v : v)为1 : 1的混合溶剂中进行重结晶,得到叶黄素晶体,纯度为97.2%.

  12. Influence of leptin on luteinizing hormone and follicle stimulating hormone secreted from cultured rat anterior pituitary cells

    Institute of Scientific and Technical Information of China (English)

    Yuebing Qiao; Xiuyan Ma; Huixian Cui

    2008-01-01

    BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect of different dosages of leptin on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from in vitro cultured rat anterior pituitary cells. DESIGN: Contrast study based on cells. SETTING: This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS: Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS: Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10-12, 1×10-11, 1×10-9, 1×10-7, and 1×10-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES: Contents of LH and FSH were detected by radioimmunology. RESULTS: Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations (P<0.01). LH release in the leptin (1×10-12, 1×10-11, 1×10-7, and 1×10-6 mol/L) groups was significantly higher than that in the control group (P<0.01). FSH content in the leptin (1×10-11, 1×10-9, and 1×10-7 mol/L) groups was significantly higher than that in the control group (P<0.01). CONCLUSION: Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a dose-dependent manner.

  13. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R; Orskov, Hans; Andersen, Ulrik B; Madsbad, Sten; Iversen, Johan; Flyvbjerg, Allan

    2004-01-01

    parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin...... concentration were increased (>90%, P < .01) and insulin sensitivity (Log10ISI(composite)) was decreased (-50%, P < .001). Total and free IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease were similar between groups (all P > .5), whereas, in LIPO, IGFBP-1 and IGFBP-2 were reduced (-36%, P < .05 and -50%, P < .01...... groups (r(p) = 0.47, P < .02), and in LIPO (r(p) = 0.71, P < .007) controlling for age, total IGF-I, and IGFBP-3. GHBP was increased, whereas GH was decreased in LIPO (all P < .05). GH correlated inversely with GHBP in pooled groups (P < .05). Taken together the similar IGFs and IGFBP-3 concentrations...

  14. Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

    International Nuclear Information System (INIS)

    The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

  15. Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches.

    Science.gov (United States)

    Jurczak, A; Domosławska, A; Bukowska, B; Janowski, T

    2016-08-01

    In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty-three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p similar in all groups. In accordance with the above-mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies. PMID:27321641

  16. Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey.

    Science.gov (United States)

    Mares-Perlman, J A; Fisher, A I; Klein, R; Palta, M; Block, G; Millen, A E; Wright, J D

    2001-03-01

    Relations of the carotenoids lutein and zeaxanthin in the diet and serum to photographic evidence of early and late age-related maculopathy (ARM) among persons over age 40 years (n = 8,222) were examined. Inverse relations of these carotenoids in the diet or serum to any form of ARM were not observed overall. There was a direct relation of dietary levels to one type of early ARM (soft drusen). However, relations differed by age and race. In the youngest age groups who were at risk for developing early (ages 40-59 years) or late (ages 60-79 years) ARM, higher levels of lutein and zeaxanthin in the diet were related to lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1, 0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9) after adjustment for age, gender, alcohol use, hypertension, smoking, and body mass index. Relations of these carotenoids to ARM may be influenced by age and race and require further evaluation in separate populations and in prospective studies. PMID:11226974

  17. Expression of 17beta- and 3beta-hydroxysteroid dehydrogenases and steroidogenic acute regulatory protein in non-luteinizing bovine granulosa cells in vitro.

    Science.gov (United States)

    Sahmi, M; Nicola, E S; Silva, J M; Price, C A

    2004-08-31

    Granulosa cells of small follicles differentiate in vitro in serum-free medium, resulting in increased estradiol secretion and abundance of mRNA encoding cytochrome P450aromatase (P450arom). We tested the hypothesis that differentiation in vitro also involves increased expression of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSD) in the absence of steroidogenic acute regulatory protein (StAR) expression, as has been observed in vivo. Granulosa cells from small (basal layer of the membrana granulosa) did not affect steroidogenesis. We conclude that under the present cell culture system granulosa cells do not luteinize, and show expression of key steroidogenic enzymes in patterns similar to those occurring in differentiating follicles in vivo. Further, the data suggest that 17beta-HSD may be as important as P450arom in regulating estradiol secretion, and that 3beta-HSD is more important than P450scc as a regulator of progesterone secretion in non-luteinizing granulosa cells. PMID:15279910

  18. Nucleoside triphosphatase and RNA helicase activities associated with GB virus B nonstructural protein 3.

    Science.gov (United States)

    Zhong, W; Ingravallo, P; Wright-Minogue, J; Skelton, A; Uss, A S; Chase, R; Yao, N; Lau, J Y; Hong, Z

    1999-09-01

    GB virus B (GBV-B) is a positive-stranded RNA virus that belongs to the Flaviviridae family. This virus is closely related to hepatitis C virus (HCV) and causes acute hepatitis in tamarins (Saguinus species). Nonstructural protein 3 (NS3) of GBV-B contains sequence motifs predictive of three enzymatic activities: serine protease, nucleoside triphosphatase (NTPase), and RNA helicase. The N-terminal serine protease has been characterized and shown to share similar substrate specificity with the HCV NS3 protease. In this report, a full-length GBV-B NS3 protein was expressed in Escherichia coli and purified to homogeneity. This recombinant protein was shown to possess polynucleotide-stimulated NTPase and double-stranded RNA (dsRNA) unwinding activities. Both activities were abolished by a single amino acid substitution, from the Lys (K) residue in the conserved walker motif A (or Ia) "AXXXXGK(210)S" to an Ala (A), confirming that they are intrinsic to GBV-B NS3. Kinetic parameters (K(m) and k(cat)) for hydrolysis of various NTPs or dNTPs were obtained. The dsRNA unwinding activity depends on the presence of divalent metal ions and ATP and requires an RNA duplex substrate with 3' unpaired regions (RNAs with 5' unpaired regions only or with blunt ends are not suitable substrates for this enzyme). This indicates that GBV-B NS3 RNA helicase unwinds dsRNA in the 3' to 5' direction. Direct interaction of the GBV-B NS3 protein with a single-stranded RNA was established using a gel-based RNA bandshift assay. Finally, a homology model of GBV-B NS3 RNA helicase domain based on the 3-dimensional structure of the HCV NS3 helicase that shows a great similarity in overall structure and surface charge distribution between the two proteins was proposed. PMID:10497107

  19. Uncoupling protein 3 expression and intramyocellular lipid accumulation by NMR following local burn trauma.

    Science.gov (United States)

    Zhang, Qunhao; Cao, Haihui; Astrakas, Loukas G; Mintzopoulos, Dionyssios; Mindrinos, Michael N; Schulz, John; Tompkins, Ronald G; Rahme, Laurence G; Tzika, A Aria

    2006-12-01

    Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e.g., starvation, fasting, cancer, sepsis). The aim of this study was to explore the effects of burn trauma on UCP3 expression, intramyocellular lipids, and plasma-free fatty acids. Mice were studied at 6 h, 1 d and 3 d after nonlethal hindlimb burn trauma. Intramyocellular lipids in hindlimb skeletal muscle samples collected from burned and normal mice were measured using 1H NMR spectroscopy on a Bruker 14.1 Tesla spectrometer at 4 degrees C. UCP3 mRNA and protein levels were also measured in these samples. Plasma-free fatty acids were measured in burned and normal mice. Local burn trauma was found to result in: 1) upregulation of UCP3 mRNA and protein expression in hindlimb myoskeletal mitochondria by 6 h postburn; 2) increased intramyocellular lipids; and 3) increased plasma-free fatty acids. Our findings show that the increase in UCP3 after burn trauma may be linked to burn-induced alterations in lipid metabolism. Such a link could reveal novel insights into how processes related to energy metabolism are controlled in burn and suggest that induction of UCP3 by burn in skeletal muscle is protective by either activating cellular redox signaling and/or mitochondrial uncoupling. PMID:17089030

  20. Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis.

    Science.gov (United States)

    Mahdi, Zainab M; Synal-Hermanns, Uta; Yoker, Aylin; Locher, Kaspar P; Stieger, Bruno

    2016-07-01

    Drug-induced liver injury is an important clinical entity resulting in a considerable number of hospitalizations. While drug-induced cholestasis due to the inhibition of the bile salt export pump (BSEP) is well investigated, only limited information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its role in the pathogenesis of drug-induced cholestasis is poorly understood. Therefore, we aimed to study the interaction of drugs with MDR3 and the effect of drugs on canalicular lipid secretion in a newly established polarized cell line system that serves as a model of canalicular lipid secretion. LLC-PK1 cells were stably transfected with human Na(+)-taurocholate cotransporting polypeptide, BSEP, MDR3, and ABCG5/G8 and grown in the Transwell system. Apical phospholipid secretion and taurocholate transport were assayed to investigate the effect of selected drugs on MDR3-mediated phospholipid secretion as well as inhibition of BSEP. The established cell line displayed vectorial bile salt transport and specific phosphatidylcholine secretion into the apical compartment. The antifungal azoles, posaconazole, itraconazole, and ketoconazole, significantly inhibited MDR3-mediated phosphatidylcholine secretion. In contrast, amoxicillin clavulanate and troglitazone did not interfere with MDR3 activity. Drugs interfering with MDR3 activity did not display a parallel inhibition of BSEP. Our in vitro model for MDR3-mediated phospholipid secretion facilitates parallel screening for MDR3 and BSEP inhibitors. Our data demonstrate that the cholestatic potential of certain drugs may be aggravated by simultaneous inhibition of BSEP and MDR3. PMID:27112167

  1. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle

    Science.gov (United States)

    The role of non-structural protein 3A in foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10–20 amino acid deletion has been implicated as being responsible for virus attenuation in cattle: a 10 amino acid deletion in t...

  2. LH (Luteinizing Hormone) Test

    Science.gov (United States)

    ... reason for the delayed puberty. Some of the causes for delayed puberty can include: Failure of the ovaries or testicles Hormone deficiency Turner syndrome Klinefelter syndrome Chronic infections Cancer Eating disorder (anorexia nervosa) ^ Back to top Is there anything ...

  3. The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function.

    Science.gov (United States)

    Hulkko, S M; Wakui, H; Zilliacus, J

    2000-08-01

    The yeast two-hybrid system was used to isolate cDNAs encoding proteins that interact with the glucocorticoid receptor (GR) ligand-binding domain in a ligand-dependent manner. One isolated cDNA encoded a fragment of death-associated protein 3 (DAP3), which has been implicated as a positive mediator of apoptosis. In vitro experiments showed that the full-length DAP3 also interacted with GR. The main interaction domain was mapped to the N-terminal region of DAP3 that had previously been shown to function in a dominant-negative fashion, protecting cells from apoptosis. Co-transfection experiments in COS-7 cells showed that DAP3 had a stimulatory effect on the ligand-induced transcriptional activation by GR and also increased the steroid-sensitivity. Furthermore, DAP3 formed a complex with several other nuclear receptors and some basic helix-loop-helix/Per-Arnt-Sim proteins, as well as with heat-shock protein 90 (hsp90) (Arnt is the aryl-hydrocarbon-receptor nuclear translocator, and Per and Sim are the Drosophila proteins Period and Single-minded). The results suggest that DAP3 could have an important role in GR action, possibly by modulating the cytoplasmic GR-hsp90 complex. Since glucocorticoids can induce apoptosis, the pro-apoptotic DAP3 protein may be involved in this function of GR. PMID:10903152

  4. Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

    Science.gov (United States)

    PEĆINA-ŠLAUS, NIVES; KAFKA, ANJA; VAROŠANEC, ANA MARIA; MARKOVIĆ, LEON; KRSNIK, ŽELJKA; NJIRIĆ, NIKO; MRAK, GORAN

    2016-01-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an

  5. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma.

    Science.gov (United States)

    Pećina-Šlaus, Nives; Kafka, Anja; Varošanec, Ana Maria; Marković, Leon; Krsnik, Željka; Njirić, Niko; Mrak, Goran

    2016-05-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the

  6. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  7. Cloning and expression of full-length human insulin-like growth factor binding protein 3 (IGFBP3 in the Escherichia coli

    Directory of Open Access Journals (Sweden)

    Emad Khodadadi

    2015-01-01

    Conclusion: DNA fragment encoding the full-length IGFBP3 protein was accurately cloned in the pET-11a expression vector and the recombinant plasmid transformed to E. coli BL21 (DE3 expression host. Results of the SDS-PAGE analysis verified that recombinant IGFBP3 (31.6 kDa are successfully expressed under the control of T7 promoter. As we shown pET-11a can be successfully used for expression of the IGFBP3 protein.

  8. The Monofunctional Glycosyltransferase of Escherichia coli Localizes to the Cell Division Site and Interacts with Penicillin-Binding Protein 3, FtsW, and FtsN▿ ‡

    OpenAIRE

    Derouaux, Adeline; Wolf, Benoît; Fraipont, Claudine; Breukink, Eefjan; Nguyen-Distèche, Martine; Terrak, Mohammed

    2007-01-01

    The monofunctional peptidoglycan glycosyltransferase (MtgA) catalyzes glycan chain elongation of the bacterial cell wall. Here we show that MtgA localizes at the division site of Escherichia coli cells that are deficient in PBP1b and produce a thermosensitive PBP1a and is able to interact with three constituents of the divisome, PBP3, FtsW, and FtsN, suggesting that MtgA may play a role in peptidoglycan assembly during the cell cycle in collaboration with other proteins.

  9. c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min-Sun; Kim, Sun-Young; Arunachalam, Sankarganesh [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Hwang, Pyoung-Han [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Yi, Ho-Keun [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Nam, Sang-Yun [Department of Alternative Therapy, School of Alternative Medicine and Health Science, Jeonju University, Jeonju 561-712 (Korea, Republic of); Lee, Dae-Yeol, E-mail: leedy@chonbuk.ac.kr [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of)

    2009-07-17

    c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

  10. Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic markers of growth hormone deficiency in infancy

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Jeppesen, Katrine Arp; Vielwerth, Signe;

    2005-01-01

    The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life.......The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life....

  11. c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

    International Nuclear Information System (INIS)

    c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

  12. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    NARCIS (Netherlands)

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  13. Low levels of the 150-kD insulin-like growth factor binding protein 3 ternary complex in patients with anorexia nervosa: effect of partial weight recovery

    DEFF Research Database (Denmark)

    Støving, René K; Hangaard, Jørgen; Hagen, Claus;

    2003-01-01

    on the ternary complex formation. Despite GH hypersecretion, serum IGF-I, IGFBP-3, and ALS levels have all been reported to be low in patients with anorexia nervosa (AN), while the degree of ternary complex formation in AN is unknown. METHODS: Serum ALS and 150-kD ternary complex formation were measured in 6...

  14. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents

    DEFF Research Database (Denmark)

    Juul, A; Dalgaard, P; Blum, W F;

    1995-01-01

    -I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass...... index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs...... in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3...

  15. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative

    Science.gov (United States)

    The purpose of this study was to examine the relationship between lutein and zeaxanthin in the diet and serum and prevalence of age-related nuclear cataract in older women. Women’s Health Initiative Observational Study participants aged 50 y+, at 3 sites, who reported high (above the 78th percentile...

  16. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  17. Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age

    NARCIS (Netherlands)

    D.C.M. van der Kaay (Danielle); F.H. de Jong (Frank); S.R. Rose (Susan); R.J.H. Odink (Roelof); W.M. Bakker-Van Waarde (Willie); E.J. Sulkers (Eric); A.C.S. Hokken-Koelega (Anita)

    2009-01-01

    textabstractAims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare gro

  18. Plant Hormone Binding Sites

    OpenAIRE

    Napier, Richard

    2004-01-01

    • Aims Receptors for plant hormones are becoming identified with increasing rapidity, although a frustrating number remain unknown. There have also been many more hormone‐binding proteins described than receptors. This Botanical Briefing summarizes what has been discovered about hormone binding sites, their discovery and descriptions, and will not dwell on receptor functions or activities except where these are relevant to understand binding.

  19. Expression of inhibin α, matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 in luteinized granulosa cells: comparison between women with and without endometriosis

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-rong; Liu Li-peng; Pu Dan-hua; Cui Yu-gui; Jiang Shi-Wen; Liu Jia-yin; Wu Jie

    2012-01-01

    Objective: To assess the differences in expression of inhibin α,MMP-2 and TIMP-1 in luteinized granulosa cells from women with and without endometriosis undergoing in vitro fertilization (IVF),and determine whether inhibin α,MMP-2 and TIMP-1 expressions correlate with the follicle development in patients with endometriosis.Methods: Thirty six infertile patients with stage Ⅲ and Ⅳ endometriosis patients (group A) and 35 tubal infertile and/or male factor patients (group B) attending to the clinic of Jiangsu Provincial Hospital Human Reproductive Center during May 2011 and December 2011 were included in this prospective study.The patients with the number of mature oocyte ≤ 4 were considered as poor responders.According to this,the two groups were further divided into four subgroups: A1 group (23 endometriosis patients with normal response),A2 group (13 endometriosis patients with poor response),B1 group (23 controls with normal response) and B2 group (12 controls with poor response).Fasting blood samples were collected on the first day of ovarian stimulation and on the day of hCG administration,and follicle fluid were collected on the day of oocytes retrieved.The concentrations of follicle stimulating hormone (FSH),Luteinizing hormone (LH) and estradiol (E2) were measured by ECILA.Granulosa was collected from follicle fluid by Percoll method,and Stepone real-time polymerase chain reaction (PCR) was used to analysis the expression level of inhibin α,MMP-2 and TIMP-1.Results: The expression of inhibin α in endometriosis group and poor responders in control group were significantly lower than those of the normal responders in control group,in which the alternation of inhibin α expression was not correlated to the variables of follicle development.Moreover,MMP-2 levels were lower and TIMP-1 levels were higher in both endometriosis and tubal/male infertility poor responders compared to normal ovarian responders.Interestingly,the correlation between MMP-2 or

  20. Nuclear actin filaments recruit cofilin and actin-related protein 3, and their formation is connected with a mitotic block

    Czech Academy of Sciences Publication Activity Database

    Kalendová, Alžběta; Kalasová, Ilona; Yamazaki, S.; Uličná, Lívia; Harata, M.; Hozák, Pavel

    2014-01-01

    Roč. 142, č. 2 (2014), s. 139-152. ISSN 0948-6143 R&D Projects: GA ČR GAP305/11/2232; GA MŠk LD12063; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : nuclear actin * transcription * mitosis * actin-related protein 3 * cofilin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.927, year: 2013

  1. Radioimmunological determination of the level of luteinizing hormone in the serum in the case of various gonadal disturbances and other endocrine diseases

    International Nuclear Information System (INIS)

    The purpose of this work was to determine radioimmunologically the level of luteinizing hormone (LH) in the serum in the case of various gonadal disturbances and other endocrine diseases with the aid of the double antibody method, and to compare the results within different diagnosis groups to each other and to compare these results with those found in the published literature. It was tested whether and with which accuracy the radioimmunological determination of LH in the serum can contribute to the diagnosis of pituitary gonad diseases and whether in the case of endocrine diseases the accompanying disturbances of the gonadotropin secretion which primarily do not affect the hypothalamo - hypophyso - gonadal circuit are demonstrable. The study results for the diagnosis groups primary and secondary hypogonadism of various genesis, gynacomastia, impotentia coeundi, primary and secondary ovarial insufficiency, hirsutism and adiposity were presented and discussed. (orig.)

  2. In utero and lactational exposure to PCB 118 and PCB 153 alter ovarian follicular dynamics and GnRH-induced luteinizing hormone secretion in female lambs

    DEFF Research Database (Denmark)

    Kraugerud, Marianne; Aleksandersen, Mona; Nyengaard, Jens Randel;

    2012-01-01

    The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes received corn oil, PCB 118, or PCB 153, and offspring was maintained until...... dynamics in lambs and modulate the responsiveness of the pituitary gland to GnRH.The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes...... 60 days postpartum. Ovarian follicles were quantified using stereology. Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured using radioimmunoassay before and after administration of a gonadotropin releasing hormone (GnRH) analog. PCB 118 exposure increased numbers of...

  3. Reactive oxygen species and transcript analysis upon excess light treatment in wild-type Arabidopsis thaliana vs a photosensitive mutant lacking zeaxanthin and lutein

    Directory of Open Access Journals (Sweden)

    Roncaglia Enrica

    2011-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are unavoidable by-products of oxygenic photosynthesis, causing progressive oxidative damage and ultimately cell death. Despite their destructive activity they are also signalling molecules, priming the acclimatory response to stress stimuli. Results To investigate this role further, we exposed wild type Arabidopsis thaliana plants and the double mutant npq1lut2 to excess light. The mutant does not produce the xanthophylls lutein and zeaxanthin, whose key roles include ROS scavenging and prevention of ROS synthesis. Biochemical analysis revealed that singlet oxygen (1O2 accumulated to higher levels in the mutant while other ROS were unaffected, allowing to define the transcriptomic signature of the acclimatory response mediated by 1O2 which is enhanced by the lack of these xanthophylls species. The group of genes differentially regulated in npq1lut2 is enriched in sequences encoding chloroplast proteins involved in cell protection against the damaging effect of ROS. Among the early fine-tuned components, are proteins involved in tetrapyrrole biosynthesis, chlorophyll catabolism, protein import, folding and turnover, synthesis and membrane insertion of photosynthetic subunits. Up to now, the flu mutant was the only biological system adopted to define the regulation of gene expression by 1O2. In this work, we propose the use of mutants accumulating 1O2 by mechanisms different from those activated in flu to better identify ROS signalling. Conclusions We propose that the lack of zeaxanthin and lutein leads to 1O2 accumulation and this represents a signalling pathway in the early stages of stress acclimation, beside the response to ADP/ATP ratio and to the redox state of both plastoquinone pool. Chloroplasts respond to 1O2 accumulation by undergoing a significant change in composition and function towards a fast acclimatory response. The physiological implications of this signalling specificity are

  4. Assessment of lutein and zeaxanthin status and dietary markers as predictors of the contrast threshold in 2 age groups of men and women.

    Science.gov (United States)

    Estévez-Santiago, Rocío; Olmedilla-Alonso, Begoña; Beltrán-de-Miguel, Beatriz

    2016-07-01

    Lutein and zeaxanthin (L + Z) status is associated with the macular pigment (MP). The relationship between MP and visual function is controversial. We hypothesized that, within the framework of nutrition, visual function was related to MP and nutritional and/or/dietary factors influencing it. A cross-sectional study was performed in 108 volunteers divided into 2 age groups (20-35 years; 45-65 years), each 27 women and 27 men, to assess the relationship between MP optical density (MPOD) and contrast threshold (CT), considering the influence of L + Z and, fruit and vegetable (F + V) intake. MPOD, L + Z in serum and dietary intake were determined using heterochromatic flicker photometry, high-performance liquid chromatography and 3-day food records, respectively. CT was measured with the CGT-1000 Contrast Glaretester at 6 stimulus sizes, with and without glare. Spearman correlation coefficient and a generalized linear model were used for the statistical study. MPOD and CT were higher and lower, respectively in younger than in elder individuals (P V intake (correlation coefficients and P values ranging from -.265 to -.176 and from .000 to .010, respectively). As predictors of CT in the total sample, MPOD, F + V (every 100 g/d) and sex were identified (β coefficients ranged from -0.01 to -1.86; from 0.01 to 0.08 and from 0.01 to 0.40, respectively). CT revealed age-specific nutritional predictors: MPOD and serum lutein in the 45- to 65-year group, and F + V intake in the 20- to 35-year group. PMID:27262538

  5. Sexual maturation, serum steroid concentrations, and mRNA expression of IGF-1, luteinizing and progesterone hormone receptors and survivin gene in Japanese quail hens.

    Science.gov (United States)

    Shit, N; Sastry, K V H; Singh, R P; Pandey, N K; Mohan, J

    2014-03-15

    In avian species, sexual maturation represents the evidence of start laying, which is a consequence of the development of ovarian follicles. These follicles are the functional reproductive unit whose maturation and viability critically depends on endocrine, paracrine, and autocrine factors beyond the signals from the central nervous system. The present study was undertaken to investigate the correlation of sexual maturity with tissue growth, mRNA expression of certain genes, and serum steroid concentrations in Japanese quail hens. To carry out the present study, a total of forty Japanese quail hens (5 weeks) were housed individually under uniform husbandry condition with ad libitum quail layer ration and water at 14-hour photo schedule. On sixth week onwards, four birds were sacrificed at each time on 1, 3, 7, 10, 13, 16, 19, 22, 25, and 28 days. Serum was extracted aseptically to analyze the gonadal steroid hormones (estrogen and progesterone) and corticosterone to investigate the liaison with sexual maturation of the species. Expression analyses of four genes i.e., insulin-like growth factor-1, luteinizing hormone receptor, progesterone receptor, and survivin were carried out in the three largest ovarian yellow follicles. A significant (P < 0.05) increase in body weight gain and oviduct weight was recorded during the phase of sexual maturation. Smaller follicles revealed higher insulin-like growth factor-1 and survivin gene expression, whereas the reverse result was manifested in both the luteinizing and progesterone hormone receptors. In biochemical study, the gonadal steroids (estrogen and progesterone) were recorded higher at the first half of the experiment when a gradual decrease in corticosterone concentration was confirmed from the very beginning of this study. This result substantiated that sexual maturation in Japanese quail may be completed by the time of 8 weeks after its birth in support of the analyzed information studied in the current investigation

  6. Expression Levels of the Oxidative Stress Response Gene ALDH3A2 in Granulosa-Lutein Cells Are Related to Female Age and Infertility Diagnosis.

    Science.gov (United States)

    González-Fernández, Rebeca; Hernández, Jairo; Martín-Vasallo, Pablo; Puopolo, Maria; Palumbo, Angela; Ávila, Julio

    2016-05-01

    Oxidative stress (OS) plays an important role in all physiological processes. The effect of OS on cellular processes is modulated by the ability of the cell to express genes implicated in the reversal of lipid, protein, and DNA injury. Aldehyde dehydrogenase 3, member A2 (ALDH3A2) is a ubiquitous enzyme involved in lipid detoxification. The objective of this study was to investigate the expression ofALDH3A2in human granulosa-lutein (GL) cells of women undergoing in vitro fertilization (IVF) and its relationship with age, infertility diagnosis, and IVF outcome variables. Relative expression levels ofALDH3A2were determined by quantitative reverse transcription-polymerase chain reaction. To investigate the effect of age onALDH3A2expression, 72 women between 18 and 44 years of age with no ovarian factor (NOF) were analyzed. To evaluate the effect of infertility diagnosis onALDH3A2expression, the following groups were analyzed: 22 oocyte donors (ODs), 24 women >40 years old (yo) with tubal or male factor and no ovarian pathology, 18 poor responders (PRs), 19 cases with endometriosis (EM), and 18 patients with polycystic ovarian syndrome (PCOS). In NOF,ALDH3A2expression correlated positively with age and with the doses of follicle-stimulating hormone and luteinizing hormone administered and negatively with the number of total and mature oocytes. When different groups were analyzed,ALDH3A2expression levels were higher in patients >40 yo and in PR compared to OD. On the contrary, EM and PCOS levels were lower than expected for age. These data suggest that GL cellALDH3A2expression levels correlate with age, cause of infertility, and ovarian response to stimulation. PMID:26449735

  7. 高效液相色谱法测定保健食品中的叶黄素%The determination of lutein in health food by HPLC

    Institute of Scientific and Technical Information of China (English)

    党亚敏; 李建平; 张明月; 渠志华; 夏义平; 马永民

    2011-01-01

    目的:建立测定保健食品中叶黄素含量的方法.方法:采用无水乙醇对试样进行提取,纯甲醇体系作为流动相,ODS C18柱,高效液相色谱(HPLC)进行分离检测.结果:方法的检出限为0.1 μg/g,线性范围在0.3 μg/ml~6.2 μg/ml之间,RSD为5.9%,平均回收率为92%~105%.结论:该方法具有简便、快速、可靠、容易推广等优点,适用于液体、片剂、粉剂、胶囊、软胶囊样品的测定.%Objective: To establish a method for the determination of lutein in health foods. Methods: The samples were extracted by alcohol, eluted with methanol on an ODS C18 column by HPLC. Results: The detection limit of the method is 0.1 μg/g, the linear range is 0.3 μg/ml -6.2 μg/ml, and the RSD is 5.9%. The average recovery is 92% - 105%. Conclusion : The method is simple, fast and reliable. It will provide a reliable analysis method for detecting the concentration of lutein in health foods, including liquid, tablet, powder, capsule and soft capsule samples.

  8. 叶黄素强化食用油缓解视疲劳效果研究%The Relieving Effect of Lutein-enriching Oil on Asthenopia

    Institute of Scientific and Technical Information of China (English)

    黄增霞; 潘丽军; 张曼

    2011-01-01

    [目的]研究叶黄素强化食用油对视疲劳的缓解效果.[方法]将叶黄素单体添加入食用油中制成叶黄素强化食用油,将50只SD大鼠随机分为正常组、模型组及叶黄素高、中、低剂量组,定期测定各组大鼠体重及血糖值,试验结束后测定各组大鼠晶状体生化指标.[结果]与正常组比较,模型组大鼠血糖明显升高(P<0.01),而体重及SOD、CAT、GSH、GR活性分别降低了21.4%、43.2%、44.1%、36.0%和18.0%,MDA含量升高了73.4%,GSH含量减少了29.7%;较之模型组,高、中、低剂量叶黄素组大鼠血糖无明显改变,体重有所增加,SOD活性分别提高了40.3%、33.9%和9.7%,CAT活性分别提高了56.4%、45.1%和8.8%,GSH-PX活性分别提高了34.0%、10.6%和1.4%,GR活性分别提高了11.1%、4.2%和3.2%,MDA含量分别降低了23.9%、14.9%和7.6%,GSH含量分别增加了20.8%、17.3%和4.7%.[结论]叶黄素强化食用油能够有效提高眼晶体的总抗氧化能力,对视疲劳具有缓解作用.%[Objective] The paper aimed to study the relieving effect of lutein-enriching oil on asthenopia. [ Method ] Lutein monomer was added into edible oil to make lutein-enriching oil. 50 SD rats were distributed to five groups randomly,including normal control group,model group and high,medium,low dose groups of lutein. Body weight,blood sugar,maleie dialdehyde (MDA) content, superoxide dismutase (SOD) activity and catalase( CAT) activity in the lens were measured. After the experiment,biochemical indicators of rats' lentil of each group were measured. [ Result] In comparison with normal control group,the blood sugar in the model group raised significantly(P<0.01) .however the body weight,SOD activity and CAT activity decreased by 21.4% ,43.2% and 44. 1% ,MDA content increased by 73.4%. Compared with the model group,the , blood sugar in the high,middle and low dose groups of lutein changed solely,the body weight

  9. Peptide displacement of [3H]5-hydroxytryptamine binding to bovine cortical membranes

    International Nuclear Information System (INIS)

    Chemical studies have demonstrated that peptides such as the encephalitogenic (EAE) peptide of myelin basic protein (MBP) and luteinizing hormone-releasing hormone (LHRH) can bind serotonin (5-hydroxytryptamine, 5-HT) in vitro. The present research was undertaken to determine whether such binding interferes with 5-HT binding to its 5-HT1 receptors on bovine cerebral cortical membranes. EAE peptide and LHRH displaced [3H]5-HT with IC50s of 4.0 x 10(-4) and 1.8 x 10(-3) M respectively. MBP itself also showed apparent displacing ability with an IC50 of 6.0 x 10(-5) M, though it also caused aggregation of cortical membranes that might have interfered with normal receptor binding. These results support previous suggestions that the tryptophan peptide region of MBP may act as a 5-HT receptor in the neural system. We also tested the effects of muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln, MD), a bacterial cell-wall breakdown product that acts as a slow-wave sleep promoter, binds to LHRH and EAE peptide, and competes for 5-HT binding sites on macrophages. It showed no significant displacement of 5-HT binding to cortical membranes (IC50 greater than 10(-1) M), but its D-Ala analogue did (IC50 = 1.7 x 10(-3) M). Thus, it seems likely that the 5-HT-related effects of naturally occurring muramyl peptides are physiologically limited by receptor types

  10. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  11. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  12. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  13. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to lutein and maintenance of normal vision (ID 1603, 1604, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to lutein and mainte......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to lutein...... into account that one human intervention study in healthy subjects did not show an effect of lutein on visual acuity or glare sensitivity, that the results of this study were inconsistent as regards contrast sensitivity, and that the evidence provided for a mechanism by which lutein could exert the claimed...

  14. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  15. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  16. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  17. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    OpenAIRE

    Dan Li; Caoqi Lei; Zhisheng Xu; Fan Yang; Huanan Liu; Zixiang Zhu; Shu Li; Xiangtao Liu; Hongbing Shu; Haixue Zheng

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co...

  18. A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene

    OpenAIRE

    Grandone, Anna; Cantelmi, Grazia; Cirillo, Grazia; Marzuillo, Pierluigi; Luongo, Caterina; Miraglia del Giudice, Emanuele; Perrone, Laura

    2015-01-01

    Background Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function ...

  19. Identification of spectrin as a calmodulin-binding component in the pituitary gonadotrope

    International Nuclear Information System (INIS)

    Gonadotropin releasing hormone (GnRH) is a hypothalamic decapeptide which stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. Ca2+ fulfills the requirements of a second messenger for this system. Inhibition of calmodulin will inhibit GnRH stimulated LH release. The aim of the present studies has been to identify the locus of action of calmodulin within the pituitary. By use of an 125I-calmodulin gel overlayer assay, five major Ca2+-dependent 125I-calmodulin labelled components of subunit Mr > 205,000; 200,000; 135,000; 60,000; and 52,000 have been identified. This labeling was found to be phenothiazine-sensitive. Ca2+-independent binding that was observed appears to be due to hydrophobic interactions of calmodulin with acid-soluble proteins, principally histones. Subcellular fractionation revealed that the Ca2+-dependent calmodulin-binding components are localized primarily in the cytosolic fraction. Separation of dispersed anterior pituitary cells through a linear Metrizamide gradient yielded gonadotrope-enriched fractions, which were found to contain all five 125I-calmodulin binding components corresponding to the major bands in the pituitary homogenate. The calmodulin-binding component levels do not appear to be differentially regulated by steroids. The calmodulin binding component with a Mr > 205,000 has been identified as spectrin. Spectrin-like immunoreactivity and 125I-calmodulin-binding activity in pituitary tissue homogenates co-migrated in various percentage acrylamide gels with avian erythrocyte spectrin. Spectrin was detected in a gonadotrope-enriched fraction by immunoblotting, and confirmed in gonadotropes by indirect immunofluorescence of cultured pituitary cells in which spectrin- and LH-immunoreactivity co-localized

  20. Partial Sequence Analysis of Merozoite Surface Proteine-3α Gene in Plasmodium vivax Isolates from Malarious Areas of Iran

    Directory of Open Access Journals (Sweden)

    H Mirhendi

    2008-12-01

    Full Text Available Background: Approximately 85-90% of malaria infections in Iran are attributed to Plasmodium vivax, while little is known about the genetic of the parasite and its strain types in this region. This study was designed and performed for describing genetic characteristics of Plasmodium vivax population of Iran based on the merozoite surface protein-3α gene sequence. Methods: Through a descriptive study we analyzed partial P. vivax merozoite surface protein-3α gene sequences from 17 clinical P. vivax isolates collected from malarious areas of Iran. Genomic DNA was extracted by Q1Aamp® DNA blood mini kit, amplified through nested PCR for a partial nucleotide sequence of PvMSP-3 gene in P. vivax. PCR-amplified products were sequenced with an ABI Prism Perkin-Elmer 310 sequencer machine and the data were analyzed with clustal W software. Results: Analysis of PvMSP-3 gene sequences demonstrated extensive polymorphisms, but the sequence identity between isolates of same types was relatively high. We identified specific insertions and deletions for the types A, B and C variants of P. vivax in our isolates. In phylogenetic comparison of geographically separated isolates, there was not a significant geo­graphical branching of the parasite populations. Conclusion: The highly polymorphic nature of isolates suggests that more investigations of the PvMSP-3 gene are needed to explore its vaccine potential.

  1. The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy -- a randomised controlled trial.

    Science.gov (United States)

    Berrow, Emma J; Bartlett, Hannah E; Eperjesi, Frank; Gibson, Jonathan M

    2013-06-01

    Lutein and zeaxanthin are lipid-soluble antioxidants found within the macula region of the retina. Links have been suggested between increased levels of these carotenoids and reduced risk for age-related macular disease (ARMD). Therefore, the effect of lutein-based supplementation on retinal and visual function in people with early stages of ARMD (age-related maculopathy, ARM) was assessed using multifocal electroretinography (mfERG), contrast sensitivity and distance visual acuity. A total of fourteen participants were randomly allocated to either receive a lutein-based oral supplement (treated group) or no supplement (non-treated group). There were eight participants aged between 56 and 81 years (65·50 (SD 9·27) years) in the treated group and six participants aged between 61 and 83 years (69·67 (SD 7·52) years) in the non-treated group. Sample sizes provided 80% power at the 5% significance level. Participants attended for three visits (0, 20 and 40 weeks). At 60 weeks, the treated group attended a fourth visit following 20 weeks of supplement withdrawal. No changes were seen between the treated and non-treated groups during supplementation. Although not clinically significant, mfERG ring 3 N2 latency (P=0·041) and ring 4 P1 latency (P=0·016) increased, and a trend for reduction of mfERG amplitudes was observed in rings 1, 3 and 4 on supplement withdrawal. The statistically significant increase in mfERG latencies and the trend for reduced mfERG amplitudes on withdrawal are encouraging and may suggest a potentially beneficial effect of lutein-based supplementation in ARM-affected eyes. PMID:23084077

  2. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  3. Effects of butorphanol on luteinizing hormone and follicle stimulating hormone levels in ovariectomized rats: comparison with the effects of morphine sulphate

    International Nuclear Information System (INIS)

    The effects of the synthetic morphine derivative, butorphanol, which was claimed to be a potent analgesic with few side effects, in comparison to the effects of the naturally occurring alkaloid, morphine on pituitary gonadotrophic hormones was investigated in ovariectomized rats. For this purpose 3 groups of ovariectomized rats were used. Rats of the first group were injected with butorphanol at 2 dose levels (1 or 2 mg/Kg b.w). Those of the second group were injected with morphine sulphate -(10 or 20 mg/Kg b.w). The third group was injected with saline and served as control. Blood samples were collected from theorbital sinus puncture just before treatment and then one hour post injection. Luteinizing hormone and follicle stimulating hormone levels were determined in blood sera of rats by radioimmunoassay. The results revealed that, the two dose levels used of morphine produced more than 90% decrease in serum LH concentration, whereas butorphanol produced more than 70% decrease in serum LH levels. Both morphine and butorphanol, at the two doses used produced more than 76% decrease in serum FSH concentration. It is concluded that butorphanol, the morphine derivative has a depressant effect on the synthesis and/or release of gonadotrophic hormones. This inhibitory effect, however, was nearly as potent as that produced by morphine sulphate.2 fig., 1 tab

  4. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Science.gov (United States)

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  5. Identification of major urinary metabolites of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in the rhesus monkey

    International Nuclear Information System (INIS)

    Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with 14C label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey

  6. Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    International Nuclear Information System (INIS)

    Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH

  7. Concentrations of progesterone, a metabolite of PGF2α, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares.

    Science.gov (United States)

    Ginther, O J; Baldrighi, J M; Castro, T; Wolf, C A; Santos, V G

    2016-04-01

    In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P mares with an IOI (n = 11) or a PCL (n = 11). An abrupt and complete decrease in P4 (luteolysis) began on Day 13 in the IOI group compared with a gradual and partial P4 decline after Day 12 in the PCL group. Concentrations of PGFM and prolactin were lower (P mares were subgrouped into those with an abrupt but incomplete P4 decrease (partial luteolysis; n = 5) at the expected time and those without partial luteolysis (n = 6). There were no significant differences between the 2 subgroups in concentrations of PGFM and prolactin, but on a tentative basis (P < 0.10), the concentration of PGFM seemed more focused on the day of the most pronounced decrease in P4 in the subgroup with partial luteolysis. Results for PCL compared with IOI indicated (1) postovulatory LH and prolactin were lower, (2) treatment to reduce postovulatory LH did not increase the incidence, and (3) both PGFM and prolactin were lower on the day of the most pronounced decrease in P4. PMID:26808976

  8. Silk fibroin film from golden-yellow Bombyx mori is a biocomposite that contains lutein and promotes axonal growth of primary neurons.

    Science.gov (United States)

    Pistone, Assunta; Sagnella, Anna; Chieco, Camilla; Bertazza, Gianpaolo; Varchi, Greta; Formaggio, Francesco; Posati, Tamara; Saracino, Emanuela; Caprini, Marco; Bonetti, Simone; Toffanin, Stefano; Di Virgilio, Nicola; Muccini, Michele; Rossi, Federica; Ruani, Giampiero; Zamboni, Roberto; Benfenati, Valentina

    2016-05-01

    The use of doped silk fibroin (SF) films and substrates from Bombyx mori cocoons for green nanotechnology and biomedical applications has been recently highlighted. Cocoons from coloured strains of B. mori, such as Golden-Yellow, contain high levels of pigments that could have a huge potential for the fabrication of SF based biomaterials targeted to photonics, optoelectronics and neuroregenerative medicine. However, the features of extracted and regenerated SF from cocoons of B. mori Golden-Yellow strain have never been reported. Here we provide a chemophysical characterization of regenerated silk fibroin (RSF) fibers, solution, and films obtained from cocoons of a Golden-Yellow strain of B. mori, by SEM, (1) H-NMR, HPLC, FT-IR, Raman and UV-Vis spectroscopy. We found that the extracted solution and films from B. mori Golden-Yellow fibroin displayed typical Raman spectroscopic and optical features of carotenoids. HPLC-analyses revealed that lutein was the carotenoid contained in the fiber and RSF biopolymer from yellow cocoons. Notably, primary neurons cultured on yellow SF displayed a threefold higher neurite length than those grown of white SF films. The results we report pave the way to expand the potential use of yellow SF in the field of neuroregenerative medicine and provide green chemistry approaches in biomedicine. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 287-299, 2016. PMID:26756916

  9. A Novel Targeted Therapy of Leydig and Granulosa Cell Tumors through the Luteinizing Hormone Receptor Using a Hecate-Chorionic Gonadotropin β Conjugate in Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Gabriel Bodek

    2005-05-01

    Full Text Available We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CGβ conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95 fragment of the human CGβ chain. Transgenic (TG mice expressing the inhibin α-subunit promoter (inhα/Simian Virus 40 T-antigen (Tag transgene, developing luteinizing hormone (LH receptor (R expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGβ conjugate for 3 weeks. Hecate-CGβ conjugate treatment reduced the testicular and ovarian tumor burden (P < .05, whereas a concomitant increase (testis; P < .05 or no change (ovary in tumor volumes occured with Hectate treatment. A drop in serum progesterone, produced by the tumors, and an increase in LH levels occured in Hecate-CGβ treated mice, in comparison with vehicle and Hecate groups, providing further support for the positive treatment response. Hecate-CGβ conjugate induced a rapid and cell-specific membrane permeabilization of LHR-expressing cells in vitro, suggesting a necrotic mode of cell death without activation of apoptosis. These results prove the principle that the Hecate-CGβ conjugate provides a novel specific lead into gonadal somatic cell cancer therapy by targeted destruction of LHR-expressing tumor cells.

  10. Activation of the cAMP-dependent protein kinase signaling pathway by luteinizing hormone in trout theca layers.

    Science.gov (United States)

    Méndez, Eva; Maeland, Mari; Skålhegg, Bjørn S; Planas, Josep V

    2003-07-31

    In the fish ovary, LH is the main factor regulating the production of steroids during the periovulatory period and its effects are believed to be mediated, at least partially, through the cAMP-dependent protein kinase (PKA) signaling pathway. However, there is no direct evidence for the presence of PKA in the fish ovary nor on the regulation of its activity by fish LH. Here, we show the identification of regulatory (R) and catalytic (C) subunits of PKA in trout theca cells by immunoblotting. DEAE-cellulose chromatography of theca cell extracts indicated the presence of PKA type I and II and showed that trout theca cells display PKA-specific phosphotransferase and cAMP-binding activities. Salmon LH (sLH) stimulated PKA activity and increased the levels of immunoreactive RIIalpha, RIIbeta and C subunits in trout theca layers. These observations, coupled with the sLH-dependent decrease in the half-life of the C subunit, as shown by pulse-chase experiments, strongly suggest that sLH activates PKA in trout theca cells. Furthermore, our results suggest that ovarian PKA activity and its regulation by LH has been well conserved from fish to humans. PMID:12890563

  11. GNL3L Inhibits Estrogen Receptor-Related Protein Activities by Competing for Coactivator Binding

    OpenAIRE

    Yasumoto, Hiroaki; Meng, Lingjun; Lin, Tao; Zhu, Qubo; Tsai, Robert Y.L.

    2007-01-01

    Guanine-nucleotide binding protein 3-like (GNL3L) is the closest homologue of a stem cell-enriched factor nucleostemin in vertebrates. They share the same yeast orthologue, Grn1p, but only GNL3L can rescue the growth-deficient phenotype in Grn1p-null yeasts. To determine the unique function of GNL3L, we identified estrogen receptor-related protein-γ (ERRγ) as a GNL3L-specific binding protein. GNL3L and ERRγ are coexpressed in the eye, kidney and muscle, and co-reside in the nucleoplasm. The i...

  12. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  13. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    2001-10-09

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  14. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, J.O.; Spevak, W.R.; Dasgupta, F.; Bertozzi, C.

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10{sup 6} fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  15. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    1999-01-01

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  16. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, J.O.; Spevak, W.R.; Dasgupta, F.; Bertozzi, C.

    1999-11-16

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10{sup 6} fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  17. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Carolyn (Albany, CA)

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  18. Molecular determinants of the interaction between coxsackievirus protein 3A and guanine nucleotide exchange factor GBF1.

    NARCIS (Netherlands)

    Wessels, E.; Duijsings, D.; Lanke, K.H.W.; Melchers, W.J.G.; Jackson, C.L.; Kuppeveld, F.J.M. van

    2007-01-01

    The 3A protein of coxsackievirus B3 (CVB3), a small membrane protein that forms homodimers, inhibits endoplasmic reticulum-to-Golgi complex transport. Recently, we described the underlying mechanism by showing that the CVB3 3A protein binds to and inhibits the function of GBF1, a guanine nucleotide

  19. 万寿菊叶黄素的提取与皂化工艺研究%The research on marigold extraction and saponification process about lutein

    Institute of Scientific and Technical Information of China (English)

    张志强; 刘进风; 吕伶俐; 向正华; 边丽霞

    2011-01-01

    试验采用了有机溶剂浸提和氢氧化钾甲醇溶液皂化的方法,研究了万寿菊叶黄素的提取与皂化的工艺条件.试验考察了提取剂种类、提取温度、提取时间、料液比对提取效果的影响,以及皂化液种类、皂化液浓度、皂化液用量、皂化温度、皂化时间、对皂化的影响.通过单因素试验确定的提取和皂化工艺条件为:提取剂为无水乙醇:石油醚(沸程为60℃~90℃)(2:1),料液比为1:100,提取温度45℃,提取时间80min,皂化液浓度20%,皂化液用量0.2mL,皂化温度40℃,皂化时间80min.选用乙醇—石油醚混合溶剂作为提取剂,具有价格便宜、低毒、沸点低、溶剂回收成本较低、生产安全性高等优点.该提取剂用于工业生产中提取叶黄素是可行的.%With the method ot organic solvent extraction and mehtanol solution ot potassium hydroxide saponuication, this research studied the extraction and saponification process conditions of lutein in marigold flower. Research examined the effects of extraction agents types, extraction temperature, extraction time, and ratio of material to liquid on extraction, as well as the effects of saponification solution types, saponification solution concentration, saponification liquid dosage, saponification temperature and saponification time on saponification. On the base of single - factor test, the optimized conditions of extraction and saponification were: extraction agents was ethanol: petroleum ether (boiling range of 60 °C~90°C ) (2:1), expected liquid ratio was 1 : 100, extraction temperature was 45°C, extraction time was 80min, saponification solution concentration was 20% , the amount of saponification solution was 0. 2mL, saponification temperature was 40 "C , saponification time was 80min. The use of ethanol - petroleum ether mixed solvent as extraction agent has the advantages of cheap, low toxicity, low boiling point, low solvent recovery costs, safe production. This

  20. Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-fei AN; Jiang-yi YU; Yi FENG; Bo-ying CHEN; Su-lin ZHANG

    2007-01-01

    Aim: To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-likel receptor (ORL1 receptor) in the estrus cycle of female rats. Method: Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphel]Nociceptin(1-13)NH2 that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohis- tochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat. Results: Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreat-ment with 20 nmol NC13. The OFQ mRNA level in the POA on pro-estrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreac-tive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and es-trus (P<0.05). Conclusion: The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on pro-estrus sug-gests that it might play a negative modulatory role in the estrus cycle.

  1. The effect of dietary supplementation with the natural carotenoids curcumin and lutein on pigmentation, oxidative stability and quality of meat from broiler chickens affected by a coccidiosis challenge.

    Science.gov (United States)

    Rajput, N; Ali, S; Naeem, M; Khan, M A; Wang, T

    2014-01-01

    1. An experiment was performed to evaluate the effectiveness of the antioxidants curcumin (CRM) and lutein (LTN) on the quality of meat from coccidiosis-infected broilers. A total of 200 one-day-old Arbor Acre chicks were randomly assigned to a treatment group with 5 replicates. The treatments included a basal diet without carotenoid supplementation (control), with 300 mg/kg CRM, with 300 mg/kg LTN or with a combination (C + L) of 150 mg/kg CRM and 150 mg/kg LTN. All chickens were challenged with Eimeria maxima at 21 d old. 2. The results revealed that the coccidiosis reduced redness of meat, while supplementation with carotenoids improved the fresh meat's redness (a*) and yellowness (b*) and contributed to colour stability maintenance after storage (1 month at -18°C and 3 d at 4°C). 3. Coccidiosis did not produce lipid and protein oxidation in fresh meat, but after storage for one month, the malondialdehyde levels and carbonyl contents were lower in the CRM and C + L birds and the sulfhydryl contents were higher in C + L birds. 4. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis banding pattern showed equivalent myosin chain fragmentations in all treatment groups, whereas lower intensity actin bands were observed in the control group (CONT). Moreover, myofibril protein denaturation (differential scanning calorimetry) profiles showed a reduction in the CONT myosin and actin peaks. Coccidiosis reduced the meat's water holding capacity in non-supplemented chicken meat and was improved by natural carotenoid. 5. These results emphasise that coccidiosis did not decrease the eating quality of fresh meat, that natural carotenoids are efficient antioxidants and that CRM (300 mg/kg) fed individually or combined with LTN was the most effective supplemented antioxidant compound. PMID:24852123

  2. Summer (subarctic) versus winter (subtropic) production affects spinach (Spinacia oleracea L.) leaf bionutrients: vitamins (C, E, Folate, K1, provitamin A), lutein, phenolics, and antioxidants.

    Science.gov (United States)

    Lester, Gene E; Makus, Donald J; Hodges, D Mark; Jifon, John L

    2013-07-24

    Comparison of spinach (Spinacia oleracea L.) cultivars Lazio and Samish grown during the summer solstice in the subarctic versus the winter solstice in the subtropics provided insight into interactions between production environment (light intensity), cultivar, and leaf age/maturity/position affecting bionutrient concentrations of vitamins (C, E, folate, K1, provitamin A), lutein, phenolics, and antioxidants. Growing spinach during the winter solstice in the subtropics resulted in increased leaf dry matter %, oxidized (dehydro) ascorbic acid (AsA), α- and γ-tocopherol, and total phenols but lower reduced (free) AsA, α-carotene, folate, and antioxidant capacity compared to summer solstice-grown spinach in the subarctic. Both cultivars had similar bionutrients, except for higher dehydroAsA, and lower α- and γ-tocopherol in 'Samish' compared to 'Lazio'. For most bionutrients measured, there was a linear, and sometimes quadratic, increase in concentrations from bottom to top canopy leaves. However, total phenolics and antioxidant capacity increased basipetally. The current study has thus demonstrated that dehydroAsA, α-tocopherol, and γ-tocopherol were substantially lower in subarctic compared to subtropical-grown spinach, whereas the opposite relationship was found for antioxidant capacity, α-carotene, and folates (vitamin B9). The observations are consistent with previously reported isolated effects of growth environment on bionutrient status of crops. The current results clearly highlight the effect of production environment (predominantly radiation capture), interacting with genetics and plant phenology to alter the bionutrient status of crops. While reflecting the effects of changing growing conditions, these results also indicate potential alterations in the nutritive value of foods with anticipated shifts in global climatic conditions. PMID:23834651

  3. A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus

    Directory of Open Access Journals (Sweden)

    Kouba Andrew J

    2012-08-01

    Full Text Available Abstract Background Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Methods Male American toads (Anaxyrus americanus were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad, human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU, or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. Results The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU, 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms. In addition to having a greater number of responders (P  Conclusion There is a clear dichotomy between the two hormones’ physiological responses on gamete production and stimulation of amplexus. Understanding how these two hormones influence physiology and reproductive behaviors in amphibians will have direct bearing on establishing similar breeding protocols for endangered species.

  4. Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-09-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction. Methods Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene. Results The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor compared to women with tubal infertility factor (p = 0.007. There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively. Conclusions High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.

  5. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Directory of Open Access Journals (Sweden)

    Rinaldi L

    2016-05-01

    Full Text Available Leonardo Rinaldi, Helmy Selman One Day Medical Center, IVF Unit, Rome, Italy Abstract: A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH and luteinizing hormone (LH to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH and recombinant LH (rLH has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I. In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. Keywords: follicular growth, gonadotropins, implantation, ovarian stimulation, pregnancy

  6. The effect of dietary monensin on th luteinizing hormone response of prepuberal heifers given a multiple gonadotropin-releasing hormone challenge.

    Science.gov (United States)

    Randel, R D; Rhodes, R C

    1980-10-01

    Ten prepuberal Simmental X Brahman-Hereford heifers (average weight 208 +/- 4 kg) were randomly assigned to receive either 2.7 kg/head/day of ground milo containing 0 mg monensin sodium (C) or 2.7 kg/head/day of ground milo containing 200 mg monensin sodium (M). Both groups of animals (n = 5) received Coastal bermudagrass hay ad libitum throughout the trial. On day 21 of the feeding period all heifers were fitted with jugular cannulas. Immediately after cannulation, the heifers were injected IM with 100 microgram of gonadotropin-releasing hormone (GnRH) and blood was collected every 10 min for 4 hours. Four hours after the first GnRH challenge, a second 100-microgram GnRH injection was administered, and blood samples were collected at 10-min intervals for an additional 5 hours. Serum was stored at -20 C until radioimmunoassayed for luteinizing hormone (LH). The amount of LH released after each GnRH injection was greater in the heifers fed M than in the controls (P less than .05). Peak LH after the first GnRH challenge was greater (P less than .05) in heifers fed M than in controls. The area under th first GnRH induced LH curve tended (P less than .20) to be greater for the M group than for the controls. Peak LH concentration was greater in heifers fed M than in control heifers, as the duration (P less than .05) and area under the second GnRH-induced LH curve. In prepuberal heifers, dietary monensin appears to increase hypophyseal capability of releasing LH after a first and second GnRH challenge. PMID:7007307

  7. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    Science.gov (United States)

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) cancer-specific survival and biochemical progression remained unclear. Non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. PMID:25523493

  8. A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E ε4 allele

    Directory of Open Access Journals (Sweden)

    Gleason Carey E

    2008-04-01

    Full Text Available Abstract Genetic and biochemical studies support the apolipoprotein E (APOE ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD, though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB and its receptor (LHCGR have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the loci of LHB, LHCGR, and APOE were associated with AD. The most strongly supported of these interactions was between an LHCGR intronic polymorphism (rs4073366; lhcgr2 and APOE in males, which was detected using all three interaction analyses: linkage disequilibrium, multi-dimensionality reduction, and logistic regression. While the APOE ε4 allele carried significant risk of AD in males [p = 0.007, odds ratio (OR = 3.08(95%confidence interval: 1.37, 6.91], ε4-positive males carrying 1 or 2 C-alleles at lhcgr2 exhibited significantly decreased risk of AD [OR = 0.06(0.01, 0.38; p = 0.003]. This suggests that the lhcgr2 C-allele or a closely linked locus greatly reduces the risk of AD in males carrying an APOE ε4 allele. The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions.

  9. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  10. Editing of the Luteinizing Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Zinc Finger Nuclease Technology with Electroporation.

    Science.gov (United States)

    Qin, Zhenkui; Li, Yun; Su, Baofeng; Cheng, Qi; Ye, Zhi; Perera, Dayan A; Fobes, Michael; Shang, Mei; Dunham, Rex A

    2016-04-01

    Channel catfish (Ictalurus punctatus) is the most important freshwater aquaculture species in the USA. Genetically enhanced fish that are sterile could both profit the catfish industry and reduce potential environmental and ecological risks. As the first step to generate sterile channel catfish, three sets of zinc finger nuclease (ZFN) plasmids targeting the luteinizing hormone (LH) gene were designed and electroporated into one-cell embryos, different concentrations were introduced, and the Cel-I assay was conducted to detect mutations. Channel catfish carrying the mutated LH gene were sterile, as confirmed by DNA sequencing and mating experiments. The overall mutation rate was 19.7 % for 66 channel catfish, and the best treatment was ZFN set 1 at the concentration 25 μg/ml. To our knowledge, this is the first instance of gene editing of fish via plasmid introduction instead of mRNA microinjection. The introduction of the ZFN plasmids may have reduced mosaicism, as mutated individuals were gene edited in every tissue evaluated. Apparently, the plasmids were eventually degraded without integration, as they were not detectable in mutated individuals using PCR. Carp pituitary extract failed to induce spawning and restoration of fertility, indicating the need for developing other hormone therapies to achieve reversal of sterility upon demand. This is the first sterilization achieved using ZFN technology in an aquaculture species and the first successful gene editing of channel catfish. Our results will help understand the roles of the LH gene, purposeful sterilization of teleost fishes, and is a step towards control of domestic, hybrid, exotic, invasive, and transgenic fishes. PMID:26846523

  11. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

    Science.gov (United States)

    Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2010-01-01

    Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation. PMID:21060208

  12. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  13. A wheat lipid transfer protein 3 could enhance the basal thermotolerance and oxidative stress resistance of Arabidopsis.

    Science.gov (United States)

    Wang, Fei; Zang, Xin-shan; Kabir, Muhammad Rezaul; Liu, Ke-lu; Liu, Zhen-shan; Ni, Zhong-fu; Yao, Ying-yin; Hu, Zhao-rong; Sun, Qi-xin; Peng, Hui-ru

    2014-10-15

    Wheat (Triticum aestivum L.) is one of the major grain crops, and heat stress adversely affects wheat production in many regions of the world. Previously, we found a heat-responsive gene named Lipid Transfer Protein 3 (TaLTP3) in wheat. TaLTP3 was deduced to be regulated by cold, ABA, MeJA, Auxin and oxidative stress according to cis-acting motifs in its promoter sequences. In this study, we show that TaLTP3 is responsive to prolonged water deficit, salt or ABA treatment in wheat seedlings. Also, TaLTP3 accumulation was observed after the plant suffered from heat stress both at the seedling and the grain-filling stages. TaLTP3 protein was localized in the cell membrane and cytoplasm of tobacco epidermal cells. Overexpression of TaLTP3 in yeast imparted tolerance to heat stress compared to cells expressing the vector alone. Most importantly, transgenic Arabidopsis plants engineered to overexpress TaLTP3 showed higher thermotolerance than control plants at the seedling stage. Further investigation indicated that transgenic lines decreased H₂O₂ accumulation and membrane injury under heat stress. Taken together, our results demonstrate that TaLTP3 confers heat stress tolerance possibly through reactive oxygen species (ROS) scavenging. PMID:25106859

  14. Cell Transformation and Proteome Alteration in QSG7701 Cells Transfected with Hepatitis C Virus Non-structural Protein 3

    Institute of Scientific and Technical Information of China (English)

    Qiongqiong HE; Deyun FENG; Ruixue CHENG; Zhuchu CHEN; Xuxian XIAO; Zhiqiang XIAO; Cui LI; Bo LI; Pengfei ZHANG; Hui ZHENG

    2007-01-01

    Persistent hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma. Non-structural protein 3 (NS3), an important part of HCV, has been implicated in the life cycle of the virus and interacts with host cellular proteins. In this study, we investigated the effect of NS3 protein on cell tranformation and related protein alteration in human hepatocyte QSG7701 cells. The results indicated that stable expression of the NS3 protein in QSG7701 cells induced transformed characters with reduced population doubling time, anchorage-independent growth and tumor development. Fifteen differentially-expressed proteins were separated and identified using 2-D electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Western blot analysis confirmed that the increase of phospho-p44/42 and phospho-p38 proteins was associated with transformed cells. These results supported the view that HCV NS3 protein plays a transforming role and provided some clues to elucidate the carcinogenesis mechanism of HCV-related hepatocellular carcinoma.

  15. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway.

    Science.gov (United States)

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  16. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    Science.gov (United States)

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  17. T-bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death-1-deficient mice.

    Science.gov (United States)

    Tahara, M; Kondo, Y; Yokosawa, M; Tsuboi, H; Takahashi, S; Shibayama, S; Matsumoto, I; Sumida, T

    2015-02-01

    Programmed cell death-1 (PD-1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD-1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3(+)) regulatory T cells (Tr(egs)). PD-1-deficient T cell-specific T-bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T-bet over-expression, increased interferon (IFN)-γ production by CD4(+) T cells and significantly low FoxP3(+) T(reg) cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3(+) T(reg) count. The study identified a unique, previously undescribed role for PD-1 in Th1 and T(reg) differentiation, with potential implication in the development of Th1 cell-targeted therapy. PMID:25219397

  18. Gene-Environment Interactions Target Mitogen-activated Protein 3 Kinase 1 (MAP3K1) Signaling in Eyelid Morphogenesis.

    Science.gov (United States)

    Mongan, Maureen; Meng, Qinghang; Wang, Jingjing; Kao, Winston W-Y; Puga, Alvaro; Xia, Ying

    2015-08-01

    Gene-environment interactions determine the biological outcomes through mechanisms that are poorly understood. Mouse embryonic eyelid closure is a well defined model to study the genetic control of developmental programs. Using this model, we investigated how exposure to dioxin-like environmental pollutants modifies the genetic risk of developmental abnormalities. Our studies reveal that mitogen-activated protein 3 kinase 1 (MAP3K1) signaling is a focal point of gene-environment cross-talk. Dioxin exposure, acting through the aryl hydrocarbon receptor (AHR), blocked eyelid closure in genetic mutants in which MAP3K1 signaling was attenuated but did not disturb this developmental program in either wild type or mutant mice with attenuated epidermal growth factor receptor or WNT signaling. Exposure also markedly inhibited c-Jun phosphorylation in Map3k1(+/-) embryonic eyelid epithelium, suggesting that dioxin-induced AHR pathways can synergize with gene mutations to inhibit MAP3K1 signaling. Our studies uncover a novel mechanism through which the dioxin-AHR axis interacts with the MAP3K1 signaling pathways during fetal development and provide strong empirical evidence that specific gene alterations can increase the risk of developmental abnormalities driven by environmental pollutant exposure. PMID:26109068

  19. Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    XUE Hao; WANG Shu-xia; WANG Xiao-jian; XIN Ying; WANG Hu; SONG Xiao-dong; SUN Kai; WANG Yi-bo; HUI Ru-tai

    2011-01-01

    Background Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.Methods Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n=2120 and n=324).Results We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI))0.58 (0.358-0.863), P=0.035; OR (95% CI)=0.477 (0.225-0.815), P<0.05,respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P<0.01).Conclusion These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

  20. Effect of different dietary concentrations of brown marine algae (Sargassum dentifebium prepared by different methods on plasma and yolk lipid profiles, yolk total carotene and lutein plus zeaxanthin of laying hens

    Directory of Open Access Journals (Sweden)

    Ahmed A. El-Deek

    2012-10-01

    Full Text Available The effect of different concentrations (0%, 3% and 6% of brown marine algae (BMA, Sargassum dentifebium prepared according to different methods (sun-dried, SBMA; boiled, BBMA; autoclaved, ABMA on plasma and yolk lipid profiles, carotene, and lutein plus zeaxanthin in egg yolks was studied in hens aged from 23 to 42 weeks (30 hens per treatment. We determined the fatty acid profiles in BMA and in the egg yolk of hens fed different levels of BMA prepared according to different methods. In addition, plasma and yolk lipid profiles, yolk total carotene, and lutein plus zeaxanthin were determined at week 42 of age. Plasma and yolk cholesterol were significantly lower in groups fed diets containing either 3% or 6% BMA than in the control group, but high-density lipoprotein (HDL significantly decreased as BMA concentration increased. There was a significant similar decline in yolk triglycerides with inclusion of either 3% or 6% BMA in the laying hen diet. Palmitic acid was the main saturated fatty acid (SFA found in BMA and oleic acid (omega-9 and linoleic acid (omega-6 were the main unsaturated fatty acids (UFA, while there was a significant increase in palmitic acid in egg yolk when BMA was included at 6%. There was a significant increase in oleic acid (omega-9 when feed containing 3% BMA was given compared to the control group, but this decreased with a further increase in BMA. Linoleic acid (omega-6 also significantly decreased with inclusion of either 3% or 6% BMA. There was a significant increase in total carotene and lutein plus zeaxanthin in the laying hen eggs as a result of feeding diets containing 3% and 6% BMA.

  1. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T;

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  2. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T;

    1997-01-01

    -IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing......Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  3. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    Science.gov (United States)

    Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

    2016-01-01

    Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

  4. Cell-penetrable mouse forkhead box protein 3 alleviates experimental arthritis in mice by up-regulating regulatory T cells.

    Science.gov (United States)

    Liu, Xia; Ji, Baoju; Sun, Mengyi; Wu, Weijiang; Huang, Lili; Sun, Aihua; Zong, Yangyong; Xia, Sheng; Shi, Liyun; Qian, Hui; Xu, Wenrong; Shao, Qixiang

    2015-07-01

    Regulatory T cells (T(regs)) have potential applications in clinical disease therapy, such as autoimmune diseases and transplant rejection. However, their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here, we generated a cell-permeable fusion protein, protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3), and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected, PTD-mFoxP3 was transduced into cells effectively, and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression, and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition, PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover, protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy. PMID:25809415

  5. Polymorphism of Merozoite Surface Protein-3α Gene of Plasmo-dium vivax in Isolates of Iran

    Directory of Open Access Journals (Sweden)

    M Asmar

    2008-04-01

    Full Text Available Background: The worldwide distribution of P. vivax has expanded significantly and the number of reported cases has been on the rise. Approximately 88% of malaria cases in Iran are caused by Plasmodium vivax, and in order to management of the disease, understanding the population genetic structure of the parasite is necessary for designing and applying drugs and vaccines. Among many potential candidates, merozoite surface protein-3α gene (PvMSP-3α is promising target to develop an effective vaccine. This study was carried out to determine the variation of this gene, as a genetic marker, in Plasmodium vivax isolates in malarious areas of Iran. Methods: Diversity in PvMSP-3α gene was assessed in 85 Plasmodium vivax isolated from four southern and east-southern provinces of the country by PCR/RFLP method. Amplification was performed with two primer pair sets in a nested PCR format and the products were digested by the enzyme HhaI in RFLP method. Results: Based on the size of the PCR products, we observed three biotypes A (about 1900bp, B (about 1400bp and C (about 1100bp of PvMSP-3α gene. Biotype A was predominant. According to RFLP patterns, 10 allelic groups of the gene were observed, that, 7, 2 and 1 groups correspond to the biotype A, B and C, respectively. Mixed genotype and multiple infections were not seen. Conclusion: RFLP method with HhaI enzyme is a useful method for determining the polymorphism of biotype A of PvMSP-3agene.

  6. Diapause-associated protein3 functions as Cu/Zn superoxide dismutase in the Chinese oak silkworm (Antheraea pernyi.

    Directory of Open Access Journals (Sweden)

    Zhenle Bi

    Full Text Available To better understand the molecular mechanism underlying of diapause in Antheraea pernyi (A. pernyi, we cloned a novel diapause-associated protein 3 (DAP3 gene from A. pernyi by reverse transcription-polymerase chain reaction (RT-PCR and studied the biological functions. Sequence analysis revealed that this gene encodes 171 amino acids and has a conserved domain of Copper/Zinc superoxide dismutase (Cu/Zn-SOD. Western blot and qRT-PCR results showed that DAP3 was mainly expressed in the pupal stage, and gradually decreased as diapause development. DAP3 was also expressed in 1st and 5th instar larvae of A. pernyi. In tissues of 5th instar larvae of A. pernyi, DAP3 was mainly expressed in the epidermis, followed by the head, hemolymph and fat body. To identify the SOD activity of DAP3, we constructed a prokaryotic expression vector by inserting the coding region sequence into plasmid pET-28a (+ and obtained the purified rHIS-DAP3 fusion protein by Ni-NTA affinitive column. Importantly, we found the SOD activity of DAP3 fusion protein was approximately 0.6674 U/µg. To further confirm the SOD activity of DAP3 in vivo, we induced the oxidative stress model of pupae by UV irradiation. The results showed that both the mRNA and protein level of DAP3 significantly increased by UV irradiation. Furthermore, the SOD activity of the total lysate of pupae increased significantly at 10 min post UV irradiation and transiently returned to normal level afterwards. These results suggested that DAP3 might be a novel protein with SOD activity getting involved in regulation of diapause in A. pernyi.

  7. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle

    Science.gov (United States)

    Non-structural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids in most FMDVs examined to date. The role of 3A in virus growth and virulence within the natural host is not well understood. Using a yeast two-hybrid approach, we identified cellular ...

  8. Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

    Directory of Open Access Journals (Sweden)

    Bernd Th Krause

    2009-06-01

    Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

  9. DNA-binding residues and binding mode prediction with binding-mechanism concerned models

    OpenAIRE

    Oyang Yen-Jen; Liu Yu-Cheng; Huang Chun-Chin; Huang Yu-Feng; Huang Chien-Kang

    2009-01-01

    Abstract Background Protein-DNA interactions are essential for fundamental biological activities including DNA transcription, replication, packaging, repair and rearrangement. Proteins interacting with DNA can be classified into two categories of binding mechanisms - sequence-specific and non-specific binding. Protein-DNA specific binding provides a mechanism to recognize correct nucleotide base pairs for sequence-specific identification. Protein-DNA non-specific binding shows sequence indepe...

  10. Carboplatin binding to histidine

    International Nuclear Information System (INIS)

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described

  11. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  12. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

  13. Prokaryotic expression and purification of fibronectin leucine rich transmembrane protein 3 C-terminal domain proteins in rats

    Institute of Scientific and Technical Information of China (English)

    Yan Cai; Jing Yang; He Huang; Fang Li; Ganqiu Wu; Jing Yang; Xuegang Luo

    2009-01-01

    BACKGROUND: Studies have suggested that fibronectin leucine-rich transmembrane protein 3 (FLRT3) is related to injury and regeneration of the nervous system. However, the expression and biological characteristics of these proteins remain poorly understood.OBJECTIVE: To obtain FLRT3 C-terminal gene fragments, to effectively express and purify the target proteins.DESIGN, TIME AND SETTING: An observational study of cellular and molecular biology was performed at the laboratory of Histology and Embryology in Xiangya School of Medicine, Central South University between October 2007 and June 2008.MATERIALS: Three Sprague Dawley adult rats were used to extract total RNA from rat brains. The pGEX4T3 and Escherichia coli (E. Coli) JM109 were purchased from Promega. E. Coil BL21 was provided by Novagen.METHODS: FLRT3 protein coding C-terminal DNA fragments, at a length of 786 bp, were amplified using RT-PCR technique from rat total RNA. The amplified products were cloned into the expression vector pGEX4T3. A recombinant expression vector was then constructed and introduced into E. Coli BL21. IsopropyI-D-thiogalactopyranoside was applied to induce expression of recombinant GST fusion proteins, followed by isolation, purification, and renaturation of inclusion bodies that comprised recombinant proteins. Finally, the purified recombinant protein was obtained.MAIN OUTCOME MEASURES: Determination of FLRT3 C-terminal DNA sequence; expression of target proteins was assayed by SDS-PAGE electrophoresis; purified recombinant protein was identified with Western blot methods.RESULTS: FLRT3 protein coding C-terminal DNA fragments, at a length of 786 bp, were successfully harvested through RT-PCR amplification, and were then cloned into the prokaryotic expression vector pGEX4T3. The results of the sequence were consistent with the known gene sequence. SDS-PAGE analysis demonstrated that there was a specific protein band in the recombinant GST fusion proteins at a relative molecular mass

  14. Collagen binding to Staphylococcus aureus

    International Nuclear Information System (INIS)

    Staphylococcus aureus can bind soluble collagen in a specific, saturable manner. We have previously shown that some variability exists in the degree of collagen binding between different strains of heat-killed, formaldehyde-fixed S. aureus which are commercially available as immunologic reagents. The present study demonstrates that live S. aureus of the Cowan 1 strain binds amounts of collagen per organism equivalent to those demonstrated previously in heat-killed, formaldehyde-fixed bacteria but has an affinity over 100 times greater, with Kd values of 9.7 X 10(-11) M and 4.3 X 10(-8) M for live and heat-killed organisms, respectively. Studies were also carried out with S. aureus killed by ionizing radiation, since this method of killing the organism seemed less likely to alter the binding moieties on the surface than did heat killing. Bacteria killed by exposure to gamma radiation bound collagen in a manner essentially indistinguishable from that of live organisms. Binding of collagen to irradiated cells of the Cowan 1 strain was rapid, with equilibrium reached by 30 min at 22 degrees C, and was fully reversible. The binding was not inhibited by fibronectin, fibrinogen, C1q, or immunoglobulin G, suggesting a binding site for collagen distinct from those for these proteins. Collagen binding was virtually eliminated in trypsin-treated organisms, indicating that the binding site has a protein component. Of four strains examined, Cowan 1 and S. aureus ATCC 25923 showed saturable, specific binding, while strains Woods and S4 showed a complete lack of binding. These results suggest that some strains of S. aureus contain high-affinity binding sites for collagen. While the number of binding sites per bacterium varied sixfold in the two collagen-binding strains, the apparent affinity was similar

  15. Melanin binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    We have determined the biodistribution an uptake by the Greene melanoma in the Syrian golden hamster with 21 radiopharmaceuticals. Maximum % uptake and the time at which this occurred are listed. It is essential to know maximum tumor to background ration and the time after injection that this occurs to determine suitability for tumor scanning. The importance of species variation deserves mention. Detection of eye melanoma in humans was quite variable whereas in hamsters it was quite easy to obtain a positive scan with a single pinhole. We then looked at brain uptake in man and found it (the brain scan) to be significant. In addition, we found a high uptake by the lung, something not found in hamsters but not entirely unsuspected of a amine, such as 123I-4,3DMQ. Finally, our clinical experience has shown us some of the vagaries of melanoma-seeking radiopharmaceuticals. This reflects the complexity of melanin and melanin-binding and points out the necessity for a more detailed analysis of the mechanisms involved in melanin binding radionuclides

  16. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm;

    2003-01-01

    seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...

  17. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Flyvbjerg, Allan; Frystyk, Jan; Müller, J; Skakkebaek, N E

    1996-01-01

    Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF...

  18. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to a combination of lutein and zeaxanthin and improved vision under bright light conditions pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to a combination of lutein and zeaxanthin and improved vision under bright light conditions pursuant to Article 13(5) of Regulation (EC) No 1924/2006....

  19. Quarkonium Binding and Entropic Force

    CERN Document Server

    Satz, Helmut

    2015-01-01

    A Q-Qbar bound state represents a balance between repulsive kinetic and attractive potential energy. In a hot quark-gluon plasma, the interaction potential experiences medium effects. Color screening modifies the attractive binding force between the quarks, while the increase of entropy with Q-Qbar separation gives rise to a growing repulsion. We study the role of these phenomena for in-medium Q-Qbar binding and dissociation. It is found that the relevant potential for Q-Qbar binding is the free energy F; with increasing Q-Qbar separation, further binding through the internal energy U is compensated by repulsive entropic effects.

  20. Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs.

    Science.gov (United States)

    Ponglowhapan, S; Church, D B; Scaramuzzi, R J; Khalid, M

    2007-01-15

    In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The

  1. Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients’ prognosis

    OpenAIRE

    Al Bashir, Samir; Alshalalfa, Mohammed; Hegazy, Samar A.; Dolph, Michael; Donnelly, Bryan; Bismar, Tarek A.

    2014-01-01

    Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for ...

  2. Analysis of Polymorphisms in the Merozoite Surface Protein-3a Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

    DEFF Research Database (Denmark)

    Schousboe, Mette L; Rajakaruna, Rupika S; Amerasinghe, Priyanie H;

    2011-01-01

    Abstract. The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3a (Pvmsp-3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3a, 11 alleles....... The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka....

  3. 口服叶黄素治疗低龄单眼弱视儿童的疗效观察%The effect of oral lutein treatment in young children with unilateral amblyopia

    Institute of Scientific and Technical Information of China (English)

    张大卫

    2016-01-01

    目的:观察综合治疗联合口服叶黄素对轻、中度单眼弱视低龄儿童的临床疗效。方法将轻、中度单眼弱视患儿随机分为两组。实验组除进行综合治疗外,同时口服叶黄素;对照组只进行配戴眼镜、健眼单眼遮盖及弱视眼精细目力训练的综合治疗。结果治疗后1个月,实验组视力提高的有效率为36.36%,高于对照组的30.43%,但差异无显著性(χ2=0.178,=0.673)。治疗后6个月视力变化比较,实验组有效率81.82%,高于对照组的64.95%,但差异无显著性(χ2=1.585,=0.208)。结论综合治疗联合口服叶黄素对轻、中度单眼弱视低龄儿童更为有效。%Objective To observe the effect of complex treatment combined with oral lutein in young children with mild and moderate unilateral amblyopia. Methods Young children with unilateral amblyopia were divided into two groups randomly, complex treatment combined with oral lutein in experimental group and complex treatment in control group which included wearing glasses, healthy eye cover and fine eyesight training for amblyopic eye. Results Effective rate of VA(visual acuity)improvement in the experimental group was 36.36%, higher than 30.43%of the control group after one month treat-ment, but there was no significant difference (χ2=0.178, =0.673).After six months treatment, VA improvement rate in the experimental group was 81.82%, higher than 64.95%of the control group, but there was no significant difference (χ2=1.585,=0.208). Conclusions Complex treatment combined with oral lutein was more effetive than complex treatment in young children with mild and moderateunilateral amblyopia.

  4. Alcohol Binding to the Odorant Binding Protein LUSH: Multiple Factors Affecting Binding Affinities

    OpenAIRE

    Ader, Lauren; Jones, David N. M.; Lin, Hai

    2010-01-01

    Density function theory (DFT) calculations have been carried out to investigate the binding of alcohols to the odorant binding protein LUSH from Drosophila melanogaster. LUSH is one of the few proteins known to bind to ethanol at physiologically relevant concentrations and where high-resolution structural information is available for the protein bound to alcohol at these concentrations. The structures of the LUSH–alcohol complexes identify a set of specific hydrogen-bonding interactions as cr...

  5. 中西医结合治疗黄素化不破裂卵泡综合症的研究近况%Research recent situation on luteinized unraptured follicle syndrome with ITCWM

    Institute of Scientific and Technical Information of China (English)

    钟紫英; 李林

    2010-01-01

    @@ 一些发育正常的成熟的卵泡不破裂而原位黄素化称为黄素化不破裂卵泡综合征(Luteinized unraptured follicle syn-drone,LUFS)、卵泡未排出而出现泡膜细胞和颗粒细胞发生原位黄素化,形成黄体并分泌孕激素,致使效应器官发生一系列类似排卵周期的改变--BBT呈双相,但其高温相呈阶梯式缓慢上升,且不稳定,由于其持续性不排卵或排卵异常,从而成为不孕症的主要原因之一.

  6. Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

    Science.gov (United States)

    Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

    2013-05-01

    Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. PMID:23528712

  7. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    High (17 nM) and low (603 nM) affinity binding sites for [3]tetrahydrotrazodone ([3] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [3]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [3] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [3]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  8. Effect of ovulation monitoring with blood estradiol, progestogen, and luteinizing hormone combined with transvaginal ultrasonography, urine luteinizing hormone peak on opportunity of intrauterine insemination%血E2、P、LH联合阴道B超、尿LH峰监测排卵对IUI手术时机的影响

    Institute of Scientific and Technical Information of China (English)

    韦冰; 邹琳; 许丽华

    2012-01-01

    Objective: To analyze the clinical data of patients receiving intrauterine insemination (IUI) , explore the effect of ovulation monitoring with blood estradiol, progestogen, and luteinizing hormone (LH) combined with transvaginal ultrasonography, urine LH peak on opportunity of IUI. Methods; A total of 89 couples (190 cycles) who received IUI treatment because of infertility in the hospital from January 2009 to December 2011 were selected, and the patients entering into cycles were randomly divided into group A ( monitoring follicular development with transvaginal ultrasonography plus urine LH peak) and group B (monitoring follicular development with transvaginal ultrasonography plus urine LH peak plus blood estradiol, progestogen, and LH) , the clinical pregnancy rates in the two groups were compared. Results; The clinical pregnancy rate in group B was statistically significantly higher than that in group A ( P < 0. 05 ) . Conclusion: The value of ovulation monitoring with blood estradiol, progestogen, and LH combined with transvaginal ultrasonography, urine LH peak during the course of IUI for predicting the opportunity of IUI was superior to that of transvaginal ultrasonography combined with urine LH peak only.%目的:分析夫精宫腔内人工授精(Intrauterine insemination,IUI)患者的临床资料,探讨IUI过程中血雌二醇(E2)、孕酮(P)、黄体生成素(LH)联合阴超以及尿LH峰监测排卵对IUI手术时机的影响.方法:选择2009年1月~2011月12月因不孕在广东医学院附属医院生殖医学中心进行IUI治疗的夫妇89对共190个周期,将进入周期的患者随机分为阴道彩超+尿LH峰监测卵泡发育组(A组)和阴道彩超+尿LH峰+血E2、P、LH监测卵泡发育组(B组),比较两组临床妊娠率的差异.结果:B组临床妊娠率高于A组,差异有统计学意义(P<0.05).结论:IUI过程中血E2、P、LH联合阴超、尿LH峰监测排卵对IUI手术时机的判断优于仅阴超+尿LH峰监测排卵.

  9. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese Transferência de luteína na fabricação de queijo prato, estabilidade da cor e aceitação sensorial

    Directory of Open Access Journals (Sweden)

    Mirian Tiaki Kaneiwa Kubo

    2013-02-01

    Full Text Available The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine the transference of the lutein (dye, added to the milk, in the whey, and cheese, to evaluate the effect of the lutein addition, light exposure, and storage time on the cheese color, and to verify the sensory acceptance of Prato cheese with addition of lutein. The lutein recovery of cheese was 95.25%. Color saturation (chrome increased during storage time resulting in a cheese with more intense color, but there were no changes in the hue of the cheese. Adjusting the amount of lutein added to Prato cheese may lead to greater acceptance. The high recovery of lutein in the cheese and the fact that the hue remained unchanged during storage under light showed that the incorporation of lutein into Prato cheese is feasible from a technical point of view.A ingestão de luteína está associada à prevenção e redução da degeneração macular relacionada à idade e a sua adição em queijo Prato, como corante de tom amarelado, é uma alternativa válida para aumentar a ingestão diária desse composto. Entretanto, parte da luteína adicionada pode ser perdida no soro durante a fabricação do queijo e também, ser degradada pela ação da luz durante armazenamento, resultando em mudanças na cor dos queijos, diminuindo a aceitação sensorial. O objetivo do trabalho foi determinar a transferência do corante luteína, adicionado ao leite, no soro e queijo, avaliar o efeito da adição de luteína, exposição à luz e tempo de armazenamento na cor do queijo e

  10. TNIP1 reduction of HSPA6 gene expression occurs in promoter regions lacking binding sites for known TNIP1-repressed transcription factors

    OpenAIRE

    Ramirez, Vincent P.; Krueger, Winfried; Aneskievich, Brian J.

    2014-01-01

    TNFα-induced protein 3-interacting protein 1 (TNIP1) represses signaling pathways initiated by specific nuclear and transmembrane receptors. This effect results in reduced activity of distinct transcription factors such as retinoic acid receptors (RAR), peroxisome-proliferator-activated receptors (PPAR), and NFκB. TNIP1-null and TNIP1-knockin defective for ubiquitin-binding mice show increased liver apoptosis, and enlarged spleen and lymph nodes, respectively. To complement current knowledge ...

  11. Windows Presentation Foundation & Data Binding

    OpenAIRE

    JANDA, Vilém

    2010-01-01

    The aim of this work is a course in the form of e-learning study materials for the interpretation of technology Data Binding in Windows Presentation Foundation (WPF). In the first, mostly theoretical part will be done a description and interpretation of the elements of technology, focusing on WPF Data Binding. In the second part, is available methodology and training course with their own interpretive audio-visual files for self-study. The lectures are supplemented by solved examples, and exa...

  12. Fast renal trapping of porcine luteinizing hormone (pLH) shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life.

    OpenAIRE

    Locatelli Alain; Magallon Thierry; Leroux Hervé; Lecompte François; Bernard Serge; Klett Danièle; Lepape Alain; Combarnous Yves

    2003-01-01

    Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH) and equine CG (eCG) which exhibit respectively a short and a long half-life. This was done first by f...

  13. Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression

    OpenAIRE

    Yang, Fang; CHEN, FENXIA; Gu, Jun; Zhang, Wenwen; Luo, Jiayan; Guan, Xiaoxiang

    2014-01-01

    The GATA binding protein 3 (GATA3) is a member of a family of 6 GATA dual zinc finger transcription factors (GATA1-6), which are required for the development and morphogenesis of the mammary gland. GATA3 is considered to play a dual role in oncogenesis and cancer development, whereas somatic GATA3 mutations have been reported in breast cancer. Variants of the GATA3 genetic 3′ untranslated region (3′UTR) microRNA (miRNA) binding sites have been associated with breast cancer risk. However, the ...

  14. 牛类胰岛素生长因子结合蛋白3基因PCR-SSCP分析%PCR-SSCP Analysis on the Insulin-like Growth Factor Binding Protein 3 Gene in Beef

    Institute of Scientific and Technical Information of China (English)

    高雪; 徐秀容; 许尚忠; 任红艳; 张英汉

    2006-01-01

    采用PCR-SSCP技术分析了牛类胰岛素生长因子结合蛋白3(IGFBP3)基因在南阳牛、鲁西牛和中国西门塔尔牛3个牛品种中的遗传多态性.结果表明:IGFBP3的第3外显子不存在遗传多态性;第2外显子在3个牛品种中检测到了AA、AB和BB基因型,而且A等位基因为3个牛群体的优势等位基因,分布较高.3个品种中,中国西门塔尔牛AA基因型频率最高,达到0.6615,而鲁西牛和南阳牛则相对较低,分别为0.4043和0.3095.对第2外显子的多态片段测序分析表明:位于IGFBP3基因第8 069 bp处发生单碱基突变T→C,并导致了苯丙氨酸变为亮氨酸.

  15. Synergistic effects of 1,25-Dihydroxyvitamin D3 and TGF-beta1 on the production of insulin-like growth factor binding protein 3 in human bone marrow stromal cell cultures

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Kassem, M

    2002-01-01

    1,25-Dihydroxyvitamin D3 (calcitriol), transforming growth factor-beta (TGF-beta), and insulin-like growth factors (IGFs) are all important bone regulatory factors known to affect proliferation and differentiation of human bone-forming cells (osteoblasts). We have previously shown that TGF-beta1 ...

  16. Effects of Insulin-Like Growth Factor (IGF)-I/IGF-Binding Protein-3 Treatment on Glucose Metabolism and Fat Distribution in Human Immunodeficiency Virus-Infected Patients with Abdominal Obesity and Insulin Resistance

    OpenAIRE

    Rao, Madhu N.; Mulligan, Kathleen; Tai, Viva; Wen, Michael J.; Dyachenko, Artem; Weinberg, Melissa; Li, Xiaojuan; Lang, Thomas; Grunfeld, Carl; Schwarz, Jean-Marc; Schambelan, Morris

    2010-01-01

    Context: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals.

  17. Angiopoietin like protein 3 (Angptl3, fatty acid binding protein 4 (FABP4 and homeostasis model assessment of insulin resistance (HOMA-IR among Indonesian obese non diabetic males

    Directory of Open Access Journals (Sweden)

    Yani Lina

    2010-08-01

    Full Text Available Aim To reveal the correlation between Angptl3, FABP4 and HOMA-IR among Indonesian obese non diabetic males.Methods This is a cross sectional study with 133 obese non diabetic males volunteers (characterized by waist circumference > 90 cm; fasting blood glucose < 126 mg/dL; and no diabetic specific symptoms age between 30-60 years which was done in Jakarta, Indonesia. We measured biochemical markers such as Angptl3, FABP4, FFA, fasting insulin and fasting glucose. We also measured weight, height, waist circumference (WC, systolic blood pressure (SBP and diastolic blood pressure (DBP. Correlation between each marker was measured using Pearson and Spearman’s analysis.Results Pearson and Spearman’s correlation analysis showed significant positive correlation between Angptl3 and FABP4 (r = 0.319; P = 0.000, Angptl3 and FFA (r = 0.171; r = 0.049, FABP4 and HOMA-IR (r = 0.202; P = 0.019, FFA and FABP4 (r = 0.506; P = 0.000, WC and HOMA-IR (r = 0.323; P = 0.000, WC and FABP4 (r = 0.387; P = 0.000, Body Mass Index (BMI and HOMA-IR (r = 0.270; P = 0.002, BMI and FABP4 (r = 0.362; P = 0.000.Conclusion This study showed positive significant correlations between Angptl3-FABP4, Angptl3-FFA, FFA-FABP4 and FABP4-HOMA-IR. We suggest that Angptl3 can activate lipolysis in adipose tissue (through its correlation with FABP4, and Angptl3 concentration is related to insulin resistance risk among Indonesian obese non diabetic males. (Med J Indones 2010;19:185-90Key words: Angptl3, FABP4, HOMA-IR, insulin resistance, lipolysis, obesity

  18. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Allen, N.E.; Key, T.J.; Appleby, P.N.; Travis, R.C.; Roddam, A.W.; Rinaldi, S.; Egevad, L.; Rohrmann, S.; Linseisen, J.; Pischon, T.; Boeing, H.; Johnsen, N.F.; Tjonneland, A.; Gronbaek, H.; Overvad, K.; Kiemeney, L.A.L.M.; Bueno-De-Mesquita, H.B.; Bingham, S.; Khaw, K.T.; Tumino, R.; Berrino, F.; Mattiello, A.; Sacerdote, C.; Palli, D.; Quiros, J.R.; Ardanaz, E.; Navarro, C.; Larranaga, N.; Gonzalez, C.; Sanchez, M.J.; Trichopoulou, A.; Travezea, C.; Trichopoulos, D.; Jenab, M.; Ferrari, P.; Riboli, E.; Kaaks, R.

    2007-01-01

    BACKGROUND: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer. METHODS: We analyzed the association between prediagnostic ser

  19. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S; Winkler, K; Jørgensen, J O; Christiansen, J S; Skakkebaek, N E

    1994-01-01

    the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset....../l after 4 months of GH treatment (p <0.0001). In addition, the molar ratio between IGF-I and IGFBP-3 increased significantlyfrom 0.22 to 0.33 after GH treatment (p <0.0001). Bone alkaline phosphatase increased significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p <0.0001), whereas...... liver-derived alkaline phosphatase was unaltered by GH. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone alkaline phosphatase correlated significantly with the increase in serum IGFBP-3 (r = 0...

  20. Diagnostic value of measurement of serum levels of insulin-like growth factor (IGF-1) and IGF binding protein 3(IGFBP-3) for children with growth hormone deficiency (GHD)

    International Nuclear Information System (INIS)

    Objective: To appraise the feasibility of establishment of diagnosis of GHD with determination of serum IGF-1 and IGFBP-3 levels. Methods: Serum IGF-1 and IGFBP-3 levels were measured with IRMA in 38 children with GHD and 42 controls. GH releasing stimulation test was also performed in these subjects with GH amount measured by chemiluminescence immunoassay (CLIA) for contrast study and verification of the diagnosis. Results: In children with GHD, the serum IGF-1 and IGFBP-3 levels were significantly lower than those in the controls (p<0.01). The amount of GH increased in the test was also significantly less. Conclusion: Determination of serum levels of IGF-1 and IGFBP-3 can be used for the diagnosis of GHD in children, which may replace the traditional GH releasing stimulation test saving the children from repeated blood withdrawal

  1. Water binding in legume seeds

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    The physical status of water in seeds has a pivotal role in determining the physiological reactions that can take place in the dry state. Using water sorption isotherms from cotyledon and axis tissue of five leguminous seeds, the strength of water binding and the numbers of binding sites have been estimated using van't Hoff analyses and the D'Arcy/Watt equation. These parameters of water sorption are calculated for each of the three regions of water binding and for a range of temperatures. Water sorption characteristics are reflective of the chemical composition of the biological materials as well as the temperature at which hydration takes place. Changes in the sorption characteristics with temperature and hydration level may suggest hydration-induced structural changes in cellular components.

  2. Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the postnatal lung.

    Science.gov (United States)

    Joshi, Rashika; Liu, Sheng; Brown, Montell D; Young, Sarah M; Batie, Matthew; Kofron, J Matthew; Xu, Yan; Weaver, Timmothy E; Apsley, Karen; Varisco, Brian M

    2016-02-01

    Lung stretch is critical for normal lung development and for compensatory lung growth after pneumonectomy (PNX), but the mechanisms by which strain induces matrix remodeling are unclear. Our prior work demonstrated an association of chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that strain triggered a near-instantaneous elastin-remodeling response. We sought to determine whether stretch regulates Cela1 expression and Cela1 binding to lung elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A, member 1, resulting in a higher molecular mass in lung homogenate compared to pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type II cells in the embryonic lung and predominantly in CD90-positive lung fibroblasts postnatally. During compensatory lung growth, Cela1 expression was induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections, stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition with soluble elastin completely abrogated this increase. Areas of stretch-induced elastase activity and Cela1 binding colocalized. The stretch-dependent expression and binding kinetics of Cela1 indicate an important role in stretch-dependent remodeling of the peripheral lung during development and regeneration. PMID:26443822

  3. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is...

  4. Computational Prediction of RNA-Binding Proteins and Binding Sites

    Directory of Open Access Journals (Sweden)

    Jingna Si

    2015-11-01

    Full Text Available Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%–8% of all proteins are RNA-binding proteins (RBPs. Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein–RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein–RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  5. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  6. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  7. Scientific Opinion on the substantiation of a health claim related to a combination of lycopene, vitamin E, lutein and selenium and “helps to prepare and activate tanning” pursuant to Article 13(5 of Regulation (EC No 1924/2006

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA

    2012-12-01

    Full Text Available Following an application from Nutrilinks Sarl, submitted pursuant to Article 13(5 of Regulation (EC No 1924/2006 via the Competent Authority of Cyprus, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to deliver an opinion on the scientific substantiation of a health claim related to a combination of lycopene, vitamin E, lutein and selenium and “helps to prepare and activate tanning”. The Panel considers that the combination of lycopene, vitamin E, lutein and selenium is sufficiently characterised. The claimed effect proposed by the applicant is “helps to prepare and activate tanning”. Tanning (i.e. increasing the pigmentation of the skin may contribute to the protection of the skin against UV-induced damage. The Panel considers that protection of the skin from UV-induced (including photo-oxidative damage is a beneficial physiological effect. A claim on a combination of lycopene, vitamin E, lutein and selenium and protection of the skin from UV-induced (including photo-oxidative damage has already been assessed by the Panel with an unfavourable outcome. The reference provided by the applicant for the scientific substantiation of this claim was the same as in the previous submission.

  8. Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy

    DEFF Research Database (Denmark)

    Horne, A W; Duncan, W C; King, A E;

    2009-01-01

    endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from...... chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to...... epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was...

  9. The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum

    DEFF Research Database (Denmark)

    Juul, A; Møller, S; Mosfeldt-Laursen, E; Rasmussen, M H; Scheike, Thomas Harder; Pedersen, S A; Kastrup, K W; Yu, Hao; Mistry, J; Rasmussen, S; Müller, J; Henriksen, J; Skakkebaek, N E

    1998-01-01

    not measurable by this approach or, alternatively, that the liver is not the primary source of circulating ALS, IGF-I, or IGFBP-3 in humans. In conclusion, we have provided extensive normal data for a novel ALS assay and found that circulating ALS levels exhibit minor diurnal variation. We suggest......Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of...

  10. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  11. Positive Emotion Facilitates Audiovisual Binding.

    Science.gov (United States)

    Kitamura, Miho S; Watanabe, Katsumi; Kitagawa, Norimichi

    2015-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level. PMID:26834585

  12. Radioligand Binding at Muscarinic Receptors

    Czech Academy of Sciences Publication Activity Database

    El-Fakahany, E. E.; Jakubík, Jan

    New York: Springer, 2016 - (Mysliveček, J.; Jakubík, J.), s. 37-68. (Neuromethods. 107). ISBN 978-1-4939-2857-6 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * radioligand binding Subject RIV: ED - Physiology

  13. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M;

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection...

  14. Interrelations between herbage yield, α-tocopherol, β-carotene, lutein, protein, and fiber in non-leguminous forbs, forage legumes, and a grass-clover mixture as affected by harvest date.

    Science.gov (United States)

    Elgersma, Anjo; Søegaard, Karen; Jensen, Søren Krogh

    2015-01-21

    Pastures with diverse botanical composition may enhance animal-derived product quality. A recent study demonstrated high vitamin concentrations and yields in some forb species. The objectives of the present study were to investigate interrelations between herbage yields, vitamin concentrations, protein and fiber contents and analyze the effect of harvest date. We hypothesized that interrelations would be similar across investigated forage species. Four nonleguminous forbs: salad burnet (Sanguisorba minor), caraway (Carum carvi), chicory (Cichorium intybus), and ribwort plantain (Plantago lanceolata), three legumes: yellow sweet clover (Melilotus officinalis), lucerne (Medicago sativa), and birdsfoot trefoil (Lotus corniculatus) and a perennial ryegrass (Lolium perenne)-white clover (Trifolium repens) mixture were sown in a field trial with two replicated and randomized blocks. Forage in 1.5 m × 9 m plots was grown in two consecutive years and cut four times per year (May-October). Analyses of variance were performed. In most herbages, α-tocopherol and β-carotene were positively correlated as were β-carotene and lutein; all vitamins were negatively correlated with fiber content and herbage yield. β-Carotene was positively correlated with protein content. α-Tocopherol and β-carotene contents were generally highest in October and lowest in July. Our results showed similar interrelationships in most investigated species, and we suggest that these species may be mixed when designing novel biodiverse mixtures for particular product quality characteristics. PMID:25573460

  15. 腹腔注射LHRH-A对黑鲷生长激素及其受体的影响%Effects of Luteinizing Hormone-releasing Hormone Analogue Injection on Growth Hormone and Its Receptor in Black Seabream

    Institute of Scientific and Technical Information of China (English)

    邓利; 林浩然

    2003-01-01

    以海水硬骨鱼类黑鲷为研究对象,腹腔注射溶于生理盐水的促性腺激素,释放激素(gonadotropin-releasing hormone,GnRH)的类似物(analogue of luteinizing hormone- releasing hormone,LHRH-A),对照组注射生理盐水.24 h后注射LHRH-A组黑鲷血清生长激素(growth hormone,GH)水平显著高于对照组(p<0.05),于36 h又恢复到对照组水平.注射LHRH-A组肝脏生长激素受体(growth hormone receptor,GHR)及GHR mRNA均与对照组无显著差异.结果表明,腹腔注射LHRH-A刺激了处于性腺成熟期黑鲷GH的分泌,但对黑鲷肝脏GHR及其基因表达无明显影响.

  16. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Previous in vivo studies have shown that Δ9-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E2 (PGE2) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

  17. Antimicrobial Peptide-Lipid Binding Interactions and Binding Selectivity

    OpenAIRE

    Lad, Mitaben D.; Birembaut, Fabrice; Clifton, Luke A.; Frazier, Richard A.; Webster, John R. P.; Green, Rebecca J.

    2007-01-01

    Surface pressure measurements, external reflection-Fourier transform infrared spectroscopy, and neutron reflectivity have been used to investigate the lipid-binding behavior of three antimicrobial peptides: melittin, magainin II, and cecropin P1. As expected, all three cationic peptides were shown to interact more strongly with the anionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-(phosphor-rac-(1-glycerol)) (DPPG), compared to the zwitterionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-phosphocho...

  18. Characteristics of human erythrocyte insulin binding sites.

    OpenAIRE

    Okada, Yoshio

    1981-01-01

    Insulin and human erythrocyte cell membrane interactions were studied with respect to binding and dissociation. The per cent of specific binding of 125I-labeled insulin to erythrocytes was directly proportional to the cell concentration. The optimum pH for binding was 8.1. The initial binding rate was directly proportional to, and the steady state insulin binding was reversely proportional to, the incubation temperature. The per cent of specific binding of 125I-labeled insulin was 12.10 +/- 1...

  19. Dissection of the Critical Binding Determinants of Cellular Retinoic Acid Binding Protein II by Mutagenesis and Fluorescence Binding Assay

    OpenAIRE

    Vasileiou, Chrysoula; Lee, Kin Sing Stephen; Crist, Rachael M.; Vaezeslami, Soheila; Goins, Sarah M.; Geiger, James H.; Borhan, Babak

    2009-01-01

    The binding of retinoic acid to mutants of Cellular Retinoic Acid Binding Protein II (CRABPII) was evaluated to better understand the importance of the direct protein/ligand interactions. The important role of Arg111 for the correct structure and function of the protein was verified and other residues that directly affect retinoic acid binding have been identified. Furthermore, retinoic acid binding to CRABPII mutants that lack all previously identified interacting amino acids was rescued by ...

  20. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen; Gammeltoft, Steen

    2012-01-01

    Proteomics and high throughput analysis for systems biology can benefit significantly from solid-phase chemical tools for affinity pull-down of proteins from complex mixtures. Here we report the application of solid-phase synthesis of phosphopeptides for pull-down and analysis of the affinity...... profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides......, without the need for phosphopeptide mimics or phosphatase inhibitors. As no proven ILKAP substrates were available, we selected phosphopeptide substrates among known PP2Cδ substrates including the protein kinases: p38, ATM, Chk1, Chk2 and RSK2 and synthesized directly on PEGA solid supports through a BAL...

  1. Optical binding of unlike particles

    Czech Academy of Sciences Publication Activity Database

    Karásek, Vítězslav; Zemánek, Pavel

    Bellingham : SPIE, 2012, 86970T: 1-6. ISBN 978-0-8194-9481-8. [CPS 2012. Czech-Polish-Slovak Optical Conference on Wave and Quantum Aspects of Contemporary Optics /18./. Ostravice (CZ), 03.09.2012-07.09.2012] R&D Projects: GA ČR GPP205/12/P868 Institutional support: RVO:68081731 Keywords : Optical binding * Optical tweezers * self-arrangement * colloids Subject RIV: BH - Optics, Masers, Lasers

  2. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  3. Positive Emotion Facilitates Audiovisual Binding

    OpenAIRE

    Kitamura, Miho S.; Watanabe, Katsumi; Kitagawa, Norimichi

    2016-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each oth...

  4. Binding effects and nuclear shadowing

    OpenAIRE

    Indumathi, D.; Wei ZHU

    1996-01-01

    The effects of nuclear binding on nuclear structure functions have so far been studied mainly at fixed target experiments, and there is currently much interest in obtaining a clearer understanding of this phenomenon. We use an existing dynamical model of nuclear structure functions, that gives good agreement with current data, to study this effect in a kinematical regime (low $x$, high $Q^2$) that can possibly be probed by an upgrade of {\\sc hera} at {\\sc desy} into a nuclear accelerator.

  5. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  6. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  7. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  8. A conformational analysis of mouse Nalp3 domain structures by molecular dynamics simulations, and binding site analysis.

    Science.gov (United States)

    Sahoo, Bikash R; Maharana, Jitendra; Bhoi, Gopal K; Lenka, Santosh K; Patra, Mahesh C; Dikhit, Manas R; Dubey, Praveen K; Pradhan, Sukanta K; Behera, Bijay K

    2014-05-01

    Scrutinizing various nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) genes in higher eukaryotes is very important for understanding the intriguing mechanism of the host defense against pathogens. The nucleotide-binding domain (NACHT), leucine-rich repeat (LRR), and pyrin domains (PYD)-containing protein 3 (Nalp3), is an intracellular innate immune receptor and is associated with several immune system related disorders. Despite Nalp3's protective role during a pathogenic invasion, the molecular features and structural organization of this crucial protein is poorly understood. Using comparative modeling and molecular dynamics simulations, we have studied the structural architecture of Nalp3 domains, and characterized the dynamic and energetic parameters of adenosine triphosphate (ATP) binding in NACHT, and pathogen-derived ligands muramyl dipeptide (MDP) and imidazoquinoline with LRR domains. The results suggested that walker A, B and extended walker B motifs were the key ATP binding regions in NACHT that mediate self-oligomerization. The analysis of the binding sites of MDP and imidazoquinoline revealed LRR 7-9 to be the most energetically favored site for imidazoquinoline interaction. However, the binding free energy calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method indicated that MDP is incompatible for activating the Nalp3 molecule in its monomeric form, and suggest its complex interaction with NOD2 or other NLRs accounts for MDP recognition. The high binding affinity of ATP with NACHT was correlated to the experimental data for human NLRs. Our binding site prediction for imidazoquinoline in LRR warrants further investigation via in vivo models. This is the first study that provides ligand recognition in mouse Nalp3 and its spatial structural arrangements. PMID:24595807

  9. Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby; Janukonyté, Jurgita; Klose, Marianne;

    2016-01-01

    CONTEXT: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. OBJECTIVES: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with...... daily GH. DESIGN AND SETTING: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. PATIENTS: Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. INTERVENTIONS AND MAIN OUTCOME MEASURES: Subjects were...... assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and...

  10. Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction.

    Science.gov (United States)

    Harada, Tanenobu; Iwai, Atsushi; Miyazaki, Tadaaki

    2010-10-01

    Death associated protein 3 (DAP3) is known to be a highly conserved protein, and is responsible for regulating apoptosis induced by various stimuli. To understand the molecular mechanism of how DAP3 induces apoptosis, we performed yeast two-hybrid screening, and identified a novel DAP3-binding protein termed death ligand signal enhancer (DELE). In this report, we show that DELE actually binds to DAP3 in mammalian cells. We found that the cells stably expressing DELE are susceptible to apoptosis induction by the stimulation of TNF-α and TRAIL. In addition, knockdown of DELE expression rescued the HeLa cells from apoptosis induction by these stimuli. Moreover, activation of caspase-3, caspase-8 and caspase-9 induced by stimulation of TNF-α, anti-Fas or TRAIL was significantly inhibited by the knockdown of DELE expression. These results demonstrated the biological significance of DELE for apoptosis signal mediated by death receptors. PMID:20563667

  11. Fast renal trapping of porcine Luteinizing Hormone (pLH shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life

    Directory of Open Access Journals (Sweden)

    Locatelli Alain

    2003-10-01

    Full Text Available Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH and equine CG (eCG which exhibit respectively a short and a long half-life. This was done first by following half-lives of pLH in piglets with hepatic portal circulation shunted or not. It was expected that such a shunt would enhance the short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and 123I-eCG was performed in intact rats to compare their routes and rates of distribution and elimination. Methods Native pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anæsthetized piglet. Blood samples were recovered sequentially over one hour time and the hormone concentrations were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and 123I-eCG was performed in rats using a OPTI-CGR gamma camera. Results In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min. In the rat, the half-life of pLH was also found to be very short (3–6 min and 123I-pLH was found to accumulate in high quantity in less than 10 min post injection at the level of kidneys but not in the liver. 123I-eCG didn't accumulate in any organ in the rats during the first hour, plasma concentrations of this gonadotropin being still elevated (80% at this time. Conclusion In both the porcine and rat species, the liver is not responsible for the rapid elimination of pLH from the circulation compared to eCG. Our scintigraphic experiments suggest that the very short circulatory half-life of LH is due to rapid renal trapping.

  12. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  13. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  14. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  15. Binding of quasi two-dimensional biexcitons

    DEFF Research Database (Denmark)

    Birkedal, Dan; Singh, J; Vadim, Lyssenko; Hvam, Jørn Märcher

    Summary form only given. In this presentation we report on a determination of the biexciton binding energies in GaAs-AlGaAs quantum wells of different widths and the results of a theoretical calculation of the ratio of the biexciton binding energy to that of the exciton. We determine the binding ...

  16. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik; Hong, Eun-Hee [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae [Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye; Um, Hong-Duck [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2013-09-27

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

  17. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    International Nuclear Information System (INIS)

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer

  18. MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3.

    Science.gov (United States)

    Zhang, Lingyun; Ke, Fang; Liu, Zhaoyuan; Bai, Jing; Liu, Jinlin; Yan, Sha; Xu, Zhenyao; Lou, Fangzhou; Wang, Hong; Zhu, Huiyuan; Sun, Yang; Cai, Wei; Gao, Yuanyuan; Li, Qun; Yu, Xue-Zhong; Qian, Youcun; Hua, Zichun; Deng, Jiong; Li, Qi-Jing; Wang, Honglin

    2015-01-01

    Peripherally derived regulatory T (pT(reg)) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pT(reg)-cell generation. miR-31 conditional deletion results in enhanced induction of pT(reg) cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pT(reg-)cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pT(reg)-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional T(reg) cells in autoimmune diseases. PMID:26165721

  19. The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

    Institute of Scientific and Technical Information of China (English)

    李家文; 李东升; 谭志建

    2004-01-01

    Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL 17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1. 1416±0. 0591, which was significantly higher than that in normal controls (0. 8788±0. 0344, P<0. 001). The expression levels of IFN-γ mRNA were 1.1142±0. 0561 and 0. 9050±0. 0263, respectively, with significant difference(P<0. 001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1. 1397 ± 0. 0521, which was markedly higher than that in normal controls (0. 8681±0. 0308, P<0. 001). These findings indicate that up regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

  20. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Flyvbjerg, Allan; Frystyk, Jan;

    1996-01-01

    Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF......-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied....

  1. Proteomic analysis of egg white heparin-binding proteins: towards the identification of natural antibacterial molecules.

    Science.gov (United States)

    Guyot, Nicolas; Labas, Valérie; Harichaux, Grégoire; Chessé, Magali; Poirier, Jean-Claude; Nys, Yves; Réhault-Godbert, Sophie

    2016-01-01

    The chicken egg resists most environmental microbes suggesting that it potentially contains efficient antimicrobial molecules. Considering that some heparin-binding proteins in mammals are antibacterial, we investigated the presence and the antimicrobial activity of heparin-binding proteins from chicken egg white. Mass spectrometry analysis of the proteins recovered after heparin-affinity chromatography, revealed 20 proteins, including known antimicrobial proteins (avidin, lysozyme, TENP, ovalbumin-related protein X and avian bêta-defensin 11). The antibacterial activity of three new egg candidates (vitelline membrane outer layer protein 1, beta-microseminoprotein-like (LOC101750704) and pleiotrophin) was demonstrated against Listeria monocytogenes and/or Salmonella enterica Enteritidis. We showed that all these molecules share the property to inhibit bacterial growth through their heparin-binding domains. However, vitelline membrane outer layer 1 has additional specific structural features that can contribute to its antimicrobial potential. Moreover, we identified potential supplementary effectors of innate immunity including mucin 5B, E-selectin ligand 1, whey acidic protein 3, peptidyl prolyl isomerase B and retinoic acid receptor responder protein 2. These data support the concept of using heparin affinity combined to mass spectrometry to obtain an overview of the various effectors of innate immunity composing biological milieus, and to identify novel antimicrobial candidates of interest in the race for alternatives to antibiotics. PMID:27294500

  2. Degradation of LIM domain-binding protein three during processing of Spanish dry-cured ham.

    Science.gov (United States)

    Gallego, Marta; Mora, Leticia; Fraser, Paul D; Aristoy, María-Concepción; Toldrá, Fidel

    2014-04-15

    Extensive proteolysis takes place during the processing of dry-cured ham due to the action of muscle peptidases. The aim of this work was to study the degradation of LIM domain binding protein 3 (LDB3), which is located at the Z-lines of the sarcomere, at different times during the Spanish dry-cured ham processing (2, 3.5, 5, 6.5, and 9 months). A total of 107 peptides have been identified by mass spectrometry, most of them generated from the first region of the protein sequence (position 1-90) providing evidence for the complexity and variability of proteolytic reactions throughout the whole process of dry-curing. Methionine oxidation has been observed in several peptides by the end of the process. The potential of some of the identified peptides to be used as biomarkers of dry-cured ham processing has also been considered. PMID:24295685

  3. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release.

    Science.gov (United States)

    D'Aniello, A; Di Fiore, M M; Fisher, G H; Milone, A; Seleni, A; D'Aniello, S; Perna, A F; Ingrosso, D

    2000-04-01

    Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D-Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D-Asp-induced LH secretion from the pituitary gland. Compared to D-Asp, NMDA elicits its hormone release action at concentrations approximately 100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D-Asp by an S-adenosylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase. PMID:10744627

  4. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  5. Glucocorticoid receptor transformation and DNA binding

    International Nuclear Information System (INIS)

    The overall goal is to probe the mechanism whereby glucocorticoid receptors are transformed from a non-DNA-binding form to their active DNA-binding form. The author has examined the effect of an endogenous inhibitor purified from rat liver cytosol on receptor binding to DNA. The inhibitor binds to transformed receptors in whole cytosol and prevent their binding to DNA. He also examined the role of sulfhydryl groups in determining the DNA binding activity of the transformed receptor and in determining the transformation process. Treatment of rat liver cytosol containing temperature-transformed, [3H]dexamethasone-bound receptors at 00C with the sulfhydryl modifying reagent methyl methanethiosulfonate inhibits the DNA-binding activity of the receptor, and DNA-binding activity is restored after addition of dithiothreitol. In addition, he has examined the relationship between receptor phosphorylation and DNA binding. Untransformed receptor complexes purified from cytosol prepared from mouse L cells grown in medium containing [32P]orthophosphate contain two components, a 100 k-Da and a 90-kDa subunit, both of which are phosphoproteins. On transformation, the receptor dissociates from the 90-kDa protein. Transformation of the complex under cell free conditions does not result in a dephosphorylation of the 100-kDa steroid-binding protein. Transformed receptor that has been bound to DNA and purified by monoclonal antibody is still in a phosphorylated form. These results suggest that dephosphorylation is not required for receptor binding to DNA

  6. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug...... is bound per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn...

  7. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  8. Heart-type fatty-acid-binding protein (FABP3) is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Science.gov (United States)

    Tsukahara, Ryoko; Haniu, Hisao; Matsuda, Yoshikazu; Tsukahara, Tamotsu

    2014-01-01

    Fatty-acid-binding protein 3, muscle and heart (FABP3), also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs). In this study, using lysophosphatidic acid (LPA)-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs). Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA). We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus. PMID:25426414

  9. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  10. Impaired Lysosomal Integral Membrane Protein 2-dependent Peroxiredoxin 6 Delivery to Lamellar Bodies Accounts for Altered Alveolar Phospholipid Content in Adaptor Protein-3-deficient pearl Mice.

    Science.gov (United States)

    Kook, Seunghyi; Wang, Ping; Young, Lisa R; Schwake, Michael; Saftig, Paul; Weng, Xialian; Meng, Ying; Neculai, Dante; Marks, Michael S; Gonzales, Linda; Beers, Michael F; Guttentag, Susan

    2016-04-15

    The Hermansky Pudlak syndromes (HPS) constitute a family of disorders characterized by oculocutaneous albinism and bleeding diathesis, often associated with lethal lung fibrosis. HPS results from mutations in genes of membrane trafficking complexes that facilitate delivery of cargo to lysosome-related organelles. Among the affected lysosome-related organelles are lamellar bodies (LB) within alveolar type 2 cells (AT2) in which surfactant components are assembled, modified, and stored. AT2 from HPS patients and mouse models of HPS exhibit enlarged LB with increased phospholipid content, but the mechanism underlying these defects is unknown. We now show that AT2 in the pearl mouse model of HPS type 2 lacking the adaptor protein 3 complex (AP-3) fails to accumulate the soluble enzyme peroxiredoxin 6 (PRDX6) in LB. This defect reflects impaired AP-3-dependent trafficking of PRDX6 to LB, because pearl mouse AT2 cells harbor a normal total PRDX6 content. AP-3-dependent targeting of PRDX6 to LB requires the transmembrane protein LIMP-2/SCARB2, a known AP-3-dependent cargo protein that functions as a carrier for lysosomal proteins in other cell types. Depletion of LB PRDX6 in AP-3- or LIMP-2/SCARB2-deficient mice correlates with phospholipid accumulation in lamellar bodies and with defective intraluminal degradation of LB disaturated phosphatidylcholine. Furthermore, AP-3-dependent LB targeting is facilitated by protein/protein interaction between LIMP-2/SCARB2 and PRDX6 in vitro and in vivo Our data provide the first evidence for an AP-3-dependent cargo protein required for the maturation of LB in AT2 and suggest that the loss of PRDX6 activity contributes to the pathogenic changes in LB phospholipid homeostasis found HPS2 patients. PMID:26907692

  11. Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1.

    Science.gov (United States)

    Pathak, Bhakti R; Breed, Ananya A; Apte, Snehal; Acharya, Kshitish; Mahale, Smita D

    2016-01-01

    Cysteine-rich secretory protein 3 (CRISP-3) is upregulated in prostate cancer as compared to the normal prostate tissue. Higher expression of CRISP-3 has been linked to poor prognosis and hence it has been thought to act as a prognostic marker for prostate cancer. It is proposed to have a role in innate immunity but its role in prostate cancer is still unknown. In order to understand its function, its expression was stably knocked down in LNCaP cells. CRISP-3 knockdown did not affect cell viability but resulted in reduced invasiveness. Global gene expression changes upon CRISP-3 knockdown were identified by microarray analysis. Microarray data were quantitatively validated by evaluating the expression of seven candidate genes in three independent stable clones. Functional annotation of the differentially expressed genes identified cell adhesion, cell motility, and ion transport to be affected among other biological processes. Prostate-specific antigen (PSA, also known as Kallikrein 3) was the top most downregulated gene whose expression was also validated at protein level. Interestingly, expression of Annexin A1 (ANXA1), a known anti-inflammatory protein, was upregulated upon CRISP-3 knockdown. Re-introduction of CRISP-3 into the knockdown clone reversed the effect on invasiveness and also led to increased PSA expression. These results suggest that overexpression of CRISP-3 in prostate tumor may maintain higher PSA expression and lower ANXA1 expression. Our data also indicate that poor prognosis associated with higher CRISP-3 expression could be due to its role in cell invasion. PMID:26369530

  12. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Risa M Wolf

    Full Text Available C1q/TNF-related protein-3 (CTRP3 is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals.This was a cross-sectional study of obese (n=44 and lean control patients (n=60. Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA.BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004 compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001, and triglycerides (p<0.001, and significantly associated with gender (p<0.01, ethnicity (p=0.05, HDL-cholesterol (p<0.01, and adiponectin (p<0.01. We found BMI (p<0.01, gender (p<0.01, and ethnicity (p<0.05 to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis.CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.

  13. Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells.

    Science.gov (United States)

    Wazir, Umar; Sanders, Andrew J; Wazir, Ahmad M A; Ye, Lin; Jiang, Wen G; Ster, Irina C; Sharma, Anup K; Mokbel, Kefah

    2015-05-01

    The death-associated protein 3 (DAP3) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP3 expression and clinicopathological parameters of human breast cancer. In the present study, we intended to determine the role of DAP3 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sub-lines of MCF7 and MDA-MB-231, and performed growth, adhesion, invasion assays and electric cell-substrate impedance sensing (ECIS) studies of post-wound migration of the cells. In addition, we studied the mRNA expression of caspase 8 and 9, death ligand signal enhancer (DELE), IFN-β promoter stimulator 1 (IPS1), cyclin D1 and p21 in the control and knockdown sub-lines. The knockdown sub-lines of MCF7 and MDA-MB-231 had significantly increased adhesion and decreased growth when compared to the controls. Furthermore, invasion and migration were significantly increased in the MDA-MB-231DAP3kd cells vs. the controls. The expression of caspase 9 and IPS1, known components of the apoptosis pathway, were significantly reduced in the MCF7DAP3kd cells (p=0.05 and p=0.003, respectively). We conclude that DAP3 silencing contributes to breast carcinogenesis by increasing cell adhesion, migration and invasion. It is possible that this may be due to the activity of focal adhesion kinase further downstream of the anoikis pathway. Further research in this direction would be beneficial in increasing our understanding of the mechanisms underlying human breast cancer. PMID:25738636

  14. Bcl-2/adenovirus E1B 19 kDa interacting protein-3 knockdown enables growth of breast cancer metastases in the lung, liver, and bone.

    Science.gov (United States)

    Manka, David; Spicer, Zachary; Millhorn, David E

    2005-12-15

    The mouse breast cancer cell lines 4T1, 4T07, and 67NR are highly tumorigenic but vary in metastatic potential: 4T1 widely disseminates, resulting in secondary tumors in the lung, liver, bone, and brain; 4T07 spreads to the lung and liver but is unable to establish metastatic nodules; 67NR is unable to metastasize. The Bcl-2/adenovirus E1B 19 kDa interacting protein-3 (Bnip-3) was recently shown to be absent after hypoxia in pancreatic cancer cell lines whereas its overexpression restored hypoxia-induced cell death. We found that Bnip-3 expression increased after 6 hours of hypoxia in all cell lines tested but was highest in the nonmetastatic 67NR cells and lowest in the highly metastatic 4T1 cells. Hypoxia-induced expression of Bnip-3 in the disseminating but nonmetastatic 4T07 cells was intermediate compared with 4T1 and 67NR cells. Cleaved caspase-3, a key downstream effector of cell death, increased after 6 hours of hypoxia in the 67NR and 4T07 cells by 1.9- and 2.5-fold, respectively. Conversely, cleaved caspase-3 decreased by 45% in the highly metastatic 4T1 cells after hypoxia. Small interfering RNA oligonucleotides targeting endogenous Bnip-3 blocked cell death and increased clonigenic survival after hypoxic challenge in vitro and increased primary tumor size and enabled metastasis to the lung, liver, and sternum of mice inoculated with 4T07 cells in vivo. These data inversely correlate the hypoxia-induced expression of the cell death protein Bnip-3 to metastatic potential and suggest that loss of Bnip-3 expression is critical for malignant and metastatic evasion of hypoxia-induced cell death. PMID:16357180

  15. Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis

    DEFF Research Database (Denmark)

    Kristensen, B; Hegedüs, Laszlo; Madsen, H O; Smith, T J; Nielsen, Claus Henrik

    2015-01-01

    T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3)...

  16. Erythropoietin binding sites in human foetal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pekonen, F.; Rosenloef, K.; Rutanen, E.-M.

    1987-01-01

    Using /sup 125/I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 10/sup 9/l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked /sup 125/I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively.

  17. Binding characteristics of swine erythrocyte insulin receptors

    International Nuclear Information System (INIS)

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine

  18. Erythropoietin binding sites in human foetal tissues

    International Nuclear Information System (INIS)

    Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 109l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively. (author)

  19. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  20. Methods for Improving Aptamer Binding Affinity

    OpenAIRE

    Hijiri Hasegawa; Nasa Savory; Koichi Abe; Kazunori Ikebukuro

    2016-01-01

    Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of a...

  1. Predicted metal binding sites for phytoremediation

    OpenAIRE

    Sharma, Ashok; Roy, Sudeep; Tripathi, Kumar Parijat; Roy, Pratibha; Mishra, Manoj; Khan, Feroz; Meena, Abha

    2009-01-01

    Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. The objective of the study is to design and analyze metal binding motifs against the genes involved in phytoremediation. This is being done on the basis of certain pre-requisite amino-acid residues known to bind metal ions/metal complexes in medicinal and aromatic plants (MAP's). Earlier work on MAP's have shown that heavy metals accumulated by aromatic and medicinal plants do no...

  2. RNA Binding Specificity of Drosophila Muscleblind†

    OpenAIRE

    Goers, Emily S.; Voelker, Rodger B.; Gates, Devika P.; Berglund, J. Andrew

    2008-01-01

    Members of the muscleblind family of RNA binding proteins found in Drosophila and mammals are key players in both the human disease myotonic dystrophy and the regulation of alternative splicing. Recently, the mammalian muscleblind-like protein, MBNL1, has been shown to have interesting RNA binding properties with both endogenous and disease-related RNA targets. Here we report the characterization of RNA binding properties of the Drosophila muscleblind protein Mbl. Mutagenesis of double-strand...

  3. Exciton Binding Energy of Monolayer WS2

    OpenAIRE

    Bairen Zhu; Xi Chen; Xiaodong Cui

    2015-01-01

    The optical properties of monolayer transition metal dichalcogenides (TMDC) feature prominent excitonic natures. Here we report an experimental approach toward measuring the exciton binding energy of monolayer WS2 with linear differential transmission spectroscopy and two-photon photoluminescence excitation spectroscopy (TP-PLE). TP-PLE measurements show the exciton binding energy of 0.71eV around K valley in the Brillouin zone. The trion binding energy of 34meV, two-photon absorption cross s...

  4. A computational model for feature binding

    Institute of Scientific and Technical Information of China (English)

    SHI ZhiWei; SHI ZhongZhi; LIU Xi; SHI ZhiPing

    2008-01-01

    The "Binding Problem" is an important problem across many disciplines, including psychology, neuroscience, computational modeling, and even philosophy. In this work, we proposed a novel computational model, Bayesian Linking Field Model, for feature binding in visual perception, by combining the idea of noisy neuron model, Bayesian method, Linking Field Network and competitive mechanism.Simulation Experiments demonstrated that our model perfectly fulfilled the task of feature binding in visual perception and provided us some enlightening idea for future research.

  5. Binding of cryptococcal polysaccharide to Cryptococcus neoformans.

    OpenAIRE

    Kozel, T R; Hermerath, C A

    1984-01-01

    Radioiodinated cryptococcal polysaccharide was used to study binding of the soluble polysaccharide to encapsulated and non-encapsulated cryptoccoci. Binding of polysaccharide to non-encapsulated cryptococci occurred rapidly over a 30-min period and was largely complete after 2 h. Bound, labeled polysaccharide was slowly eluted from Cryptococcus neoformans after the addition of unlabeled polysaccharide, indicating reversibility of binding. Non-encapsulated cryptococci bound polysaccharide in t...

  6. A computational model for feature binding

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The "Binding Problem" is an important problem across many disciplines, including psychology, neuroscience, computational modeling, and even philosophy. In this work, we proposed a novel computational model, Bayesian Linking Field Model, for feature binding in visual perception, by combining the idea of noisy neuron model, Bayesian method, Linking Field Network and competitive mechanism. Simulation Experiments demonstrated that our model perfectly fulfilled the task of feature binding in visual perception and provided us some enlightening idea for future research.

  7. Muscle uncoupling protein 3 expression is unchanged by chronic ephedrine/caffeine treatment: results of a double blind, randomised clinical trial in morbidly obese females.

    Directory of Open Access Journals (Sweden)

    Renata Bracale

    Full Text Available Ephedrine/caffeine combination (EC has been shown to induce a small-to-moderate weight loss in obese patients. Several mechanisms have been proposed, among which an increased thermogenic capacity of skeletal muscle consequent to the EC-induced up-regulation of uncoupling protein 3 (UCP3 gene expression. We did a parallel group double-blind, placebo-controlled, 4-week trial to investigate this hypothesis. Thirteen morbidly obese women (25-52 years of age, body-mass index 48.0±4.0 kg/m2, range 41.1-57.6 were randomly assigned to EC (200/20 mg, n = 6 or to placebo (n = 7 administered three times a day orally, before undergoing bariatric surgery. All individuals had an energy-deficit diet equal to about 70% of resting metabolic rate (RMR diet (mean 5769±1105 kJ/day. The RMR analysed by intention to treat and the UCP3 (long and short isoform mRNA levels in rectus abdominis were the primary outcomes. Body weight, plasma levels of adrenaline, noradrenaline, triglycerides, free fatty acids, glycerol, TSH, fT4, and fT3 were assessed, as well as fasting glucose, insulin and HOMA index, at baseline and at the end of treatments. Body weight loss was evident in both groups when compared to baseline values (overall -5.2±3.2%, p<0.0001 without significant differences between the treated groups. EC treatment increased the RMR (+9.2±6.8%, p = 0.020, differently from placebo which was linked to a reduction of RMR (-7.6±6.5%, p = 0.029. No significant differences were seen in other metabolic parameters. Notably, no changes of either UCP3 short or UCP3 long isoform mRNA levels were evident between EC and placebo group. Our study provides evidence that 4-week EC administration resulted in a pronounced thermogenic effect not related to muscle UCP3 gene expression and weight loss in morbidly obese females under controlled conditions.ClinicalTrials.gov NCT02048215.

  8. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.

    Directory of Open Access Journals (Sweden)

    Christian Roussilhon

    2007-11-01

    Full Text Available BACKGROUND: Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite to molecules that are considered as valuable vaccine candidates. METHODS AND FINDINGS: We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults. The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3, was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week. Finally, the target epitopes of these antibodies were found to be fully conserved. CONCLUSIONS: Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be

  9. Copper(II) binding properties of hepcidin

    OpenAIRE

    Kulprachakarn, Kanokwan; Chen, Yu-Lin; Kong, Xiaole; Arno, Maria Chiara; Hider, Robert Charles; Srichairatanakool, Somdet; Bansal, Sukhvinder

    2016-01-01

    Hepcidin is a peptide hormone that regulates the homeostasis of iron metabolism. The N-terminal domain of hepcidin is conserved amongst a range of species and is capable of binding CuII and NiII through the amino terminal copper–nickel binding motif (ATCUN). It has been suggested that the binding of copper to hepcidin may have biological relevance. In this study we have investigated the binding of CuII with model peptides containing the ATCUN motif, fluorescently labelled hepcidin and hepcidi...

  10. Advances on Plant Pathogenic Mycotoxin Binding Proteins

    Institute of Scientific and Technical Information of China (English)

    WANG Chao-hua; DONG Jin-gao

    2002-01-01

    Toxin-binding protein is one of the key subjects in plant pathogenic mycotoxin research. In this paper, new advances in toxin-binding proteins of 10 kinds of plant pathogenic mycotoxins belonging to Helminthosporium ,Alternaria ,Fusicoccum ,Verticillium were reviewed, especially the techniques and methods of toxin-binding proteins of HS-toxin, HV-toxin, HMT-toxin, HC-toxin. It was proposed that the isotope-labeling technique and immunological chemistry technique should be combined together in research of toxin-binding protein, which will be significant to study the molecular recognition mechanism between host and pathogenic fungus.

  11. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  12. 女生初潮年龄提前与黄体生成素受体基因Asp578Gly突变%Asp578 Gly mutation of luteinizing hormone receptor in girls with early menarche

    Institute of Scientific and Technical Information of China (English)

    朱丁; 钱红丹; 徐勇; 张敏婕; 沈惠芬; 刘起展

    2011-01-01

    目的 研究黄体生成素受体(LHR)基因Asp57s Gly突变与女生初潮年龄提前的关系,为青少年青春期发育研究提供依据.方法 分层整群抽取无锡市177名初潮年龄提前(初潮年龄<11岁)女生,外周血提取DNA,用5’-CAC TGC TGG CTT TTT CAC TGT ATT-3’和5’-TGA AGG CAG CTG AGA TGG CAA AAA-3作引物,经常规PCR扩增后,用限制性内切酶Msp I消化,以检测LHR基因是否存在A1733G的碱基突变.结果 初潮年龄提前组LH水平高于正常组(P<0.05),而两组FSH差异无统计学意义(P>0.05).177名初潮年龄提前女生的LHR基因均末检测到Asp578 Gly突变.结论 Asp578 Gly突变与女性初潮年龄提前无直接关系.%Objective To identify the relationship between early menarche and Asp578 Gly mutation of luteinizing hormone receptor) LHR). Methods A total of 177 girls defined as early menarche ( age of menarche less than 11 years old) were as subjects. The peripheral blood samples were taken from every girl. Genomic DNA was amplified by polymerase chain reaction, using primers of 5'-CAC TGC TGG CTT TIT CAC TGT ATT - 3' and 5-TGA AGG CAG CTG AGA TGG CAA AAA-3'. Then, the PCR product was treated with Msp 1 to examine whether a transition of A to G of nucleotide 1733 of the LHR cDNA existed in these girls. Results The LH level of the girls with early menarche was higher than the normal ones (P0.05). The Asp578 Gly activating mutation of LHR was not identified in the 177 girls. Conclusion The Asp578 Gly mutation of LHR gene is not related with early menarche.

  13. Identification of a conserved linear epitope using a monoclonal antibody against non-structural protein 3B of foot-and-mouth disease virus.

    Science.gov (United States)

    Li, Chaosi; Liang, Weifeng; Liu, Wenming; Yang, Decheng; Wang, Haiwei; Ma, Wenge; Zhou, Guohui; Yu, Li

    2016-02-01

    Foot-and-mouth disease virus (FMDV) is a member of the family Picornaviridae that has caused severe economic losses in many countries of the world. Regular vaccinations have been effectively used to control foot-and-mouth disease (FMD) in countries where the disease is enzootic. Distinguishing between infected and vaccinated animals in herds after immunization is an important component of effective eradication strategies. Nonstructural protein (NSP) 3B of FMDV is part of a larger antigen that is used for this differential diagnosis. In this study, an FMDV serotype-independent monoclonal antibody (MAb) against NSP 3B, 5D12, was generated. Using western blot, it was revealed that MAb 5D12 binds to three fragments of 3B displaying the motifs G(1)PYAGPLERQKPLK(14), K(18)LPQQEGPYAGPMER(32) and V(45)KEGPYEGPVKKPVA(59). The motif G(1)PYAGPLERQKPLK(14) was chosen for further mapping. Different truncated motifs derived from the motif G(1)PYAGPLERQKPLK(14) were expressed as GST-fusion constructs for western blot analysis. The results showed that the 5-aa peptide P(2)YAGP(6) was the minimal epitope reactive to MAb 5D12. Subsequent alanine-scanning mutagenesis analysis revealed that Pro(2), Gly(5) and Pro(6) were crucial for MAb 5D12 binding to P(2)YAGP(6). Furthermore, through sequence alignment analysis, the epitope PxxGP recognized by 5D12 was found to be present not only in 3B-1 but also in 3B2 and 3B3 and was highly conserved in seven serotypes of FMDV strains. Western blot analysis also revealed that the peptide epitope could be recognized by sera from FMDV-infected pigs and cattle. Thus, the 5D12-recognized 3B epitope identified here provides theoretical support for the development of MAb 5D12 as a differential diagnosis reagent for FMDV infection. PMID:26563318

  14. Excited-state kinetics of the carotenoid S//1 state in LHC II and two-photon excitation spectra of lutein and beta-carotene in solution Efficient Car S//1 yields Chl electronic energy transfer via hot S//1 states?

    CERN Document Server

    Walla, P J; Linden, Patricia A; Ohta, Kaoru

    2002-01-01

    The excited-state dynamics of the carotenoids (Car) in light- harvesting complex II (LHC II) of Chlamydomonas reinhardtii were studied by transient absorption measurements. The decay of the Car S //1 population ranges from similar to 200 fs to over 7 ps, depending on the excitation and detection wavelengths. In contrast, a 200 fs Car S//1 yields Chlorophyll (Chl) energy transfer component was the dominant time constant for our earlier two-photon fluorescence up- conversion measurements (Walla, P.J. ; et al. J. Phys. Chem. B 2000, 104, 4799-4806). We also present the two-photon excitation (TPE) spectra of lutein and beta-carotene in solution and compare them with the TPE spectrum of LHC II. The TPE-spectrum of LHC II has an onset much further to the blue and a width that is narrower than expected from comparison to the S//1 fluorescence of lutein and beta-carotene in solution. Different environments may affect the shape of the S//1 spectrum significantly. To explain the blue shift of the TPE spectrum and the d...

  15. Thermodynamics of ligand binding to acyl-coenzyme A binding protein studied by titration calorimetry

    DEFF Research Database (Denmark)

    Færgeman, Nils J.; Sigurskjold, B W; Kragelund, B B;

    1996-01-01

    Ligand binding to recombinant bovine acyl-CoA binding protein (ACBP) was examined using isothermal microcalorimetry. Microcalorimetric measurements confirm that the binding affinity of acyl-CoA esters for ACBP is strongly dependent on the length of the acyl chain with a clear preference for acyl-...

  16. Molecularly Responsive Binding through Co-occupation of Binding Space: A Lock-Key Story.

    Science.gov (United States)

    Awino, Joseph K; Hu, Lan; Zhao, Yan

    2016-04-01

    When two guest molecules co-occupy a binding pocket of a water-soluble host, the first guest could be used as a signal molecule to turn on the binding of the second. This type of molecularly responsive binding strongly depends on the size of the two guests and the location of the signal molecule. PMID:27001464

  17. CTCF Binding Polarity Determines Chromatin Looping

    NARCIS (Netherlands)

    de Wit, Elzo; Vos, Erica S M; Holwerda, Sjoerd J B; Valdes-Quezada, Christian; Verstegen, Marjon J A M; Teunissen, Hans; Splinter, Erik; Wijchers, Patrick J; Krijger, Peter H L; de Laat, Wouter

    2015-01-01

    CCCTC-binding factor (CTCF) is an architectural protein involved in the three-dimensional (3D) organization of chromatin. In this study, we assayed the 3D genomic contact profiles of a large number of CTCF binding sites with high-resolution 4C-seq. As recently reported, our data also suggest that ch

  18. Localization-enhanced biexciton binding in semiconductors

    DEFF Research Database (Denmark)

    Langbein, Wolfgang Werner; Hvam, Jørn Märcher

    1999-01-01

    The influence of excitonic localization on the binding energy of biexcitons is investigated for quasi-three-dimensional and quasi-two-dimensional AlxGa1-xAs structures. An increase of the biexciton binding energy is observed for localization energies comparable to or larger than the free biexcito...

  19. Gravitational Binding Energy in Charged Cylindrical Symmetry

    CERN Document Server

    Sharif, M

    2014-01-01

    We consider static cylindrically symmetric charged gravitating object with perfect fluid and investigate the gravitational binding energy. It is found that only the localized part of the mass function provides the gravitational binding energy, whereas the non-localized part generated by the electric coupling does not contribute for such energy.

  20. [3H]opipramol labels a novel binding site and sigma receptors in rat brain membranes

    International Nuclear Information System (INIS)

    Opipramol (OP), a clinically effective antidepressant with a tricyclic structure, is inactive as an inhibitor of biogenic amine uptake. [3H]Opipramol binds saturably to rat brain membranes (apparent KD = 4 nM, Bmax = 3 pmol/mg of protein). [3H]Opipramol binding can be differentiated into haloperidol-sensitive and -resistant components, with Ki values for haloperidol of 1 nM (Bmax = 1 pmol/mg of protein) and 350 nM (Bmax = 1.9 pmol/mg of protein), respectively. The drug specificity of the haloperidol-sensitive component is the same as that of sigma receptors labeled with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperdine. The haloperidol-resistant component does not correspond to any known neurotransmitter receptor or uptake recognition site. It displays high affinity for phenothiazines and related structures such as perphenazine, clopenthixol, and flupenthixol, whose potencies are comparable to that of opipramol. Because certain of these drugs are more potent at the haloperidol-resistant opipramol site than in exerting any other action, it is possible that this opipramol-selective site may mediate their therapeutic effects