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Sample records for binding globulin shbg

  1. 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 ...

  2. Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro

    NARCIS (Netherlands)

    Laurent, Michael R.; Helsen, Christine; Antonio, Leen; Schollaert, Dieter; Joniau, Steven; Vos, Michel J.; Decallonne, Brigitte; Hammond, Geoffrey L.; Vanderschueren, Dirk; Claessens, Frank

    2016-01-01

    Biochemical assessments of androgen status (hyper- or hypoandrogenism) are usually based on serum testosterone concentrations. According to the free hormone hypothesis, sex hormone-binding globulin (SHBG) determines free and bioavailable testosterone concentrations. Previous studies have suggested t

  3. Association between sex hormone-binding globulin (SHBG and metabolic syndrome among men

    Directory of Open Access Journals (Sweden)

    Emmanuela Quental Callou de Sá

    Full Text Available CONTEXT AND OBJECTIVE: Metabolic syndrome consists of a set of factors that imply increased risk of cardiovascular diseases. The objective here was to evaluate the association between sex hormone-binding globulin (SHBG, sex hormones and metabolic syndrome among men. DESIGN AND SETTING: Retrospective analysis on data from the study "Endogenous oestradiol but not testosterone is related to coronary artery disease in men", conducted in a hospital in São Paulo. METHODS: Men (aged 40-70 who underwent coronary angiography were selected. The age, weight, height, waist circumference, body mass index and prevalence of dyslipidemia, hypertension and diabetes of each patient were registered. Metabolic syndrome was defined in accordance with the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII. Serum samples were collected to assess the levels of glucose, total cholesterol, HDL-cholesterol (high density lipoprotein, triglycerides, albumin, SHBG, estradiol and total testosterone (TT. The levels of LDL-cholesterol (low density lipoprotein were calculated using Friedewald's formula and free testosterone (FT and bioavailable testosterone (BT using Vermeulen's formula. RESULTS: 141 patients were enrolled in the study. The prevalence of metabolic syndrome was significantly higher in the first SHBG tercile than in the second and third terciles. A statistically significant positive association between the SHBG and TT values was observed, but no such association was seen between SHBG, BT and FT. CONCLUSION: Low serum levels of SHBG are associated with higher prevalence of metabolic syndrome among male patients, but further studies are required to confirm this association.

  4. Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Perry, John R B; Weedon, Michael N; Langenberg, Claudia;

    2010-01-01

    Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiologi...

  5. 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....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  6. High Sex Hormone Binding Globulin (SHBG) Levels in Older Patients with Acute Hip Fracture Are Correlated with Worse Function and Increased Bone Resorption

    Science.gov (United States)

    Previous studies suggested that higher SHBG levels are associated with an increased hip fracture risk and that higher testosterone levels may reduce the odds of falling among men and women age 65 and older. The objective of this study is to examine the correlation of serum testosterone and SHBG with...

  7. Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromsø Study.

    Science.gov (United States)

    Svartberg, J; Schirmer, H; Wilsgaard, T; Mathiesen, E B; Njølstad, I; Løchen, M-L; Jorde, R

    2014-03-01

    Low testosterone levels are associated with metabolic and cardiovascular disease risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM), myocardial infarction (MI) and all-cause mortality. It is not known if these associations are causal or not. Recently, it has been shown that the serum testosterone levels are associated with single-nucleotide polymorphisms (SNPs), and we therefore studied the associations between one of these SNPs, rs1799941 on the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA was prepared from men who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death and a randomly selected control group. For mortality, the observation time was set from 1994, and for the other endpoints from birth. The endpoint data were completed up to 2010-2013. Genetic analyses were successfully performed in 5309 men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in 2226 who had died. Men with the minor homozygote genotype had significantly higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men with the major homozygote genotype, whereas free testosterone levels did not differ significantly between the genotypes. The SNP rs1799941 was not significantly associated with MI, T2DM, cancer or mortality. Thus, our result does not support a causal relationship between total testosterone and SHBG and MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a marker of poor health.

  8. Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Munch-Andersen, Thor;

    2009-01-01

    Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of ...

  9. Development of predictive models for predicting binding affinity of endocrine disrupting chemicals to fish sex hormone-binding globulin.

    Science.gov (United States)

    Liu, Huihui; Yang, Xianhai; Yin, Cen; Wei, Mengbi; He, Xiao

    2017-02-01

    Disturbing the transport process is a crucial pathway for endocrine disrupting chemicals (EDCs) exerting disrupting endocrine function. However, this mechanism has not received enough attention compared with that of hormones receptors and synthetase. Recently, we have explored the interaction between EDCs and sex hormone-binding globulin of human (hSHBG). In this study, interactions between EDCs and sex hormone-binding globulin of eight fish species (fSHBG) were investigated by employing classification methods and quantitative structure-activity relationships (QSAR). In the modeling, the relative binding affinity (RBA) of a chemical with 17β-estradiol binding to fSHBG was selected as the endpoint. Classification models were developed for two fish species, while QSAR models were established for the other six fish species. Statistical results indicated that the models had satisfactory goodness of fit, robustness and predictive ability, and that application domain covered a large number of endogenous and exogenous steroidal and non-steroidal chemicals. Additionally, by comparing the log RBA values, it was found that the same chemical may have different affinities for fSHBG from different fish species, thus species diversity should be taken into account. However, the affinity of fSHBG showed a high correlation for fishes within the same Order (i.e., Salmoniformes, Cypriniformes, Perciformes and Siluriformes), thus the fSHBG binding data for one fish species could be used to extrapolate other fish species in the same Order.

  10. Low level of serum sex hormone binding globulin is associated with the occurrence of metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    缪琳

    2013-01-01

    Objective To investigate the relationship between serum sex hormone binding globulin (SHBG) and metabolic syndrome (MS) in Chinese young population.Methods A total of 797 patients were enrolled and subdivided into MS group (n=377) and non-MS group (n=420) .Body height and weight were measured for body

  11. Increased sex hormone-binding globulin levels in children and adolescents with thyrotoxicosis

    DEFF Research Database (Denmark)

    Nielsen, J; Jensen, Rikke Bodin Beck; Juul, Anders

    2013-01-01

    Thyrotoxicosis is a rare condition in pediatric patients, and optimal treatment can be difficult to achieve in some children. To our knowledge, no studies have evaluated sex hormone-binding globulin (SHBG) levels in hyperthyroid children and adolescents in relation to age- and gender...

  12. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation

    NARCIS (Netherlands)

    A.D. Coviello (Andrea); R. Haring (Robin); M. Wellons (Melissa); D. Vaidya (Dhananjay); T. Lehtimäki (Terho); S. Keildson (Sarah); K.L. Lunetta (Kathryn); C. He (Chunyan); M. Fornage (Myriam); V. Lagou (Vasiliki); M. Mangino (Massimo); N.C. Onland-Moret (Charlotte); B. Chen (Benjamin); J. Eriksson (Joel); M. Garcia (Melissa); Y. Liu (Yongmei); A. Koster (Annemarie); K. Lohman (Kurt); L.-P. Lyytikäinen; A.K. Petersen; C.A.J. Prescott; L. Stolk (Lisette); L. Vandenput (Liesbeth); A.R. Wood (Andrew); W.V. Zhuang; A. Ruokonen (Aimo); A.L. Hartikainen; A. Pouta (Anneli); S. Bandinelli (Stefania); R. Biffar (Reiner); G. Brabant (Georg); D.G. Cox (David); S. Cummings; L. Ferrucci (Luigi); M.J. Gunter (Marc J.); S.E. Hankinson (Susan); H. Martikainen (Hannu); A. Hofman (Albert); G. Homuth (Georg); T. Illig (Thomas); J.O. Jansson; A.D. Johnson (Andrew); D. Karasik (David); M. Karlsson (Magnus); J. Kettunen (Johannes); D.P. Kiel (Douglas); P. Kraft (Peter); O.̈. Ljunggren; M. Lorentzon (Mattias); M. Maggio (Marcello); M.R.P. Markus (Marcello R. P.); D. Mellström (Dan); I. Miljkovic (Iva); D. Mirel (Daniel); S. Nelson (Sarah); L. Morin Papunen (Laure); P.H.M. Peeters; I. Prokopenko (Inga); L.J. Raffel (Leslie); M. Reincke (Martin); A.P. Reiner (Alex); K. Rexrode (Kathryn); F. Rivadeneira Ramirez (Fernando); S.M. Schwartz (Stephen); D.S. Siscovick (David); N. Soranzo (Nicole); D. Stöckl (Doris); S. Tworoger (Shelley); A.G. Uitterlinden (André); C.H. van Gils (Carla); R.S. Vasan (Ramachandran Srini); H.E. Wichmann (Erich); G. Zhai (Guangju); S. Bhasin (Shalender); M. Bidlingmaier; S.J. Chanock (Stephen); I. de Vivo (Immaculata); T.B. Harris (Tamara); D. Hunter (David); M. Kähönen (Mika); P. Ouyang (Pamela); T.D. Spector (Timothy); Y.T. van der Schouw (Yvonne); J. Viikari (Jorma); H. Wallaschofski (Henri); M.I. McCarthy (Mark); T.M. Frayling (Timothy); J.C. Murray (Jeffrey); S. Franks (Steve); M.R. Jarvelin; F.A. de Jong (Floris); O. Raitakari (Olli); A. Teumer (Alexander); C. Ohlsson (Claes); J. Murabito (Joanne); J.R.B. Perry (John)

    2012-01-01

    textabstractSex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers s

  13. Hormonal and nonhormonal factors affecting sex hormone-binding globulin levels in blood.

    Science.gov (United States)

    Thijssen, J H

    1988-01-01

    Researchers in Utrecht, the Netherlands have studied the effects of different factors, such as oral contraceptives (OCs), on sex hormone binding globulin (SHBG) levels in blood. The SHBG levels in women who continuously used OCs consisting only of .05 mg of ethinyl estradiol (EE2) rose as high as 260% + or - 25% of those in women not using OCs. Further, mean SHBG levels of women using combination OCs of EE2 and levonorgestrel were 10-60% higher than women not using OCs. SHBG levels were significantly higher than the use of a sequential OC containing decreasing amounts of EE2 and increasing amounts of levonorgestrel than those cause by use of a continuous combined OC with .03 mg and .15 mg respectively. As the dosage of EE2 increased in combination OCs with 2.5 mg lynestrenol, the SHBG increased from 20% (.05 mg EE2) to 150% (.75 mg EE2). SHBG levels after taking EE2 and cyproterone acetate increased significantly more (240%) than levels after EE2 and desogestrel (170%), or after EE2 and gestoden (140%) [p.001]. SHBG levels of women who took OCs containing only .03 mg of levonorgestrel daily decreased 35% (p.01). These levels fell by 30% in women who received 150 mg of medroxyprogesterone acetate intramuscularly every 3 months (p.001). SHBG concentrations increased when estrogens were taken orally for noncontraceptive purposes, but they did not change when they were administered percutaneously. As body weight increased the SHBG levels decreased despite hormonal status or sex. Further, the lower the fat content of one's diet the higher the SHBG levels and vice versa. SHBG levels are higher in males with flaccid lungs than they are in males with healthy lungs.

  14. Determination of SHBG-bound sex hormones by selective ammonium sulphate precipitation.

    Science.gov (United States)

    Ratajczak, T; Monaco, E M; Hähnel, R

    1981-03-05

    This paper describes a direct method for determining sex hormone binding globulin (SHBG)-bound sex hormones in human plasma after separation of SHBG-bound and unbound hormone fractions by selective precipitation with ammonium sulphate. In normal women variations in SHBG-bound and -free hormone generally paralleled fluctuations in total hormone. Changes in SHBG-free estradiol did not have any marked effect on plasma SHBG and sHBG-free testosterone. Our results suggest a buffer role for SHBG through which the biological response to sudden changes in sex hormone concentration is moderated.

  15. Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol.

    Science.gov (United States)

    Matsui, Sumika; Yasui, Toshiyuki; Kasai, Kana; Keyama, Kaoru; Yoshida, Kanako; Kato, Takeshi; Uemura, Hirokazu; Kuwahara, Akira; Matsuzaki, Toshiya; Irahara, Minoru

    2017-03-20

    Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group. In addition, the women received dydrogesterone continuously (5 mg) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.

  16. Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity

    OpenAIRE

    Galloway, P; Donaldson, M.; WALLACE, A

    2001-01-01

    BACKGROUND—Overweight children become obese adults who are prone to develop the "metabolic syndrome" and premature coronary arterial disease (CAD).
AIMS—To assess whether sex hormone binding globulin (SHBG) is a potential marker for hyperinsulinaemia/insulin resistance in prepubertal obese children.
METHODS—Twenty five obese children (body mass index (BMI) >2SD) who warranted investigation on clinical grounds were enrolled. Their insulin response to an oral glucose tolera...

  17. Isoflavone supplementation reduced serum sex hormone-binding globulin concentration in postmenopausal women

    Directory of Open Access Journals (Sweden)

    ML. Edy Parwanto

    2015-12-01

    The bone loss that occurs with ageng in postmenopausal women is related to a decrease in serum levels of bioavailable estrogen and testosterone, which are mainly bound to sex hormone-binding globulin (SHBG and albumin. Phytoestrogens are thought to exert hormonal effects in the body due to their structural resemblance to 17â-estradiol. The objective of this study was to evaluate the effect of isoflavone supplementation on levels of SHBG in postmenopausal women aged 47- 60 years. Methods A study of pre and post test design with controls was conducted in 70 women aged 47- 60 years. Subjects were randomly divided into 2 groups, the isoflavone group received 100 mg isoflavones/day + calcium 500 mg/day and the control group calcium 500 mg/day for 6 months. Measurement of bone mineral density was performed prior to supplementation, and serum SHBG levels before and after supplementation. Results Supplementation of isoflavones for 6 months reduced the SHBG levels by 31.1% in the isoflavone group (p=0.000, whereas supplementation of calcium for 6 months did not affect the levels of SHBG in the control group (p=0.359. Supplementation of isoflavones for 6 months reduced SHBG levels of postmenopausal women in the isoflavone group with either osteopenia (p=0.028 or osteoporosis (p=0.008. Conclusion Supplementation of isoflavones for 6 months decreased the SHBG levels of postmenopausal women in the isoflavone group with osteopenia and osteoporosis. Our findings suggest that phytoestrogens may significantly decreased SHBG levels in postmenopausal women.

  18. Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin

    Directory of Open Access Journals (Sweden)

    Karina Danilowicz

    2014-10-01

    Full Text Available It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i determine reference ranges for serum testosterone (T and sex hormone binding globulin (SHBG appropriate to our laboratory and population, and (ii to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a 30 selected non-hyperandrogenic women, (b 87 non-selected healthy female blood donors, (c 53 women with hyperandrogenism, and (d 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a. Using our results for this selected control group as new reference values, 12 out of 38 (31.6% women with hyperandrogenic disorders without apparent hyperandrogenemia (group d were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4% non-selected, normal weight, women (group b, were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.

  19. Determination of sex hormone-binding globulin in human semen by selective ammonium sulphate precipitation.

    Science.gov (United States)

    Morvay, J; Traub, A

    1984-01-01

    A simple method was developed to measure the SHBG capacities of human serum, semen and sperm cells. After suitable dilution, disintegration and addition of labelled dihydrotestosterone-1,2-3 H or testosterone-1,2-3 H, the SHBG was precipitated by the addition of saturated ammonium sulphate in a final concentration of 42.3%. The precipitate was centrifuged and the activity of the non-bound, labelled steroid was counted in an aliquot of the supernatant. Subtraction of this result from the total activity yielded the SHBG-bound steroid in microgram/100 ml or nmol/l. Examination of 52 males gave normal values of means = 13.91 nmol/l (S.E.M. = 0,746) dihydrotestosterone binding globulin (DHTBG) and means = 11.67 nmol/l (S.E.M. = 0.555) testosterone binding globulin (TBG) in serum, while the concentrations in the seminal plasma were means = 10.89 nmol/l (S.E.M. = 0,723) DHTBG and means = 8.93 nmol/l (S.E.M. = 0.625) TBG. means = 5.57 ng/mg protein (S.E.M. = 0.516) DHTBG and means = 4.91 ng/mg protein (S.E.M. = 0.440) TBG were found in the disintegrated sperm cells.

  20. Testosterone, Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men : An Individual Participant Data Meta-Analysis of Observational Studies

    NARCIS (Netherlands)

    Brand, Judith S.; Rovers, Maroeska M.; Yeap, Bu B.; Schneider, Harald J.; Tuomainen, Tomi-Pekka; Haring, Robin; Corona, Giovanni; Onat, Altan; Maggio, Marcello; Bouchard, Claude; Tong, Peter C. Y.; Chen, Richard Y. T.; Akishita, Masahiro; Gietema, Jourik A.; Gannage-Yared, Marie-Helene; Unden, Anna-Lena; Hautanen, Aarno; Goncharov, Nicolai P.; Kumanov, Philip; Chubb, S. A. Paul; Almeida, Osvaldo P.; Wittchen, Hans-Ulrich; Klotsche, Jens; Wallaschofski, Henri; Voelzke, Henry; Kauhanen, Jussi; Salonen, Jukka T.; Ferrucci, Luigi; van der Schouw, Yvonne T.

    2014-01-01

    Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives: We aimed to investigate whether associations differ across specific

  1. Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children

    DEFF Research Database (Denmark)

    Birkebaek, N H; Lange, Aksel; Holland-Fischer, P

    2010-01-01

    Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated....... The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis....

  2. Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate

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    de Torres Inés

    2009-06-01

    Full Text Available Abstract Background The human Sex Hormone Binding Globulin (SHBG gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines. Results Using a combination of in silico and in vitro studies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A, contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B. Conclusion The identification of multiple transcription start sites (TSS upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate

  3. Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Genome-wide association studies (GWAS have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS data from the Nurses' Health Study (NHS, and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ~1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint β = -0.126; joint P = 2.09 × 10(-16, downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P<10(-5, several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ~900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P<10(-5 was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk.

  4. Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study

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    Yeager Meredith

    2007-04-01

    Full Text Available Abstract Background The sex hormone-binding globulin (SHBG is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer. Methods The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs in SHGB and five in ATP1B2 were selected to capture most common variation in this region. Results None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259 and -67G>A 5'UTR (rs1799941. However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG. Conclusion These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk.

  5. Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men

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    A.F. Reis

    1998-12-01

    Full Text Available Low levels of sex hormone-binding globulin (SHBG are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years with normal glucose tolerance and body mass indexes (BMI ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P28 kg/m2, N = 8 and nonobese (BMI £25 kg/m2, N = 10 groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand.

  6. Sex Hormone Binding Globulin Deficiency Due to a Homozygous Missense Mutation

    NARCIS (Netherlands)

    Vos, M. J.; Mijnhout, G. S.; Rondeel, J. M. M.; Baron, W.; Groeneveld, P. H. P.

    2014-01-01

    Context: SHBG is known as the major sex steroid binding protein in plasma, and it regulates the bioavailability of both T and estradiol levels required for effects on target tissues. We identified a man with an undetectable SHBG concentration in combination with low total T. He presented with a 7-ye

  7. SHBG-C57BL/ksJ-db/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development.

    Science.gov (United States)

    Saéz-López, Cristina; Rivera-Giménez, Marta; Hernández, Cristina; Simó, Rafael; Selva, David M

    2015-12-01

    Low plasma sex hormone-binding globulin (SHBG) levels in overweight individuals are a biomarker for the metabolic syndrome and are predictive of type 2 diabetes and cardiovascular disease risk. There are no in vivo models to study SHBG expression and regulation during obesity development. The main reason for this is that the obesity-prone rodent models cannot be used to study this issue, because rodents, unlike humans, do not express the SHBG gene in their livers. We have developed a unique mouse model that expresses the human SHBG, and it develops obesity, by crossing the human SHBG transgenic mice with the C57BL/ksJ-db/db mice. The results obtained with the SHBG-C57BL/ksJ-db/db mouse model have allowed us to determine that the SHBG overexpression in the C57BL/ksJ-db/db reduced the body weight gain but did not change the metabolic profile of these mice. Moreover, we elucidated the molecular mechanisms and transcription factors causing the SHBG down-regulation during obesity development, which involved changes in liver hepatocyte nuclear factor 4α and peroxisome proliferator-activated receptor-γ mRNA and protein levels. Furthermore, these results were confirmed using human liver biopsies. Importantly, we also showed that this model resembles what occurs in human obese subjects, because plasma SHBG and total testosterone levels where reduced in obese mice when compared with lean mice. Future research using this unique mouse model will determine the role of SHBG in the development and progression of obesity, type 2 diabetes, or fatty liver disease.

  8. Sex hormone binding globulin decrease as potential pathogenetic factor for hirsutism in adolescent girls Disminución de la globulina transportadora de hormonas sexuales como factor patogénico de hirsutismo en la adolescencia

    Directory of Open Access Journals (Sweden)

    Graciela Cross

    2008-04-01

    Full Text Available We investigated 252 non-obese female subjects aged 13-39 years to evaluate if an exaggerated descent of sex hormone binding globulin (SHBG levels during adolescence can play a role in the development of hirsutism. Body hair was assessed according to Ferriman and Gallwey (FG, with a stringent criterion of normality of 4 and controls (FG Se investigaron 252 mujeres con peso normal, de 13 a 39 años de edad, para evaluar si un descenso exagerado en los niveles de la globulina transportadora de hormonas sexuales ("sex hormone binding globulin"; SHBG puede tener un rol en el desarrollo de hirsutismo. Este signo fue evaluado con la escala de Ferriman y Gallwey (FG, empleando un criterio riguroso de normalidad 4 y controles (FG < 4, ciclos menstruales regulares, sin acné. En adolescentes de 15-18 años, los valores de SHBG fueron menores en las "hirsutas", los niveles de FT fueron similares en ambos grupos y el índice de FG correlacionó inversamente con SHBG. En las mujeres de 19-39 años, los niveles de FT fueron mayores en las "hirsutas", los valores de SHBG fueron similares en ambos grupos y FG correlacionó positivamente con FT. Los valores más bajos de SHBG se observaron entre 15 y 18 años, pero la pendiente de disminución a partir de los valores de 13-14 años fue mayor en el grupo de "hirsutas". Los valores de FT se incrementaron progresivamente con la edad, pero el aumento fue mayor en el grupo de "hirsutas". Estos resultados sugieren un rol importante del descenso de SHBG en la adolescencia vs. un incremento más acentuado de los niveles de testosterona en las adultas, como factores que condicionan el desarrollo del hirsutismo en esos dos diferentes periodos de la vida.

  9. Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study: a case control study

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    Goto Atsushi

    2012-10-01

    Full Text Available Abstract Background Sex hormone-binding globulin (SHBG levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver. Methods We conducted a case–control study that included 300 diabetes cases (215 men and 85 women and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels ≥126 mg/dL, 2-h post-load glucose levels ≥200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI, a validated measure derived from serum triglyceride levels, body mass index (BMI, waist circumference, and γ-glutamyltransferase levels. Results After adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02–0.96], but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01–1.17]. In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23–0.89], but not among women. Conclusions Our findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.

  10. The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial

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    Wedick Nicole M

    2012-10-01

    Full Text Available Abstract Background Findings from observational studies suggest that sex hormone-binding globulin (SHBG and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels. Findings After a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42 were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate]. No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone. Conclusions Our data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.

  11. Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: Relation to sex hormone-binding globulin

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    Altan Onat, Gülay Hergenç, Dursun Dursunoğlu, Zekeriya Küçükdurmaz, Serkan Bulur, Günay Can

    2008-01-01

    Full Text Available It is unclear whether serum adiponectin concentrations diminish linearly with increasing adiposity and, if not, which factors codetermine this association. These issues were investigated cross-sectionally in 1188 men and women, representative of middle-aged and elderly Turkish adults. Serum total adiponectin was assayed by ELISA. Serum adiponectin values in men, though declining significantly in transition from the bottom to the mid tertile of body mass index (BMI and waist circumference (WC, were similar in the two respective upper tertiles. In women, serum adiponectin concentrations were not significantly different in any tertile of these indices, were significantly correlated with BMI or WC within the low tertiles and not within the two higher tertiles. In a linear regression analysis for WC (or BMI in a subset of the sample in which serum sex hormone-binding globulin (SHBG was available and which additionally comprised adiponectin, fasting insulin and other confounders, only insulin and, in women SHBG, were significantly associated, but not adiponectin. In linear regression analyses for covariates of adiponectin in two models comprising 12 variables, insulin and SHBG concentrations were significantly associated in both genders though not BMI. Whereas in men HDL-cholesterol and CRP were covariates of adiponectin (both p<0.01, SHBG and apolipoprotein B positively associated in women (p<0.001, independent of BMI and fasting insulin levels. Conclusions: Relationship between excess adiposity and adiponectin levels is inconsistent in Turkish adults. Independently from obesity and hyperinsulinemia, serum adiponectin discloses significant relationship with inflammatory markers and HDL only in men, not in women in whom it is influenced by SHBG, with consequent attenuation of its anti-inflammatory activities.

  12. Sex hormone-binding globulin, type 2 diabetes and obesity%性激素结合球蛋白与2型糖尿病及肥胖

    Institute of Scientific and Technical Information of China (English)

    张敏; 闫丽丽; 王玉环

    2011-01-01

    Sex hormone binding globulin (SHBG) is a glycoprotein secreted by the liver, which mediates and (or) activates adenylate cyclase system directly through binding with peculiar SHBG receptor in surface of organic cells, thereby regulates cell function. Many studies have explored that, SHBG is related with type 2 diabetes and obesity, and could reflect the extent of insulin resistance in type 2 diabetic patients with obesity. The lower level of SHBG could increase the risk of insulin resistance and type 2 diabetes, and lead to central obesity. Higher serum SHBG reduces diseases such as type 2 diabetes and obesity through regulating fasting blood glucose, but not through improving insulin secretion and androgen mechanism.%性激素结合球蛋白(SHBG)是由肝脏产生的一种糖蛋白,通过与组织细胞表面的特异性受体结合介导和(或)直接激活腺苷酸环化酶系统,从而调节组织细胞功能.研究显示,SHBG与2型糖尿病和肥胖相关,可反映肥胖2型糖尿病患者的胰岛素抵抗程度.低SHBG水平可增加胰岛素抵抗及2型糖尿病的发病风险,可导致腹型肥胖.高血清SHBG通过调整空腹血糖,而不是通过改善胰岛素分泌或雄激素机制,延缓糖尿病及肥胖等疾病的发生.

  13. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

    Science.gov (United States)

    Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

  14. SHBG, Sex Steroids, and Kyphosis in Older Men: The MrOS Study.

    Science.gov (United States)

    Woods, Gina N; Huang, Mei-Hua; Cawthon, Peggy M; Laughlin, Gail A; Schousboe, John T; McDaniels-Davidson, Corinne; Cauley, Jane A; Orwoll, Eric; Barrett-Connor, Elizabeth; Kado, Deborah M

    2016-12-01

    Accentuated kyphosis is associated with adverse health outcomes, including falls and fractures. Low bone density is a risk factor for hyperkyphosis, and each vertebral fracture adds roughly 4° to forward spine curvature. Sex steroids, in particular low bioavailable estradiol and high sex hormone-binding globulin (SHBG), are associated with bone loss and high SHBG is associated with vertebral fractures in older men. We, therefore, hypothesized that low bioavailable estradiol and high SHBG would be associated with worse kyphosis. To test this hypothesis, we examined the cross-sectional associations between individual bioavailable sex hormones and SHBG with radiographically assessed kyphosis. Participants included 1500 men aged 65 and older from the Osteoporotic Fractures in Men (MrOS) Study, in whom baseline measures of kyphosis and sex hormones were available. Modified Cobb angle of kyphosis, calculated from T4 through T12, was assessed from supine lateral spine radiographs. Serum total estradiol and total testosterone were measured by mass spectrometry, and bioavailable sex steroids were calculated from mass action equations. After adjustment for age and other confounding variables, no association was found between bioavailable estradiol or testosterone and Cobb angle, either when kyphosis was analyzed as a continuous variable or dichotomized into highest versus lower three quartiles. In linear regression models adjusted for age and clinic site, there was a significant association between SHBG and kyphosis (parameter estimate = 0.76 per SD increase, p = 0.01). In the fully adjusted model, this association was weakened and of only borderline statistical significance (parameter estimate = 0.61 per SD, p = 0.05). Logistic models demonstrated similar findings. Although associated with bone loss, we did not demonstrate that low bioavailable estradiol translates into worse kyphosis in older men. High SHBG is associated with bone loss and vertebral

  15. Grizzly bear corticosteroid binding globulin: Cloning and serum protein expression.

    Science.gov (United States)

    Chow, Brian A; Hamilton, Jason; Alsop, Derek; Cattet, Marc R L; Stenhouse, Gordon; Vijayan, Mathilakath M

    2010-06-01

    Serum corticosteroid levels are routinely measured as markers of stress in wild animals. However, corticosteroid levels rise rapidly in response to the acute stress of capture and restraint for sampling, limiting its use as an indicator of chronic stress. We hypothesized that serum corticosteroid binding globulin (CBG), the primary transport protein for corticosteroids in circulation, may be a better marker of the stress status prior to capture in grizzly bears (Ursus arctos). To test this, a full-length CBG cDNA was cloned and sequenced from grizzly bear testis and polyclonal antibodies were generated for detection of this protein in bear sera. The deduced nucleotide and protein sequences were 1218 bp and 405 amino acids, respectively. Multiple sequence alignments showed that grizzly bear CBG (gbCBG) was 90% and 83% identical to the dog CBG nucleotide and amino acid sequences, respectively. The affinity purified rabbit gbCBG antiserum detected grizzly bear but not human CBG. There were no sex differences in serum total cortisol concentration, while CBG expression was significantly higher in adult females compared to males. Serum cortisol levels were significantly higher in bears captured by leg-hold snare compared to those captured by remote drug delivery from helicopter. However, serum CBG expression between these two groups did not differ significantly. Overall, serum CBG levels may be a better marker of chronic stress, especially because this protein is not modulated by the stress of capture and restraint in grizzly bears.

  16. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

    Directory of Open Access Journals (Sweden)

    Andrea D Coviello

    Full Text Available Sex hormone-binding globulin (SHBG is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106, PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11, GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16, ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09, JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35, SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08, NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12, ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14, TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14, LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07, BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08, and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08, women p = 0.66, heterogeneity p = 0.003. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion

  17. SHBG gene polymorphism (rs1799941 associates with metabolic syndrome in children and adolescents.

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    Marquitta J White

    Full Text Available Metabolic syndrome (MetS is a complex disorder characterized by coexistence of several cardiometabolic (CM factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD. The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs, previously shown to modulate lipid or sex hormone binding globulin (SHBG levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls.Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006. The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012, while in cases there was no association between rs1799941 and SHBG levels (p = 0.963.The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

  18. The effect of endurance training on the relationships between sex hormone binding globulin, high density lipoprotein cholesterol, apoprotein A1 and physical fitness in pre-menopausal women with mild obesity.

    Science.gov (United States)

    Kumagai, S; Shono, N; Kondo, Y; Nishizumi, M

    1994-04-01

    The purpose of the present study was to investigate the relationships of change in high density lipoprotein cholesterol (HDL-C) with changes in sex hormone binding globulin (SHBG), physical fitness and spontaneous dietary intake before and after endurance training. Ten pre-menopausal obese women (32 to 49 years) who had never smoked or regularly drunk alcohol participated in this study. Physical training at an intensity of lactate threshold was performed for six months at a frequency of three times per week for 60 minutes using a cycle ergometer. Together with a reduction in body weight (-4.1 kg; P < 0.05) and with increases in maximal oxygen uptake (VO2max = +3.4 ml/kg/min or +0.09 l/min; P < 0.05), the training induced some changes in both plasma lipid and lipoprotein. Although the total cholesterol (total-C), triglyceride, HDL2-C and apoprotein A1 (Apo A1) levels did not change, significant increases in HDL-C and HDL3-C, and significant reductions in Apo B, total-C/HDL-C ratio and fasting insulin concentrations were found after training. SHBG levels tended to increase after endurance training, but the changes were not significant. No alteration was observed in spontaneous dietary intake after training. A significant correlation (r = 0.648) was observed between the change in VO2 max(l/min) and the change in SHBG. In addition, changes in both VO2 max(l/min) and SHBG were significantly associated with changes in HDL-C, HDL2-C and Apo A1. The changes in dietary intake did not correlate with the changes in SHBG, VO2max, HDL-C, HDL2-C and Apo A1.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Late Pregnancy Thyroid-Binding Globulin Predicts Perinatal Depression

    Science.gov (United States)

    Pedersen, Cort; Leserman, Jane; Garcia, Nacire; Stansbury, Melissa; Meltzer-Brody, Samantha; Johnson, Jacqueline

    2016-01-01

    Previously we found that late pregnancy total and free thyroxine (TT4, FT4) concentrations were negatively related to greater pre and/or postpartum depressive symptoms. In a much larger cohort, the current study examined whether these thyroid indices measured earlier in the third trimester (31-33 weeks) predict subsequent perinatal depression and anxiety ratings as well as syndromal depression. Thyroid-binding globulin (TBG) concentrations increase markedly during pregnancy and may be an index of sensitivity to elevated estrogen levels. TBG was examined in this study because prior findings suggest that postpartum depression is related to sensitivity to mood destabilization by elevated sex hormone concentrations during pregnancy. Our cohort was 199 euthyroid women recruited from a public health obstetrics clinic (63.8% Hispanic, 21.6% Black). After screening and blood draws for hormone measures at pregnancy weeks 31-33, subjects were evaluated during home visits at pregnancy weeks 35-36 as well as postpartum weeks 6 and 12. Evaluations included psychiatric interviews for current and life-time DSM-IV psychiatric history (M.I.N.I.-Plus), subject self-ratings and interviewer ratings for depression and anxiety (Edinburgh Postnatal Depression Scale, Montgomery-Ǻsberg Depression Rating Scale; Spielberger State-Trait Anxiety Inventory, Hamilton Anxiety Inventory), as well as a standardized interview to obtain life-time trauma history. Numerous covariates were included in all regression analyses. Trauma and major depression history were robustly significant predictors of depression and anxiety ratings over the study period when these variables were analyzed individually or in a combined model including FT4 or TBG (pdepression and anxiety ratings (pdepression history, were significant individual predictors of syndromal depression during the study period (pdepression history, FT4 and TBG generally were not significantly predictive of depression or anxiety ratings, and FT4

  20. 21 CFR 862.1685 - Thyroxine-binding globulin test system.

    Science.gov (United States)

    2010-04-01

    ... protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroxine-binding globulin test system. 862.1685 Section 862.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  1. Metabolic syndrome, circulating RBP4, testosterone, and SHBG predict weight regain at 6 months after weight loss in men

    DEFF Research Database (Denmark)

    Wang, Ping; Menheere, Paul P C A; Astrup, Arne

    2013-01-01

    , adiponectin, retinol-binding protein 4 (RBP4), luteinizing hormone, prolactin, progesterone, total and free testosterone, and sex hormone-binding globulin (SHBG) were measured at baseline, after 8-week low-calorie diet-induced active weight loss, and after a subsequent 26-week ad libitum weight maintenance...... diet, and analyzed together with anthropometrical and physiological parameters. RESULTS AND CONCLUSIONS: Overweight and obese men with MetS at baseline had higher risk to regain weight (odds ratio=2.8, P=0.015). High baseline RBP4, and low total testosterone and low SHBG are predictors of weight loss......OBJECTIVE: Weight loss helps reduce the symptoms of the metabolic syndrome (MetS) in the obese, but weight regain after active weight loss is common. We investigated the changes and predictive role of circulating adipokines and sex hormones for weight regain in men during dietary intervention...

  2. Cortisol levels, binding, and properties of corticosteroid-binding globulin in the serum of primates.

    Science.gov (United States)

    Klosterman, L L; Murai, J T; Siiteri, P K

    1986-01-01

    New World primates have exceptionally high plasma levels of cortisol and other steroid hormones when compared with humans and other primates. It has been suggested that this difference can be explained by either low affinity or concentration of cellular steroid receptors. We have assessed cortisol availability in serum from several species of New and Old World primates under physiological conditions (whole serum at 37 degrees C). Measurements were made of total and free cortisol, corticosteroid-binding globulin (CBG) binding capacity and affinity for cortisol, distribution of cortisol in serum, and its binding to albumin. In agreement with earlier reports, plasma free cortisol levels in Old World primates, prosimians, and humans range from 10-300 nM. However, very high total plasma cortisol together with low CBG binding capacity and affinity result in free cortisol concentrations of 1-4 microM in some New World primates (squirrel monkey and marmosets) but not in others such as the titi and capuchin. In squirrel monkeys, free cortisol levels are far greater than might be predicted from the affinity of the glucocorticoid receptor estimated in cultured skin fibroblasts. In addition to low affinity, CBG from squirrel monkeys and other New World primates exhibits differences in electrophoretic mobility and sedimentation behavior in sucrose density ultracentrifugation, suggestive of a molecular weight that is approximately twice that of CBG from other species. Together with other data these results indicate that the apparent glucocorticoid resistance found in New World primates is a complex phenomenon that is not easily explained by present concepts of glucocorticoid action.

  3. THE EFFECTS OF COPPER AND ZINC IONS DURING THEIR BINDING WITH HUMAN SERUM γ-GLOBULIN

    Directory of Open Access Journals (Sweden)

    S. B. Cheknev

    2006-01-01

    Full Text Available Abstract. Conformational changes of human serum γ-globulin were studied during and after its binding with copper and zinc ions, using molecular ultrafiltration and differential spectrophotometry. The contents of nonbound metals in the filtrate were evaluated, resp., with sodium diethyl thyocarbamate and o-phenanthroline. It has been shown that copper and zinc exhibited common biological properties during their interactions with protein, but the binding differed sufficiently under similar experimental conditions. E.g., it was confirmed that copper was more active at the external sites of γ-globulin molecule, whereas zinc demonstrated tropicity for the areas of protein intraglobular compartments. The metal-binding sites have been described that differ in their parameters of interactions with cations and their spatial location within globular domains. Approaches are suggested for dynamic analysis of saturation for these differently located sites by the metal ions. We discuss the issues of altered conformational state of the γ-globulin molecule during the binding of cations, as well as potential usage of these data in clinical immunology.

  4. Interaction of xenobiotics with estrogen receptors α and β and a putative plasma sex hormone-binding globulin from channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    Gale, William L.; Patino, Reynaldo; Maule, Alec G.

    2004-01-01

    Estrogens are important regulators of physiological functions. Although environmental contaminants (xenoestrogens) which interfere with estrogen signaling are of increasing concern, there is only limited information about their ability to interact with estrogen-binding proteins (SHBG) or receptors (ER). Recombinant ER?? and ?? were obtained after transient transfection of COS-7 cells with channel catfish ER cDNA. Plasma from adult female channel catfish was the source of SHBG. Tritiated estradiol ( 3H-E2) was used in standard radioligand-binding assays to characterize the binding properties of channel catfish SHBG (ccfSHBG) and to estimate the inhibition constants for various estrogenic compounds. Binding of 3H-E2 to ccfSHBG was saturable and of high affinity with a Kd (??SE) of 1.9??0.14nM and a Bmax of 14.3??2.4pmol/mg protein (n=3 assays). Additionally, ccfSHBG displayed binding specificity for androgens and estrogens. Endosulfan, 4-nonylphenol, and 4-octylphenol displaced 3H-E2 binding to ccfSHBG albeit only at very high concentrations, whereas dieldrin and atrazine showed little displacement activity even at the highest concentrations used. The synthetic estrogen ethynylestradiol had higher affinity than E2 for ccfSHBG. This finding differs from results with human and rainbow trout SHBG. The alkylphenolic compounds (4-octylphenol and 4-nonylphenol) displayed some ability to displace 3H-E2 binding from ER?? and ?? at high concentrations, but dieldrin and atrazine had little binding activity for both ER subtypes and endosulfan for ER??. The xenobiotics tested generally showed equivalent or greater affinity for ER?? than ER??, whereas natural estrogens had much greater affinity for ER?? than ER??. These observations suggest that results of studies using fish tissue ER extracts must be interpreted with caution, since both ER subtypes may be present, and that the binding of xenoestrogens to SHBG must be taken into account for proper assessment of endocrine

  5. Relationship between sex hormone binding globulin and metabolic syndrome in elderly males%性激素结合球蛋白与老年男性代谢综合征的相关性研究

    Institute of Scientific and Technical Information of China (English)

    庞晓娜; 沈继平; 袁颖; 孙璇; 查小云; 胡予

    2013-01-01

    To investigate the relationship between sex hormone binding globulin (SHBG) and metabolic syndrome in elderly males in Shanghai,all the subjects (≥ 60 years old,male) underwent measurements of weight,height,waist and hip circumferences,and blood pressures,serum levels of fasting plasma glucose,total cholesterol,triglyceride,high density lipoprotein-cholesterol (HDL-C),and low density lipoprotein-cholesterol were determined (Hitachi,7600),while the levels of serum insulin,total testosterone,and SHBG were determined by using chemiluminescence methods.Free testosterone was calculated by using the Vermeulen equation.Metabolic syndrome was defined according to the criteria of the Chinese Diabetes Society (CDS 2004).The SHBG level in the metabolic syndrome group was significantly lower than that in non-metabolic syndrome group [(40.50 ± 26.16) nmol/L vs (47.80± 20.34) nmol/L,P<0.01].With increasing number of metabolic syndrome components,the level of SHBG became lowered progressively.The subjects were divided into four subgroups according to SHBG Quartiles.From Quartile 1 to Quartile 4,body mass index,waist-hip ratio,diastolic blood pressure,fasting plasma glucose,triglyceride,fasting insulin,homeostasis model assessment for insulin resistance(HOMA-IR),free testosterone,free androgen index,and free testosterone percentage became progressively lowered,while age and HDL-C became raised (P<0.05).SHBG was correlated significantly with age,body mass index,waist-hip ratio,diastolic blood pressure,fasting plasma glucose,HDL-C,and triglyceride.Age,HDL-C,and body mass index remained independently associated with SHBG in the multivariate regression analysis.In a logistic regression taking metabolic syndrome as the dependent variable,SHBG and HOMA-IR were included in the final model with statistical significance.Lowered SHBG is a risk factor of metabolic syndrome in elderly males.SHBG may be an independent predictor of metabolic syndrome,but the mechanism of how SHBG is

  6. Menstrual irregularity and bone mass in premenopausal women: Cross-sectional associations with testosterone and SHBG

    Directory of Open Access Journals (Sweden)

    Otahal Petr

    2010-12-01

    Full Text Available Abstract Background There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG and bone mass in a population-based sample of premenopausal women. Methods Cross-sectional study (N = 382, mean age 31.5 years. Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI. Results Women with irregular cycles (n = 41, 11% had higher free androgen index (FAI, P = 0.01 and higher QUS measurements including speed of sound (SOS, 1%, P Conclusion Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone.

  7. Inhibition of corticosteroid-binding globulin gene expression by glucocorticoids involves C/EBPβ.

    Directory of Open Access Journals (Sweden)

    Nicolette Verhoog

    Full Text Available Corticosteroid-binding globulin (CBG, a negative acute phase protein produced primarily in the liver, is responsible for the transport of glucocorticoids (GCs. It also modulates the bioavailability of GCs, as only free or unbound steroids are biologically active. Fluctuations in CBG levels therefore can directly affect GC bioavailability. This study investigates the molecular mechanism whereby GCs inhibit the expression of CBG. GCs regulate gene expression via the glucocorticoid receptor (GR, which either directly binds to DNA or acts indirectly via tethering to other DNA-bound transcription factors. Although no GC-response elements (GRE are present in the Cbg promoter, putative binding sites for C/EBPβ, able to tether to the GR, as well as HNF3α involved in GR signaling, are present. C/EBPβ, but not HNF3α, was identified as an important mediator of DEX-mediated inhibition of Cbg promoter activity by using specific deletion and mutant promoter reporter constructs of Cbg. Furthermore, knockdown of C/EBPβ protein expression reduced DEX-induced repression of CBG mRNA, confirming C/EBPβ's involvement in GC-mediated CBG repression. Chromatin immunoprecipitation (ChIP after DEX treatment indicated increased co-recruitment of C/EBPβ and GR to the Cbg promoter, while C/EBPβ knockdown prevented GR recruitment. Together, the results suggest that DEX repression of CBG involves tethering of the GR to C/EBPβ.

  8. Clinically insignificant improvement of prostate cancer prediction by addition of sex steroid hormones and SHBG serum levels to serum PSA, fPSA%, and age in a screening setting.

    Science.gov (United States)

    Heidegger, Isabel; Popovscaia, Marina; Ramoner, Reinhold; Schäfer, Georg; Stenzel, Birgit; Bektic, Jasmin; Horninger, Wolfgang; Klocker, Helmut

    2012-10-01

    Abstract Various findings implicate sex hormones in prostate growth and development and also in prostate carcinogenesis. We investigated if addition of sex steroid hormone and sex hormone binding globulin (SHBG) serum levels to standard risk assessment parameters [prostate-specific antigen (PSA), free PSA percentage (fPSA%), and age] improves prostate cancer prediction in a PSA screening setting. Steroid hormones testosterone (T), free testosterone (fT), and estradiol (E2), and binding protein SHBG levels were measured in 762 men undergoing prostate biopsy due to suspect PSA serum levels. Prostate cancer was diagnosed in 286 (37.5%) of these men. Our data confirmed that PSA (mean BE=5.09; mean CA=6.05; p=1.24×10-5), fPSA% (mean BE=22.08; mean CA=18.67; p=1.97×10-7), and age (mean BE=60.64; mean CA=64.5; p=7.05×10-10) differentiate men with cancer (CA) and men with benign disease (BE), such as benign prostate hyperplasia. In addition, SHBG (mean BE=50.3; mean CA=54.9; p=0.008) also differed statistically significantly between these two groups. All hormones except E2 and tumor markers correlated significantly with age (T: ρ=-0.09; fT: ρ=-0.27; SHBG: ρ=0.21; PSA: ρ=0.32; and fPSA%: ρ=0.22). Furthermore, we found that PSA correlates with E2 (ρ=0.08), and fPSA% with SHBG (ρ=0.1) and fT (ρ=-0.09). Addition of hormones and SHBG to a baseline marker model including PSA, fPSA%, and age improved cancer prediction in three multivariate classification methods; however, the improvement was minimal. The best improvement by 0.8% was obtained in the logistic regression model with the addition of T and SHBG or of E2 and SHBG, or in the support vector machine model with the addition of SHBG and all steroid hormones to the combination of standard markers PSA, fPSA%, and age; however, this additional gain of accuracy is too small to justify the additional efforts and costs.

  9. Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain.

    Science.gov (United States)

    Moisan, M P; Minni, A M; Dominguez, G; Helbling, J C; Foury, A; Henkous, N; Dorey, R; Béracochéa, D

    2014-03-01

    Corticosteroid binding globulin (CBG) is a glycoprotein synthesized in liver and secreted in the blood where it binds with a high affinity but low capacity glucocorticoid hormones, cortisol in humans and corticosterone in laboratory rodents. In mammals, 95% of circulating glucocorticoids are bound to either CBG (80%) or albumin (15%) and only the 5% free fraction is able to enter the brain. During stress, the concentration of glucocorticoids rises significantly and the free fraction increases even more because CBG becomes saturated. However, glucocorticoids unbound to CBG are cleared from the blood more quickly. Our studies on mice totally devoid of CBG (Cbg k.o.) showed that during stress these mutant mice display a lower rise of glucocorticoids than the wild-type controls associated with altered emotional reactivity. These data suggested that CBG played a role in the fast actions of glucocorticoids on behavior. Further analyses demonstrated that stress-induced memory retrieval impairment, an example of the fast action of glucocorticoids on the brain is abolished in the Cbg k.o. mice. This effect of stress on memory retrieval could be restored in the Cbg k.o. mice by infusing corticosterone directly in the hippocampus. The mechanisms explaining these effects involved an increased clearance but no difference in corticosterone production. Thus, CBG seems to have an important role in maintaining in blood a glucocorticoid pool that will be able to access the brain for the fast effects of glucocorticoids.

  10. The reactive centre loop of corticosteroid-binding globulin (CBG) is a protease target for cortisol release.

    Science.gov (United States)

    Lewis, John G; Elder, Peter A

    2014-03-25

    Corticosteroid-binding globulin (CBG) binds more than 90% of circulating cortisol and is a non-inhibitory member of the family of serine protease inhibitors (SERPINS) with an exposed elastase sensitive reactive centre loop (RCL). At sites of inflammation neutrophil activation can release elastase which may cleave the RCL and result in cortisol release from CBG. The RCL sequence also has two theoretical chymotrypsin cleavage sites and we used a monoclonal antibody with specificity for the RCL to investigate chymotrypsin cleavage of CBG. Here we show, for the first time, rapid chymotrypsin cleavage of the RCL of CBG, resulting in undetectable levels of intact CBG, whereas total CBG levels were unchanged. Coincident with both chymotrypsin and elastase cleavage there was an increase in the free cortisol fraction of serum to levels similar to when CBG had been inactivated by heat indicating total cortisol release from CBG. These findings demonstrate a new mechanism for cortisol release from its binding globulin.

  11. Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women.

    Science.gov (United States)

    Fernandez-Real, José-Manuel; Pugeat, Michel; López-Bermejo, Abel; Bornet, Hubert; Ricart, Wifredo

    2005-05-01

    Inflammatory pathways are increasingly recognized to be tightly associated with insulin resistance in humans. The promoter region of the adiponectin gene--Apm1--encompasses consensus sequences for glucocorticosteroid receptor responsive element. Dexamethasone induced downregulation of adiponectin secretion in vitro, whereas prednisolone administration increased circulating adiponectin concentrations. As previous studies have demonstrated an inverse relationship between corticosteroid-binding globulin (CBG), body mass index, and insulin resistance, we studied whether CBG could explain cortisol-to-adiponectin relationship. One hundred twenty-two healthy subjects were enrolled in a cross-sectional study. Plasma CBG and serum cortisol concentration were measured by radioimmunoassay. The cortisol-to-CBG ratio was used to calculate free cortisol. An RIA kit (Linco Research, St Louis, MO) was used to measure adiponectin levels. Insulin resistance was calculated using the homeostatis model of assessment (HOMA) value. Circulating adiponectin was associated with serum CBG ( r = 0.38, P fasting cortisol ( P = .019) contributed to 14% and 4%, respectively, of CBG variance. In summary, circulating adiponectin, CBG concentration, and fasting cortisol were significantly interrelated in healthy subjects. A significant sexual dimorphism exists in this association.

  12. The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

    Science.gov (United States)

    Larzul, C; Terenina, E; Foury, A; Billon, Y; Louveau, I; Merlot, E; Mormede, P

    2015-12-01

    In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but

  13. Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study.

    Science.gov (United States)

    Fernandez-Real, José-Manuel; Pugeat, Michel; Grasa, Mar; Broch, Montserrat; Vendrell, Joan; Brun, Jocelyne; Ricart, Wifredo

    2002-10-01

    It has been suggested that a low grade inflammatory state could predispose for developing insulin resistance and contribute to the development of obesity and type 2 diabetes. Corticosteroid-binding globulin (CBG), the main plasma protein transport for cortisol, has been shown to be negatively regulated by insulin and IL-6, at least in vitro, suggesting that insulin resistance and inflammation may both contribute to decreasing CBG levels. In the present study we measured CBG concentrations in a human healthy population and investigated the relationships of CBG with anthropometric and biochemical markers for inflammation and/or insulin resistance. The data showed that the mean serum CBG level was significantly lower in males (n = 151) than in females (n = 113; 32.5 +/- 9.1 vs. 39.2 +/- 13.9 mg/liter; P fasting cortisol/CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age. BMI (P < 0.0001), free cortisol (P = 0.003), and CBG (P = 0.009), but not WHR and age, contributed to 20%, 6%, and 8%, respectively, of HOMA variance in women in a multiple regression analysis. In this model only BMI (P < 0.0001) independently contributed to HOMA variance in men. These findings support the hypothesis that the CBG level is an interesting indicator for both insulin resistance and low grade inflammation. Whether the decrease in CBG levels is genetic by nature or directly associated to increased insulin and/or IL-6 merits further investigation. Nevertheless, because CBG has been shown to be expressed by the adipose tissue, decreased CBG could create locally increased cortisol disposal, with no change in circulating cortisol, and facilitate fat accumulation, insulin resistance, and type 2 diabetes.

  14. Emerging Role of Corticosteroid Binding Globulin in Glucocorticoid-driven Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Marie-Pierre Moisan

    2016-12-01

    Full Text Available Glucocorticoid hormones (GCs are critical for survival since they ensure energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism and storage. However, in order to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g. Cushing’s syndrome or Addison’s disease are associated with severe alterations of energy metabolism. Corticosteroid Binding Globulin (CBG, through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels. Genetic studies in various species including humans have revealed that CBG is the major factor influencing inter-individual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all of these genetic studies have also provided data linking CBG levels to body composition. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. The importance of CBG is even more striking when animals are submitted to high-fat diet combined to chronic stress, mimicking our occidental lifestyle. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

  15. Protein chemical characterization of Gc globulin (vitamin D-binding protein) isoforms; Gc-1f, Gc-1s and Gc-2

    DEFF Research Database (Denmark)

    Christiansen, Maja; Jørgensen, Charlotte S; Laursen, Inga;

    2007-01-01

    exchange chromatography. The separated isoforms and several commercial preparations of individual isoforms were characterized by mass spectrometry. This revealed that the major isoforms were non-glycosylated. Compared to the Gc-1f isoform the other dominating isoforms represented an Asp/Glu substitution......Gc globulin, also called vitamin D-binding protein, is a plasma protein involved in the extracellular actin-scavenger system, vitamin D transport and possibly also other biological activities. Low levels of Gc globulin have been found to correlate with multiple organ failure and non......-survival of patients with fulminant hepatic failure and trauma. Here, we characterize the dominant isoforms of plasma-derived Gc globulin from Cohn fraction IV paste with respect to amino acid sequence and posttranslational modifications. Gc globulin was purified in large scale and the isoforms separated by ion...

  16. Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, D.O.; Catterall, J.F. [Population Council, New York, NY (United States); Carino, C. [Instituto National de la Nutricion, Mexico City, MX (United States)] [and others

    1995-04-01

    Steroid hormone-binding globulin in human serum displays different isoelectric focusing (IEF) patterns among individuals, suggesting genetic variation in the gene for this extracellular steroid carrier protein. Analysis of allele frequencies and family studies suggested the existence of two codominant alleles of the gene. Subsequent determination of the molecular basis of a variant of the gene was carried out using DNA from homozygous individuals from a single Belgian family. It was of interest to characterize other variant individuals to determine whether all variants identified by IEF phenotyping were caused by the same mutation or whether other mutations occurred in the gene in different populations. Previous studies identified Mexican subjects who were heterozygous for the variant IEF phenotype. Denaturing gradient gel electrophoresis was used to localize the mutation in these subjects and to purify the variant allele for DNA sequence analysis. The results show that the mutation in this population is identical to that identified in the Belgian family, and no other mutations were detected in the gene. These data represent the first analysis of steroid hormone-binding globulin gene variation in heterozygous subjects and further support the conclusion of biallelism of the gene worldwide. 11 refs., 2 figs., 1 tab.

  17. IgE-binding epitopic peptide mapping on a three-dimensional model built for the 13S globulin allergen of buckwheat (Fagopyrum esculentum).

    Science.gov (United States)

    Sordet, Camille; Culerrier, Raphaël; Granier, Claude; Didier, Alain; Rougé, Pierre

    2009-06-01

    The three-dimensional model built for the 13S globulin allergen of buckwheat (Fagopyrum esculentum) consists of three protomers exhibiting the cupin motif, arranged in a homotrimer around a three-fold symmetry axis. Using the SPOT technique, 11 continuous IgE-binding epitopic peptides were characterized on the molecular surface of the 13S globulin allergen of buckwheat. Except for one of them, they all correspond to well exposed regions containing electropositiveley and/or electronegatively charged residues, which cover up to 40% of the molecular surface of the allergen. Some of these epitopes come in close contact to probably create more extended discontinuous epitopes, especially those located on the edge of the 13S globulin homotrimer. Half of the identified epitope peptides remain unaltered in a core structure protected against hydrolysis by digestive proteases and are thus assumed to promote the allergenicity of the 13S globulin. In addition, a few of these epitopes coincide with sequential IgE-binding epitopes previously characterized in soybean 11S globulins, that could account for the IgE-binding cross-reactions observed between soybean and buckwheat in Western blot experiments.

  18. Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide.

    Science.gov (United States)

    Fingerhut, Anja; Reutrakul, Sirimon; Knuedeler, Sebastian D; Moeller, Lars C; Greenlee, Carol; Refetoff, Samuel; Janssen, Onno E

    2004-05-01

    We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.

  19. Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

    Directory of Open Access Journals (Sweden)

    Jennifer L Bolton

    2014-07-01

    Full Text Available Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma, and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG. Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136 influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

  20. Electrophoretic mobility shift assay identifies vitamin D binding protein (Gc-globulin) in human, rat, and mouse sera.

    Science.gov (United States)

    Tang, W X; Bazaraa, H M; Magiera, H; Cooke, N E; Haddad, J G

    1996-06-01

    Serum vitamin D binding protein (DBP, also known as Gc-globulin) is a multifunctional protein capable of binding both vitamin D metabolites and actin. DBP can be visualized when analyzed by polyacrylamide gel electrophoresis followed by staining. Confirmation of its identity had previously required immunoprecipitation with specific anti-DBP antisera or occupancy of the protein with radioactive vitamin D sterols. We present studies showing that preincubation of G-actin with mammalian sera produced a discernible DBP protein band shift on native gel electrophoresis. Addition of DNaseI, a 33-kDa intracellular protein with an avid actin-binding site, to the incubations resulted in a supershift of DBP-actin complexes to an even more cathodal region of the gels. Following incubations with human, rat, and murine sera the same actin shift occurred as did the actin plus DNaseI supershift. The migrations of each complex were correlated with purified DBP migrations under identical conditions. It was confirmed that the supershifted bands contained DBP by Western blotting and detection of DBP by binding of 25-OH[3H]D3. After intravenous G-actin injections into living mice, a serum DBP-actin complex could be detected on native gels as the uncomplexed DBP band decreased in intensity. This simple, direct-staining technique appears to be suitable for identifying DBP/Gc phenotypes in human populations as well as for semiquantitatively monitoring the plasma actin-scavenger system in vivo in animal models or in human diseases.

  1. Cholesterol crystal binding of biliary immuno globulin A: visualization by fluorescence light microscopy

    Institute of Scientific and Technical Information of China (English)

    Frank Lammert; Stefan Sudfetd; Norbert Busch; Siegfried Matern

    2001-01-01

    AIM To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA.METHODS Crystal-binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography. Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)-conjugated anti-lgA at 37C. Samples were examined under polarizing and fluorescence light microscopy with digital image processing.RESULTS Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC-conjugated anti-lgA antibodies. Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence.CONCLUSION Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystalbinding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.

  2. Changes in Testosterone Levels and Sex Hormone-Binding Globulin Levels in Extremely Obese Men after Bariatric Surgery

    Science.gov (United States)

    Laichuthai, Nitchakarn; Suwannasrisuk, Preaw; Houngngam, Natnicha; Udomsawaengsup, Suthep; Snabboon, Thiti

    2016-01-01

    Objective. Obesity is a risk factor for hypogonadotropic hypogonadism in men. Weight loss has been shown to improve hypogonadism in obese men. This study evaluated the early changes in sex hormones profile after bariatric surgery. Methods. This is a prospective study including 29 morbidly obese men. Main outcomes were changes in serum levels of total testosterone (TT), free testosterone (cFT), SHBG, estradiol, adiponectin, and leptin at 1 and 6 months after surgery. Results. The mean age of patients was 31 ± 8 years and the mean BMI was 56.8 ± 11.7 kg/m2. Fifteen patients underwent Roux-en-Y gastric bypass and 14 patients underwent sleeve gastrectomy. At baseline, 22 patients (75.9%) had either low TT levels (<10.4 nmol/L) or low cFT levels (<225 pmol/L). Total testosterone and SHBG levels increased significantly at 1 month after surgery (p ≤ 0.001). At 6 months after surgery, TT and cFT increased significantly (p ≤ 0.001) and 22 patients (75.9%) had normalized TT and cFT levels. There were no changes in estradiol levels at either 1 month or 6 months after surgery. Conclusions. Increases in TT and SHBG levels occurred early at 1 month after bariatric surgery while improvements in cFT levels were observed at 6 months after bariatric surgery.

  3. Purification of equine Gc-globulin

    DEFF Research Database (Denmark)

    Houen, Gunnar; Pihl, Tina Holberg; Andersen, Pia Haubro;

    Objectives With the aim of producing antibodies for an equine Group specific component (Gc)-globulin assay, the protein was purified from normal equine plasma. Methods Equine Gc-globulin was purified from healthy horse plasma using ion exchange chromatography (Q-Sepharose, CM...... for measuring Gc-globulin in horses. Studies in rodents and humans have shown that Gc-globulin is a multifunctional acute phase plasma protein, which removes actin from the blood by binding it and facilitating its clearance from the circulation by the liver. As such, Gc-globulin prevents hyper coagulation......-globulin infusions. Reference List    1.   Vasconcellos CA and Lind SE. Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin and vitamin D-binding protein. Blood 1993;82:3648-3657....

  4. Serum levels of sex hormone binding globulin, androgen and insulin in polycystic ovarian syndrome women during pregnancy%多囊卵巢综合征患者妊娠中期血清性激素结合球蛋白、雄激素和胰岛素水平对妊娠的影响

    Institute of Scientific and Technical Information of China (English)

    陶俊; 顾金萍; 范建霞

    2012-01-01

    目的 了解多囊卵巢综合征(polycystic ovarian syndrome,PCOS)患者妊娠中期血清性激素结合球蛋白(sex hormone binding globulin,SHBG)、游离睾酮指数(free testosterone index,FTI)、胰岛素抵抗水平变化及与妊娠期糖尿病(gestational diabetes mellitus,GDM)、妊娠期高血压疾病(hypertensive disorder complicating pregnancy,HDP)的关系. 方法 对32例孕前诊断为PCOS孕妇的妊娠12~16周血清行血清总睾酮、SHBG、胰岛素水平测定,计算FTI、稳态模型评估法计算胰岛素抵抗指数,并对影响GDM和HDP的因素行逐步Logistic回归分析,以32例非PCOS孕妇为对照.2组相关资料的比较采用t检验或卡方检验. 结果 PCOS组的血清空腹胰岛素、FTI、SHBG、稳态模型评估胰岛素抵抗水平、总睾酮分别为(8.0±1.5) mU/L、0.96 (0.52~1.41)、325(312~355) nmol/L、1.53±0.32和2.95(1.61~4.40) nmol/L,与对照组的(7.1±1.5) mU/L、0.61(0.40~0.79)、360(347~373) nmol/L、1.36±0.36和2.15(1.50~2.80) nmol/L比较,差异有统计学意义(t值分别为2.32、3.02、4.13、2.04和2.55,P均<0.05).PCOS组的剖宫产率(84%与50%,x2=8.58,P<0.01)、HDP发生率(25%与3%,x2=4.65,P<0.05)均高于对照组.PCOS合并GDM 6例,妊娠12~16周血清SHBG水平显著低于26例无合并GDM者[(293±42)和(333±40) nmol/L,t=2.22,P<0.05],PCOS合并HDP8例,血清总睾酮、FTI明显高于24例无合并HDP者[(4.34±1.29)和(2.49±1.44) nmol/L,1.42±0.52和0.81±0.59,t值分别为3.23和2.61,P<0.05].逐步Logistic回归分析显示,SHBG是PCOS孕妇发生GDM的影响因素(OR=0.98,95%CI:0.96~1.00,P<0.05); FTI是HDP发生的影响因素(OR=5.53,95% CI:1.20~25.61,P<0.05).结论 SHBG与雄激素水平可作为预测PCOS孕妇发生GDM及HDP的指标.%Objective To investigate the changes of serum levels of sex hormone binding globulin (SHBG),free testosterone index (FTI) and insulin resistance; and to investigate the relationship among them and

  5. Effect of atrazine and fenitrothion at no-observed-effect-levels (NOEL) on amphibian and mammalian corticosterone-binding-globulin (CBG).

    Science.gov (United States)

    Hernández, Sandra E; Sernia, Conrad; Bradley, Adrian J

    2014-11-01

    This study determines the effect of atrazine and fenitrothion no-observed-effect-levels (NOEL) on the binding of corticosterone (B) to corticosterone-binding-globulin (CBG) in an amphibian and a mammal. Plasma from five cane toads and five Wistar rats was exposed to atrazine and fenitrothion at the NOEL approved for Australian fresh water residues and by the World Health Organization (WHO). The concentration required to displace 50% (IC50) of B binding to CBG was determined by a competitive microdialysis protein assay. Competition studies showed that both atrazine and fenitrothion at NOEL are able to compete with B for CBG binding sites in toad and rat plasma. The IC50 levels for atrazine in toads and rats were 0.004 nmol/l and 0.09 nmol/l respectively. In the case of fenitrothion the IC50 level found in toads was 0.007 nmol/l, and 0.025 nmol/l in rats. Plasma dilution curves showed parallelism with the curve of B, demonstrating that these agro-chemicals are competitively inhibiting binding to CBG. The displacement of B by atrazine and fenitrothion would affect the total:free ratio of B and consequently disrupt the normal stress response. This is the first time that the potential disruptive effect of atrazine and fenitrothion on B-CBG interaction at the NOELs has been demonstrated in amphibian and mammalian models.

  6. Coping with extreme: highland Eurasian tree sparrows with molt-breeding overlap express higher levels of corticoserone-binding globulin than lowland sparrows.

    Science.gov (United States)

    Li, Dongming; Zhang, Ji; Liu, Dan; Zhang, Li; Hu, Yonghong; Duan, Xianglin; Wu, Yuefeng

    2013-10-01

    In birds, suppressed expression of stress-induced corticosterone (CORT) during pre-basic molt is generally thought to reflect a physiological trade-off in self-maintenance. And reduced CORT during breeding in extreme environments may maximize reproductive success and optimize their fitness. Highland Eurasian tree sparrows (Passer montanus) are known to express significantly higher stress-induced CORT levels during the pre-basic molt stage. Here, we show that these highland sparrows are characterized by a life history strategy of molt-breeding overlap, with higher corticosterone-binding globulin (CBG) levels favoring molt and breeding consistent with fitness optimization on the Tibetan Plateau. These unique behavioral and physiological strategies reflect natural selection under strong evolutionary pressures in extreme high-altitude environments.

  7. Purification of equine Gc-globulin

    DEFF Research Database (Denmark)

    Houen, Gunnar; Pihl, Tina Holberg; Andersen, Pia Haubro;

    Objectives With the aim of producing antibodies for an equine Group specific component (Gc)-globulin assay, the protein was purified from normal equine plasma. Methods Equine Gc-globulin was purified from healthy horse plasma using ion exchange chromatography (Q-Sepharose, CM-Sepharose) and prepa......Objectives With the aim of producing antibodies for an equine Group specific component (Gc)-globulin assay, the protein was purified from normal equine plasma. Methods Equine Gc-globulin was purified from healthy horse plasma using ion exchange chromatography (Q-Sepharose, CM......-Sepharose) and preparative PAGE. Results Equine Gc-globulin has successfully been purified from healthy horse plasma and rabbits and mice are being immunized to produce specific antibodies. Conclusions Purification of equine Gc-globulin and the production of specific antibodies will make it possible to develop an assay...... for measuring Gc-globulin in horses. Studies in rodents and humans have shown that Gc-globulin is a multifunctional acute phase plasma protein, which removes actin from the blood by binding it and facilitating its clearance from the circulation by the liver. As such, Gc-globulin prevents hyper coagulation...

  8. Influx of testosterone-binding globulin (TeBG) and TeBG-bound sex steroid hormones into rat testis and prostate

    Energy Technology Data Exchange (ETDEWEB)

    Sakiyama, R.; Pardridge, W.M.; Musto, N.A.

    1988-07-01

    The availability of testosterone and estradiol to Sertoli and prostate cells is dependent upon 1) the permeability properties of the blood-tubular barrier (BTB) of the testis or prostate cell membrane, and 2) sex steroid binding to plasma proteins, such as albumin or testosterone-binding globulin (TeBG). Sex steroid influx into these tissues was studied after in vivo arterial bolus injections of (/sup 3/H)testosterone or (/sup 3/H)estradiol in anesthetized rats. Both testosterone and estradiol were readily cleared across the BTB or prostate cell membrane in the absence of plasma proteins and in the presence of human pregnancy serum, in which testosterone or estradiol are 80-95% distributed to TeBG. The extravascular extraction of (/sup 3/H)TeBG across the BTB or prostate plasma membrane (73 +/- 2% (+/- SE) and 92 +/- 9%, respectively) was significantly greater than extraction of (/sup 3/H)albumin or other plasma space markers and indicative of a rapid first pass clearance of TeBG by Sertoli or prostate cells. In summary, these studies indicate that 1) testosterone and estradiol are readily cleared by Sertoli and prostate cells; 2) albumin- and TeBG-bound sex steroids represent the major circulating pool of bioavailable hormone for testis or prostate; and 3) the TeBG-sex steroid complex may be nearly completely available for influx through the BTB or prostate plasma membrane.

  9. 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-for- ......-for- gestational-age girls (n = 355) hormones showed a marked interindividual variation, with concentrations up to pubertal values [medians (95% confidence intervals): inhibin B, 82 pg/ml (...

  10. 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......-for- gestational-age girls (n = 355) hormones showed a marked interindividual variation, with concentrations up to pubertal values [medians (95% confidence intervals): inhibin B, 82 pg/ml (...

  11. Development of a formula for estimating plasma free cortisol concentration from a measured total cortisol concentration when elastase-cleaved and intact corticosteroid binding globulin coexist.

    Science.gov (United States)

    Nguyen, Phuong T T; Lewis, John G; Sneyd, James; Lee, Rita S F; Torpy, David J; Shorten, Paul R

    2014-05-01

    Cortisol bound to corticosteroid binding globulin (CBG) contributes up to 90% of the total cortisol concentration in circulation. Therefore, changes in the binding kinetics of cortisol to CBG can potentially impact on the concentration of free cortisol, the only form that is responsible for the physiological function of the hormone. When CBG is cleaved into elastase-cleaved CBG (eCBG) by the activity of neutrophil elastase, its affinity for cortisol is reduced. Therefore, when eCBG coexists with intact CBG (iCBG) in plasma, the calculation of free cortisol concentration based on the formulae that considers only one CBG pool with the same affinity for cortisol may be inappropriate. In this study, we developed in vivo and in vitro models of cortisol partitioning which considers two CBG pools, iCBG and eCBG, with different affinities for cortisol, and deduce a new formula for calculating plasma free cortisol concentration. The formula provides better estimates of free cortisol concentration than previously used formulae when measurements of the concentrations of the two CBG forms are available. The model can also be used to estimate the affinity of CBG and albumin for cortisol in different clinical groups. We found no significant difference in the estimated affinity of CBG and albumin for cortisol in normal, sepsis and septic shock groups, although free cortisol was higher in sepsis and septic shock groups. The in vivo model also demonstrated that the concentration of interstitial free cortisol is increased locally at a site of inflammation where iCBG is cleaved to form eCBG by the activity of elastase released by neutrophils. This supports the argument that the cleavage of iCBG at sites of inflammation leads to more lower-affinity eCBG and may be a mechanism that permits the local concentration of free cortisol to increase at these sites, while allowing basal free cortisol concentrations at other sites to remain unaffected.

  12. SHBG, Sex Hormones, and Inflammatory Markers in Older Women

    Science.gov (United States)

    Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Corsi, Anna Maria; Giallauria, Francesco; Guralnik, Jack M.; Zuliani, Giovanni; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'Aglio, Elisabetta; Ceresini, Graziano; Basaria, Shehzad; Ferrucci, Luigi

    2011-01-01

    Context: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. Objective: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. Design and Patients: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. Results: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state. PMID:21239514

  13. Gc globulin as a diagnostic and prognostic marker in horses

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg

    Group specific (Gc) globulin also known as vitamin D-binding protein is part of the extracellular actin-scavenging system that removes actin from the circulation. Actin is an intracellular structural protein, which is released to blood in patients with tissue injury and cell death. Circulating...... can prevent development of shock and thereby increase survival chances. The in vivo toxicity of Gc-globulin infusion is currently being investigated in horses and other species. Gc-globulin has been demonstrated in horse plasma and its structure closely resembles that of human Gc-globulin. Gc...

  14. Identification of Albizia lebbeck seed coat chitin-binding vicilins (7S globulins with high toxicity to the larvae of the bruchid Callosobruchus maculatus

    Directory of Open Access Journals (Sweden)

    A.J. Souza

    2012-02-01

    Full Text Available Seed coat is a specialized maternal tissue that interfaces the embryo and the external environment during embryogenesis, dormancy and germination. In addition, it is the first defensive barrier against penetration by pathogens and herbivores. Here we show that Albizia lebbeck seed coat dramatically compromises the oviposition, eclosion and development of the bruchid Callosobruchus maculatus. Dietary supplementation of bruchid larvae with A. lebbeck seed coat flour causes severe weight loss and reduces survival. By means of protein purification, mass spectrometry and bioinformatic analyses, we show that chitin-binding vicilins are the main source of A. lebbeck tegumental toxicity to C. maculatus. At concentrations as low as 0.1%, A. lebbeck vicilins reduce larval mass from 8.1 ± 1.7 (mass of control larvae to 1.8 ± 0.5 mg, which corresponds to a decrease of 78%. Seed coat toxicity constitutes an efficient defense mechanism, hindering insect predation and preventing embryo damage. We hypothesize that A. lebbeck vicilins are good candidates for the genetic transformation of crop legumes to enhance resistance to bruchid predation.

  15. Physiologically based pharmacokinetic model for ethyl tertiary-butyl ether and tertiary-butyl alcohol in rats: Contribution of binding to α2u-globulin in male rats and high-exposure nonlinear kinetics to toxicity and cancer outcomes.

    Science.gov (United States)

    Borghoff, Susan J; Ring, Caroline; Banton, Marcy I; Leavens, Teresa L

    2017-05-01

    In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat-specific protein α2u-globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC0-∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male-rat-specific mode of action for TBA-induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC0-∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

  16. Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy

    DEFF Research Database (Denmark)

    Würtz, Anne Mette Lund; Tjønneland, Anne; Christensen, Jane Hvarregaard;

    2012-01-01

    Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT.......Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT....

  17. Total Protein and Albumin/Globulin Ratio Test

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? Total Protein and Albumin/Globulin (A/G) Ratio Share this ... Globulin Ratio; A/G Ratio Formal name: Total Protein; Albumin to Globulin Ratio Related tests: Albumin ; Liver ...

  18. Profile of total protein, albumin, globulin and albumin globulin ratio in bulls

    Directory of Open Access Journals (Sweden)

    Ida Zahidah Irfan

    2014-06-01

    Full Text Available Determination of serum total protein concentration and main fractions (albumin and globulin can be used as an important diagnostic tool in clinical biochemistry. Several factors can affect the concentration of total protein, albumin, globulin and albumin globulin ratio (A/G. The aim of this study is to obtain serum protein profiles, albumin, globulin and A/G ratio based on breed, age and BCS (body condition score. Blood samples from 160 bulls were collected. Blood chemistry were analyzed by photometer principle using a commercial kit. There were significant (P<0.001 breed variation on total protein, albumin, globulin and albumin globulin ratio. Significant age differences were observed on total protein and albumin concentration (P<0.001, while globulin concentration and A/G ratio were also significant (P<0.05. Amongs groups of BCS, significant difference was verified only in the albumin concentration (P<0.05. The concentration of total proteins, albumins and globulins in the serum of the bulls are higher than standard values for cattle, while A/G ratio is lower.

  19. Gc globulin as a diagnostic and prognostic marker in horses

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg

    can prevent development of shock and thereby increase survival chances. The in vivo toxicity of Gc-globulin infusion is currently being investigated in horses and other species. Gc-globulin has been demonstrated in horse plasma and its structure closely resembles that of human Gc-globulin. Gc...

  20. Methyl isobutyl ketone exposure-related increases in specific measures of α2u-globulin (α2u) nephropathy in male rats along with in vitro evidence of reversible protein binding.

    Science.gov (United States)

    Borghoff, S J; Poet, T S; Green, S; Davis, J; Hughes, B; Mensing, T; Sarang, S S; Lynch, A M; Hard, G C

    2015-07-03

    Chronic exposure to methyl isobutyl ketone (MIBK) resulted in an increase in the incidence of renal tubule adenomas and occurrence of renal tubule carcinomas in male, but not female Fischer 344 rats. Since a number of chemicals have been shown to cause male rat renal tumors through the α2u nephropathy-mediated mode of action, the objective of this study is to evaluate the ability of MIBK to induce measures of α2u nephropathy including renal cell proliferation in male and female F344 rats following exposure to the same inhalation concentrations used in the National Toxicology Program (NTP) cancer bioassay (0, 450, 900, or 1800ppm). Rats were exposed 6h/day for 1 or 4 weeks and kidneys excised approximately 18h post exposure to evaluate hyaline droplet accumulation (HDA), α2u staining of hyaline droplets, renal cell proliferation, and to quantitate renal α2u concentration. There was an exposure-related increase in all measures of α2u nephropathy in male, but not female rat kidneys. The hyaline droplets present in male rat kidney stained positively for α2u. The changes in HDA and α2u concentration were comparable to d-limonene, an acknowledged inducer of α2u nephropathy. In a separate in vitro study using a two-compartment vial equilibration model to assess the interaction between MIBK and α2u, the dissociation constant (Kd) was estimated to be 1.27×10(-5)M. This Kd is within the range of other chemicals known to bind to α2u and cause nephropathy. Together, the exposure-related increase in measures of α2u nephropathy, sustained increase in renal cell proliferation along with an indication of reversible binding of MIBK to α2u, support the inclusion of MIBK in the category of chemicals exerting renal effects through a protein droplet α2u nephropathy-mediated mode of action (MoA).

  1. Trial of Immune Globulin in Infant Botulism

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-02-01

    Full Text Available A 5-year, randomized, double-blind, placebo-controlled trial of the orphan drug Human Botulism Immune Globulin Intravenous (BIG-IV in 122 infants in California with confirmed infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin was conducted at the California Department of Health Services, Richmond, CA; National Botulism Surveillance and Reference Laboratory, CDC and P, Atlanta; and Division of Biostatistics, University of California, Berkeley.

  2. 21 CFR 640.100 - Immune Globulin (Human).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Immune Globulin (Human). 640.100 Section 640.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Immune Globulin (Human) § 640.100...

  3. Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity.

    Science.gov (United States)

    Yang, Luanna; Wu, Eveline Y; Tarrant, Teresa K

    2016-07-01

    Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness.

  4. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B

    1993-01-01

    levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during...

  5. Characterization and cloning of an 11S globulin with hemagglutination activity from Murraya paniculata.

    Science.gov (United States)

    Singh, Anamika; Selvakumar, Purushotham; Saraswat, Akhilesh; Tomar, Prabhat P S; Mishra, Manisha; Singh, Pradhyumna K; Sharma, Ashwani K

    2015-01-01

    A ~56 kDa protein having hemagglutination activity was purified and characterized from the Murraya paniculata seeds. The gel electrophoresis studies demonstrated that protein is primarily of two different subunits, molecular weight ~ 35 and 21 kDa held together by disulfide-linkages and predominantly by secondary forces. The cloning and sequence analysis revealed that the protein exhibited a substantial sequence identity to seed storage 11S globulin family proteins. The sequence analysis of Murraya paniculata globulin (MPG) demonstrated higher and lower molecular weight polypeptides to be acidic (α) and basic (β) respectively. The sequence analysis further showed that it possesses a characteristic bi-cupin motif and a putative metal binding pocket. CD analysis revealed that the MPG was a β/α protein with a slightly higher content of the former. Conformational changes in protein have been studied by fluorescence spectrometry by using various chemical treatments. The results demonstrated that MPG belongs to 11S globulin family and exhibit's hemagglutination activity, which implicates it to be possessing lectin-like property.

  6. Increasing incidence of premature thelarche in the Central Region of Denmark - Challenges in differentiating girls less than 7 years of age with premature thelarche from girls with precocious puberty in real-life practice

    DEFF Research Database (Denmark)

    Sømod, Mia Elbek; Vestergaard, Esben Thyssen; Kristensen, Kurt

    2016-01-01

    RH) stimulated LH and follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, and sex-hormone binding globulin (SHBG). Apart from SHBG there was considerable overlap of the variables between the PT and the PP groups. CONCLUSIONS: First, the incidence of PT appears to increase. Second, SHBG...... was the variable which best discriminated PT from PP. Third, stimulated LH in 1-3 years old girls with PT is similar to stimulated LH in 5-7 years old girls with PP. Age, BMISDS, ethnicity, bone age, stimulated gonadotropins and LH/FSH and SHBG are all useful variables for differentiating PP from PT. However...

  7. Serum levels of sex hormone binding globulin,androgen and Insulin in polycystic ovarian syndrome women during pregnancy%血清性激素结合球蛋白、雄激素和胰岛素抵抗对多囊卵巢综合征孕妇的影响研究

    Institute of Scientific and Technical Information of China (English)

    余国丽

    2014-01-01

    Objective Toinvestigatethechangesofserumlevelsofsexhormonebindingglobulin(SHBG),freetestosteroneindex ( FTI)and insulin resistance,and to investigate the relationship among them and prevalence of gestation diabetes mellitus( GDM)and hyperten-sivedisordercomplicatingpregnancy(HDP)inpolycysticovariansyndrome(PCOS)womenduringpregnancy.Methods Serumsamplesof50P-COS women and 50 non-PCOS women with comparable age and body mass index( BMI)were collected during their gestational age from 12 to l6 weeks. Serum levels of total testosterone(TT),SHBG,total cholesterol(TC),triglyceride(TG)and fasting insulin(FINS)were detected. Free testosterone index( FTI)and homeostasis model assessment for insulin resistance( HOMA-IR)were calculated. Risk factors of GDM and HDPwereanalyzedbybinarylogisticregression.Results SerumTC,FINS,FTI,HOMA-IRlevelsandTTwerehigherinPCOSgroupthan those of control group. SHBG level was lower in PCOS group than that of control group( P <0. 05). Cesarean section rate,premature delivery rate,GDM and HDP incidence were higher in PCOS group than those of control group(84. 0% vs. 50. 0%,P <0. 01;22. 0% vs. 6. 0%,P <0. 05;20. 0% vs. 4. 0%,P <0. 05;26. 0% vs. 4. 0%,P <0. 01,respectively). Binary logistic regression analysis showed that high SHBG was the risk factor of GDM(OR=0. 97,95% CI:0. 95~1. 00,P <0. 05). FTI was the risk factor of HDP in PCOS women(OR=5. 47,95%CI:2.20~24.32,P<0.05).Conclusion FTIandSHBGlevelscouldbepredictorsforGDMandHDPinPCOSwomenduringtheirpregnan-cies.%目的:评估多囊卵巢综合征( PCOS)患者妊娠期血清性激素结合球蛋白( SHBG)、游离睾酮指数( FTI)、胰岛素抵抗水平变化及与妊娠期糖尿病(GDM)、妊娠期高血压疾病(HDP)的关系。方法50例孕前诊断为PCOS的孕妇于妊娠12~16周检测血清总睾酮( TT)、SHBG、总胆固醇( TC)、甘油三酯( TG)、空腹胰岛素( FINS)水平,计算FTI,稳态模型评估法评定胰岛素抵抗指数( HOMA

  8. Characterisation of different digestion susceptibility of lupin seed globulins.

    Science.gov (United States)

    Czubinski, Jaroslaw; Dwiecki, Krzysztof; Siger, Aleksander; Neunert, Grazyna; Lampart-Szczapa, Eleonora

    2014-01-15

    This study describes in vitro digestion of lupin seed globulins by pancreatin, trypsin and chymotrypsin. Lupin seed globulins turned out to be almost totally susceptible to chymotrypsin digestion. When panceratin or trypsin were used for digestion of lupin seed globulins, γ-conglutin appeared to be resistant to proteolysis. Different fluorescence spectroscopic methods such as fluorescence anisotropy, fluorescence lifetimes and fluorescence quenching measurements were used for detailed characterisation of this phenomenon. A potential reason for γ-conglutin insensitivity to digestion may be related to the fact that lysine, as well as arginine, are positively charged at cell physiological pH. Simultaneously, flavonoids at this pH are partially ionised, which may lead to the occurrence of ionic interactions between these molecules at pH 7.5. The confirmation of this explanation may be the fact that γ-conglutin and vitexin form a static complex, which was observed using fluorescence quenching measurements.

  9. A gene encoding a vicilin-like protein is specifically expressed in fern spores. Evolutionary pathway of seed storage globulins.

    Science.gov (United States)

    Shutov, A D; Braun, H; Chesnokov, Y V; Bäumlein, H

    1998-02-15

    The isolation and characterisation of a cDNA coding for a vicilin-like protein of the fern Matteuccia struthiopteris is described. The corresponding gene is specifically expressed during late stages of spore development. Extensive sequence comparisons suggest that the fern protein can be considered as a molecular missing link between single-domain germin/spherulin-like proteins and two-domain seed storage globulins of gymnosperms and angiosperms. Further, evidence is provided for the existence of a superfamily of structurally related, functionally different proteins which includes storage globulins of the vicilin and legumin families, a membrane-associated sucrose-binding protein of soybean, a Forssman antigen-binding lectin of velvet bean, the precursor of the vacuolar membrane bound proteins MP27/MP32 of pumpkin, the embryogenesis-specific protein Gea8 of carrot, the fern-spore-specific protein described here as well as the functionally diverse family of germins/germin-like proteins and the spherulins of myxomycetes. We propose that seed storage globulins of spermatophytes evolved from desiccation-related single-domain proteins of prokaryotes via a duplicated two-domain ancestor that is best represented by the extant fern spore-specific vicilin-like protein.

  10. Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1990-01-01

    Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared...... micrograms DNA). Unstimulated glucose uptake was increased in cells from patients with NTI (2.03 +/- 0.49 mmol/l per mg DNA per h, P less than 0.01) compared with controls (1.13 +/- 0.20 mmol/l per mg DNA per h). Thyroxine-stimulated glucose uptake (stimulated glucose uptake--unstimulated glucose uptake......) was increased in cells from patients with NTI (2.06 +/- 1.67 mmol/l per mg DNA per h, P less than 0.01) compared with controls (0.26 +/- 0.12 mmol/l per mg DNA per h), and T3-stimulated glucose uptake was also increased in cells from patients with NTI (1.34 +/- 0.81 mmol/l per mg DNA per h, P less than 0...

  11. 21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin...

  12. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew;

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

  13. 21 CFR 862.1330 - Globulin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  14. 21 CFR 640.102 - Manufacture of Immune Globulin (Human).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Manufacture of Immune Globulin (Human). 640.102 Section 640.102 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... microorganisms. Preservatives to inhibit growth of microorganisms shall not be used during processing. (c)...

  15. Adsorption of antibody and globulin onto glass surfaces.

    Science.gov (United States)

    Mizutani, T

    1980-10-01

    The amount of globulin adsorbed onto surfaces (97 m2) of porous glass (1 g) in phospate-buffered saline (pH 7.2) was estimated to be 83 mg by frontal analysis. In the adsorption chromatography of rabbit antiserum (the immunoglobulin G class) to horse serum albumin on a porous glass column, immunoglobulin G was not eluted with saline but was eluted with 0.2 M glycine (pH 9) with a recovery of 12%. The yield of immunoglobulin M antibody to sheep red blood cells recovered by elution with saline was 12.3%, and the total yield of immunoglobulin M was 15.8%. Thus, antibody and globulin were well adsorbed onto glass surfaces in physiological saline; immunoglobulin G had a stronger affinity to glass surfaces than did immunglobulin M. These facts should be considered when glass containers are used for purified antiserum.

  16. Worsening Bradycardia Following Antithymocyte Globulin Treatment of Severe Aplastic Anemia

    OpenAIRE

    2011-01-01

    Immunosuppressive regimens, which include antithymocyte globulin (ATG), are widely used for the treatment of severe aplastic anemia (SAA). However, bradycardia has been reported only as a rare side effect of ATG therapy in the manufacturer's product information and, in rare cases, in the adult literature. We present an adolescent with SAA and preexisting bradycardia who underwent immunosuppression therapy with ATG, methylprednisolone, and tacrolimus and developed profound sinus bradycardia wi...

  17. Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

    Science.gov (United States)

    Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

    2017-03-24

    For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using HLA-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, p<0.001) and chronic (20% versus 9%, p<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3 year overall survival, 87% and 92%, p=0.76. Among recipients of unrelated donor transplants acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, p<0.001) but not chronic graft-versus-host disease (38% versus 32%, p=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, p=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

  18. High-throughput bioaffinity mass spectrometry for screening and identification of designer anabolic steroids in dietary supplements

    NARCIS (Netherlands)

    Aqai, P.; Cevik, E.; Gerssen, A.; Haasnoot, W.; Nielen, M.W.F.

    2013-01-01

    A generic high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of known and unknown recombinant human sex hormone-binding globulin (rhSHBG)-binding designer steroids in dietary supplements. For screening,

  19. A study of a polymorphic globulin in the serum of Silurus glanis L.

    Science.gov (United States)

    Stratil, A; Bobák, P; Kouril, J; Hamácková, J

    1984-01-01

    A polymorphism of S-globulin was detected in serum of Silurus glanis L. by starch gel electrophoresis. Three phenotypes were observed which are apparently controlled by two codominant alleles, SgA and SgB, of an autosomal locus, Sg. Although on electrophoresis S-globulin and transferrin have similar mobilities, the properties of the two proteins differ.

  20. Strain-specific renal toxicity of heterologous antilymphocyte [gamma]-globulin in mice7

    NARCIS (Netherlands)

    Cohen, B.J.; Vries, M.J. de; Noord, M.J. van; Lubbe, F.H.

    1970-01-01

    Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte [gamma]-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit [gamma]-globulin (NRG) to RFM mice also caused renal

  1. Acute Lung Injury during Antithymocyte Globulin Therapy for Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Ewan Christopher Goligher

    2009-01-01

    Full Text Available The case of a 33-year-old man with aplastic anemia who experienced recurrent episodes of hypoxemia and pulmonary infiltrates during infusions of antithymocyte globulin (ATG is described. With the use of high-dose corticosteroids, the patient’s original episodes resolved, and were subsequently prevented before additional administrations of ATG. Rare reports of an association between ATG and acute lung injury are found in the literature, but this is the first report of successful steroid-supported re-exposure. Although the mechanism of ATG-related acute lung injury remains uncertain, it may be parallel to the mechanism of transfusion-related acute lung injury because the pathogenesis of the latter relies, in part, on antileukocyte antibodies. ATG-related toxicity should be included in the differential diagnosis of new, infusion-associated pulmonary infiltrates, and corticosteroids may be a useful therapeutic consideration in the management.

  2. STUDIES ON THE BLOOD PROTEINS : I. THE SERUM GLOBULINS IN BACTERIAL INFECTION AND IMMUNITY.

    Science.gov (United States)

    Hurwitz, S H; Meyer, K F

    1916-11-01

    The progress of an infection is usually associated with marked changes in the serum proteins. There may be an increase in the percentage of the total protein during some stage of the infection, and there is usually a change in the albumin-globulin ratio with an increase in the total globulins. This rise may antedate the development of any resistance by a considerable period of time. The non-protein constituents of the blood show fluctuations with a tendency to rise as the infection progresses. The process of immunization is in almost all instances associated with a definite increase in the globulins of the blood, and in some cases with a complete inversion of the normal albumin-globulin ratio. This may be produced both by living and dead organisms and by bacterial endotoxins. Massive doses usually result in an upset which shows no tendency to right itself during the period of observation. A rise in the globulins has been shown to occur long before the animal develops immune bodies in any appreciable concentration; and where the globulin curve and antibody curve appear to parallel one another, it can be shown by a careful analysis of both curves that there is a definite lack of correspondence at various periods of the experiment. Animals possessing a basic immunity show a more rapid rise in the globulin curve following inoculation. There is no parallelism between the leukocytic reaction and the globulin reaction. During periods of leukopenia the globulins may be as high as during the period of a leukocytosis. Bacterial endotoxins produce as striking an increase in the serum globulins as do living and killed bacteria. This would seem to indicate that a bacterial invasion of the organism is not absolutely essential for the globulin changes, and that the toxogenic factor in infection and immunity must play a part in the production of the changes noted. Inflammatory irritants injected intraperitoneally also result in a globulin increase. In this case the changes

  3. A corm-specific gene encodes tarin, a major globulin of taro (Colocasia esculenta L. Schott).

    Science.gov (United States)

    Bezerra, I C; Castro, L A; Neshich, G; de Almeida, E R; de Sá, M F; Mello, L V; Monte-Neshich, D C

    1995-04-01

    A gene encoding a globulin from a major taro (Colocasia esculenta L. Schott) corm protein family, tarin (G1, ca. 28 kDa) was isolated from a lambda Charon 35 library, using a cDNA derived from a highly abundant corm-specific mRNA, as probe. The gene, named tar1, and the corresponding cDNA were characterized and compared. No introns were found. The major transcription start site was determined by primer extension analysis. The gene has an open reading frame (ORF) of 765 bp, and the deduced amino acid sequence indicated a precursor polypeptide of 255 residues that is post-translationally processed into two subunits of about 12.5 kDa each. The deduced protein is 45% homologous to curculin, a sweet-tasting protein found in the fruit pulp of Curculigo latifolia and 40% homologous to a mannose-binding lectin from Galanthus nivalis. Significant similarity was also found at the nucleic acid sequence level with genes encoding lectins from plant species of the Amaryllidaceae and Lilliaceae families.

  4. Postmenopausal sex hormones in relation to body fat distribution

    NARCIS (Netherlands)

    Liedtke, S.; Schmidt, M.E.; Vrieling, A.; Lukanova, A.; Becker, S.; Kaaks, R.; Zaineddin, A.K.; Buck, K.; Benner, A.; Chang-Claude, J.; Steindorf, K.

    2012-01-01

    Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate

  5. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?

    NARCIS (Netherlands)

    Beek, C.; Thijssen, J.H.; Cohen-Kettenis, P.T.; Goozen, S.H. van

    2004-01-01

    Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic f

  6. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

    NARCIS (Netherlands)

    Rad, M.; Kluft, C.; Kam, M.L. de; Meijer, P.; Cohen, A.F.; Grubb, G.S.; Constantine, G.D.; Burggraaf, J.

    2011-01-01

    Objectives?To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG). Methods?Randomised, open-labe

  7. Peripheral markers of thyroid function

    DEFF Research Database (Denmark)

    Schmidt, Ulla; Nygaard, Birte; Winther Jensen, Ebbe;

    2013-01-01

    the combination therapy. HYPOTHESIS: Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy. METHODS: Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT...

  8. Interactions and compatibility of 11 S globulin from Vicia faba seeds and sodium salt of carboxymethylcellulose in an aqueous medium.

    Science.gov (United States)

    Antonov, Yu A; Dmitrochenko, A P; Leontiev, A L

    2006-02-28

    This work studies specific interactions and compatibility between a legumin and a linear carboxylated polysaccharide using gel permeation chromatography, sedimentation analysis, SDS gel electrophoresis, viscometry and phase analysis measurements. It uses the system water/11 S globulin/CMC as a model. Carboxymethylcellulose (CMC) molecules are able to cause a partial dissociation of the protein, subsequent formation of soluble interbiopolymeric complexes and partial aggregation of the free non combined protein at room temperature and pH 6.0-6.5. The maximal binding of biopolymers is observed at their equimolar ratio. The decrease in temperature of the mixture from 293 to 277 K leads to formation of the complex coacervate. The increase in pH from 6.0 to 7.6 results in suppression of complex formation and manifestation of the phenomenon of thermodynamic incompatibility if the total concentration of biopolymers in the system exceeds the critical concentration of segregative phase separation.

  9. SIFAT FUNGSIONAL PRODUK INTERAKSI FRAKSI GLOBULIN 7S KOMAK (Dolichos lablab DAN GUM XANTAN [Functional Properties of the Interaction Product Between Globulin of 7S Fraction of Lablab Bean (Dolichos lablab with Xantan Gum

    Directory of Open Access Journals (Sweden)

    Sukamto1*

    2009-12-01

    Full Text Available Lablab bean (Dolichos lablab seeds is a potential source of protein globulin.The bean’s protein content is 20.86 %, and the amount of globulin was more than 60% from the total protein, having major fractions of 7S and 11S. The objectives of this research were to explore the 7S globulin fractions, to study interaction between 7S globulin fractions with xanthan gum, and to observe the functional properties of the product of the interaction. The research was conducted in 2 steps. The first step was to fractionate the 7S fractions from globulin. The second steps was to interact 7S globulin fraction with xanthan gum. The yield of these interaction were examined for its physicochemical and functional properties. The results showed that the 7S globulin fractions could be interacted by xanthan gum at pH 7. The interacted product of globulin 7S fraction 10 % with xanthan gum 0,75 % had good functional properties than globulin 7S fraction, such as oil holding capacity, foaming capacity, and emulsion activity. Water holding capacity could not be detected because the yield became soluble. However,the foaming and emulsifying stability were still lower than those of soybean protein isolates. The research concluded that xanthan gum could be used to improve the physicochemical and functional properties of globulin 7S fraction.

  10. Treatment of Severe Aplastic Anemia by Immunosuppressor Anti-lymphocyte Globulin/Anti-thymus Globulin as the Chief Medicine in Combination with Chinese Drugs

    Institute of Scientific and Technical Information of China (English)

    郑兵荣; 沈建平; 庄海峰; 林圣云; 沈一平; 周郁鸿

    2009-01-01

    Objective:To study the therapeutic effect of combined therapy with Chinese drugs and immunosuppressors, mainly anti-lymphocyte globulin/anti-thymus globulin(ALG/ATG),for the treatment of severe aplastic anemia(SAA),the efficacy associated factors and adverse effects as well.Methods:A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A,androgen,hematopoietic growth factor,etc.Results:Of the 57 patients followed-up,26 (45.6%) we...

  11. Contribution of polymorphisms in ESR1, ESR2, FSHR, CYP19A1, SHBG and NRIP1 genes to migraine susceptibility in Turkish population

    Indian Academy of Sciences (India)

    Salih Coşkun; Yavuz Yücel; Abdullah Çim; Beyhan Cengiz; Serdar Oztuzcu; Sefer Varol; Hasan H. Özdemir; Ertuğrul Uzar

    2016-03-01

    Migraine, a highly prevalent headache disorder, is regarded as a polygenic multifactorial disease. Single-nucleotide polymorphisms (SNPs) in the genes that involved in sex hormone metabolism may comprise risk for migraine, but the results of previous genetic association studies are conflicting. The aim of this study was to evaluate genetic variants in genes involved in oestrogen receptor and oestrogen hormone metabolism in a Turkish population. A total of 12 SNPs in the ESR1, ESR2, FSHR, CYP19A1, SHBG and NRIP1 genes were genotyped in 142 migraine cases and 141 nonmigraine controls, using a BioMark 96.96 dynamic array system. In addition, gene–gene interactions were analysed using generalized multifactor dimensionality reduction (GMDR) methods. According to GMDR analysis, our results indicated that there was a significant association between migraine and gene–gene interaction among the CYP19A1, FSHR, ESR1 and NRIP1. Single-gene variant analysis showed that a significant association was observed between the TT genotype of rs10046 and migraine susceptibility.When the analysis was performed only in women, the GG genotype of rs2229741 was different between migraineurs and controls. When the female migraine patients were divided into two groups, migraine related to menstruation (MRM) or migraine not related to menstruation (MNRM), GG genotype of rs726281 was significantly associated with MRM. These results suggested that rs10046 could play a potential role in migraine susceptibility in Turkish population. Also, the rare GG genotype of rs726281 appears to influence migraine susceptibility in a recessive manner in MRM subgroup of female patients. In addition, variant GG genotype of rs2229741 may reduce the risk of migraine in Turkish women.

  12. Study of the influence of homologous serum globulin preparations on the intestinal automicroflora in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pinegin, B.V.; Klemparskaya, N.N.; Mal' tsev, V.N.; Korshunov, G.A.; Shal' nova, G.A.; Kuz' mina, T.D.

    1984-09-01

    In spite of considerable experience of practical use of serum globulin preparations, their effect on automicroflora wasn't studied. The favorable effect of therapeutic injection of homologous serum globulin preparations on automicroflora of small and large intestine of mices was established for the model of acute radiation sickness caused by /sup 60/Co irradiation with 700 R dose. The effect of injecting two types of globulin preparations was studied: ones prepared of blood of intact and hemostimulated mices (to increase the content of normal antitissue antibodies in the serum). Besides the general globulin fraction isolated by ammonium sulfate precipitation a study was made on the effect of purified IgG and IgM preparations. Threefold subcutaneous or intraperitoneal globulin in ection of 1 ..mu..g dose in a mice prevented after 2, 24, 48 h after irradiation the development of bacteriosis, typical for radiation injury - decreased accumulation of putrefactive bacteria and reduced the suppression of lactobacilli content. Globulin preparations and fractions of hemostimulated mice serum, enriched by normal antitissue antibodies are the most effective ones.

  13. Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Jensen, Tina K; Juul, Anders;

    2007-01-01

    Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function....

  14. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives.

    NARCIS (Netherlands)

    Raps, M.; Helmerhorst, F.; Fleischer, K.; Thomassen, S.; Rosendaal, F.; Rosing, J.; Ballieux, B.; Vliet, H. van

    2012-01-01

    BACKGROUND: It takes many years to obtain reliable values for the risk of venous thrombosis of hormonal contraceptive users from clinical data. Measurement of activated protein C (APC) resistance via thrombin generation is a validated test for determining the thrombogenicity of hormonal contraceptiv

  15. Sex hormone binding globulin and incident Alzheimer's disease in elderly men and women

    NARCIS (Netherlands)

    Muller, Majon; Schupf, Nicole; Manly, Jennifer J.; Mayeux, Richard; Luchsinger, Jose A.

    2010-01-01

    It has been suggested that low levels of estradiol and testosterone increase dementia risk. However, results of the existing observational studies examining associations of endogenous sex hormones with cognition and dementia are conflicting. A possible explanation for these inconsistent findings cou

  16. Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Human Gc Globulin (Vitamin D Binding Protein)

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jørgensen, Charlotte Svaerke; Santoni-Rugiu, Eric

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...... toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies...

  17. Safety pharmacology, toxicology and pharmacokinetic assesment of human Gc globulin (vitamin d binding protein)

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jørgensen, Charlotte Sværke; Santoni Rugiu, Eric

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...... toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies...

  18. Plasma androgenic activity in women with acne vulgaris and in healthy girls before, during and after puberty.

    Science.gov (United States)

    Odlind, V; Carlström, K; Michaëlsson, G; Vahlqvist, A; Victor, A; Mellbin, T

    1982-03-01

    The possible relationship between plasma androgenic activity and acne vulgaris was investigated. Plasma testosterone and sex hormone binding globulin (SHBG) levels were determined in healthy girls during different stages of puberty, in healthy adult women and in women with acne vulgaris. Testosterone increase during puberty, whereas SHBG decreased during the early stages before it increased and stabilized plasma concentrations of testosterone and SHBG. Women with severe acne vulgaris had testosterone levels in the same range but the SHBG levels were significantly lower than those of healthy women and women with mild acne. These results show a high androgenic activity in the intermediate stages of puberty, when acne vulgaris is a common complaint and an increased androgenic activity in adult women with severe acne vulgaris.

  19. ALTERATIONS IN TOTAL PROTEIN CONCENTRATION, SERUM PROTEIN FRACTIONS AND ALBUMIN/GLOBULIN RATIO IN HEALTHY RABBITS

    Directory of Open Access Journals (Sweden)

    Nuzhat Sultana

    2013-08-01

    Full Text Available This study assessed the effect of oral administration of Aloe vera and was to evaluate total serum protein, albumin and globulin concentrations as well as albumin / globulin (A / G ratio. Twenty rabbits weighing 1000 – 1800 g were divided into 2 groups. Each group consisted of ten animals. One served as control and other group served as experimental group. Results show that animals after 07, 15 and 30 days dosing of Aloe vera showed highly significant decrease in total protein and globulin and highly significant decrease in Albumin after 15 and 30 days of dosing of Aloe vera in comparison to control animals group. It is concluded that the long-term use of Aloe vera may cause hypoglobinemia and hypoalbuminemia at 30 days of dosing and it could be due to the liver diseases, evidence of hepatotoxicity induced Aloe vera also reported in previous studies.

  20. Proteomic analysis of albumin and globulin fractions of pea (Pisum sativum L. seeds

    Directory of Open Access Journals (Sweden)

    Jerzy Dziuba

    2014-06-01

    Full Text Available Background. Proteomic analysis is emerging as a highly useful tool in food research, including studies of food allergies. Two-dimensional gel electrophoresis involving isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis is the most effective method of separating hundreds or even thousands of proteins. In this study, albumin and globulin tractions of pea seeds cv. Ramrod were subjected to proteomic analysis. Selected potentially alergenic proteins were identified based on their molecular weights and isoelectric points. Material and methods. Pea seeds (Pisum sativum L. cv. Ramrod harvested over a period of two years (Plant Breeding Station in Piaski-Szelejewo were used in the experiment. The isolated albumins, globulins and legumin and vicilin fractions of globulins were separated by two-dimensional gel electrophoresis. Proteomic images were analysed in the ImageMaster 2D Platinum program with the use of algorithms from the Melanie application. The relative content, isoelectric points and molecular weights were computed for all identified proteins. Electrophoregrams were analysed by matching spot positions from three independent replications. Results. The proteomes of albumins, globulins and legumin and vicilin fractions of globulins produced up to several hundred spots (proteins. Spots most characteristic of a given fraction were identified by computer analysis and spot matching. The albumin proteome accumulated spots of relatively high intensity over a broad range of pi values of -4.2-8.1 in 3 molecular weight (MW ranges: I - high molecular-weight albumins with MW of -50-110 kDa, II - average molecular-weight albumins with MW of -20-35 kDa, and III - low molecular-weight albumins with MW of -13-17 kDa. 2D gel electrophoregrams revealed the presence of 81 characteristic spots, including 24 characteristic of legumin and 14 - of vicilin. Conclusions. Two-dimensional gel electrophoresis proved to be a useful tool for

  1. Modification of solubility and heat-induced gelation of amaranth 11S globulin by protein engineering.

    Science.gov (United States)

    Carrazco-Peña, Laura; Osuna-Castro, Juan A; De León-Rodríguez, Antonio; Maruyama, Nobuyuki; Toro-Vazquez, Jorge F; Morales-Rueda, Juan A; Barba de la Rosa, Ana P

    2013-04-10

    The primary structure of amaranth 11S globulin (Ah11S) was engineered with the aim to improve its functional properties. Four continuous methionines were inserted in variable region V, obtaining the Ah11Sr+4M construction. Changes on protein structure and surface characteristics were analyzed in silico. Solubility and heat-induced gelation of recombinant amaranth 11S proglobulin (Ah11Sr and Ah11Sr+4M) were compared with the native protein (Ah11Sn) purified from amaranth seed flour. The Ah11Sr+4 M showed the highest surface hydrophobicity, but as consequence the solubility was reduced. At low ionic strength (μ = 0.2) and acidic pH (proteins Ah11Sr and Ah11Sr+4 M had the highest and lowest solubility values, respectively. All globulins samples formed gels at 90 °C and low ionic strength, but Ah11Sn produced the weakest and Ah11Sr the strongest gels. Differential scanning calorimetry analysis under gel forming conditions revealed only exothermic transitions for all amaranth 11S globulins analyzed. In conclusion, the 3D structure analysis has revealed interesting molecular features that could explain the thermal resistance and gel forming ability of amaranth 11S globulins. The incorporation of four continuous methionines in amaranth increased the hydrophobicity, and self-supporting gels formed had intermediate hardness between Ah11Sn and Ah11Sr. These functional properties could be used in the food industry for the development of new products based on amaranth proteins.

  2. Identification of three wheat globulin genes by screening a Triticum aestivum BAC genomic library with cDNA from a diabetes-associated globulin

    Directory of Open Access Journals (Sweden)

    MacFarlane Amanda J

    2009-07-01

    Full Text Available Abstract Background Exposure to dietary wheat proteins in genetically susceptible individuals has been associated with increased risk for the development of Type 1 diabetes (T1D. Recently, a wheat protein encoded by cDNA WP5212 has been shown to be antigenic in mice, rats and humans with autoimmune T1D. To investigate the genomic origin of the identified wheat protein cDNA, a hexaploid wheat genomic library from Glenlea cultivar was screened. Results Three unique wheat globulin genes, Glo-3A, Glo3-B and Glo-3C, were identified. We describe the genomic structure of these genes and their expression pattern in wheat seeds. The Glo-3A gene shared 99% identity with the cDNA of WP5212 at the nucleotide and deduced amino acid level, indicating that we have identified the gene(s encoding wheat protein WP5212. Southern analysis revealed the presence of multiple copies of Glo-3-like sequences in all wheat samples, including hexaploid, tetraploid and diploid species wheat seed. Aleurone and embryo tissue specificity of WP5212 gene expression, suggested by promoter region analysis, which demonstrated an absence of endosperm specific cis elements, was confirmed by immunofluorescence microscopy using anti-WP5212 antibodies. Conclusion Taken together, the results indicate that a diverse group of globulins exists in wheat, some of which could be associated with the pathogenesis of T1D in some susceptible individuals. These data expand our knowledge of specific wheat globulins and will enable further elucidation of their role in wheat biology and human health.

  3. Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin.

    Science.gov (United States)

    Saito, K; Kaneko, H; Isobe, N; Nakatsuka, I; Yoshitake, A; Yamada, H

    1992-11-30

    Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.

  4. Circulating hormones and breast cancer risk in premenopausal women: a randomized trial of low-dose tamoxifen and fenretinide.

    Science.gov (United States)

    Johansson, Harriet; Bonanni, Bernardo; Gandini, Sara; Guerrieri-Gonzaga, Aliana; Cazzaniga, Massimiliano; Serrano, Davide; Macis, Debora; Puccio, Antonella; Sandri, Maria Teresa; Gulisano, Marcella; Formelli, Franca; Decensi, Andrea

    2013-12-01

    Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

  5. Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia.

    Science.gov (United States)

    Thadhani, Ravi; Ecker, Jeffrey L; Mutter, Walter P; Wolf, Myles; Smirnakis, Karen V; Sukhatme, Vikas P; Levine, Richard J; Karumanchi, S Ananth

    2004-05-01

    Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGFxSHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia.

  6. Soy 11S Globulin Acid Subunits as the Novel Food Polymer Carrier

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2015-01-01

    Full Text Available Aflatoxins were conjugated with soy 11S globulins acid subunits and the hapten-specific monoclonal antibodies (McAbs cross-reactive with four major aflatoxins were achieved using indirect competitive ELISA screening procedure. The two antibodies (clones 1B2 and 2D3 had similar reaction efficiency with aflatoxins B1, B2, and G1 but showed a weak cross-reaction to G2. The clone 4C5 exhibited the highest sensitivity for all four aflatoxins. The concentrations of aflatoxins B1, B2, G1, and G2 at 50% inhibition for 4C5 were 1.1, 1.2, 2.1, and 17.6 pg mL−1. The results indicated that soy 11S globulin acid subunits were suitable novel carriers for aflatoxin antigen in immunization experiments and clone 4C5 could be used for simultaneous analysis of total aflatoxins.

  7. Characterization of a cashew allergen, 11S globulin (Ana o 2), conformational epitope.

    Science.gov (United States)

    Robotham, Jason M; Xia, Lixin; Willison, LeAnna N; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H

    2010-05-01

    Both linear and conformational epitopes likely contribute to the allergenicity of tree nut allergens, yet, due largely to technical issues, few conformational epitopes have been characterized. Using the well studied recombinant cashew allergen, Ana o 2, an 11S globulin or legumin, we identified a murine monoclonal antibody which recognizes a conformational epitope and competes with patient IgE Ana o 2-reactive antibodies. This epitope is expressed on the large subunit of Ana o 2, but only when associated with an 11S globulin small subunit. Both Ana o 2 and the homologous soybean Gly m 6 small subunits can foster epitope expression, even when the natural N-terminal to C-terminal subunit order is reversed in chimeric molecules. The epitope, which is also expressed on native Ana o 2, is readily susceptible to destruction by physical and chemical denaturants.

  8. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin.

    Science.gov (United States)

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana

    2003-06-27

    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  9. Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene.

    Science.gov (United States)

    Hammond, G L; Bocchinfuso, W P; Orava, M; Smith, C L; van den Ende, A; van Enk, A

    1994-10-01

    A cross-over study of two oral contraceptive formulations, containing 30 micrograms ethinylestradiol in combination with 150 micrograms desogestrel (Marvelon) or 75 micrograms gestodene (Femovan), has been performed to compare the serum distribution and pharmacokinetics of gestodene and the active metabolite of desogestrel, namely 3-ketodesogestrel. Serum concentrations of both sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) were also measured and were increased more than 3-fold and 2-fold, respectively, on day 21 of the treatment cycle, with no statistically significant difference between treatment groups. In addition, 35 days after ingestion of either oral contraceptive had ceased, the serum SHBG and CBG concentrations were similar to the pretreatment values. During treatment cycles, increased serum SHBG levels were associated with a redistribution of 3-ketodesogestrel and gestodene such that the non-protein-bound (NPB) and albumin-bound fractions were reduced in concert with an increase in the relative proportions bound to SHBG. The proportion of gestodene bound to SHBG was consistently higher than that observed for 3-ketodesogestrel, and this undoubtedly reflects the higher affinity of SHBG for gestodene (Kd = 1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel (Kd = 4.7 nM at 37 degrees C). It also probably accounts, in part, for the much higher total serum levels of gestodene (8.58 nmol/L) when compared to 3-ketodesogestrel (2.37 nmol/L) during the treatment cycles. Consequently, the absolute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are significantly higher than those measured for 3-ketodesogestrel. It is concluded that ethinylestradiol-induced increases in serum SHBG levels during treatment with Marvelon or Femovan, influenced the distribution and total amount of 3-ketodesogestrel and gestodene in serum, respectively, and that this, combined with the higher affinity of SHBG for gestodene, results in a

  10. Does breastfeeding influence future sperm quality and reproductive hormones?

    DEFF Research Database (Denmark)

    Laustsen, J M; Jensen, M S; Thulstrup, Ane Marie;

    2011-01-01

    was not statistically significantly associated with sperm concentration, total sperm count, sperm motility or morphology, oligozoospermia, follicle-stimulating hormone, inhibin B, luteinizing hormone, sex hormone-binding globulin (SHBG), the calculated level of free testosterone, free oestradiol, the free testosterone...... testosterone nor free oestradiol was different between the two groups. This study shows no association between breastfeeding and sperm quality or reproductive hormones and a strong association is unlikely. A larger study would be needed to detect more subtle effects....

  11. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    DEFF Research Database (Denmark)

    Mendiola, J; Jørgensen, N; Andersson, A-M

    2010-01-01

    metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses...... inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary...

  12. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    DEFF Research Database (Denmark)

    Mendiola, J; Jørgensen, N; Andersson, A-M

    2011-01-01

    metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses...... inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary...

  13. [Heteroimmune hemolytic anemia associated with antilymphocyte globulin treatment in a patient with aplastic anemia].

    Science.gov (United States)

    Goldztein, S; Carreras Vescio, L A; Salamone, H J; Calahonra, R; Kohan, A I; Sánchez Avalos, J C

    1990-01-01

    A 24-year-old male patient with a severe aplastic anemia (SAA) was treated with equine-antilymphocyte globulin (ALG). As complication of this treatment he developed a severe heteroimmune hemolytic anemia mediated by anti-species pan-agglutinin antibodies present in ALG. In spite of the fact that ALG is absorbed with red-cell stroma and platelets to remove anti-erythrocyte and anti-platelet contaminating antibodies, often only partial absorption is achieved, and the remaining antibodies are passively acquired by the recipient. Neutropenia and especially thrombocytopenia are usual complications of this treatment, but it is also possible to detect anti-erythrocyte antibodies in the serum and on the red cells of those patients. However, the unusual severity of the hemolysis suffered by our patient, with a striking decrease of the hemoglobin levels (Fig. 1) can be ascribed to the administration of ALG at a time at which the hematocrit was close to normal as a result of the previous administration of anabolics. It is likely that in severely anemic patients, with a high transfusional demand, such a hemolytic episode may remain undetected. The patient acquired reactivity to the direct antiglobulin test, as well as the positive results of investigation of unexpected antibodies and compatibility testing can be accounted for by the fact that commercial antihuman globulin serum (AGS) contains antibodies reacting with a globulin component shared by human and horse sera. Neutralization of AGS with ALG administered to the patient removed those cross-reacting antibodies, making it possible to perform reliable transfusion compatibility testing and to rule out the eventual presence of hidden alloantibodies or warm autoantibodies. Neutralized Coombs serum maintained its human antiglobulin properties unaltered (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Case of cytomegalovirus-associated direct anti-globulin test-negative autoimmune hemolytic anemia.

    Science.gov (United States)

    Kaneko, Saeko; Sato, Masanori; Sasaki, Goro; Eguchi, Hiroyuki; Oishi, Tsutomu; Kamesaki, Toyomi; Kawaguchi, Hiroyuki

    2013-12-01

    A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct anti-globulin test. The concentration of erythrocyte membrane-associated immunoglobulin G, determined using an immunoradiometric assay, correlated with disease activity. He was positive for cytomegalovirus (CMV) both serologically and by quantitative real-time polymerase chain reaction, indicating that his autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction between erythrocyte antigens and CMV was not likely a causative factor for hemolysis.

  15. Rabbit anti-thymocyte globulin induction in renal transplantation: review of the literature

    Directory of Open Access Journals (Sweden)

    Andress L

    2014-01-01

    Full Text Available Leah Andress,1 Anjali Gupta,2 Nida Siddiqi,3 Kwaku Marfo2,3 1University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, Buffalo, 2Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine Department of Abdominal Organ Transplant Program, Bronx, 3Montefiore Medical Center, Department of Pharmacy, Bronx, NY, USA Abstract: Rabbit anti-thymocyte globulin (rATG has proven benefit as induction therapy in renal transplant recipients, achieving reduced acute rejection rates and better short-term allograft function, with slightly higher rates of complications such as infections and malignancy. Compared with other agents, the most benefit from rATG induction has been observed in renal transplant recipients at high immunologic risk for rejection. However, in special populations, such as pediatrics, the elderly, and hepatitis C-positive and human immunodeficiency virus-positive renal transplant recipients, additional information is needed to delineate the absolute benefit of rATG induction compared with other induction agents. Selection of rATG as the choice of induction therapy in renal transplant recipients should be guided by a cost-effective approach in balancing efficacy, safety, and cost. This review summarizes the published literature on efficacy, safety, and cost of rATG induction in renal transplantation. Keywords: anti-thymocyte globulin, renal transplantation, induction therapy

  16. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan Rajagopalan

    2006-08-31

    The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful for targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.

  17. Relationship between in vitro Fe and Zn dialysability and peptide composition of albumin and globulins extracted from cooked bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Lombardi-Boccia, G; Carbonaro, M; Cappelloni, M; Carnovale, E

    1996-11-01

    In vitro dialysability of iron, zinc and protein was determined from whole bean (Phaseolus vulgaris), albumin and globulin (G1, G2) after cooking. Albumin showed the highest iron, zinc, protein and phytic acid content. Cooking increased iron and protein dialysability only in whole bean and albumin. Compared to globulins, albumin also presented a higher in vitro protein digestibility and cystine chemical reactivity. HPLC analysis of peptides in dialysates of bean and protein fractions suggested that some aggregation occurred during dialysis. The percentage of amino acids in dialysed peptides was found to be different between albumin and globulins. The difference in iron and zinc dialysability between albumin and globulins seems to depend on the phytic acid content of the albumin fraction and the protein properties of globulins.

  18. Guidelines on the use of intravenous immune globulin for hematologic conditions.

    Science.gov (United States)

    Anderson, David; Ali, Kaiser; Blanchette, Victor; Brouwers, Melissa; Couban, Stephen; Radmoor, Paula; Huebsch, Lothar; Hume, Heather; McLeod, Anne; Meyer, Ralph; Moltzan, Catherine; Nahirniak, Susan; Nantel, Stephen; Pineo, Graham; Rock, Gail

    2007-04-01

    Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions

  19. Konsentrasi Protein Total, Albumin, dan Globulin Anak Kambing Peranakan Etawah Setelah Pemberian Berbagai Sediaan Kolostrum* (TOTAL PROTEIN, ALBUMIN, AND GLOBULIN CONCENTRATIONS ON ETTAWAH CROSSBREED NEONATES FOLLOWING THE ADMINISTRATION OF VARIOUS FORM O

    Directory of Open Access Journals (Sweden)

    Anita Esfandiari

    2014-10-01

    Full Text Available This experiment was conducted to study the profile of total protein, albumin, and globulin concentrationson Ettawah crossbreed neonates after consuming various colostrums. Twenty four healthy neonatal kidswere used in this study. The neonates were divided into four groups. Each group received fresh maternal(goat colostrum, frozen-thawed bovine colostrum, bovine spray dried colostrum, and bovine powdercommercial colostrum, respectively. Colostrums were given at 10% of body weight directly after birth andfollowed by the same amount every 12 hours, for three days. The blood was taken from jugular vein at 0, 12,24, 48, 72, and 168 hours after birth to determine total protein, albumin, and globulin concentrations.Results of this study indicated that the serum total protein and globulin concentration increased andreached the peak at 24 hours after birth. Compared to the concentration at birth, the increase of totalprotein concentration were 62.77%, 59.26%, 48.05%, and 66.67% in fresh maternal (goat, frozen-thawedbovine, bovine spray dried, and commercial bovine colostrum, respectively. Serum globulin concentrationincreased 4.9, 4.4, 4.8, and 14.6 times in fresh matermnal goat, frozen-thawed bovine, spray dried, andcommercial bovine colostrums respectively, compared to the concentration at birth. In conclusion, theconsumption of various colostrums i.e. fresh maternal goat colostrums, bovine colostrums (frozen-thawed,spray dried and commercial colostrums would increase the concentration of blood total protein and globulin,which both reached the highest concentration at 24 h after birth.

  20. Brief Report: Dysregulated Immune System in Children with Autism: Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics.

    Science.gov (United States)

    Gupta, Sudhir; And Others

    1996-01-01

    Children (ages 3-12) with autism (n=25) were given intravenous immune globulin (IVIG) treatments at 4-week intervals for at least 6 months. Marked abnormality of immune parameters was observed in subjects, compared to age-matched controls. IVIG treatment resulted in improved eye contact, speech, behavior, echolalia, and other autistic features.…

  1. Self-Assembly of Nano Hydroxyapatite or Aragonite Induced by Molecular Recognition to Soy Globulin 7S or 11S.

    Science.gov (United States)

    Liu, Dagang; Tian, Huafeng; Kumar, Rakesh; Zhang, Lina

    2009-09-01

    Molecular self-assembly is emerging as a viable 'bottom-up' approach to build stable organic/inorganic nanometer-scale blocks. Herein, under the conditions of appropriate pH and ionic strength, soy globulin 7S or 11S were coprecipitated with hydroxyapatite (HAp) or aragonite (Arag), respectively, to fabricate two organic/inorganic hybrids: 7S/HAp and 11S/Arag. Results from high-resolution transmission electron microscopy show that the hybrids exhibit a nanosized core-shell structure with globulin monomer 7S or 11S as core and HAp or Arag as shells. 7S/HAp and 11S/Arag present a disk and hexagon shape, respectively. After calcinations, monodispersed HAp without support from globulins existed as nanospheres. It was revealed that the globulin as host induces the self-assembly and growth layer by layer of HAp or Arag nanocrystals. The factors of molecular recognition and surface potential definitely affected the size and shape of the hierarchical blocks. This work provided a novel pathway to controllably synthesize a wide variety of precise plant protein/biomineral hybrid biomaterials.

  2. Polycystic ovary syndrome, hyperandrogenemia, sex hormone-binding globulin, and risks of pregnancy complications in singleton pregnancies after assisted reproduction

    DEFF Research Database (Denmark)

    Naver, Klara

    2014-01-01

    Et klinisk prospektivt multicenterstudie. Projektet består af prægravid karakteristik af kvinder med og uden polycystisk ovariesyndrom (PCOS) før de opstarter fertilitetsbehandling. Når deltagerne er blevet gravide følges de i graviditeten med ultralydskanninger og målinger af insulin resistens, ...

  3. Antithymocyte globulin-induced acute respiratory distress syndrome after renal transplantation: a case report

    Institute of Scientific and Technical Information of China (English)

    TU Guo-wei; JU Min-jie; XU Ming; RONG Rui-ming; ZHU Tong-yu; LUO Zhe

    2012-01-01

    Antithymocyte globulin (ATG) has long been used for immune-induction and anti-rejection treatments for solid organ transplantations.To date,few cases of ATG-induced acute respiratory distress syndrome (ARDS) have been published.Here,we present a case of ARDS caused by a single low-dose of ATG in a renal transplant recipient and the subsequent treatments administered.Although the patient suffered from ARDS and delayed graft function,he was successfully treated.We emphasize that the presence of such complications should be considered when unexplained respiratory distress occurs.Early use of corticosteroids,adjustment of immunosuppressive regimens,and conservative fluid management,as well as empiric antimicrobial therapies,may be effective strategies for the treatment of ARDS caused by ATG.

  4. Detection of opsonic antibodies against Enterococcus faecalis cell wall carbohydrates in immune globulin preparations.

    Science.gov (United States)

    Hufnagel, M; Sixel, K; Hammer, F; Kropec, A; Sava, I G; Theilacker, C; Berner, R; Huebner, J

    2014-08-01

    Three different commercially available polyvalent immune globulins (IG) were investigated for the existence of antibodies against cell wall carbohydrates of four different E. faecalis serotypes (using a cell wall carbohydrate-enzyme-linked immunosorbent assay), and whether these antibodies mediated opsonic killing (using an opsonic-killing assay). All three IG preparations contained antibodies against all four serotypes (CPS-A to CPS-D). However, only one of the three IG preparations showed opsonic killing against all four serotypes. Average killing was higher against serotypes A and B (72 and 79 %, respectively) than against serotypes C and D (30 and 37 %, respectively). Such IG preparations could play a role as an adjuvant therapeutic option in life-threatening infections with E. faecalis, particularly when resistant strains are involved.

  5. Characterization of the 11S globulin gene family in the castor plant Ricinus communis L.

    Science.gov (United States)

    Chileh, Tarik; Esteban-García, Belén; Alonso, Diego López; García-Maroto, Federico

    2010-01-13

    The 11S globulin (legumin) gene family has been characterized in the castor plant Ricinus communis L. Phylogenetic analysis reveals the presence of two diverged subfamilies (RcLEG1 and RcLEG2) comprising a total of nine genes and two putative pseudogenes. The expression of castor legumin genes has been studied, indicating that it is seed specific and developmentally regulated, with a maximum at the stage when cellular endosperm reaches its full expansion (around 40-45 DAP). However, conspicuous differences are appreciated in the expression timing of individual genes. A characterization of the 5'-proximal regulatory regions for two genes, RcLEG1-1 and RcLEG2-1, representative of the two legumin subfamilies, has also been performed by fusion to the GUS reporter gene. The results obtained from heterologous expression in tobacco and transient expression in castor, indicating seed-specific regulation, support the possible utility of these promoters for biotechnological purposes.

  6. Comparison of Two Soy Globulins on the Dynamic-Mechanical Properties of the Dough and the Quality of Steamed Bread

    Directory of Open Access Journals (Sweden)

    Xue-Li Gao

    2016-01-01

    Full Text Available To investigate the effect of the soy protein concentrate (CSP and 7S and 11S soy globulin on wheat dough and steamed bread (SB, mixing properties of the dough were assessed by farinograph and dynamic-mechanical analyzer (DMA. The quality attributes of SB were assessed by texture profile analyzer (TPA, sensory analysis, and scanning electron microscope (SEM. The results showed that CSP, 7S, or 11S (each from 2.0 to 4.0% significantly decreased gluten content (from 29.4 to 26.0, 36.7 to 31.8, and 31.6 to 30.7%, when those were added to wheat flour. The CSP/wheat dough stability was increased (from 6.5 to 8.4, 6.5 to 8.5, and 6.5 to 8.3 min and the degree of softening was decreased (from 71.0 to 68.0, 71.0 to 64.0, and 71.0 to 62.0 min, but 7S or 11S had the opposite result. Moreover, the ratio of 7S and 11S has a significant effect on the quality of the dough. The storage modulus and loss modulus of soy/wheat dough decreased in the order of CSP, control, 11S soy globulin, and 7S soy globulin. The hardness, chewiness, and cohesiveness of SB decreased in the order of control, CSP, 11S soy globulin, and 7S soy globulin. Microstructure demonstrated that gluten network was interfered by SPC, 7S, and 11S soy protein, which was in agreement with the texture analysis index. The quality of SB with 3% 11S was the best in texture, microstructure, and sensory. These findings indicate that 11S has the potential to be used as a special soy protein for SB making.

  7. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)

    Science.gov (United States)

    Ahn, Jiyoung; Schumacher, Fredrick R.; Berndt, Sonja I.; Pfeiffer, Ruth; Albanes, Demetrius; Andriole, Gerald L.; Ardanaz, Eva; Boeing, Heiner; Bueno-de-Mesquita, Bas; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Diver, W. Ryan; Feigelson, Heather Spencer; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hoover, Robert N.; Kolonel, Laurence N.; Kraft, Peter; Ma, Jing; Le Marchand, Loïc; Overvad, Kim; Palli, Domenico; Stattin, Pär; Stampfer, Meir; Stram, Daniel O.; Thomas, Gilles; Thun, Michael J.; Travis, Ruth C.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Kaaks, Rudolf; Hunter, David J.; Hayes, Richard B.

    2009-01-01

    Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3α-androstanediol-glucuronide (N = 4767) and 17β-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 × 10−21), consistent with previous studies, and testosterone (P = 7.54 × 10−15), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 × 10−6) and SRD5A2 with 3α-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 × 10−6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones. PMID:19574343

  8. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant

    Science.gov (United States)

    Ruggeri, Annalisa; Sun, Yuqian; Labopin, Myriam; Bacigalupo, Andrea; Lorentino, Francesca; Arcese, William; Santarone, Stella; Gülbas, Zafer; Blaise, Didier; Messina, Giuseppe; Ghavamzadeh, Ardeshi; Malard, Florent; Bruno, Benedetto; Diez-Martin, Jose Luis; Koc, Yener; Ciceri, Fabio; Mohty, Mohamad; Nagler, Arnon

    2017-01-01

    Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3–4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09–2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04–2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03–2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98–2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post

  9. Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

    Directory of Open Access Journals (Sweden)

    CUPO Palmira

    2001-01-01

    Full Text Available An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG prevented the execution of the skin sensitivity test (SST and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP, a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71% received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2 and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP, with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out

  10. Update on the use of intravenous immune globulin in the treatment of patients with inflammatory muscle disease.

    Science.gov (United States)

    Dalakas, M C

    1995-11-01

    The inflammatory myopathies consist of three distinct groups: dermatomyositis, polymyositis, and inclusion body myositis. Dermatomyositis is distinguished by its characteristic rash, while polymyositis is a diagnosis of exclusion. Inclusion body myositis is characterized by early involvement of distal muscle groups and the quadriceps. Definitive diagnosis is made by muscle biopsy, which demonstrates histological features characteristic for each disorder. Immune mechanisms play a role in the pathogenesis of the inflammatory myopathies. A complement-mediated microangiopathy is seen in dermatomyositis, while there is evidence for a T cell-mediated process in polymyositis and inclusion body myositis. Treatment with prednisone is helpful to a majority of patients for a period of time. Immunosuppressive drugs have met with limited success. We describe a group of patients with dermatomyositis, resistant to available therapies, whose muscle strength, skin changes, and muscle biopsies improved significantly during treatment with intravenous immune globulin. The treatment of polymyositis and inclusion body myositis with intravenous immune globulin is currently under study.

  11. Interactions of protein content and globulin subunit composition of soybean proteins in relation to tofu gel properties.

    Science.gov (United States)

    James, Andrew T; Yang, Aijun

    2016-03-01

    The content and globulin subunit composition of soybean proteins are known to affect tofu quality and food-grade soybeans usually have higher levels of proteins. We studied the tofu quality of soybeans with high (44.8%) or low (39.1%) protein content and with or without the 11S globulin polypeptide, 11SA4. Both protein content and 11SA4 significantly affected tofu gel properties. Soybeans containing more protein had smaller seeds which produced significantly firmer (0.663 vs.0.557 N, pprotein subunits, which may have contributed to the improvement in tofu gel properties. These results suggest that, in combination with higher protein content, certain protein subunits or their polypeptides can also be targeted in selecting soybeans to further improve soy food quality.

  12. Proteomic and genetic analysis of wheat endosperm albumins and globulins using deletion lines of cultivar Chinese Spring

    DEFF Research Database (Denmark)

    Merlino, Marielle; Bousbata, Sabrina; Svensson, Birte;

    2012-01-01

    Albumins and globulins from the endosperm of Triticum aestivum L. cv Chinese Spring (CS) were analysed to establish a proteome reference map for this standard wheat cultivar. Approximately, 1,145 Coomassie-stained spots were detected by two-dimensional gel electrophoresis (2DE), 410 of which were...... the composition and genetics of a complex tissue, such as the wheat endosperm.......Albumins and globulins from the endosperm of Triticum aestivum L. cv Chinese Spring (CS) were analysed to establish a proteome reference map for this standard wheat cultivar. Approximately, 1,145 Coomassie-stained spots were detected by two-dimensional gel electrophoresis (2DE), 410 of which were...... in endosperm proteins due to chromosomal deletions. This differential analysis of spots allowed structural or regulatory genes, encoding 211 proteins, to be located on segments of the 21 wheat chromosomes. In addition, variance analysis of quantitative variations in spot volume showed that the expression...

  13. Positive predictive value of albumin: globulin ratio for feline infectious peritonitis in a mid-western referral hospital population.

    Science.gov (United States)

    Jeffery, Unity; Deitz, Krysta; Hostetter, Shannon

    2012-12-01

    Low albumin to globulin ratio has been found previously to have a high positive predictive value for feline infectious peritonitis (FIP) in cats with clinical signs highly suggestive of the disease. However, FIP can have a more vague clinical presentation. This retrospective study found that the positive predictive value of an albumin:globulin (A:G) ratio of <0.8 and <0.6 was only 12.5% and 25%, respectively, in a group of 100 cats with one or more clinical signs consistent with FIP. The negative predictive value was 100% and 99% for an A:G ratio of <0.8 and A:G<0.6%, respectively. Therefore, when the prevalence of FIP is low, the A:G ratio is useful to rule out FIP but is not helpful in making a positive diagnosis of FIP.

  14. Retrospective diagnosis of Q fever in a country abattoir by the use of specific IgM globulin estimations

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, A.M.; Hunt, J.G.

    1981-10-03

    Twenty-two cases of pyrexial illness which occurred amongst workers in a country abattoir were investigated retrospectively for Q fever, brucellosis, and leptospirosis. In 18, the illness was shown to be Q fever. No diagnoses were established for the other four. The demonstration of circulating Q-fever-specific IgM globulin was instrumental in establishing the diagnosis in many of the cases.

  15. Effect of colostrum type on serum gamma globulin concentration, growth and health of goat kids until three months

    OpenAIRE

    Iepema, G.L.; Eekeren, N. van

    2008-01-01

    In this study the effect of three colostrum types; goat, cow and artificial colostrum, on serum gamma globulin concentration (GGC), growth and health of goat kids during the first three months of the rearing phase was measured. Thirty newborn goat kids were randomly assigned to three experimental groups; goat colostrum (GC), cow colostrum (CC) and artificial colostrum (AC). At 2, 28, 56 and 86 days serum GGC and live weight were measured. The three colostrum types were analysed on immunoglobu...

  16. Preparation and use of erythrocyte-globulin conjugates to Lassa virus in reversed passive hemagglutination and inhibition.

    OpenAIRE

    1980-01-01

    Conditions were defined for functional covalent coupling of anti-Lassa virus globulins to glutaraldehyde-fixed chicken erythrocytes. Tolylene-2,4-diisocyanate in a reaction mixture containing not more than 0.01 M NaCl produced uniformly good conjugates which were used in reversed passive hemagglutination (RPH) and reversed passive hemagglutination inhibition (RPHI) tests to detect Lassa virus antigens in infected cell cultures and specific antigens in Vero cell cultures. Identical results wer...

  17. Genetic determinants of serum testosterone concentrations in men.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    2011-10-01

    Full Text Available Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871 and two de novo replication cohorts (n = 4,620 to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG locus (17p13-p12 were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41 and rs6258, p = 2.3×10(-22. Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16. The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01. Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

  18. Effects of storage time on total protein and globulin concentrations in bovine fresh frozen plasma obtained for transfusion.

    Science.gov (United States)

    Proverbio, D; Spada, E; Baggiani, L; Bagnagatti De Giorgi, G; Roggero, N; Belloli, A; Pravettoni, D; Perego, R

    2015-01-01

    To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at -20°C. Significant differences in concentrations were found in the median concentration of total protein (P=0.0336), between 0 months and 1 month (P=0.0108), 0 and 6 months (P=0.0023), and 0 and 12 months (P=0.0027), in mean concentration (g/dL) of albumin (P=0.0394), between 0 months and 1 month (P=0.0131), 0 and 6 months (P=0.0035), and 0 and 12 months (P=0.0038), and beta-2 fraction (P=0.0401), between 0 and 6 months (P=0.0401) and 0 and 12 months (P=0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at -20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at -20°C.

  19. [Serum gamma globulin concentration in goat kids after colostrum administration: effect of time of administration, volume and type of colostrum].

    Science.gov (United States)

    Orsel, K; van Amerongen, J J; Zadoks, R N; van Doorn, D C; Wensing, T

    2000-12-01

    In this study, which was performed on a Dutch dairy goat farm, several aspects of the administration of colostrum to new-born goat kids were examined. Time of colostrum administration and amount and type of colostrum administered were compared. Effectiveness was measured as total serum protein content and gamma globulin fraction. No significant differences in serum gamma globulin titre were observed between kids that received colostrum at 30 or 60-90 minutes post partum, respectively. Titres were significantly lower in kids that received 100 ml of colostrum instead of 150-200 ml. The effect of sheep colostrum replacer or cow colostrum was also examined. Gamma globulin titres were significantly high with goat colostrum than with cow colostrum or sheep colostrum replacer, and titres were higher with cow colostrum than with sheep colostrum replacer. Based on the results of this experiment, the following protocol is suggested for colostrum administration to goat kids: single administration of 150-200 ml of goat colostrum within 90 minutes of birth. Use of cow colostrum is not advised because it may lead to transmission of paratuberculosis. Use of sheep colostrum replacer as a source of passive immunity is not recommended.

  20. Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, C.E.; Taylor, P.E.; Tong, M.J.; Toy, P.T.; Vyas, G.N.; Nair, P.V.; Weissman, J.Y.; Krugman, S.

    1987-05-15

    A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, the authors administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5-/sup +/g doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. Hepatitis surface antigen and antibodies were detected by radioimmunoassay. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state.

  1. PROFIL PROTEIN TOTAL, ALBUMIN DAN GLOBULIN PADA AYAM BROILER YANG DIBERI KUNGIY, BAWANG PUTIH DAN ZINC (ZN

    Directory of Open Access Journals (Sweden)

    Sus Derthi Widhyari

    2011-12-01

    Full Text Available The objective of this experiment was to study the effectiveness of turmeric, garlic and zinc supplementation on protein, albumin and globulin concentration of broiler. One hundred DOC were divided into five treatments, four replications, consist of five chicks in each replicate. The treatments were R0 (basal diet as a control, R1 (R0 + 1,5% turmeric powder +2,5 % garlic powder, R2 (R0 + 2,5% garlic powder + 120 ppm zinc, R3 (R0 +1,5% turmeric powder + 120ppm zinc and R4 (R0 +1,5 turmeric powder + 2,5% garlic powder + 120 ppm zinc. The diet contain 23,5% crude protein and 3215 kcal metabolizable energy. Blood samples were taken from axillary veins at the three and six weeks of age. The results showed that total protein and globulin concentration at 6 weeks slightly higher than 3 weeks old chicks but not significantly different (P>0.05. Albumin concentration were highest on R3 treatment. Total protein and globulin concentration was highest on the R2 treatment. In conclusion, the supplementation of garlic (2.5% and ZnO (120 ppm showed the best combination to improve immune response in broiler

  2. Preoperative albumin-to-globulin ratio and prognostic nutrition index predict prognosis for glioblastoma

    Science.gov (United States)

    Xu, Wen-Zhe; Li, Feng; Xu, Zhen-Kuan; Chen, Xuan; Sun, Bin; Cao, Jing-Wei; Liu, Yu-Guang

    2017-01-01

    Objective Impaired immunonutritional status has disadvantageous effects on outcomes for cancer patients. Preoperative albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) have been used as prognostic factors in various cancers. We aimed to evaluate the clinical significance of the AGR and PNI in glioblastoma. Materials and methods This retrospective analysis involved 166 patients. Demographic, clinical, and laboratory data were collected. AGR and the PNI were calculated as AGR = albumin/(total serum protein − albumin) and PNI = albumin (g/L) + 5 × total lymphocyte count (109/L). Overall survival (OS) was estimated by Kaplan–Meier analysis. Receiver-operating characteristic analysis was used to assess the predictive ability of AGR and the PNI. Cox proportional-hazard models estimating hazard ratios (HRs) and 95% confidence intervals (CIs) were used for univariable and multivariable survival analyses. Results The cutoff values of AGR and PNI were 1.75 and 48. OS was enhanced, with high AGR (>1.75) and the PNI (>48) (Pglioblastoma. AGR and the PNI could also help in developing good adjuvant-therapy schedules. PMID:28223828

  3. Self-Assembly of Rice Bran Globulin Fibrils in Electrostatic Screening: Nanostructure and Gels

    Directory of Open Access Journals (Sweden)

    Lihua Huang

    2014-01-01

    Full Text Available The effects of various ionic strengths and protein concentrations on the fibrils structure and gel properties of rice bran globulin (RBG at pH 2.0 were investigated using atomic force microscopy (AFM, rheometer, and scanning electron microscope (SEM. AFM images showed the morphology of assembling RBG fibrils from strand beads to becoming branch clustered, when electrostatic repulsive forces attenuated gradually with increasing ionic strength. NaCl seems to accelerate the kinetics of fibrils formation, resulting in a significant increase in Th T fluorescence intensity. The increased ionic strengths promote particle size increasing and zeta potential decreasing synchronously. The percolation model G'~C-Cpn be used to calculate theoretical RBG gels concentration at various ionic strengths (0–500 mM, which decreased from 15.17 ± 0.63 to 2.26 ± 0.27 wt%. SEM images exhibited a granular mesh-like gel structure. A more homogenous structure occurred in low ionic strength. This study elucidates properties of RBG fibrils and gels as a bioactive material.

  4. Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1996-05-01

    High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy for patients with inflammatory myopathies who have become unresponsive to, or cannot tolerate, conventional therapies. In a double-blind, placebo-controlled study, using objective criteria for improvement, IVIG demonstrated moderate to dramatic improvement in 75% of the patients with dermatomyositis. Preliminary results from a controlled study in inclusion-body myositis show that IVIG may also exert a mild benefit, but only in a small number of patients and in certain muscle groups. In some patients with polymyositis, IVIG is reported to be of benefit but controlled studies have not yet been completed. Immunocytochemical, immunological and in vitro studies on the patients' repeated muscle biopsies and follow-up sera showed that IVIG exerts its action in inflammatory myopathies by: (i) inhibiting myotoxic cytokines, such as TNF-alpha and IL-1; (ii) blockade of Fc receptors on endomysial macrophages interfering with Fc receptor-mediated phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the formation and deposition of membranolytic attack complex on the endomysial capillaries.

  5. Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Liu; Jian-Lin Wu; Jian Liang; Tao Zhang,; Qing-Shou Sheng

    2012-01-01

    AIM:To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.METHODS:We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals.Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis.A new fibrosis index [globulin/platelet (GP) model] was developed,including globulin (GLOB) and platelet count (PLT).GP model =GLOB (g/mL) x 100/PLT (x 109/L).We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.RESULTS:Thirteen clinical biochemical and hematological variables [sex,age,PLT,alanine aminotransferase,aspartate aminotransferase (AST),albumin,GLOB,total bilirubin (T.bil),direct bilirubin (D.bil),glutamyl transferase,alkaline phosphatase,HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1,F2-F3 and F4).Bivariate Spearman's rank correlation analysis showed that six variables,including age,PLT,T.bil,D.bil,GLOB and PT,were correlated with the three fibrosis stages (FS).Correlation coefficients were 0.23,-0.412,0.208,0.220,0.314 and 0.212; and P value was 0.014,< 0.001,0.026,0.018,0.001 and 0.024,respectively.Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT:F =11.772,P <0.001; GLOB:F =6.612,P =0.002).Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R2 =0.237).By Spearman's rank correlation analysis,GP model was significantly correlated with the three FS (r =0.466,P < 0.001).The median values in F0-F1,F2-F3 and F4 were 1.461,1.720 and 2.634.Compared with the six available models (fibrosis index,AST-platelet ratio,FIB-4,fibrosis-cirrhosis index and age-AST model and age-PLT ratio),GP model showed a highest correlation

  6. Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

    Science.gov (United States)

    Miles, Judith H; Takahashi, T Nicole

    2007-07-01

    Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable.

  7. What the world's religions teach, applied to vaccines and immune globulins.

    Science.gov (United States)

    Grabenstein, John D

    2013-04-12

    For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about

  8. A systematic review of intravenous gamma globulin for therapy of acute myocarditis

    Directory of Open Access Journals (Sweden)

    Crumley Ellen

    2005-06-01

    Full Text Available Abstract Background Intravenous gamma globulin (IVGG is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. Methods We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. Results Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10 showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21 versus historic controls (n = 25. Ten case reports and two case series (total n = 21 described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. Conclusion There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG.

  9. Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

    Directory of Open Access Journals (Sweden)

    Dorward Heidi

    2007-01-01

    Full Text Available Abstract Background Hereditary Inclusion Body Myopathy (HIBM is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM, has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG, in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22% directly after IVIG loading to 25.6 kg (+35% at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44% directly after IVIG loading to 6.0 kg (+46% at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.

  10. Low-dose rabbit anti-thymoglobin globulin versus basiliximab for induction therapy in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Himanshu V Patel

    2014-01-01

    Full Text Available We conducted a single-center prospective double-arm open-labeled study on kidney transplant patients from 2010 to 2011 to evaluate the efficacy of induction therapy using low, single-dose rabbit-antithymocyte globulin (r-ATG, 1.5 mg/kg on Day 0 (n = 80, 60 males, mean age 35.9 years, versus basiliximab (Interleukin-2 blocker 20 mg on Days 0 and 4 (n = 20, 12 males, mean age 45.1 years on renal allograft function in terms of serum creatinine (SCr, rejec-tion and infection episodes and patient/graft survival and cost. Demographic and post-transplant follow-up including immunosuppression was similar in both groups. In the r-ATG group, donors were unrelated (spouse, n = 25, deceased (n = 31 and parents/siblings (others, with a mean HLA match of 1.58. Donors in the basiliximab group were living unrelated (spouse, n = 15 and deceased (n = 5, with a mean HLA match of 1.56. No patient/graft was lost in the r-ATG group over a mean of one year follow-up, and the mean SCr was 1.28 mg/dL with 7.5% acute rejection (AR episodes; infections were also not observed. In the basiliximab group, over the same period of follow-up, there was 95% death-censored graft survival, and the mean SCr was 1.23 mg/dL with 10% AR episodes. One patient died due to bacterial pneumonia and one succumbed to coronary artery disease; one graft was lost due to uncontrolled acute humoral and cellular rejection. The cost of r-ATG and basiliximab were $600 and $2500, respectively. We conclude that induction immunosuppressive therapy with a low-dose r-ATG may be a better option as compared with basiliximab in terms of graft function, survival and cost benefit in kidney transplant patients.

  11. Transgenic rabbits that overexpress the neonatal Fc receptor (FcRn generate higher quantities and improved qualities of anti-thymocyte globulin (ATG.

    Directory of Open Access Journals (Sweden)

    Mária Baranyi

    Full Text Available Immune suppression with rabbit anti-thymocyte globulin (rATG is a well-established therapeutic concept for preventing host rejection of transplanted organs and graft versus host disease. Increasing the efficiency of rATG production by reducing the number of animals would be highly beneficial to lower cost and to improve quality standards. We have developed transgenic (Tg mice and rabbits that overexpress the neonatal Fc receptor (FcRn and have shown an augmented humoral immune response in these animals. To test whether our FcRn Tg rabbits produced rATG more efficiently, we immunized them and their New Zealand White controls with live Jurkat cells. By day 21 after immunization, Tg animals produced significantly, 1.5 times higher amount of total IgG compared to their wt littermates. Also, the binding efficiency of Tg sera to Jurkat cells and their complement-mediated cytotoxicity was significantly higher. The purified Tg IgG preparation contained 2.6 the amount of Jurkat specific IgG as the wt preparation analyzed by complement-mediated lysis, suggesting greater antigen-specific B cell activation in the Tg rabbits. To test this hypothesis, immunization with ovalbumin and human α1-antitrypsin was performed, resulting in significantly greater numbers of antigen-specific B-cells in the FcRn Tg rabbits as compared with wt controls. The shift towards significantly larger populations of antigen-specific B cells relative to the non-specific B cell pool is further corroborated by our previous findings in FcRn Tg mice. Consequently, our FcRn Tg rabbits have the potential to offer substantial qualitative and quantitative improvements for the production of rATG and other polyclonal or monoclonal antibodies.

  12. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.

    LENUS (Irish Health Repository)

    Kenny-Walsh, E

    2012-02-03

    BACKGROUND AND METHODS: In February 1994, batches of anti-D immune globulin used in Ireland during 1977 and 1978 to prevent Rh isoimmunization were found to be contaminated with hepatitis C virus (HCV) from a single infected donor. In March 1994, a national screening program was initiated for all women who had received anti-D immune globulin between 1970 and 1994. Of the 62,667 women who had been screened when this study began, 704 (1.1 percent) had evidence of past or current HCV infection, and 390 of those 704 (55 percent) had positive tests for serum HCV RNA on reverse-transcription-polymerase-chain-reaction analysis. All 390 were offered a referral for clinical assessment and therapy. We evaluated 376 of these 390 women (96 percent); the other 14 were not seen at one of the designated treatment centers. RESULTS: The mean (+\\/-SD) age of the 376 women was 45+\\/-6 years at the time of screening. They had been infected with hepatitis C for about 17 years. A total of 304 women (81 percent) reported symptoms, most commonly fatigue (248 [66 percent]). Serum alanine aminotransferase concentrations were slightly elevated (40 to 99 U per liter) in 176 of 371 women (47 percent), and the concentrations were 100 U per liter or higher in 31 (8 percent). Liver biopsies showed inflammation in 356 of 363 women (98 percent); in most cases the inflammation was slight (41 percent) or moderate (52 percent). Although the biopsy samples from 186 of the 363 women (51 percent) showed evidence of fibrosis, only 7 women (2 percent) had probable or definite cirrhosis. Two of the seven reported excessive alcohol consumption. CONCLUSIONS: Most of the women with HCV infection 17 years after receiving HCV-contaminated anti-D immune globulin had evidence of slight or moderate hepatic inflammation on liver biopsy, about half had fibrosis, and 2 percent had probable or definite cirrhosis.

  13. Androgen levels in women using a single implant of nomegestrol acetate.

    Science.gov (United States)

    Barbosa, I; Coutinho, E; Athayde, C; Ladipo, O A; Olsson, S E; Ulmsten, U

    1996-01-01

    This study was undertaken to evaluate the effects of a single implant containing nomegestrol acetate (Uniplant) on plasma levels of sex hormone-binding globulin (SHBG), testosterone, free testosterone, androstenedione and on blood pressure, body weight, and the development of acne vulgaris. Plasma levels of sex hormone-binding globulin, testosterone, free testosterone and androstenedione were measured. Blood pressure and body weight were determined. The development of acne vulgaris was evaluated. Total testosterone and androstenedione decreased significantly during two years of Uniplant use but all levels were within the normal range. There were no significant differences in sex hormone-binding globulin and free testosterone during 24 months of Uniplant use. All changes observed in this study were within normal range. SHBG was not affected by Uniplant use. No significant increase in androgen levels and in the development of acne vulgaris was observed in these women using nomegestrol acetate implant during two years. Based on these results, it is possible to conclude that Uniplant had no androgenic effect in women during this study.

  14. The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: the osteoporotic fractures in men (MrOS) study.

    Science.gov (United States)

    Barrett-Connor, Elizabeth; Laughlin, Gail A; Li, Hong; Nielson, Carrie M; Wang, P Ying; Dam, Tien T; Cauley, Jane A; Ensrud, Kristine E; Stefanick, Marcia L; Lau, Edith; Hoffman, Andrew R; Orwoll, Eric S

    2012-11-01

    Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case-cohort design. "Abnormal" was defined as lowest quartile for VitD (59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6-year median follow-up was 1.2 (0.8-1.8) for low VitD alone; 1.3 (0.9-1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1-2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health.

  15. Timing and modality of the sclerosing agents binding to the human proteins: laboratory analysis and clinical evidences

    Directory of Open Access Journals (Sweden)

    Lorenzo Tessari

    2014-07-01

    Full Text Available Sclerosing agents (SA are blood inactivated. Nevertheless, investigations concerning the interaction among SA and blood components have never been deeply investigated. Aim of the study is to precisely identify SA blood ligands, to determine their binding time and to highlight the clinical consequences. Thirty-one blood samples were collected from chronic venous disease patients and tested by capillary and agarose gel (AGE electrophoresis before and after adding polidocanol (POL and sodiumtetradecylsulphate (STS. The two different types of electrophoresis allowed an evaluation of the blood proteins binding with the sclerosing agents, with a reaction time lower than 8 seconds for the AGE. Subsequently six patients underwent foam sclerotherapy and then were subdivided in group A (4 patients and B (2 patients. In group A blood sample was obtained from the ipsilateral brachial vein immediately before (T0 and repeated 1, 3, 5, and 10 minutes after injection of STS 3% injection into the GSV. In group B, the same procedure was performed with the same timing from the ipsilateral femoral vein. Free STS (fSTS and total proteinbound STS (bSTS were measured. POL mainly binds to β-globulins (11%, while STS to albumin and α-globulins (62.6% and 30.7% on the protidogram, respectively. Both in the brachial and in the femoral vein, the average fSTS was always 0. STS binds to albumin (62.6% and α-globulins (30.7%, while POL is bound mainly by the b-globulins (11%. The present paper demonstrates how the vast majority of the sclerosing agent is bound to the blood proteins, suggesting the need to look for possible sclerotherapy complications factors also in the used gas and/or in the subsequent cathabolites release.

  16. 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.

  17. Research progress on globulins of edible legumes%食用豆类球蛋白研究进展

    Institute of Scientific and Technical Information of China (English)

    刘红; 康玉凡

    2013-01-01

    This article analyzed and compared the storage protein content and composition of soybean (Glycine max L.),mung bean(Vigna radiate L. Wilczek),pea(Pisum staivum)and faba bean (Vicia faba)respectively. A summary was made on the structures and properties of the main globulin components:11S,7S and 8S. Extraction methods,functional properties and research trends of globulin were also discussed in this article to provide a theoretical and practical reference on the further study of legume proteins.%  该文比较分析大豆、绿豆、豌豆、蚕豆等蛋白含量及组成,就豆类蛋白主要成分―11S球蛋白、7S球蛋白和8S球蛋白亚基结构及性质,球蛋白提取方法及功能特性进行概述,并展望其研究发展趋势,以期为豆类球蛋白进一步研究及应用提供参考。

  18. Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin

    Directory of Open Access Journals (Sweden)

    Samir J. Patel

    2014-01-01

    Full Text Available Ganciclovir-resistant cytomegalovirus (CMV is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

  19. Study on Differences in Spermatogenic Suppression between Azoospermic and Oligozoospermic Responders Treated with Levonorgestrel Implant Plus Testosterone Undecanoate Injectable in Chinese Men

    Institute of Scientific and Technical Information of China (English)

    Si-tian LIU; You-lun GUI; W.J. Bremner; Er-sheng GAO; Chang-hai HE

    2003-01-01

    Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate(TU) injectable Methods Totally 21 Chinese male volunteers were given treatment with LNG implants (four rods, 75 mg/rod) and intramuscular injection of TU (500 mg, bimonthly for 3 times). According to the effects of treatment, they were divided into two groups, namely, azoospermia group (group A) and oligozoospermia group (group 0). Then seminal FSH, LH, T and estradiol (E2)were determined by immunoenzymetric assay, while seminal and serum dihydrotachysterol (DHT)and serum sex hormone binding globulin (SHBG) were by radioimmunoassay, and seminal transferrin (Tf) by scatter turbidimetry assay.Results Seminal FSH, LH and serum DHT, SHBG, FTI (T/SHBG × 100) levels were significantly lower in group A than in group O, while higher seminal concentrations of E2 were observed in azoospermia group.Conclusion The differences in the spermatogenic suppression in Chinese men might be attributed to different rate of peripheral androgen metabolism, variations in serum SHBG levels,5a-reductase activity and individual aromatase activity during LNG plus TU administration. In addition, seminal sex hormones might be more sensitive indexes to assess the extent of feedback inhibition on hypothalamus-pituitary-testis with exogenous testosterone plus progestogen in the efficacy hormone male contraceptive trials.

  20. Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Farholt, S

    1991-01-01

    significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations......In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were......, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione...

  1. Effect of Endurance and Resistance Training on Parameters Related to Sexual Function in Men

    Directory of Open Access Journals (Sweden)

    This paper should be cited as: Barari A, Ayatollahi AA, Shirali S, Ghasemi M, Hosseini A, Ekrami A, Khandan Del A . [ Effect of Endurance and Resistance Training on Parameters Related to Sexual ]. mlj goums . 201 4 ; 8 ( 3 : [Article in Persi an] Barari, A. (PhD

    2014-09-01

    Full Text Available Background and Objective: The hormonal responses are different, according to type, intensity and the duration of training. We aimed to compare the effect of endurance and resistance training in untrained men on the level sexual hormone including testosterone, estradiol, and on sex hormone binding globulin (SHBG. Material and Methods: this study was conducted on male Student Volunteers divided randomly into three groups of eight members, including endurance, resistance and control. To measure the variables, we performed sampling before and after the training program. Results: the levels of testosterone and estradiol, in both groups have a significant (p<0.05 increase and decrease respectively. SHBG level was significantly increased only in endurance group (p<0.05, But LH level was meaningfully increased only in the resistance group (p<0.05. Conclusion: The endurance and resistance training can increase the production of testosterone .Increased testosterone and decreased estradiol in men lead to sperm production and improve fertility.

  2. Organon OD 14 (tibolone) and menopausal dynamic hormone profiles.

    Science.gov (United States)

    Abdalla, H I; Hart, D M; Lindsay, R; Beastall, G H

    1986-03-01

    Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

  3. Evaluating the binding efficiency of pheromone binding protein with its natural ligand using molecular docking and fluorescence analysis

    Science.gov (United States)

    Ilayaraja, Renganathan; Rajkumar, Ramalingam; Rajesh, Durairaj; Muralidharan, Arumugam Ramachandran; Padmanabhan, Parasuraman; Archunan, Govindaraju

    2014-06-01

    Chemosignals play a crucial role in social and sexual communication among inter- and intra-species. Chemical cues are bound with protein that is present in the pheromones irrespective of sex are commonly called as pheromone binding protein (PBP). In rats, the pheromone compounds are bound with low molecular lipocalin protein α2u-globulin (α2u). We reported farnesol is a natural endogenous ligand (compound) present in rat preputial gland as a bound volatile compound. In the present study, an attempt has been made through computational method to evaluating the binding efficiency of α2u with the natural ligand (farnesol) and standard fluorescent molecule (2-naphthol). The docking analysis revealed that the binding energy of farnesol and 2-naphthol was almost equal and likely to share some binding pocket of protein. Further, to extrapolate the results generated through computational approach, the α2u protein was purified and subjected to fluorescence titration and binding assay. The results showed that the farnesol is replaced by 2-naphthol with high hydrophobicity of TYR120 in binding sites of α2u providing an acceptable dissociation constant indicating the binding efficiency of α2u. The obtained results are in corroboration with the data made through computational approach.

  4. Virus de la inmunodeficiencia felina (VIF: evaluación de las globulinas en pacientes infectados espontáneamente Feline immunodeficiency virus (FIV: study of globulins in patients with natural infections

    Directory of Open Access Journals (Sweden)

    N Gómez

    2006-12-01

    Full Text Available Fueron estudiadas las posibles correlaciones de parámetros tales como la Alfa glicoproteína ácida (AGP, proteína de fase aguda, fracciones electroforéticas de las proteínas séricas y títulos de Toxoplasma gondii en gatos infectados por el Virus de Inmunodeficiencia Felina (VIF. Los títulos de Toxoplasma gondii obtenidos por Inmunofluorescencia Indirecta (IFI no correlacionaron con los valores de Proteínas Totales ni con los de las globulinas. Sí se halló múltiple correlación entre todas las proteínas estudiadas (r: 0,98, pStatistical correlation between parameters such as globulins, Alpha- Glycoprotein AGP, serum proteins fractions by electrophoresis and Toxoplasma gondii titles in cats infected with Feline Immunodeficiency Virus (FIV were studied. Indirect Immunofluorecence titles to Toxoplasma gondii did not showed correlation with Total proteins and globulins. It was observed correlation between all types of proteins studied (r: 0,98, p<0,04. Total proteins versus globulins showed positive correlation (r:0,93, p <0,0001. Total protein versus alpha-globulin evidenced negative correlation (r:-0,75, p<0,01. AGP and alpha-globulins did not showed correlation and it was detected negative correlation with gamma-globulins (r:-0, 94, p<0,0001 and with globulins (r:-0,67, p<0,03. The patients evaluated showed a high level of Total proteins because of the increase of globulins. Gamma-Globulins were detected increased but there was not correlation with Toxoplasma gondii titles. It was not observed correlation between AGP and Alfa-globulins.

  5. Addition of an Enzymatic Hydrolysate of Bovine Globulins to Bread and Determination of Hypotensive Effects in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Lafarga, Tomas; Gallagher, Eimear; Aluko, Rotimi E; Auty, Mark A E; Hayes, Maria

    2016-03-02

    The aim of this study was to develop bread containing a papain hydrolysate of bovine α- and β-globulins (GPH) with in vitro and in vivo antihypertensive activities. The physical characteristics of the formulated bread were assessed over a six day period and results suggested that the overall quality and acceptance of bread was not affected by the inclusion of GPH at a concentration of 4% (w/w). Bright field light microscopy and confocal scanning laser microscopy images were used to visualize the main ingredients of the bread. In addition, the antihypertensive activity of the bread was assessed in spontaneously hypertensive rats (SHRs) over a 24 h period where a maximum significant decrease in systolic blood pressure of 36.2 ± 1.9 mmHg was observed 8 h after oral administration. Results demonstrate that the antihypertensive activity of GPH was resistant to the baking process and shows potential for use as a functional antihypertensive ingredient.

  6. Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009–2010

    Science.gov (United States)

    Cui, Xizhong; Nolen, Leisha D.; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P.; Boyer, Anne E.; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A.

    2017-01-01

    We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009–2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0–5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6–11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak. PMID:27983504

  7. [The macrophage disappearance reaction in guinea pigs sensitized with bovine gamma globulin or human scrum albumin (author's transl)].

    Science.gov (United States)

    Schimke, R; Bernstein, B; Ambrosius, H

    1977-01-01

    The macrophage disappearance reaction (MDR) is a suitable test for detection of cell mediated immunity against bovine gamma globulin (BGG) and human serum albumin (HSA) in guinea pigs. The MDR is a technical simple, good manipulable, and quantifiable test. The optimal test conditions for the antigens BGC and HSA are the following: Peritoneal exudat cells (PEC) were stimulated with paraffin oil. On the 5th day after receiving oil the animals were injected with 80 microgram BGG or 30 microgram HSA i.p. 5 hours later the PEC were harvested and counted. With the MDR it is possible to detect differences with respect to degree of cell-mediated immunity. Supernatants of sensitized lymphocytes produces the MDR too.

  8. Preparation and development of equine hyperimmune globulin F(ab')2 against severe acute respiratory syndrome coronavirus

    Institute of Scientific and Technical Information of China (English)

    Jia-hai LU; Bing L WONG; Nan-shan ZHONG; Zhong-min GUO; Wen-yu HAN; Guo-ling WANG; Ding-mei ZHANG; Yi-fei WANG; Sheng-yun SUN; Qin-he YANG; Huan-ying ZHENG

    2005-01-01

    Aim: The resurgence of severe acute respiratory syndrome (SARS) is still a threat because the causative agent remaining in animal reservoirs is not fully understood,and sporadic cases continue to be reported. Developing high titers of anti-SARS hyperimmune globulin to provide an alternative pathway for emergent future prevention and treatment of SARS. Methods: SARS coronavirus (CoV)F69 (AY313906)and Z2-Y3 (AY394989) were isolated and identified from 2 different Cantonese onset SARS patients. Immunogen was prepared from SARS-CoV F69 strain. Six health horses were immunized 4 times and serum was collected periodically to measure the profile of specific IgG and neutralizing antibodies using indirect enzyme-linked immunosorbent assay and a microneutralization test. Sera were collected in large amounts at the peak, where IgG was precipitated using ammonium sulphate and subsequently digested with pepsin. The product was then purified using anion-exchange chromatography to obtain F(ab')2 fragments. Results: The specific IgG and neutralizing antibody titers peaked at approximately week 7 after the first immunization, with a maximum value of 1:14210. The sera collected at the peak were then purified. Fragment of approximately 15 g F(ab')2 was obtained from 1 litre antiserum and the purity was above 90% with the titer of 1:5120, which could neutralize the other strain (SARS-CoV Z2-Y3) as well. Conclusion: This research provides a viable strategy for the prevention and treatment of SARS coronavirus infection with equine hyperimmune globulin, with the purpose of combating any resurgence of SARS.

  9. Predictive value of prostate specific antigen in a European HIV-positive cohort

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Álvaro H; Ravn, Lene

    2016-01-01

    BACKGROUND: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case...... control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional...

  10. 睾酮替代疗法之利弊%Advantages and Disadvantages of testosterone replacement therapy

    Institute of Scientific and Technical Information of China (English)

    黄宇烽

    2010-01-01

    @@ 睾酮是主要的循环雄激素,与男性的性别分化、生长以及生殖道的功能、第二性征和性欲有关[1-2].大部分循环睾酮(约65%)与性激素结合球蛋白(sex hormone-binding globulin, SHBG)紧密结合或与清蛋白松散结合.

  11. MANAGEMENT OF ARTAVAKSHAYA (HYPOMENORRHOEA WITH OBESITY BY A HERBAL COMPOUND

    Directory of Open Access Journals (Sweden)

    Vivek Mahalwar

    2012-12-01

    Full Text Available Obesity per se represents a condition of sex hormone imbalance in women. Obesity is associated with three biochemical alterations that affect normal ovulation e.g. 1. Hyperinsulinaemia 2. Increased peripheral conversion of androgen to estrogen and 3. Decrease level of sex hormone binding globulin (SHBG resulting in increased level of free oestradiol and testosterone. Level of sex hormone binding protein (SHBG tends to linearly decrease with increasing body fat and this may lead to an increased fraction of free androgens and thus estrogen level decreases. SHBG levels are regulated by a complex of factor including estrogen, iodothyronies and growth hormone as stimulating agents and androgens and insulin as inhibiting factor. The net balance of this regulation with the dominant role of insulin which inhibits SHBG synthesis in the liver may be responsible for the decrease of SHBG concentration observed in obesity. Fat represent a site of intensive sex hormone metabolism and interconversion due to the presence of several steroidaogenetic enzymes such as 3 beta dehydrogenese, 17 beta hydroxydehydrogenase and the aromatase systems. Obesity may thus add further specific mechanism in the development of androgen excess in women and decreases oestrogen. The present clinical study was planned to assess the efficacy of an indigenous compound in sthoulya janya artavakshaya, which contains Sunthi, Pippali, Maricha, Vidanga, Tvak, Guggullu, Gomutra in equal quantity and was made vati and given in the doses of 1 gm three times a day with luke warm water. The effect of indigenous compound as evident in the clinical trial was recorded along with detailed data pertaining to the case history.

  12. The 11S globulin Sin a 2 from yellow mustard seeds shows IgE cross-reactivity with homologous counterparts from tree nuts and peanut

    Directory of Open Access Journals (Sweden)

    Sirvent Sofía

    2012-12-01

    Full Text Available Abstract Background The 11S globulin Sin a 2 is a marker to predict severity of symptoms in mustard allergic patients. The potential implication of Sin a 2 in cross-reactivity with tree nuts and peanut has not been investigated so far. In this work, we studied at the IgG and IgE level the involvement of the 11S globulin Sin a 2 in cross-reactivity among mustard, tree nuts and peanut. Methods Eleven well-characterized mustard-allergic patients sensitized to Sin a 2 were included in the study. A specific anti-Sin a 2 serum was obtained in rabbit. Skin prick tests (SPT, enzyme-linked immunosorbent assay (ELISA, immunoblotting and IgG or IgE-inhibition immunoblotting experiments using purified Sin a 2, Sin a 1, Sin a 3, mustard, almond, hazelnut, pistachio, walnut or peanut extracts were performed. Results The rabbit anti-Sin a 2 serum showed high affinity and specificity to Sin a 2, which allowed us to demonstrate that Sin a 2 shares IgG epitopes with allergenic 11S globulins from tree nuts (almond, hazelnut, pistachio and walnut but not from peanut. All the patients included in the study had positive skin prick test to tree nuts and/or peanut and we subdivided them into two different groups according to their clinical symptoms after ingestion of such allergenic sources. We showed that 11S globulins contain conserved IgE epitopes involved in cross-reactivity among mustard, tree nuts and peanut as well as species-specific IgE epitopes. Conclusions The allergenic 11S globulin Sin a 2 from mustard is involved in cross-reactivity at the IgE level with tree nuts and peanut. Although the clinical relevance of the cross-reactive IgE epitopes present in 11S globulins needs to be investigated in further detail, our results contribute to improve the diagnosis and management of mustard allergic patients sensitized to Sin a 2.

  13. The 11S globulin Sin a 2 from yellow mustard seeds shows IgE cross-reactivity with homologous counterparts from tree nuts and peanut

    Science.gov (United States)

    2012-01-01

    Background The 11S globulin Sin a 2 is a marker to predict severity of symptoms in mustard allergic patients. The potential implication of Sin a 2 in cross-reactivity with tree nuts and peanut has not been investigated so far. In this work, we studied at the IgG and IgE level the involvement of the 11S globulin Sin a 2 in cross-reactivity among mustard, tree nuts and peanut. Methods Eleven well-characterized mustard-allergic patients sensitized to Sin a 2 were included in the study. A specific anti-Sin a 2 serum was obtained in rabbit. Skin prick tests (SPT), enzyme-linked immunosorbent assay (ELISA), immunoblotting and IgG or IgE-inhibition immunoblotting experiments using purified Sin a 2, Sin a 1, Sin a 3, mustard, almond, hazelnut, pistachio, walnut or peanut extracts were performed. Results The rabbit anti-Sin a 2 serum showed high affinity and specificity to Sin a 2, which allowed us to demonstrate that Sin a 2 shares IgG epitopes with allergenic 11S globulins from tree nuts (almond, hazelnut, pistachio and walnut) but not from peanut. All the patients included in the study had positive skin prick test to tree nuts and/or peanut and we subdivided them into two different groups according to their clinical symptoms after ingestion of such allergenic sources. We showed that 11S globulins contain conserved IgE epitopes involved in cross-reactivity among mustard, tree nuts and peanut as well as species-specific IgE epitopes. Conclusions The allergenic 11S globulin Sin a 2 from mustard is involved in cross-reactivity at the IgE level with tree nuts and peanut. Although the clinical relevance of the cross-reactive IgE epitopes present in 11S globulins needs to be investigated in further detail, our results contribute to improve the diagnosis and management of mustard allergic patients sensitized to Sin a 2. PMID:23231956

  14. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.

    Science.gov (United States)

    Nagasawa, Hideko; Uto, Yoshihiro; Sasaki, Hideyuki; Okamura, Natsuko; Murakami, Aya; Kubo, Shinichi; Kirk, Kenneth L; Hori, Hitoshi

    2005-01-01

    The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research.

  15. Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men

    Directory of Open Access Journals (Sweden)

    K. G. R. Yamaçake

    2016-04-01

    Full Text Available ABSTRACT Objectives: To study the impact of obesity, age and varicocele on sexual hormones fof adult and elderly men. Materials and Methods: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI, serum levels of total testosterone (TT, free testosterone (FT, sex hormone-binding globulin (SHBG, luteinizing hormone (LH and follicular stimulating hormone (FSH. Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Results: Obese patients had lower levels of TT, FT and SHBG (p<0.001 compared to underweight or normal weight patients. There were no differences in age (p=0.113, FSH serum levels (p=0.863 and LH serum levels (p=0.218 between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05. There was no difference in the SHBG levels (p=0.120 among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Conclusions: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.

  16. Trends in sex hormone concentrations in US males: 1988-1991 to 1999-2004.

    Science.gov (United States)

    Nyante, S J; Graubard, B I; Li, Y; McQuillan, G M; Platz, E A; Rohrmann, S; Bradwin, G; McGlynn, K A

    2012-06-01

    Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988-1991 and 1999-2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988-1991: N = 1,413; 1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided p-values were calculated; p 1988-1991 and 1999-2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = -1.83 ng/mL, p 1988-1991 and 1999-2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men.

  17. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

    OpenAIRE

    Hughes, Richard; Donofrio, Peter; Bril, Vera; Dalakas, Marinos; Deng, Chunqin; Hanna, Kim; Hartung, H P; Latov, Norman; Merkies, Ingemar; van Doorn, Pieter

    2008-01-01

    textabstractBackground: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treat...

  18. Sensitization with 7S Globulins from Peanut, Hazelnut, Soy or Pea Induces IgE with Different Biological Activities Which Are Modified by Soy Tolerance

    DEFF Research Database (Denmark)

    Kroghsbo, Stine; Bøgh, Katrine Lindholm; Rigby, Neil M.

    2011-01-01

    times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. Results: The 4 related 7S globulins induced a response with an almost identical......, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their ‘normal’ matrix. Methods: Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3...... level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Conclusions: Although the 4 7S globulins are structurally...

  19. A BIOCHEMICAL STUDY OF THE PHENOMENA KNOWN AS COMPLEMENT-SPLITTING : FIRST PAPER: SPLITTING OF THE COMPLEMENT ASSOCIATED WITH GLOBULIN PRECIPITATION.

    Science.gov (United States)

    Bronfenbrenner, J; Noguchi, H

    1912-06-01

    It is generally accepted that complement may be split into a mid-piece and an end-piece. The mid-piece is thought to be in the globulin fraction, and the end-piece in the albumin fraction. The restoration of complement activity by putting together the albumin and globulin fractions does not prove, however, that each fraction contained a part of the complement, for the albumin fraction can be reactivated in the absence of the globulin fraction. Complement-splitting as brought about by hydrochloric acid, carbon dioxid, and dialysis, is really an inactivation of the whole complement by certain acids or alkalis, either added in the free state to the serum, or liberated as a result of the dissociation of certain electrolytes. That the whole complement, and not a part only, is present in the albumin fraction of the serum can be demonstrated by the removal of the inhibitory action of the acid or alkali. This can be effected by the addition, not only of alkali or acid, but also of any amphoteric substance. When hydrochloric acid, carbon dioxid, or dialysis are employed to produce the phenomenon known as complement-splitting, the complement is merely inactivated, not split.

  20. Heat-denaturation and aggregation of quinoa (Chenopodium quinoa) globulins as affected by the pH value.

    Science.gov (United States)

    Mäkinen, Outi E; Zannini, Emanuele; Koehler, Peter; Arendt, Elke K

    2016-04-01

    The influence of heating (100 °C; 0-15 min) on the relative molecular mass, protein unfolding and secondary structure of quinoa globulins was studied at pH 6.5 (low solubility), 8.5 and 10.5 (high solubility). The patterns of denaturation and aggregation varied with pH. Heating triggered the disruption of the disulfide bonds connecting the acidic and basic chains of the chenopodin subunits at pH 8.5 and 10.5, but not at pH 6.5. Large aggregates unable to enter a 4% SDS-PAGE gel were formed at pH 6.5 and 8.5, which became soluble under reducing conditions. Heating at pH 10.5 lead to a rapid dissociation of the native chenopodin and to the disruption of the subunits, but no SDS-insoluble aggregates were formed. No major changes in secondary structure occurred during a 15 min heating, but an increase in hydrophobicity indicated unfolding of the tertiary structure in all samples.

  1. Efficacy of rabbit antithymocyte globulin as first-line treatment of severe aplastic anemia: an Asian multicenter retrospective study.

    Science.gov (United States)

    Chuncharunee, Suporn; Wong, Raymond; Rojnuckarin, Ponlapat; Chang, Cheng-Shyong; Chang, Kian Meng; Lu, Meng-Yao; Hwang, Wen-Li; Koh, Liang Piu; Chen, Tsai-Yun; Leung, Anskar Yh; Norasetthada, Lalita; Wang, Shih-Chung; Chang, Ming-Chih; Wu, Kang-Hsi; Issaragrisil, Surapol

    2016-10-01

    Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2-year OS with rabbit ATG were comparable to historical results obtained with horse ATG.

  2. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party.

    Science.gov (United States)

    Marsh, Judith C; Bacigalupo, Andrea; Schrezenmeier, Hubert; Tichelli, Andre; Risitano, Antonio M; Passweg, Jakob R; Killick, Sally B; Warren, Alan J; Foukaneli, Theodora; Aljurf, Mahmoud; Al-Zahrani, H A; Höchsmann, Britta; Schafhausen, Philip; Roth, Alexander; Franzke, Anke; Brummendorf, Tim H; Dufour, Carlo; Oneto, Rosi; Sedgwick, Philip; Barrois, Alain; Kordasti, Shahram; Elebute, Modupe O; Mufti, Ghulam J; Socie, Gerard

    2012-06-07

    Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.

  3. Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Mao-Lin Yan; Yong-Bing Chen; Lu-Nan Yan; Bo Li; Yong Zeng; Tian-Fu Wen; Wen-Tao Wang; Jia-Yin Yang; Ming-Qing Xu; Zhi-Hui Li

    2006-01-01

    BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has signiifcantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identiifed 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the ifrst week and intramuscularly thereafter. RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9%(2/51). The overall patient survival was 88.3%, and 82.4%after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1%(4/7) and 62.5%(5/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION:Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.

  4. Expression and characterization of a His-tagged 11S seed globulin from Amaranthus hypochondriacus in Escherichia coli.

    Science.gov (United States)

    Medina-Godoy, Sergio; Nielsen, Niels C; Paredes-López, Octavio

    2004-01-01

    DNA encoding a His-tagged 11S globulin from Amaranthus hypochondriacus (amarantin) was successfully expressed in Escherichia coli strains BL21 (DE3) and Origami (DE3). The two strains produced different accumulation patterns. Whereas most of the proamarantin expressed in BL21 (DE3) was localized in inclusion bodies, that produced in Origami (DE3) was soluble (76 mg/L). Sucrose density gradient ultracentrifugation analysis of the expressed soluble proamarantin revealed that the protein was assembled into trimers. Treatment of proamarantin trimers in vitro using purified asparaginyl endopeptidase resulted in the appearance of peptides of the sizes expected for acidic and basic chains. Because the proamarantin assembles into trimers with the expected sedimentation characteristics and is cleaved into acidic and basic chains rather than being degraded, the results suggest that the protein folding occurring in E. coli is similar to that taking place in seeds. The His-tagged proamarantin was purified in a single step by immobilized metal affinity chromatography with a final yield of 48 mg/L. The overexpression of proamarantin in E. coli, together with the one-step purification will facilitate further investigation of this storage protein through site-directed mutagenesis.

  5. Targeting of natural killer cells by rabbit antithymocyte globulin and campath-1H: similar effects independent of specificity.

    Directory of Open Access Journals (Sweden)

    Diana Stauch

    Full Text Available T cell depleting strategies are an integral part of immunosuppressive regimens widely used in the hematological and solid organ transplant setting. Although it is known to induce lymphocytopenia, little is known about the effects of the polyclonal rabbit antithymocyte globulin (rATG or the monoclonal anti-CD52 antibody alemtuzumab on Natural Killer (NK cells in detail. Here, we demonstrate that induction therapy with rATG following kidney/pancreas transplantation results in a rapid depletion of NK cells. Treatment of NK cells with rATG and alemtuzumab in vitro leads to impairment of cytotoxicity and induction of apoptosis even at a 10-fold lower concentration (0.1 microg/ml compared with T and B cells. By generating Fc-parts of rATG and alemtuzumab we illustrate that their ligation to FcgammaRIII (CD16 is sufficient for the significant induction of degranulation, apoptosis and inflammatory cytokine release (FasL, TNFalpha and IFNgamma exclusively in CD3(-CD56(dim NK cells whereas application of rATG and alemtuzumab F(ab fragments abolishes these effects. These findings are of general importance as our data suggest that NK cells are also mediators of the clinically relevant cytokine release syndrome and that their targeting by therapeutic antibodies should be considered as they are functionally relevant for the effective clearance of opportunistic viral infections and anti-tumor activity posttransplantation.

  6. Agrobacterium-mediated transformation of the β-subunit gene in 7S globulin protein in soybean using RNAi technology.

    Science.gov (United States)

    Qu, J; Liu, S Y; Wang, P W; Guan, S Y; Fan, Y G; Yao, D; Zhang, L; Dai, J L

    2016-04-26

    The objective of this study was to use RNA interference (RNAi) to improve protein quality and decrease anti-nutritional effects in soybean. Agrobacterium tumefaciens-mediated transformation was conducted using RNAi and an expression vector containing the 7S globulin β-subunit gene. The BAR gene was used as the selective marker and cotyledonary nodes of soybean genotype Jinong 27 were chosen as explant material. Regenerated plants were detected by molecular biology techniques. Transformation of the β-subunit gene in the 7S protein was detected by PCR, Southern blot, and q-PCR. Positive plants (10 T0, and 6 T1, and 13 T2) were tested by PCR. Hybridization bands were detected by Southern blot analysis in two of the T1 transgenic plants. RNAi expression vectors containing the soybean 7S protein β-subunit gene were successfully integrated into the genome of transgenic plants. qRT-PCR analysis in soybean seeds showed a clear decrease in expression of the soybean β-subunit gene. The level of 7S protein β-subunit expression in transgenic plants decreased by 77.5% as compared to that of the wild-type plants. This study has established a basis for the application of RNAi to improve the anti-nutritional effects of soybean.

  7. Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens

    NARCIS (Netherlands)

    Vliet, van Huib A.A.M.; Frolich, Marijke; Christella, M.; Thomassen, L.G.D.; Doggen, Carine J.M.; Rosendaal, Frits R.; Rosing, Jan; Helmerhorst, Frans M.

    2005-01-01

    BACKGROUND: Epidemiological studies have shown that both the estrogen dose and progestogen type of oral contraceptives contribute to the increased risk of thrombosis in oral contraceptive users. Thrombin generation-based activated protein C (APC) sensitivity is a global test for the net prothromboti

  8. Testosterone-estradiol-binding globulin in patients with Turner's syndrome: effects of estrogens and acute growth hormone administration

    Energy Technology Data Exchange (ETDEWEB)

    Bergink, E.W.; Wolf, D.L.; Wittliff, J.L.; Bruining, G.J.; Bryson, M.F.; Forbes, G.B.

    1976-06-01

    The TeBG activity of plasma from patients with Turner's syndrome was measured quantitatively using polyacrylamide gel electrophoresis. Human growth hormone administration did not significantly change the plasma TeBG levels. However, oral replacement therapy with estrogens elevated plasma TeBG within 3 days; after 9 days these levels reached a maximum of three- to four-fold greater than that observed at a time prior to therapy.

  9. The Potential Biochemical Diagnosis Criteria and Therapeutic Effect Indexes: Sex Hormone Binding Globulin Levels and Free Androgen Index in Blood of Patients With Polycystic Ovary Syndrome

    Science.gov (United States)

    2013-02-02

    The Investigators Collected 534 PCOS Patients as the Case Group,and 580 Infertile Women With Normal Ovulatory Cycle of the Control Group;; At the Same Time, the Investigators Continuedly Collect Cases to October 2012, and Totally Collected 579 Patients With PCOS Altogether;; 534 Patients in the Cases Group and 580 Women in the Control Group Received no Measures, While 579 Patients Received Drugs;; The Investigators Monitored Basic Indexes in Blood of All the Subjects in This Suvey,and Also Monitored Indexes of 579 Patients After Treatment.

  10. 葡聚糖对大豆7S球蛋白的物性修饰%Properties of soybean 7S globulin modified by dextran

    Institute of Scientific and Technical Information of China (English)

    张曦; 齐军茹; 杨晓泉; 卓秀英

    2012-01-01

    Soybean 7S globulin-dextran covalent conjugate was prepared via Maillard reaction in macromolecular crowding condition in liquid system, the covalent attachment of dextran to globulin was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Gel permeation chromatography ( GPC ), Haake rheometer, fluorescence spectrophotometer and UV-visible spectrophotometer were used to confirm the formation of covalent conjugate and analyze the functional characteristics of protein after the covalent attachment of polysaccharide. The results showed that 5% 7S globulin and 15% dextran in pH7. 0, at 95℃ for 6 h, obtained higher degree of grafting. Soybean 7S globulin and dextran macromolecule covalent conjugate was formed. GPC spectra showed that the reaction products of 7S globulin and dextran were composed of a mixture of various molecular weights. Within a specific range, apparent viscosity of the covalent conjugate gradually increased with increasing reaction time. The emulsification activity of covalent conjugate increased by about 221. 7%.%通过大分子拥挤环境下液相体系中发生Maillard反应制备大豆7S球蛋白-葡聚糖共价复合物,采用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)技术证实大豆7S球蛋白和葡聚糖发生了共价结合.采用凝胶渗透色谱(GPC)、哈克流变仪、荧光分光光度计、紫外可见分光光度计系统研究了共价复合物的形成及葡聚糖共价键入后对蛋白特性的影响.结果表明:5%的7S球蛋白与15%的葡聚糖在pH7.0条件下,95℃反应6h得到的产物接枝度较高,大豆7S球蛋白和葡聚糖形成了大分子的共价复合物,产物乳化活性提升了约221.7%.

  11. Adsorption of biopolymers human serum albumin and human gamma globulin to well-defined surfaces of self-assembled monolayers

    Science.gov (United States)

    Cregger, Tricia Ann

    The tenacity with which the blood proteins Human Serum Albumin (HSA) and Human Gamma Globulin (HGG) adsorb to a surface modified with a monomolecular coating varies with the packing of the alkyl chains in the coating. The adsorption of proteins onto well-defined surfaces of self-assembled monolayers (SAMs) was studied with X-ray reflectometry (XR), neutron reflectometry (NR), optical reflectometry, and total internal reflection fluorescence (TIRF). NR and XR was used to study adsorption in the absence of flow, while optical reflectometry and TIRF were used to probe the adsorption under flow conditions. In particular, competitive adsorption measurements of binary solutions of HSA, HGG and Fibrinogen (FIB) were performed with TIRE The properties of the surface were varied by altering the alkyl chains' packing density and the chain end functionality of the SAMs. The depth profiles of protein concentration near the adsorbing surface measured by NR were dependent upon the chain packing density in the case of HSA. The concentration depth profile of HGG was unaltered by varying chain packing density. Measurements performed under flow using optical reflectometry showed a different behavior: the surface excess of adsorbed HSA was relatively independent of the surface packing, while the surface excess of HGG depended on the packing density of the SAM. The tenacity with which the proteins adsorbed to different functionalized surfaces was determined by attempting to remove the protein using a strong surfactant, sodium dodecyl sulfate (SDS). Ex situ XR measurements suggested that both HSA and HGG adsorb more tenaciously to a less densely-packed monolayer, almost independent of surface functionality. Two exceptions were a less densely-packed vinyl-terminated monolayer and a less densely-packed bromine-terminated monolayer, from which HSA could not be removed at all.

  12. A retrospective comparison of cyclophosphamide plus antithymocyte globulin with cyclophosphamide plus busulfan as the conditioning regimen for severe aplastic anemia

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    L.V.M. Ommati

    2009-03-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (AHSCT is the treatment of choice for young patients with severe aplastic anemia (SAA. The association of antithymocyte globulin (ATG and cyclophosphamide (CY is the most frequently used conditioning regimen for this disease. We performed this retrospective study in order to compare the outcomes of HLA-matched sibling donor AHSCT in 41 patients with SAA receiving cyclophosphamide plus ATG (ATG-CY, N = 17 or cyclophosphamide plus busulfan (BU-CY, N = 24. The substitution of BU for ATG was motivated by the high cost of ATG. There were no differences in the clinical features between the two groups, including age, gender, cytomegalovirus status, ABO match, interval between diagnosis and transplant, and number of total nucleated cells infused. No differences were observed in the time to neutrophil and platelet engraftment, or in the risk of veno-occlusive disease and hemorrhage. However, there was a higher risk of mucositis in the BU-CY group (71 vs 24%, P = 0.004. There were no differences in the incidence of neutrophil and platelet engraftment, acute and chronic graft-versus-host disease, and transplant-related mortality. There was a higher incidence of late rejection in the ATG-CY group (41 vs 4%, P = 0.009. Although the ATG-CY group had a longer follow-up (101 months than the BU-CY group (67 months, P = 0.04, overall survival was similar between the groups (69 vs 58%, respectively, P = 0.32. We conclude that the association BU-CY is a feasible option to the conventional ATG-CY regimen in this population.

  13. Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin

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    de-Medeiros C.R.

    2000-01-01

    Full Text Available Severe aplastic anemia (SAA is probably an immune-mediated disorder, and immunosuppressive therapy is recommended for patients with no available donor for bone marrow transplant. Between October 1984 and November 1987, 25 consecutive children and adolescents with SAA with no HLA-compatible marrow donor received equine antithymocyte globulin (ATG (15 mg kg-1 day-1 for 10 days. The patients were evaluated 6 weeks, 6 months, and 12 months after starting ATG treatment. Thereafter, patients were evaluated yearly until July 1998. Median age was 10 years (range, 1.5-20 years, granulocyte counts on referral ranged from 0.032 to 1.4 x 10(9/l (median 0.256 x 10(9/l, and 12 patients had granulocyte counts <0.2 x 10(9/l. At a median follow-up of 9.6 years (range, 8.6-11.8 years, 10 patients (40% remained alive with good marrow function. No morphologic evidence of hematological clonal disorders has been observed, although two patients probably have acquired clonal chromosomal abnormalities (trisomy 8 and del(6q21, respectively. Responses to ATG were observed between 6 weeks and 6 months from the start of treatment in 60% of evaluable patients. The response rate was not different in patients whose granulocyte count at diagnosis was <0.2 x 10(9/l, or in those who were <10 years of age. This study supports the view that, when compared with supportive measures, ATG is an effective treatment for children or adolescents with SAA. Although these results are inferior to those reported for marrow transplantation or more intensive immunosuppressive regimens, these patients who responded to ATG are long-term survivors with stable peripheral blood counts and a low rate of relapse.

  14. New directions for rabbit antithymocyte globulin (Thymoglobulin(®)) in solid organ transplants, stem cell transplants and autoimmunity.

    Science.gov (United States)

    Mohty, Mohamad; Bacigalupo, Andrea; Saliba, Faouzi; Zuckermann, Andreas; Morelon, Emmanuel; Lebranchu, Yvon

    2014-09-01

    In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection. It is an appropriate first choice in patients with moderate or high immunological risk, and may be used in low-risk patients receiving a calcineurin inhibitor (CNI)-sparing regimen from time of transplant, or if early steroid withdrawal is planned. Kidney transplant patients at risk of delayed graft function may also benefit from the use of rATG to facilitate delayed CNI introduction. In hematopoietic stem cell transplantation, rATG has become an important component of conventional myeloablative conditioning regimens, following demonstration of reduced acute and chronic graft-versus-host disease. More recently, a role for rATG has also been established in reduced-intensity conditioning regimens. In autoimmunity, rATG contributes to the treatment of severe aplastic anemia, and has been incorporated in autograft projects for the management of conditions such as multiple sclerosis, Crohn's disease, and systemic sclerosis. Finally, research is underway for the induction of tolerance exploiting the ability of rATG to induce immunosuppresive cells such as regulatory T-cells. Despite its long history, rATG remains a key component of the immunosuppressive armamentarium, and its complex immunological properties indicate that its use will expand to a wider range of disease conditions in the future.

  15. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

    Science.gov (United States)

    Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

    2005-08-01

    Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

  16. The effect of TACE combined with tumor interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer

    Institute of Scientific and Technical Information of China (English)

    Bu-Tian Li; Sheng-Ping Zhang

    2016-01-01

    Objective:To explore the effect of TACE combined with interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer.Methods:A total of 95 patients with liver cancer from March 2013 to April 2015 in the hospital were selected, and they were randomly divided into group A (n = 47) and group B (n=48), patients in group A were given simple TACE treatment, while patients in group B underwent TACE + tumor interstitial therapy (percutaneous liver tumor injection of lipiodol chemotherapy). Immune globulin, complement and T lymphocyte subsets in peripheral blood preoperative 1w and postoperative 4w were observed.Results: After treatment, the lipiodol deposition rate, local control rate and tumor reduction rate of group B were significantly higher than that in group A, which had statistically significant difference between the two groups. Compared with that before treatment, CD3+, CD4+, CD4+/CD8+ were significantly increased, CD8+ was significantly decreased after treatment. There were significantly differences in CD3+, CD4+, CD4+/CD8+, CD8+ between the two groups after treatment. The immune globulin and complement levels increased in group A after treatment, but had no significant difference. Immunoglobulin and complement levels increased significantly in group B, there were significantly differences in immunoglobulin and complement levels in the two groups after treatment.Conclusions:The results showed that single TACE treatment in patients with liver cancer could enhance immune function, which had little effect on the humoral immunity. TACE combined with interstitial therapy could improve patients' cellular immunity and humoral immunity, which was benefit for prognosis.

  17. Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

    Science.gov (United States)

    Dardis, Christopher; Aung, Thandar; Shapiro, William; Fortune, John; Coons, Stephen

    2015-01-01

    We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin. PMID:25873887

  18. Serum albumin and globulin analysis for hepatocellular carcinoma detection avoiding false-negative results from alpha-fetoprotein test negative subjects

    Science.gov (United States)

    Wang, Jing; Feng, Shangyuan; Lin, Juqiang; Zeng, Yongyi; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

    2013-11-01

    Surface-enhanced Raman spectroscopy (SERS) of serum albumin and globulin were employed to detect hepatocellular carcinoma (HCC). Tentative assignments of SERS bands show specific biomolecular changes associated with cancer development. These changes include a decrease in relative amounts of tryptophan, glutamine, glycine, and serine, indicating excessive consumption of amino acids for protein duplication. Principal component analysis was also introduced to analyze the obtained spectra, resulting in both diagnostic sensitivity and specificity of 100%. More importantly, it reveals that this method can detect HCC patients with alpha-fetoprotein negative test results, suggesting its great potential as a new alternative to detect HCC.

  19. Effect of hepatitis B vaccine combined with hepatitis B immune globulin on infection in newborn infants of HBsAg-positive mothers

    Institute of Scientific and Technical Information of China (English)

    Si-Jia Yang; Jin-Hong Liu; Xue-Lian Tong; Ming Chen

    2016-01-01

    Objective:To investigate the effect of hepatitis B vaccine combined with hepatitis B immune globulin on infection in newborn infants of HBsAg-positive mothers. Methods:Two hundred newborn infants of HBsAg-positive mothers who had received prenatal examination and given birth to their child were selected as the study subjects and divided into the control group and the observation group in accordance with the voluntary principle. Newborn infants in the control group received 100 IU of vaccinations of hepatitis B vaccine and hepatitis B immune globulin at postnatal 24 h, 1 month and 6 months, while lying-in women in the observation group were continuously given 200 IU of immune globulin injection at the 27th, 30th, 33rd and 36th weeks of pregnancy. The infection condition and the influence of different delivery modes in infants of the two groups would be observed 12 months after birth. Results:The HBsAg positive rate and HBsAb positive rate of infants in the observation group were 1.00%and 59.00%respectively, while the control group’s were 10.00%and 73.00%. The HBsAg positive rate and HBsAb positive rate of infants in the observation group were significantly lower than those of the control group. The data showed statistical significances. Seven cases of infants born vaginally showed positive HBsAg. One of them belonged to the observation group and the other six were in the control group. Four cases of infants delivered by cesarean section showed positive HBsAg and they all belonged to the control group. The HBsAg positive rate of the observation group was obviously lower than that of the control group no matter what deliver mode those children had received. Conclusions:Hepatitis B vaccine combined with hepatitis B immune globulin could effectively decrease the morbidity rate of positive HBsAg for newborn infants no matter what birth way they had received.

  20. Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

    Directory of Open Access Journals (Sweden)

    Christopher Dardis

    2015-02-01

    Full Text Available We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin.

  1. Survey for late-onset hypogonadism among old and middle-aged males in Shanghai communities

    Institute of Scientific and Technical Information of China (English)

    Kai Sun; Guo-Qing Liang; Xiang-Feng Chen; Ping Ping; Wen-Liang Yao; Shi-Jun Zhang; Bo Wang; Ying-Hao Sun; Zheng Li

    2012-01-01

    This study sought to investigate late-onset hypogonadism (LOH) in old and middle-aged males in Shanghai communities,using symptom score evaluation systems and measurements of sex hormone levels.One thousand cases of males aged 40-70 years were investigated.The aging male symptoms (AMS) scale and androgen deficiency in aging males (ADAM) questionnaire were used at the beginning of the investigation,followed by measurement of the sex hormone-related factors (total testosterone (TT),free testosterone (fT),sex hormone-binding globulin (SHBG) and bioavailability of testosterone (Bio-T)).There were 977 valid questionnaires.The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%,respectively; values increased with the age of the patients.There were 946 results related to sex hormone measurements,which showed the following results:TT was not related to aging (P>0.05); levels of SHBG increased with age; and fT and Bio-T decreased with age.There was a significant difference in fT between LOH-positive and LOH-negative patients,as shown by the ADAM.In summary,TT levels were not related to aging,even though SHBG did increase while fT and Bio-T decreased with aging.Clinically,the diagnosis of LOH cannot be based on serum TT level.

  2. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

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    Marta Sacchetti

    2015-01-01

    Full Text Available Purpose. Vernal keratoconjunctivitis (VKC is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT, cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P<0.001. Prepubertal and early pubertal VKC showed a significant decrease in DHT (P=0.007 and P=0.028, resp. and SHBG (P=0.01 and P=0.002, resp. when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P=0.007. Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC.

  3. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

    Science.gov (United States)

    Sacchetti, Marta; Lambiase, Alessandro; Moretti, Costanzo; Bonini, Stefano

    2015-01-01

    Purpose. Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC. PMID:25756057

  4. Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study

    Institute of Scientific and Technical Information of China (English)

    Samuel YS Wong; Jason C Leung; Timothy Kwok; Claes Ohlsson; Liesbeth Vandenput; Ping C Leung; Jean Woo

    2011-01-01

    This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone,dehydroepiandrosterone (DHEA),DHEA sulphate (DHEAS),oestradiol and sex hormone-binding globulin (SHBG) levels,and the free androgen index.Cross-sectional data from 1147 community-dwelling elderly men,aged 65 and older,were used.Depressive symptoms were measured using the Chinese Geriatric Depression Scale (GDS).Total testosterone,free testosterone,DHEA,DHEAS,total oestradiol,the free androgen index and SHBG levels were assessed.DH EA was significantly associated with GDS score,and there was a trend towards DHEAS association,but this was not significant (β=0.110,P=0.015;β=0.074,P=0.055).However,no association was seen between depressive symptoms and total testosterone levels,free testosterone levels,oestradiol levels or SHBG levels.In terms of the presence of clinically relevant depressive symptoms,there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels.Similarly to Western studies,our study shows that DHEA and DHEAS levels are associated with depressive symptoms.

  5. Interictal hyposexuality in male patients with epilepsy

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    Silveira Diosely C.

    2001-01-01

    Full Text Available The purpose of this study was to compare the serum levels of androgens between hyposexual and non-hyposexual patients with epilepsy. Adult male patients with epilepsy were investigated. Serum levels of testosterone (T and free-T, estradiol, and sex hormone binding globulin (SHBG were measured and the free androgen index (FAI was calculated. While there were no differences between hyposexual and non-hyposexual patients in the serum levels of T, free-T, and estradiol, or to the FAI, the serum levels of SHBG were significantly higher in hyposexual patients than in non-hyposexual patients. Thus, the effects of increased SHBG upon serum levels of testosterone biologically active in patients with epilepsy and hyposexuality were not detected by the methods used in this study. Four (44% of nine hyposexual patients who were re-evaluated after two years follow-up improved sexual performance. Thus, clinical treatment that results in good seizure control may improve sexual performance in some patients with epilepsy.

  6. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism.

    Science.gov (United States)

    Batukan, Cem; Muderris, Iptisam Ipek; Ozcelik, Bulent; Ozturk, Ahmet

    2007-01-01

    Combined oral contraceptives (COCs) are considered the first-line treatment for women with hirsutism. They diminish androgen release from the ovary and decrease plasma free testosterone levels by increasing sex hormone-binding globulin (SHBG) concentrations. COCs containing cyproterone acetate (CPA) and drospirenone (DRSP) have been proved effective for the treatment of acne and facial hirsutism. This study prospectively compared the clinical and biochemical efficacy of 3 mg DRSP/30 microg ethinyl estradiol (EE) and 2 mg CPA/35 microg EE combinations in a total of 91 patients with hirsutism. Individuals randomly received a cyclic combination of either DRSP/EE (n=48) or CPA/EE (n=43) for 12 months. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and SHBG levels, as well as Ferriman-Gallwey scores, were determined before and after treatment. Both COCs achieved a similar effect on clinical hirsutism scores, in addition to serum androgen and SHBG levels, after completion of therapy. The percentage reductions in total hirsutism score (median % (min-max)) during therapy were 0.70 (0-0.58) vs. 0.57 (0.10-1.00) at 6 months (p = 0.028) and 0.80 (0-0.42) vs. 0.81 (0-0.75) at 12 months (p = 0.6) in the DRSP/EE and CPA/EE groups, respectively. In conclusion, the DRSP/EE combination is at least as effective as the CPA/EE combination in improving hirsutism scores.

  7. Clinical, ultrasound and hormonal markers of androgenicity in acne vulgaris.

    Science.gov (United States)

    Walton, S; Cunliffe, W J; Keczkes, K; Early, A S; McGarrigle, H H; Katz, M; Reese, R A

    1995-08-01

    Androgenic stimulation of sebaceous glands is an important factor in the development of acne. We examined 36 females (aged 14-34 years), selected because none had received oral contraceptives, anti-androgen therapy, or systemic antibiotics during the previous year, or isotretinoin therapy, prior to their participation in the study. Subjects were divided into groups on the basis of acne severity, as follows: physiological, mild and moderate. Only two patients had polycystic ovaries on ultrasound examination. Seven patients had irregular menses; none had evidence of hirsutism. We found that the severity of acne, based on the acne grade, was highly correlated with the inflammatory lesion count, and less correlated with the sebum excretion rate. Either acne grade or inflammatory lesion count could be related to some of the five androgenic hormone determinants; free testosterone (TESTOS), delta 4 androstenedione (DELTA 4), sex hormone binding globulin (SHBG), dehydroepiandrostenedione sulphate (DHEAS) and dihydrotestosterone (DHT). Multiple linear regression analysis determined the best model for predicting ACNE scores as involving DELTA 4 and DHEAS (positive effects), and SHBG (negative effect), P < 0.005, R2 = 0.36). In none of the patients were the levels of DHEAS or SHBG outside the normal range. The findings in the two patients with polycystic ovaries did not differ significantly from those in the remainder of the patients.

  8. Late-Onset Hypogonadism in Male Patients Over 60 Years of Age with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Ekrem Kara

    2013-06-01

    Full Text Available Purpose: The aim of the study was to determine serum androgen levels and the frequency of late-onset hypogonadism (LOH in patients over 60 years of age with metabolic syndrome (MS and its correlation with parameters of MS. Material and Method: Men over 60 years of age who were diagnosed with MS according to the Adult Treatment Panel III (ATP III criteria in the internal medicine outpatient clinics at Cerrahpasa Medical School (n=30 and healthy controls (n=30 were included in the study. Total testosterone and sex hormone binding globulin (SHBG levels were analysed. Bioavailable and free testosterone levels were calculated. The participants filled up the Beck Depression Inventory (BDI and Aging Male Symptoms (AMS questionnaire forms themselves without any help of the physician. Results: LOH rates were 30% and 13.3% in the MS group and healthy control group, respectively (p=0.11. Serum total testosterone and SHBG levels were significantly lower in the MS group compared to controls (p=0.004 and p=0.003, respectively. A negative correlation was found between total testosterone and MS components. BDI and AMS questionnaire scores in the two groups were not significantly different.Discussion: Serum total testosterone and SHBG levels were lower in the MS group, and inversely proportional to this, insulin resistance and intensity of MS components were increased. Turk Jem 2013; 17: 22-7

  9. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  10. De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin.

    Science.gov (United States)

    Fu, Rong; Chen, Tong; Song, Jia; Wang, Guojin; Li, Lijuan; Ruan, Erbao; Liu, Hui; Wang, Yihao; Wang, Huaquan; Xing, Limin; Wu, Yuhong; Liu, Hong; Qu, Wen; Shao, Zonghong

    2017-02-01

    We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.

  11. Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients

    Institute of Scientific and Technical Information of China (English)

    WANG Dong; WU Wei-zhen; YANG Shun-liang; CHEN Jin-hua; TAN Jian-ming

    2006-01-01

    Background Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single- bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients.Methods A total of 56 patients were divided into two groups according to the level of panel reactive antibody(PRA): non-sensitized group (PRA<10%, n=30) and sensitized group (PRA≥ 10%, n=26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG(iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A,MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. X2 test and t test were used to analyze the data.Results During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4(15.4%) in the sensitized group (P=0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P=0.757, 0.890). The safety of the drugs,which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13-25 days (mean, 16.7±3.3) in the nonsensitized group and 14-29 days (mean, 16.2±3.1) in the sensitized group, respectively (P=0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates

  12. High affinity binding of /sup 125/I-labeled mouse interferon to a specific cell surface receptor. II. Analysis of binding properties

    Energy Technology Data Exchange (ETDEWEB)

    Aguet, M.; Blanchard, B.

    1981-12-01

    Direct ligand-binding studies with highly purified /sup 125/I-labeled virus-induced mouse interferon on mouse lymphoma L 1210 cells revealed a direct correlation of specific high-affinity binding with the biologic response to interferon. Neutralization of the antiviral effect by anti-interferon gamma globulin occurred at the same antibody concentration as the inhibition of specific binding. These results suggest that specific high-affinity binding of /sup 125/I-interferon occurred at a biologically functional interferon receptor. Competitive inhibition experiments using /sup 125/I- and /sup 127/I-labeled interferon provided strong evidence that the fraction of /sup 125/I-interferon inactivated upon labeling did not bind specifically. Scatchard analysis of the binding data yielded linear plots and thus suggested that interferon binds to homogeneous noncooperative receptor sites. In contrast to a characteristic property of several peptide hormone systems, binding of /sup 125/I-interferon to its specific receptor did not induce subsequent ligand degradation. At 37/sup o/ bound interferon was rapidly released in a biologically active form without evidence for molecular degradation. The expression of interferon receptors was not modified by treatment with interferon. Trypsin treatment of target cells and inhibition of protein synthesis abolished the specific binding of /sup 125/I-interferon. Three major molecular weight species of Newcastle disease virus-induced mouse C 243 cell interferon were isolated, separated, and identified as mouse ..cap alpha.. and ..beta.. interferons. These interferons were shown to inhibit competitively the specific binding of the highly purified labeled starting material thus providing evidence for a common receptor site for mouse interferon.

  13. Use of oral contraceptives in the management of acne

    Directory of Open Access Journals (Sweden)

    Melis GB

    2011-11-01

    Full Text Available Gian Benedetto Melis, Marisa Orrù, Maria Francesca Marotto, Monica Pilloni, Mariagrazia Perseu, Stefano Lello, Anna Maria PaolettiClinica Ginecologica Ostetrica e di Fisiopatologia della Riproduzione Umana, Universita' di Cagliari, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, ItalyAbstract: The pathogenesis of acne (the most common disorder involving the sebaceous gland originates from increased sebum production by the sebaceous gland followed by colonization of the hair follicle with Propionibacterium acnes, hyperkeratinization of the upper follicle, and release of inflammatory mediators into the skin. Androgens are the main stimulators of sebum production. Androgens originate from the gonads and adrenal glands, but can also be locally produced within the sebaceous gland from dehydroepiandrosterone sulfate. In the presence of high androgen levels, which can be either a normal pattern of adolescence or a consequence of gonadal or adrenal disease, overproduction of sebum triggers the pathogenesis of acne which, mainly in adolescent women, has deleterious psychological consequences. Estrogens exert the opposite action on sebum production, probably due to the reduction of androgen availability, a direct consequence of estrogen-related increased production of hepatic sex hormone-binding globulin (SHBG. The inhibition of the hypothalamus-pituitary axis induced by oral contraceptives is followed by reduced androgen production. Oral contraceptives containing ethinyl estradiol, which has strong estrogenic activity, amplify the hypoandrogenic effect via estrogen-related stimulation of SHBG. The hypoandrogenic effect of oral contraceptives is modulated by the progestin compound. Progestins derived from 19-nortestosterone bind androgenic receptors, whereas others exert antiandrogenic properties by antagonizing the binding of androgens to their receptors, reduce 5α-reductase, and do not bind SHBG. Through this last effect, SHBG is freely

  14. Study on decolorization of hydrolytic porcine blood serum globulin%酶解猪血制备血球蛋白粉的脱色工艺研究

    Institute of Scientific and Technical Information of China (English)

    周庆; 刘学文; 张欣

    2009-01-01

    The pig blood was hydrolyzed by compound enzyme, then absorbed by activated carbon to be decolorized. The serum globulin flour can be obtained after spray-drying. The results showed that the best processing condition for decolorizing was as follow: pH 4,temperature 70 ℃ ,dosage of activated carbon 3.5% ,time 100min. Compared with Spray-dried porcine globulin without decolorization as controls, the hydrolytic protein powder was superior to blood powder on the color, ador, particle shape and texture.%猪血通过复合酶水解,用活性炭对其水解液吸附脱色,经喷雾干燥,制作得到脱色血球蛋白粉.结果表明,脱色效果最佳的工艺条件为:pH 4、温度70℃、活性炭用量3.5%,脱色时间100 min.与未水解和脱色的猪血粉相比,产品在颜色、气味、颗粒形状、质地等方面都有着很大的优势和提高.

  15. An Analysis of Albumin and Globulin of Qinghai Faba Bean Varieties with SDS-PAGE%青海蚕豆清蛋白与球蛋白分级提取SDS-PAGE比较分析

    Institute of Scientific and Technical Information of China (English)

    李萍; 侯万伟; 严清彪; 刘玉皎

    2011-01-01

    The albumin and globulin of 2005 -00 and Qinghai 13, two varieties of Qinghai Faba bean were studied by improved SDS - PAGE. At the same time by using micro - Kjeldahl Method the appropriate protein content were measured. The result showed that the content of globulin was twice that of albumin.Therefore globulin was the main component of the total protein content. Almost all the albumin and globulin were extracted after extraction for five times with extract solution Ⅰ which included NaCl. But only the globulin were obtained with extract solution Ⅰ for one time after with extraction for four times extract solution Ⅱ which didn't include NaC1, and the globulin had the same mobility as the albumin. The result indicated that albumin was also extracted while extracting globulin, but globulin was not extracted while extracting albumin.%利用改进的SDS-聚丙烯酰胺凝胶电泳,对2种青海蚕豆品种2005-00和青海13号的清蛋白、球蛋白进行研究,并采用微量凯氏定氮法测得相应的蛋白质含量.结果表明:球蛋白含量比清蛋白含量高,是总蛋白含量的主要成分.用含有NaCl的球蛋白提取液Ι提取5次蛋白质后,清蛋白和球蛋白被同时提取出来;而用不含NaCl的清蛋白提取液Π提取4次蛋白质后,再用提取液Ι提取,可得到球蛋白组分,而且和清蛋白一样也有相同迁移位置的谱带存在.表明对球蛋白进行提取操作时,总有清蛋白相伴随;而对清蛋白进行提取分析时一般不会有球蛋白的存在.

  16. LENTIL TANNIN-GLOBULIN INTERACTIONAND AND IN VITRO HYDROLYSIS INTERAÇÃO TANINO-GLOBULINA DE LENTILHA E HIDRÓLISE IN VITRO

    Directory of Open Access Journals (Sweden)

    Valdir A. NEVES

    1998-08-01

    Full Text Available Protein fractions were isolated from lentil cotyledons and tannins were isolated and purified from lentil seed coats. The globulin fraction corresponded to 42.7% of the total lentil flour nitrogen, representing the major protein fraction. Acetone:water (7:3 was the best extractant for seed coat tannins compared to methanol or methanol-HCl 1%. Native and heated (99oC/15 min. isolated lentil globulin and casein were hydrolyzed with trypsin and pepsin in the absence of tannins and at 1:40, 1:20, 1:10, 1:5 and 1:2.5 tannin-to-protein ratios. The tryptic and peptic hydrolysis of the unheated proteins were reduced with increasing tannin-to-protein ratios. Unheated casein showed to be more susceptible to trypsin than globulin and the opposite effect was observed with pepsin. Heating followed by tannin interaction and hydrolysis had a more pronounced effect on tryptic than peptic digestion for both proteins.As frações protéicas foram isoladas dos cotiledones e os taninos isolados e purificados da casca da lentilha. A fração globulina correspondeu a 42,7 % do nitrogenio total da farinha de lentilha representando a fração protéica majoritária. Comparativamente ao metanol e metanol-HCl 1% a mistura acetona:água (7:3 representou o melhor meio extrator para os taninos da casca. A fração globulina isolada, nativa e aquecida (99oC/15 min, e caseína foram hidrolisadas com tripsina e pepsina na ausência de taninos e na presença de relações tanino:proteína de 1:40, 1:20, 1:10, 1:5 e 1:2,5. A hidrólise tríptica e péptica das proteínas não-aquecidas foram reduzidas com o aumento da relação tanino-proteína. A caseína não aquecida mostrou ser mais susceptível à tripsina que à globulina, o oposto sendo observado com a pepsina. O aquecimento seguido de interação com os taninos e hidrólise teve um efeito mais pronunciado sobre a digestão com tripsina que com pepsina para ambas proteínas.

  17. Endogenous estradiol and the risk of incident fracture in postmenopausal women: the OPUS study.

    Science.gov (United States)

    Finigan, J; Gossiel, F; Glüer, C C; Felsenberg, D; Reid, D M; Roux, C; Eastell, R

    2012-07-01

    Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.

  18. Comparative study of the plasma globulin level, CD21(-) B-cell counts and FOXP3 mRNA expression level in CD4(+) T-cells for different clinical stages of feline immunodeficiency virus infected cats.

    Science.gov (United States)

    Takano, Tomomi; Hosoya, Shinobu; Shibao, Akari; Nagasaki, Bunpei; Yoshioka, Hisao; Satoh, Ryoichi; Hohdatsu, Tsutomu

    2012-02-01

    Feline immunodeficiency virus (FIV) infection leads to hypergammaglobulinemia through mechanisms that remain poorly understood. We investigated changes in plasma globulin level, B cells, and T cells with progression of the clinical stage of FIV-infected cats. We classified FIV-infected cats into the stage of Asymptomatic carrier (AC) and AIDS-related complex (ARC) based on the clinical symptoms, and measured the plasma globulin level, the CD4(+) T-cell counts, and analyzed surface markers of B cells. We investigated the relationship between the plasma globulin level and regulatory T cells (Tregs) using the Forkhead box P3 (FOXP3) mRNA expression level. In FIV-infected cats, the plasma globulin level and the surface immunoglobulin (sIg)(+) CD21(-) B-cell counts were increased, whereas the CD4(+) T-cell counts were decreased compared with specific-pathogen free (SPF) cats. The mRNA expression of Blimp-1 (master gene of plasma cells) was increased in peripheral blood, and the FOXP3 mRNA expression level was decreased in CD4(+) T-cells. These immunological changes were marked in the ARC stage. These data indicate that the decrease of Tregs and the increase of plasma cells lead to hypergammaglobulinemia.

  19. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  20. Seasonal changes in plasma androgens, glucocorticoids and glucocorticoid-binding proteins in the marsupial sugar glider Petaurus breviceps.

    Science.gov (United States)

    Bradley, A J; Stoddart, D M

    1992-01-01

    An investigation spanning two breeding seasons was carried out to examine endocrine changes associated with reproduction in a wild population of the marsupial sugar glider Petaurus breviceps, a small arboreal gliding possum. Using techniques of equilibrium dialysis and polyacrylamide gel electrophoresis at steady-state conditions, a high-affinity, low-capacity glucocorticoid-binding protein was demonstrated in the plasma of Petaurus breviceps. Equilibrium dialysis at 36 degrees C using cortisol gave a high-affinity binding constant of 95 +/- 5.2 litres/mumol for a presumed corticosteroid-binding globulin (CBG) while the binding constant for the cortisol-albumin interaction was 3.5 +/- 0.4 litres/mmol. There was no difference between the sexes in the affinity of binding of cortisol to CBG; however, the cortisol-binding capacity underwent seasonal variation in both sexes. Progesterone was bound strongly to the presumed CBG while neither oestradiol nor aldosterone appeared to be bound with high affinity to P. breviceps plasma. In the males, peaks in the plasma concentration of testosterone coincided with the July-September breeding season in both years. A significant inverse relationship was shown to exist between the plasma testosterone concentration and the CBG-binding capacity. In both sexes an increase occurred in the plasma concentration of free cortisol during the first breeding season, a pattern which was not repeated in the subsequent breeding season, possibly due to a lower population density in that year.

  1. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  2. Ureaplasma urealyticum binds mannose-binding lectin.

    Science.gov (United States)

    Benstein, Barbara D; Ourth, Donald D; Crouse, Dennis T; Shanklin, D Radford

    2004-10-01

    Mannose-binding C-type lectin (MBL) is an important component of innate immunity in mammals. Mannose-binding lectin (MBL), an acute phase protein, acts as an opsonin for phagocytosis and also activates the mannan-binding lectin complement pathway. It may play a particularly significant role during infancy before adequate specific protection can be provided by the adaptive immune system. Ureaplasma urealyticum has been linked to several diseases including pneumonia and chronic lung disease (CLD) in premature infants. We therefore investigated the ability of U. urealyticum to bind MBL. A guinea pig IgG anti-rabbit-MBL antiserum was produced. An immunoblot (dot-blot) assay done on nitrocellulose membrane determined that the anti-MBL antibody had specificity against both rabbit and human MBL. Pure cultures of U. urealyticum, serotype 3, were used to make slide preparations. The slides containing the organisms were then incubated with nonimmune rabbit serum containing MBL. Ureaplasma was shown to bind rabbit MBL with an immunocytochemical assay using the guinea pig IgG anti-rabbit MBL antiserum. Horseradish peroxidase (HRP)-labeled anti-guinea pig IgG was used to localize the reaction. The anti-MBL antiserum was also used in an immunocytochemical assay to localize U. urealyticum in histological sections of lungs from mice specifically infected with this organism. The same method also indicated binding of MBL by ureaplasma in human lung tissue obtained at autopsy from culture positive infants. Our results demonstrate that ureaplasma has the capacity to bind MBL. The absence of MBL may play a role in the predisposition of diseases related to this organism.

  3. Ligand binding mechanics of maltose binding protein.

    Science.gov (United States)

    Bertz, Morten; Rief, Matthias

    2009-11-13

    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  4. Protein Binding Pocket Dynamics.

    Science.gov (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  5. 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 ...

  6. 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.

  7. 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

  8. Factors influencing the uptake of {sup 18}F-fluoroestradiol in patients with estrogen receptor positive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Lanell M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Kurland, Brenda F. [Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Link, Jeanne M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Schubert, Erin K. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Stekhova, Svetlana [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, WA (United States); Mankoff, David A., E-mail: dam@u.washington.edu [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States)

    2011-10-15

    Introduction: {sup 18}F-Fluoroestradiol (FES) PET imaging provides a non-invasive method to measure estrogen receptor (ER) expression in tumors. Assessment of factors that could affect the quantitative level of FES uptake is important as part of the validation of FES PET for evaluating regional ER expression in breast cancer. Methods: This study examines FES uptake in tumors from 312 FES PET scans (239 patients) with documented ER+ primary breast cancer. FES uptake was compared to clinical and laboratory data, treatment prior to or at time of scan, and properties of FES and its metabolism and transport. Linear mixed models were used to explore univariate, threshold-based and multivariate associations. Results: Sex hormone-binding globulin (SHBG) was inversely associated with FES SUV. Average FES uptake did not differ by levels of plasma estradiol, age or rate of FES metabolism. FES tumor uptake was greater for patients with a higher body mass index (BMI), but this effect did not persist when SUV was corrected for lean body mass (LBM). In multivariate analysis, only plasma SHBG binding was an independent predictor of LBM-adjusted FES SUV. Conclusions: Calculation of FES SUV, possibly adjusted for LBM, should be sufficient to assess FES uptake for the purpose of inferring ER expression. Pre-menopausal estradiol levels do not appear to interfere with FES uptake. The availability and binding properties of SHBG influence FES uptake and should be measured. Specific activity did not have a clear influence on FES uptake, except perhaps at higher injected mass per kilogram. These results suggest that FES imaging protocols may be simplified without sacrificing the validity of the results.

  9. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  10. 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)

  11. 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.

  12. Thermodynamics of fragment binding.

    Science.gov (United States)

    Ferenczy, György G; Keserű, György M

    2012-04-23

    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  13. Prophylaxis of acute viral hepatitis by immune serum globulin, hepatitis B vaccine, and health education: a sixteen year study of Japan overseas cooperation volunteers.

    Science.gov (United States)

    Ohara, H; Ebisawa, I; Naruto, H

    1997-01-01

    From 1978 to 1993 a study of acute viral hepatitis contracted by the Japan Overseas Cooperation Volunteers (JOCV) during their assignments in tropical and subtropical countries was conducted. Of 10,509 subjects in this study, 240 cases of acute viral hepatitis were confirmed (hepatitis A = 139, hepatitis B = 72, and non-A, non-B hepatitis = 29). The annual morbidity was 5.1% in 1978 and 4.9% in 1979, with hepatitis A accounting for 80% of the cases. However, it decreased significantly after the prophylactic inoculation with immune serum globulin (ISG) was started in 1980. A significant decrease of hepatitis B from 1.2% in 1980 to 0.1% in 1990 was also seen after vaccination was introduced for all volunteers in 1988. Health education concerning food and water sanitation, and providing general information on viral hepatitis, was also conducted throughout this period. These results indicate that acute viral hepatitis could be successfully prevented in the JOCV with a combination of ISG, hepatitis B vaccination, and health education.

  14. Softening temperature of lyophilized bovine serum albumin and gamma-globulin as measured by spin-spin relaxation time of protein protons.

    Science.gov (United States)

    Yoshioka, S; Aso, Y; Kojima, S

    1997-04-01

    We investigated the usefulness of the spin-spin relaxation time (T2) of protein protons as a probe for evaluating the molecular flexibility of freeze-dried protein formulations. It is proposed that the microscopic softening temperature determined from changes in the T2 of protein protons (Ts(T2)) is an important characteristic of freeze-dried protein formulations, the glass transition temperature (Tg) of which is generally difficult to determine by differential scanning calorimetry. We determined the molecular flexibility of lyophilized bovine serum albumin (BSA) and bovine gamma-globulin (BGG) by measuring the T2 of protein and water protons as well as the spin-lattice relaxation time (T1) of the latter as a function of temperature. The flexibility of freeze-dried BSA and BGG cakes markedly varied at temperatures above and below the Ts(T2), affecting the stability of the proteins. The denaturation and subsequent aggregation of lyophilized BSA and BGG cakes with a relatively high water content was enhanced in the softened state at temperatures above the Ts(T2). Lyophilized cakes with an extremely low water content were significantly denatured, even in the unsoftened state at temperatures below the Ts(T2), probably due to the thermodynamically unstable structures of protein molecules generated by a loss of structural water.

  15. Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.

    Directory of Open Access Journals (Sweden)

    Srinivas Kammanadiminti

    Full Text Available BACKGROUND: We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. METHODS: Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30-96 hours after anthrax exposure. RESULTS: The majority of treated animals (>88% survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. CONCLUSIONS: The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

  16. The Benefit of Sirolimus Maintenance Immunosuppression and Rabbit Antithymocyte Globulin Induction in Liver Transplant Recipients That Develop Acute Kidney Injury in the Early Postoperative Period

    Directory of Open Access Journals (Sweden)

    Benjamin T. Duhart

    2015-01-01

    Full Text Available Published data are limited describing renal outcomes in orthotopic liver transplant (OLT recipients prescribed sirolimus (SRL maintenance immunosuppression (MIS and rabbit antithymocyte globulin (rATG induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85% received TAC and 29 (15% received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P<0.05. The eGFR was significantly (P<0.05 higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P<0.05 greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

  17. The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte globulin induction in liver transplant recipients that develop acute kidney injury in the early postoperative period.

    Science.gov (United States)

    Duhart, Benjamin T; Ally, Winston A; Krauss, Amy G; Hudson, Joanna Q; Eason, James D; Rao, Vinaya; Vanatta, Jason M

    2015-01-01

    Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was significantly (P < 0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P < 0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

  18. Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine.

    Science.gov (United States)

    Hama, Asahito; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ito, Masafumi; Narita, Atsushi; Kosaka, Yoshiyuki; Tsuchida, Masahiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-11-01

    The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony-stimulating factor more frequently and for longer durations than other patients (Paplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia.

  19. Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti-thymocyte globulin, and total body irradiation are additive risk factors.

    Science.gov (United States)

    Kullberg-Lindh, C; Mellgren, K; Friman, V; Fasth, A; Ascher, H; Nilsson, S; Lindh, M

    2011-04-01

    Viral opportunistic infections remain a threat to survival after stem cell transplantation (SCT). We retrospectively investigated infections caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV6), or adenovirus (AdV) during the first 6-12 months after pediatric SCT. Serum samples from 47 consecutive patients were analyzed by quantitative real-time polymerase chain reaction assay. DNAemia at any time point occurred for CMV in 47%, for EBV in 45%, for HHV6 in 28%, and for AdV in 28%. Three patients (6.3%) died of CMV-, EBV-, or AdV-related complications 4, 9, and 24 weeks after SCT, respectively, representing 21% of total mortality. These 3 cases were clearly distinguishable by DNAemia increasing to high levels. Serum positivity for CMV immunoglobulin G in either recipient or donor at the time of SCT, total body irradiation, and anti-thymocyte globulin conditioning were independent risk factors for high CMV or EBV DNA levels. We conclude that DNAemia levels help to distinguish significant viral infections, and that surveillance and prophylactic measures should be focused on patients with risk factors in whom viral complications rapidly can become fatal.

  20. Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Željka Večerić-Haler

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG. We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1, glutathione peroxidase (GPx, and hem oxygenase-1 (HO-1. Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.

  1. Complex histopathologic response in rat kidney to oral β-myrcene: an unusual dose-related nephrosis and low-dose alpha2u-globulin nephropathy.

    Science.gov (United States)

    Cesta, Mark F; Hard, Gordon C; Boyce, John T; Ryan, Michael J; Chan, Po C; Sills, Robert C

    2013-01-01

    Oral gavage studies with β-myrcene in male F344 rats showed a complex renal pathology comprising both alpha2u-globulin (α2u-g) nephropathy, an unusual nephrosis involving the outer stripe of outer medulla (OSOM), and an increased incidence of renal tubule tumors by 2 years. In the 90-day and 2-year studies, respectively, α2u-g nephropathy and linear papillary mineralization were observed in males at the two lower doses but were absent from the high dose. Nephrosis was characterized by dilation of the S3 tubules, nuclear enlargement (including karyomegaly), and luminal pyknotic cells, all in the outermost OSOM. Nephrosis was minimal at the higher doses in the 90-day study, but progressed to a severe grade in males dosed with 1,000 mg/kg for 2 years. Renal tubule tumors developed in treated groups with incidences up to 30% in the 250 and 500 mg/kg male dose groups. Tumors at the lower doses in males may have been associated with α2u-g nephropathy, while those at higher doses in both sexes may have been due to the nephrosis. Because β-myrcene induced a complex spectrum of renal pathology, the α2u-g nephropathy mechanism cannot be the sole mechanism of carcinogenesis in these rats.

  2. Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer.

    Science.gov (United States)

    McLaughlin, John M; Olivo-Marston, Susan; Vitolins, Mara Z; Bittoni, Marisa; Reeves, Katherine W; Degraffinreid, Cecilia R; Schwartz, Steven J; Clinton, Steven K; Paskett, Electra D

    2011-05-01

    To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.

  3. Possible impact of phthalates on infant reproductive health

    DEFF Research Database (Denmark)

    Poulsen, Grete Lottrup; Andersson, A-M; Leffers, H;

    2006-01-01

    discusses two recent studies on perinatal phthalate exposure, which indicated that human testicular development might be susceptible to phthalates. One study analysed phthalate monoesters in breast milk and reproductive hormone levels in infants. Five of six phthalates [monoethyl-(MEP), monobutyl- (MBP......), monomethyl- (MMP), mono-2-ethylhexyl- (MEHP) and mono-isononyl phthalate (MiNP)] showed correlation with hormone levels in healthy boys, which were indicative of lower androgen activity and reduced Leydig cell function. MEP and MBP were positively correlated with serum sex hormone-binding globulin (SHBG...... be due to differences in exposure routes (inhalation and dermal absorption which circumvents liver detoxification in addition to oral) and metabolism, or this association could be spurious. As phthalates are produced as bulk chemicals worldwide, these new findings raise concern about the safety...

  4. Genetic Polymorphisms Related to Testosterone Metabolism in Intellectually Gifted Boys

    Science.gov (United States)

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n = 95) and control (n = 67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities. PMID:23382957

  5. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys.

    Science.gov (United States)

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n = 95) and control (n = 67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities.

  6. Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick;

    1983-01-01

    affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20......). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately...

  7. Oral contraceptives in the treatment of acne.

    Science.gov (United States)

    Tan, J K; Degreef, H

    2001-02-01

    Oral contraceptives (OCs) can reduce acne by lowering the production of adrenal and ovarian androgens, by inhibiting 5-alpha-reductase, which in turn, reduces the levels of dihydrotestosterone, and by stimulating sex hormone binding globulin (SHBG), thus reducing the levels of free testosterone. In newer OCs, such as Tricyclen and Diane-35, the progestin component is minimally androgenic and anti-androgenic respectively, thereby enhancing the favorable profile of these products in the treatment of hyperandrogenic disorders, including acne. The efficacy of these agents and their long-term safety profile supports their use in various grades of acne in females: * As adjunctive therapy to topical agents for women with mild non-scarring acne desiring oral contraception * As primary therapy for patients with moderate non-scarring acne in combination with topical therapy and systemic antibiotics * As one of two preferred methods of contraception in patients with scarring and severe inflammatory acne being treated with systemic isotretinoin.

  8. The Role of Testosterone in the Etiology and Treatment of Obesity, the Metabolic Syndrome, and Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    Farid Saad

    2011-01-01

    Full Text Available Obesity has become a major health problem. Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol, and a proinflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.

  9. Androgens and estrogens in postmenopausal insulin-treated diabetic women

    DEFF Research Database (Denmark)

    Nyholm, H; Djursing, H; Hagen, C;

    1989-01-01

    Diabetic women may have an increased risk of developing endometrial carcinoma. Ovarian and adrenal activity seem to be factors in the genesis of this cancer. We have measured serum sex hormone-binding globulin (SHBG), free and bound fractions of estrogens and androgens, and gonadotropins in 20...... consecutive postmenopausal insulin-treated diabetic women and 16 normal postmenopausal women. The diabetics were nonketoacidotic, without nephropathy and without proliferative retinopathy. The groups were comparable regarding age and percent ideal body weight. The diabetic group had significantly increased...... levels were similar in the two groups, while serum PRL was significantly lower in the diabetic group (P less than 0.02). The hormonal changes in the diabetics were not related to control of the diabetes. We conclude that total estrogen levels are increased in postmenopausal women with insulin...

  10. Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick; Svenstrup, Bo

    1988-01-01

    The aim of this study was to examine the serum concentrations of sex steroids and pituitary hormones in a randomly selected group of alcoholic cirrhotic men participating in a randomized, placebo-controlled study on the efficacy of oral testosterone treatment on the liver. Before treatment......, patients (n = 25) had median serum concentrations of testosterone, oestradiol, non-protein bound oestradiol, non-sex hormone binding globulin (SHBG) bound oestradiol and oestrone sulphate which did not differ significantly from those of healthy controls (n = 16), but the patients had significantly (P less...... than 0.01) higher median serum concentrations of oestrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. The patients were randomized to treatment with either oral micronized testosterone (200 mg t.d.s.) or placebo for a median duration of 1 year. In the placebo group (n...

  11. Prospective study of effects of endogenous estrogens on myocardial no-reflow risk in postmenopausal women with acute myocardial infarction.

    Science.gov (United States)

    Dong, Mei; Mu, Nan; Ren, Faxin; Sun, Xiaojian; Li, Fengli; Zhang, Chuanhuan; Yang, Jun

    2014-10-01

    The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no-reflow in postmenopausal women with ST-elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal-reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C-reaction protein (Hs-CRP) were significantly higher in the no-reflow group (P women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no-reflow. However, our results need to be confirmed in a larger population.

  12. Urinary concentrations of di(2-ethylhexyl) phthalate metabolites and serum reproductive hormones

    DEFF Research Database (Denmark)

    Mendiola, Jaime; Meeker, John D; Jørgensen, Niels

    2012-01-01

    Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families...... the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones-follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B......, and estradiol (E(2))-and sex hormone-binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite...

  13. Combined N-glycome and N-glycoproteome analysis of the Lotus japonicus seed globulin fraction shows conservation of protein structure and glycosylation in legumes.

    Science.gov (United States)

    Dam, Svend; Thaysen-Andersen, Morten; Stenkjær, Eva; Lorentzen, Andrea; Roepstorff, Peter; Packer, Nicolle H; Stougaard, Jens

    2013-07-01

    Legume food allergy, such as allergy toward peanuts and soybeans, is a health issue predicted to worsen as dietary advice recommends higher intake of legume-based foods. Lotus japonicus (Lotus) is an established legume plant model system for studies of symbiotic and pathogenic microbial interactions and, due to its well characterized genotype/phenotype and easily manipulated genome, may also be suitable for studies of legume food allergy. Here we present a comprehensive study of the Lotus N-glycoproteome. The global and site-specific N-glycan structures of Lotus seed globulins were analyzed using mass spectrometry-based glycomics and glycoproteomics techniques. In total, 19 N-glycan structures comprising high mannose (∼20%), pauci-mannosidic (∼40%), and complex forms (∼40%) were determined. The pauci-mannosidic and complex N-glycans contained high amounts of the typical plant determinants β-1,2-xylose and α-1,3-fucose. Two abundant Lotus seed N-glycoproteins were site-specifically profiled; a predicted lectin containing two fully occupied N-glycosylation sites carried predominantly pauci-mannosidic structures in different distributions. In contrast, Lotus convicilin storage protein 2 (LCP2) carried exclusively high mannose N-glycans similar to its homologue, Ara h 1, which is the major allergen in peanut. In silico investigation confirmed that peanut Ara h 1 and Lotus LCP2 are highly similar at the primary and higher protein structure levels. Hence, we suggest that Lotus has the potential to serve as a model system for studying the role of seed proteins and their glycosylation in food allergy.

  14. Salt-induced delay in cotyledonary globulin mobilization is abolished by induction of proteases and leaf growth sink strength at late seedling establishment in cashew.

    Science.gov (United States)

    Ponte, Luiz Ferreira Aguiar; Silva, André Luis Coelho da; Carvalho, Fabrício Eulálio Leite; Maia, Josemir Moura; Voigt, Eduardo Luiz; Silveira, Joaquim Albenisio Gomes

    2014-09-15

    Seedling establishment in saline conditions is crucial for plant survival and productivity. This study was performed to elucidate the biochemical and physiological mechanisms involved with the recovery and establishment of cashew seedlings subjected to salinity. The changes in the Na+ levels and K/Na ratios, associated with relative water content, indicated that osmotic effects were more important than salt toxicity in the inhibition of seedling growth and cotyledonary protein mobilization. Salinity (50mM NaCl) induced a strong delay in protein breakdown and amino acid accumulation in cotyledons, and this effect was closely related to azocaseinolytic and protease activities. In parallel, proline and free amino acids accumulated in the leaves whereas the protein content decreased. Assays with specific inhibitors indicated that the most important proteases in cotyledons were of serine, cysteine and aspartic types. Proteomic analysis revealed that most of the cashew reserve proteins are 11S globulin-type and that these proteins were similarly degraded under salinity. In the late establishment phase, the salt-treated seedlings displayed an unexpected recovery in terms of leaf growth and N mobilization from cotyledon to leaves. This recovery coordinately involved a great leaf expansion, decreased amino acid content and increased protein synthesis in leaves. This response occurred in parallel with a prominent induction in the cotyledon proteolytic activity. Altogether, these data suggest that a source-sink mechanism involving leaf growth and protein synthesis may have acted as an important sink for reserve mobilization contributing to the seedling establishment under salinity. The amino acids that accumulated in the leaves may have exerted negative feedback to act as a signal for the induction of protease activity in the cotyledon. Overall, these mechanisms employed by cashew seedlings may be part of an adaptive process for the efficient rescue of cotyledonary proteins

  15. Anti-T-lymphocyte globulin-based non-myeloablative stem cell transplantation followed by HLA-identical donor lymphocyte infusion for hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    毛平; 王顺清; 王汉平; 李庆山; 许艳丽; 莫文健; 应逸; 朱志刚

    2003-01-01

    Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 106/kg followed by the escalated dosage in the range of (0.5-1.5)×108/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.

  16. Comparison between spousal donor transplantation treated with anti-thymocyte globulin induction therapy and, living related donor transplantation treated with standard immunosuppression

    Directory of Open Access Journals (Sweden)

    Erkan Demir

    2014-01-01

    Full Text Available The worldwide shortage of organs available for transplantation has led to the use of living-unrelated kidney donors. In this context, spouses represent an important source of organ donors. We compared the allograft outcomes of spousal donor transplantation (SDT with anti-thymocyte globulin (ATG induction therapy and living related donor transplantation (LRDT with triple immonosuppression and basiliximab, in addition. Among the 335 living and deceased donor kidney transplantations performed between April 2001 and June 2010, there were 274 living donor kidney transplantations including 34 SDT and 240 LRDT. The minimum follow-up period was 36 months. All recipients of SDT received ATG (1.5 mg/kg induction therapy, which was stopped five to seven days after surgery. Maintenance immunosuppression included tacrolimus (TAC, mycophenolate mofetil (MMF and prednisolone. LRDT recipients received triple immunosuppressive protocol consisting of cyclosporine or TAC, MMF and prednisolone, in addition to basiliximab. There was a significant difference between the two groups in recipient age, while pre-operative duration on dialysis, recipient sex and donor age and sex were not significantly different. There was also a significant difference between the two groups in the number of human leukocyte antigen (HLA mismatches. The 1-, 3- and 5-year graft survival rates of SDT were 94.1%, 88.2% and 79.4%, respectively, and the frequency of acute rejection episodes was 5.8% (two cases. The 1-, 3- and 5-year graft survival rates of LRDT were 95.8%, 91.6% and 83.3%, respectively, with the frequency of acute rejection being 16.2%. The graft survival rates of SDT were as good as LRDT, while the acute rejection rates in SDT were lower than in LRDT, although the difference was not statistically different (P = 0.13.

  17. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  18. Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.

    Science.gov (United States)

    Kuhnz, W; Baumann, A; Staks, T; Dibbelt, L; Knuppen, R; Jütting, G

    1993-10-01

    The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively

  19. 绿豆种子8S球蛋白基因启动子的克隆及分析%Molecular Cloning and Characterization of the Promoter of Vigna radiata 8S Globulin Gene

    Institute of Scientific and Technical Information of China (English)

    徐超; 杨悦宁; 王吟; 张梦晗; 谢伟红; 杨维东; 刘洁生; 李宏业

    2011-01-01

    根据绿豆种子8S球蛋白α'亚基基因的末端序列设计3个特异反向引物.以绿豆基因组DNA为模板,采用基因组步移法,获得了8S球蛋白α'亚基基因起始密码子上游784 bp的DNA片段,通过序列测定和生物信息学分析,发现该序列含有启动子核心区以及大量的种子特异表达相关的顺式作用元件,表明此序列为种子特异启动子序列.通过PCR方法在启动子3'端加上翻译增强序列TMV-omega序列,构建了植物双元表达载体pBI-8SG α'-omega-gus,并成功将其转化进入农杆菌.%According to the sequence of Vigna radiata 8S globulin α’ isoform gene from GenBank,we designed and synthesized three reverse primers.A DNA fragment of 784 bp up stream of the coding sequence of V.radiata 8S globulin α’ isoform gene was amplified by Genome Walking with the genomic DNA of mung bean as the template.Sequence analysis suggested that the fragment is the seed specific promoter.Subjoined the TMV-omega sequence in the 3’ end of promoter of V.radiata 8S globulin alpha isoform gene by PCR.Constructed plant binary expression vector pBI-8SG α’-omega-gus, and then transformed into Agrobacterium cells.

  20. 丙种球蛋白对白血病化疗者感染和输血的影响%Effect of gamma globulin on leukemia chemotherapy infection and blood transfusion

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective To explore the effect of gamma globulin in acute leukemia (AL)of chemotherapy infection and blood transfusion.Methods According to application of gamma globulin,95 AL patients were divided into experimental group (36 cases )and control group (59 cases ).The infection,humoral immunity and blood transfusion were observed in two groups of patients.Results The immunoglobulin and complement level of two groups showed no significant difference.The experimental group showed significant decrease in anti-infection time,the number of platelet transfusion,adverse reaction of blood transfusion.Conclusion During AL chemotherapy,the application of gamma globulin is in favor of infection control,reduces support for treatment costs.%目的:探讨应用丙种球蛋白对急性白血病(AL)化疗者感染和输血的影响。方法95例 AL 患者根据是否应用丙种球蛋白分为实验组(36例)和对照组(59例)。观察对两组患者感染、体液免疫情况及输血的影响。结果两组免疫球蛋白和补体水平差异不大;实验组抗感染时间明显减少,输注血小板数量减少,输血不良反应率降低。结论在 AL 化疗期间应用丙种球蛋白利于感染控制,减少支持治疗费用。

  1. Are the Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire suitable for the screening of late-onset hypogonadism in aging Chinese men?

    Science.gov (United States)

    Chen, Wei; Liu, Zhi-Yong; Wang, Lin-Hui; Zeng, Qin-Song; Wang, Hui-Qing; Sun, Ying-hao

    2013-09-01

    The Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire have been widely used for screening men suspected of late-onset hypogonadism (LOH). We evaluated the consistency of the two questionnaires with sex hormone levels. A total of 985 men completed the two questionnaires, as well as an analysis of the serum levels of total testosterone (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone-binding globulin (SHBG). No correlation was observed between any hormone level and the psychological or somatic section of the AMS score, whereas the sexual section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant correlations were observed between the result of the two questionnaires and these hormone levels. When LOH was defined as TT AMS scale were 54.0% and 41.2% compared with 78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated with the two questionnaires, but neither of these questionnaires had sufficient sensitivity and specificity. It is necessary to provide a new questionnaire applicable to the Chinese population to screening LOH.

  2. Sleep, sex steroid hormones, sexual activities, and aging in Asian men.

    Science.gov (United States)

    Goh, Victor H-H; Tong, Terry Y-Y

    2010-01-01

    This was a cross-sectional study to examine the different associations of age and sleep duration with sex steroid hormones and sexual activities in 531 Asian Chinese men aged between 29 and 72 years old. Sleep duration and sexual activities were evaluated through a self-administered questionnaire, and total testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) were measured by established immunoassay methods in a single blood sample collected between 8:00 and 11:00 am. Bioavailable T (BioT) was calculated using the Vermeulen formula. Age was a major determinant of sleep, sex steroid hormones, and sexual activities in men. BioT, DHEAS, coital frequency, masturbation, and sleep duration declined with age. On the other hand, SHBG and E2 increased with age. Sleep duration, independently of age, aerobic exercise, and body fat, was positively associated with T and BioT, but not with DHEAS, E2, or any of the sexual activities studied. Men who masturbated had higher levels of both T and BioT. DHEAS was significantly associated with coital frequency and desire for sex. The present study showed that besides age, sleep duration was associated with androgen concentrations in men, and thus the evaluation of sleep hygiene may be beneficial in the management of men with low androgen concentrations. DHEAS may be independently associated with some sexual functions in men.

  3. Treatment of hirsutism with combined pill containing drospirenone.

    Science.gov (United States)

    Gregoriou, Odisseas; Papadias, Kostantinos; Konidaris, Sokratis; Bakalianou, Kostantina; Salakos, Nikolaos; Vrachnis, Nikolaos; Creatsas, George

    2008-04-01

    The aim of the present study was to evaluate the biochemical and clinical effects of the combined pill consisting of ethinyl estradiol (EE) and drospirenone (DRSP) in hirsute patients. Fifty-two adolescents or young women from Greece were treated with 30 mug EE and 3 mg DRSP for 1 year. Hirsutism was evaluated by the Ferriman-Gallway (FG) score in the initial visit and at 3, 6 and 12 months. Follicle-stimulating hormone, luteinizing hormone, etradiol, free and total testosterone (T), sex hormone-binding globulin (SHBG), androstenedione and dehydroepiandrosterone sulfate were determined at the same intervals. Hirsutism improved and FG scores reduced to 77.4%, 67.2% and 51.8% at 3, 6 and 12 months, respectively. Plasma SHBG levels rose, while free and total T levels reduced from the third month onwards. In conclusion, the EE/DRSP pill improves hirsutism in women via antiandrogenic and antimineralocorticoid action. The biochemical manifestations of hyperandrogenism are also improved.

  4. Effect of low-dose oral contraceptives on androgenic markers and acne.

    Science.gov (United States)

    Thorneycroft, I H; Stanczyk, F Z; Bradshaw, K D; Ballagh, S A; Nichols, M; Weber, M E

    1999-11-01

    Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

  5. Effects of Metformin Combined with Cyproterone Acetate on Clinical Features, Endocrine and Metabolism of Non-obese Women with Polycystic Ovarian Syndrome

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In order to explore the effects of metformin combined with cyproterone acetate (CPA) on the clinical features, endocrine and metabolism of the patients with polycystic ovarian syndrome (PCOS), 50 cases of non-obese PCOS were randomly subjected to CPA (CPA treatment group, n=25) and CPA+metformin (n= 25) treatment for 6 months. Before and after treatment the body mass index (BMI), waist: hip ratio (WHR), ovarian volume, serum gonadotrophin, androgen and sex hormone-binding globulin (SHBG) levels, and fasting lipid, glucose and insulin levels were measured. The results showed that all of the parameters in two groups were similar before treatment. After treatment for 6 months in the CPA+ metformin group, BMI and WHR were significantly decreased, while insulin sensitivity was significantly decreased as compared with those before treatment. In CPA group, no significant changes were found before and after treatment. Combined use of CPA and metformin could result in the reduction of serum androstenedione and increases of serum SHBG levels as compared with the CPA treatment alone. It was concluded that combined use of CPA and metformin could improve the insulin sensitivity, and further suppress the hyperandrogenism in non-obese women with PCOS.

  6. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Lim, S S; Norman, R J; Davies, M J; Moran, L J

    2013-02-01

    While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone-binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total-cholesterol and low-density lipoprotein-cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.

  7. Associations of blood lead levels with reproductive hormone levels in men and postmenopausal women: Results from the SPECT-China Study

    Science.gov (United States)

    Chen, Chi; Wang, Ningjian; Zhai, Hualing; Nie, Xiaomin; Sun, Honglin; Han, Bing; Li, Qin; Chen, Yi; Cheng, Jing; Xia, Fangzhen; Zhao, Li; Zheng, Yanjun; Shen, Zhoujun; Lu, Yingli

    2016-11-01

    We examined whether blood lead levels (BLLs) were associated with reproductive hormone levels in a cross-sectional study using data from the SPECT-China study. We selected 2286 men and 1571 postmenopausal women without hormone replacement therapy. BLLs, blood cadmium, total testosterone (TT), oestradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin(SHBG) levels were measured. The results showed that median values (interquartile range) of BLLs were 44.00 μg/L (29.00–62.30) for men and 41.00 μg/L (27.00–59.81) for postmenopausal women. In linear regression, after adjusting for age, current smoking status, body mass index, systolic blood pressure, diabetes and blood cadmium level, TT (P for trend = 0.001) and SHBG (P for trend reproductive hormone levels in the general population of Chinese men and postmenopausal women, which may have important implications for human health. Concerted efforts to reduce adult lead exposure are warranted.

  8. Effect of Rosiglitazone on Endocrine, Metabolism and Ovulatory Performance in Patients with Polycystic Ovary Syndrome and Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    吕立群; 刘义

    2004-01-01

    The effect of rosiglitazone on endocrine, metabolism and ovulatory performance in the paitents with polycystic ovary syndrome(PCOS) and insulin resistance was investigated. Twentyfive patients diagnosed as having polycystic ovary syndrome (PCOS) combined with insulin resistance were treated with rosiglitazone for 12 weeks. Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (A), sex hormone binding globulin (SHBG), insulin and glucose concentration, total cholesterol, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholestero (LDL-C), apolipoprotein A, apolipoprotein B levels and ovulatory performance were determined. The results showed that after treatment serum insulin levels was decreased significantly (P<0.01). The HDL-C was increased while LDL-C decreased significantly (P<0.05, P<0.01). The serum LH, T, A concentrations and the ratio of LH/FSH were decreased, while SHBG levels increased significantly (P<0.01). The ovulation rate during clomiphene citrate therapy was 72 %, significantly higher than that before treatment. It is likely that reduction of hyperinsulinemia that is produce by rosiglitazone may effectively improve the endocrine, metabolism and ovulatory performance in the patients with PCOS and insulin resistance.

  9. Race differences in obesity and its relationship to the sex hormone milieu.

    Science.gov (United States)

    Perry, Arlette C; Martin, Lorena

    2014-09-01

    A sexual dimorphism exists in which increased abdominal and visceral adipose tissue (VAT) - found in women and marked by low sex hormone binding globulin (SHBG) and high bioavailable testosterone (BT) - is related to the metabolic risk profile. In men, increased BT is related to decreased abdominal obesity and a decrease in the metabolic risk profile. In women, race differences have been found in androgenic sex steroids including SHBG and BT as well as central fat distribution, creating inherently greater metabolic risk for certain populations. Estrogen and estrogen receptor isoforms play a role in fat deposition and distribution and may influence the changes that occur during the menopausal transition. Androgenic sex steroids serve a mediating role, influencing VAT accumulation and its associated metabolic risk factors while VAT also serves a mediating role influencing the androgenic sex steroid-metabolic risk relationship in women. Furthermore, androgenic sex steroids and VAT may independently contribute to the variance in several metabolic variables associated with cardiovascular disease, type 2 diabetes, and their antecedent conditions such as the metabolic syndrome. Race has been shown to modify the relationship between androgenic sex steroids and metabolic variables associated with risk for diabetes in Black and White women. Further research is warranted to examine the mechanisms involved in race differences. Total adiposity and central fat distribution in accordance with changes in the hormone and metabolic milieu influence breast cancer risk, which varies by race and menopausal status. These findings have broader implications for the study of health promotion/disease prevention in women.

  10. Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess: a prospective study

    Science.gov (United States)

    Yuan, Chun; Liu, Xiaoqiang; Mao, Yundong; Diao, Feiyang; Cui, Yugui; Liu, Jiayin

    2016-01-01

    Abstract Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome (PCOS). There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index (BMI), total testosterone (TT), modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin (SHBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index (FAI) between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyperandrogenism had significantly higher BMI (P < 0.05), but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong predictor of hyperandrogenism in PCOS. PMID:27526961

  11. Terms of Binding

    NARCIS (Netherlands)

    Sevcenco, A.

    2006-01-01

    The present dissertation aimed at achieving two goals. First, it constitutes an attempt to widen the search for phenomena that bear relevance to the idea that binding has a syntactic residue and is not, therefore, an exclusively semantic matter. Second, it tried to provide the technical means to acc

  12. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  13. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  14. 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.

  15. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  16. Role of hormones and blood lipids in the pathogenesis of acne vulgaris in non-obese, non-hirsute females

    Directory of Open Access Journals (Sweden)

    Ola Ahmed Bakry

    2014-01-01

    Full Text Available Context: Acne vulgaris (AV is a common disease affecting all ages and ethnic groups. Androgens, skin and serum lipids, inflammatory signaling and regulatory neuropeptides seem to be involved in this multi-factorial process. Aim: The aim of this work was to determine hormonal levels and lipid profile in non-obese, non-hirsute females with AV. Subjects and Methods: A total of 60 non-obese, non-hirsute female cases with different grades of AV and 60 age- and gender-matched healthy volunteers were included. Measurement of serum total and free testosterone, sex hormone binding globulin (SHBG, estradiol and progesterone and blood lipids was done during the luteal phase of the menstrual cycle. Results: Total testosterone, free testosterone (FT and progesterone levels were significantly higher (P < 0.001 for all while estradiol levels (P < 0.001 and SHBG (P < 0.01 were significantly lower in cases than controls. Total cholesterol and low density lipoprotein cholesterol (LDL-C levels were significantly higher (P < 0.001 for both while high density lipoprotein cholesterol (HDL-C and apolipoprotein A-1 (ApoA-1 levels were significantly lower (P < 0.001 for both in cases than controls. Higher values of FT (P = 0.03 and SHBG (P = 0.02 and lower values of estradiol (P = 0.04 levels were significantly in favor of severe acne. Higher values of cholesterol (P < 0.001 and LDL-C (P = 0.03 and lower values of HDL-C (P = 0.01 and ApoA-1 (P = 0.02 levels were significantly associated with severe acne. Conclusion: Changes in hormone levels and lipid profile in non-obese and non-hirsute females with AV should be considered in disease pathogenesis and in treatment prescription of these patients.

  17. Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

    Directory of Open Access Journals (Sweden)

    Maciel Maria

    2011-02-01

    Full Text Available Abstract Background Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. Methods A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. Results Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. Conclusions We found higher levels of

  18. Associations of sex steroid hormones with mortality in women with breast cancer.

    Science.gov (United States)

    Duggan, Catherine; Stanczyk, Frank; Campbell, Kristin; Neuhouser, Marian L; Baumgartner, Richard N; Baumgartner, Kathy B; Bernstein, Leslie; Ballard, Rachel; McTiernan, Anne

    2016-02-01

    Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.

  19. Hyperandrogenemia association with acne and hirsutism severity in Croatian women with polycystic ovary syndrome.

    Science.gov (United States)

    Pavičić Baldani, Dinka; Škrgatić, Lana; Bukvić Mokos, Zrinka; Trgovčić, Iva

    2013-01-01

    Clinical traits associated with androgen, acne and hirsutism, are important diagnostic features of polycystic ovary syndrome (PCOS). As androgens are necessary for the development of cutaneous signs of PCOS, patients with severe forms of clinical hyperandrogenism are expected to present with higher levels of plasma androgens. This relationship has not been well established and studies examining the relationship have produced inconsistent results. The aim of this study was to analyze the correlation between the severity of clinical traits caused by androgen, acne and hirsutism, with plasma levels of androgens in Croatian women diagnosed with PCOS. One hundred and forty-five women of reproductive age with isolated acne (n=61) or isolated hirsutism (n=84), oligo/amenorrhea and polycystic morphology of the ovaries were enrolled in the study. Acne grade, hirsutism grade, body mass index (BMI) and waist to hip ratio (WHR) were recorded. Hormonal profiles were measured and assessment of insulin resistance was performed. There were no significant associations between acne severity and BMI, WHR and examined hormonal and insulin resistance parameters. There was a significant correlation between sex-hormone binding globulin (SHBG) and free testosterone levels and the severity of hirsutism (ρ=-0.611, Pacne severity in PCOS patients is not linearly associated with serum androgen levels; therefore, their levels should not be used to determine the dose of anti-androgen therapy. The observed negative correlation between serum SHBG levels and the degree of hirsutism suggests that hormonal contraception, which elevates SHBG, should be used as primary therapy in hirsute PCOS patients.

  20. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  1. Mineralocorticoid specificity of renal type I receptors: in vivo binding studies

    Energy Technology Data Exchange (ETDEWEB)

    Sheppard, K.; Funder, J.W.

    1987-02-01

    The authors have injected rats with (TH)aldosterone or (TH) corticosterone, plus 100-fold excess of the highly specific glucocorticoid RU 28362, with or without excess unlabeled aldosterone or corticosterone and compared type I receptor occupancy in kidney and hippocampus. Thirty minutes after subcutaneous injection (TH)aldosterone was well retained in renal papilla-inner medulla, renal cortex-outer medulla, and hippocampus; in contrast, (TH)corticosterone was well retained only in hippocampus. Competition studies for (TH)aldosterone binding sites showed corticosterone to be a poor competitor in the kidney compared with hippocampus. Time-course studies, with rats killed 10-180 min after tracer administration, showed very low uptake/retention of (TH)corticosterone by kidney; in hippocampus (TH)corticosterone retention was similar to that of (TH)aldosterone in kidney, and retention of (TH)aldosterone by hippocampus was much more prolonged than of either tracer in any other tissue. Studies in 10-day-old rats, with very low levels of corticosteroid binding globulin (CBG), showed a high degree of aldosterone selectivity in both zones of the kidney, whereas 9TH)aldosterone and (TH)corticosterone were equivalently bound in hippocampus. They interpret these data as evidenced for a mechanism unrelated to extravascular CBG conferring mineralocorticoid specificity on renal type I receptors and propose two models derived from their findings consistent with such differential selectivity.

  2. Structural basis for variant-specific neuroligin-binding by α-neurexin.

    Directory of Open Access Journals (Sweden)

    Hiroki Tanaka

    Full Text Available Neurexins (Nrxs are presynaptic membrane proteins with a single membrane-spanning domain that mediate asymmetric trans-synaptic cell adhesion by binding to their postsynaptic receptor neuroligins. α-Nrx has a large extracellular region comprised of multiple copies of laminin, neurexin, sex-hormone-binding globulin (LNS domains and epidermal growth factor (EGF modules, while that of β-Nrx has but a single LNS domain. It has long been known that the larger α-Nrx and the shorter β-Nrx show distinct binding behaviors toward different isoforms/variants of neuroligins, although the underlying mechanism has yet to be elucidated. Here, we describe the crystal structure of a fragment corresponding to the C-terminal one-third of the Nrx1α ectodomain, consisting of LNS5-EGF3-LNS6. The 2.3 Å-resolution structure revealed the presence of a domain configuration that was rigidified by inter-domain contacts, as opposed to the more common flexible "beads-on-a-string" arrangement. Although the neuroligin-binding site on the LNS6 domain was completely exposed, the location of the α-Nrx specific LNS5-EGF3 segment proved incompatible with the loop segment inserted in the B+ neuroligin variant, which explains the variant-specific neuroligin recognition capability observed in α-Nrx. This, combined with a low-resolution molecular envelope obtained by a single particle reconstruction performed on negatively stained full-length Nrx1α sample, allowed us to derive a structural model of the α-Nrx ectodomain. This model will help us understand not only how the large α-Nrx ectodomain is accommodated in the synaptic cleft, but also how the trans-synaptic adhesion mediated by α- and β-Nrxs could differentially affect synaptic structure and function.

  3. 阿伦和达珠单抗与抗胸腺蛋白对肾移植的有效性及安全性比较%Efficacy and safety of alemtuzumab, daclizumab and antithymocyte globulin in kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    王涛; 郝文静; 宗焕涛; 张勇

    2015-01-01

    BACKGROUND:Immunosuppressants fight against acute rejections by influencing humoral and celular immune to suppress the immune function, and then improve patient/renal graft survival. OBJECTIVE:To evaluate the effectiveness and safety of alemtuzumab, daclizumab and antithymocyte globulin in inducing immunosuppression in kidney transplantation. METHODS:The randomized controled trials of alemtuzumab or daclizumabversusATG in kidney tranplantation published from 1966 to 2011 were enroled by searching PubMed and EMBASE using Cochrane systematic review. We colected data and major outcomes. And a meta-analysis was conducted on homogeneous studies. RESULTS AND CONCLUSION: A total of 9 randomized controled trials (777 patients) about kidney transplantation were included. The meta-analysis results showed that the safety items including patient/renal graft survival and acute rejection at a folow-up of 24 months had no statistical differences among the three drugs (al P > 0.05). But there was a significant difference between the infection rates of alemtuzumab and antithymocyte globulin at 36 months of folow-up (P 0.05)。随访36个月时,阿伦单抗感染率显著低于抗胸腺蛋白(P<0.05)。分析结果表明,3种药物的免疫诱导效果相近;随访36个月时,阿伦单抗较抗胸腺蛋白的感染率低。

  4. Binding Principles A and B

    Institute of Scientific and Technical Information of China (English)

    陈源

    2014-01-01

    This paper focuses on the discussion of how Binding Principle A and Binding Principe B help with the interpretation of reference in English and Chinese. They are supposedly universal across languages.

  5. 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.

  6. The treatment effect observation of intravenous gamma globulin for in-fectious mononucleosis%静注丙种球蛋白治疗传染性单核细胞增多症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    何洲; 彭升; 古超群

    2015-01-01

    目的:探讨静注丙种球蛋白(IVIG)治疗传染性单核细胞增多症的临床疗效。方法选择2013年9月~2014年8月我院接收的传染性单核细胞增多症患者80例,随机分为观察组和对照组,各40例。观察组应用静注丙种球蛋白进行治疗,而对照组则使用病毒唑加IFN-α(干扰素-α)进行治疗,对比分析两组的有效率、临床症状及生命体征的变化。结果观察组患者的临床症状、生命体征及治愈率均显著优于对照组(P<0.05)。结论使用静注丙种球蛋白治疗传染性单核细胞增多症疗效确切,安全性强,值得临床推广和运用。%Objective To investigate the clinical effect of intravenous injection of gamma globulin in the treatment of infectious mononucleosis. Methods All 80 cases of child patients with infectious mononucleosis from September 2013 to August 2014 in our hospital were randomly divided into the observation group and control group ,each group included 40 cases. The observation group was treated with gamma globulin , while the control group were given ribavirin plus IFN-α treatment, the efficiency, the clinical symptoms and signs of life changes were compared between two groups. Results The clinical symptom,life signs and the cure rate of observation group were significantly better than the control group (P<0.05). Conclusion Gamma globulin in treatment of infectious mononucleosis has define effect and safety, worthy of clinical promotion and application.

  7. Analytic QCD Binding Potentials

    CERN Document Server

    Fried, H M; Grandou, T; Sheu, Y -M

    2011-01-01

    This paper applies the analytic forms of a recent non-perturbative, manifestly gauge- and Lorentz-invariant description (of the exchange of all possible virtual gluons between quarks ($Q$) and/or anti-quarks ($\\bar{Q}$) in a quenched, eikonal approximation) to extract analytic forms for the binding potentials generating a model $Q$-$\\bar{Q}$ "pion", and a model $QQQ$ "nucleon". Other, more complicated $Q$, $\\bar{Q}$ contributions to such color-singlet states may also be identified analytically. An elementary minimization technique, relevant to the ground states of such bound systems, is adopted to approximate the solutions to a more proper, but far more complicated Schroedinger/Dirac equation; the existence of possible contributions to the pion and nucleon masses due to spin, angular momentum, and "deformation" degrees of freedom is noted but not pursued. Neglecting electromagnetic and weak interactions, this analysis illustrates how the one new parameter making its appearance in this exact, realistic formali...

  8. Prevención de la isoinmunización materna al RhD, con gamma-globulina anti-D Prevention of maternal RhD isoimmunization with anti-D gamma globulin

    Directory of Open Access Journals (Sweden)

    Héctor Alfredo Baptista-González

    2001-02-01

    Full Text Available OBJETIVO: Presentar la experiencia institucional en la prevención de la isoinmunización al RhD, mediante el empleo de 150 µg de gamma-globulina anti-D en las mujeres Rh negativo. MATERIAL Y MÉTODOS: Se registraron los antecedentes inmunohematológicos de los casos consecutivos de todas las mujeres Rh negativo que acudieron, para su atención médica, al Instituto Nacional de Perinatología entre 1982 y 1995. A las mujeres con riesgo de isoinmunización se les aplicó 150 µg de gamma-globulina anti-D, con fines preventivos. RESULTADOS: En el periodo de estudio ingresaron 4 857 mujeres Rh negativo (4.85% del total de mujeres, de las cuales 629 (13.0%, presentaron isoinmunización al RhD. De estas últimas, 542 (86.2% ya se encontraron isoinmunizadas desde antes de su ingreso al Instituto. En 22 casos (3.5%, la isoinmunización ocurrió a pesar de que recibieron la dosis adecuada de gamma-globulina anti D. De las 2 605 pacientes (53.6% sometidas a prevención, a 2 039 se les aplicó una sola dosis, y a 475, hasta dos dosis. En 22 casos se documentó la falla de la prevención; sin embargo, en cuatro de ellos, se registraron embarazos múltiples, y los restantes 18 presentaron patología obstétrica asociada. CONCLUSIONES: Mediante este programa de prevención, consistente en administrar 150 µg de gamma-globulina anti-D por dosis, es posible reducir la isoinmunización a menos de un caso por cada 1 000 mujeres. Los fracasos en la prevención de la isoinmunización se asociaron a condiciones obstétricas agregadas y al incumplimiento de las guías o lineamientos del programa. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlOBJECTIVE: To report our experience in preventing RhD maternal isoimmunization by using anti-D gamma globulin among Rh-negative women. MATERIAL AND METHODS: Between 1982 and 1995, immunologic and hematologic data were collected from all Rh-negative women seen at Mexico

  9. B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Hanaoka

    2015-09-01

    Full Text Available B-cell lymphoproliferative disorder (B-LPD is generally characterized by the proliferation of Epstein-Barr virus (EBV-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.

  10. Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

    Directory of Open Access Journals (Sweden)

    Manal K. Al Kindi

    2012-11-01

    Full Text Available Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosteronein females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG, free androgen index (FAI, and calculated free testosterone (CFT in the assessment of androgen status in women investigated for suspected hyperandrogenism.Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18. The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19, hirsutism (group 3; n=18, menstrual disturbances (irregularities or infertility (group 4; n=49, as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5;n=18. Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation.Results: There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73

  11. Clinical and hormonal effects of ethinylestradiol combined with gestodene and desogestrel in young women with acne vulgaris.

    Science.gov (United States)

    Mango, D; Ricci, S; Manna, P; Miggiano, G A; Serra, G B

    1996-03-01

    The effect of gestodene 75 micrograms (GTD) versus desogestrel 150 micrograms (DSG) combined with 30 micrograms of ethinylestradiol (EE) on acne lesions and plasma androstenedione (A), total testosterone (T), sex hormone binding globulin (SHBG) and "free androgen index" (FAI) was evaluated in an open study on 19 patients aged 18-35 years affected with postpubertal or persistent non-severe acne vulgaris. The patients were randomly allocated into two groups receiving EE-GTD (n = 8) and EE-DSG (n = 11), 21 tablets per cycle for 9 consecutive cycles. Clinical and hormonal evaluations were made between days 17-21 in the cycle before treatment and between days 17-21 of the cycle 3, 6 and 9 of treatment. During treatment, acne improved in most patients, reaching at cycle 9 a low score (absent or minimal) in 62% of the cases in the GTD group (mean acne score = 1.25) and in 90% of the cases in the DSG group (mean acne score = 0.90). Before treatment, about 75% of the patients showed one or more signs of biochemical hyperandrogenism, including elevated FAI (57%), elevated A (15%), elevated total T (15%) and decreased SHBG (21%), and there was evidence of inverse correlation between SHBG and acne scores (p < 0.05). The echogenic texture of the ovaries was multifollicular in 55% of the cases. By the end of the third cycle of treatment, the hormonal changes observed in both groups included significant decreases, with normalization of individual elevated levels of T, and a 3-fold rise of the initial values of plasma SHBG, which showed a further gradual increase at cycle 9 of EE-DSG administration. At cycle 9, normalization of the echogenic ovarian texture was observed. Acne improvement under treatments with estrogen and progestin (EP) could be significantly correlated with the normalization of biochemical hyperandrogenism. In conclusion, the biochemical and clinical efficacy of EE-GTD and EE-DSG indicate that both these preparations can be a good choice in the therapy of acne

  12. Interaction of gold and silver nanoparticles with human plasma: Analysis of protein corona reveals specific binding patterns.

    Science.gov (United States)

    Lai, Wenjia; Wang, Qingsong; Li, Lumeng; Hu, Zhiyuan; Chen, Jiankui; Fang, Qiaojun

    2017-04-01

    Determining how nanomaterials interact with plasma will assist in understanding their effects on the biological system. This work presents a systematic study of the protein corona formed from human plasma on 20nm silver and gold nanoparticles with three different surface modifications, including positive and negative surface charges. The results show that all nanoparticles, even those with positive surface modifications, acquire negative charges after interacting with plasma. Approximately 300 proteins are identified on the coronas, while 99 are commonly found on each nanomaterial. The 20 most abundant proteins account for over 80% of the total proteins abundance. Remarkably, the surface charge and core of the nanoparticles, as well as the isoelectric point of the plasma proteins, are found to play significant roles in determining the nanoparticle coronas. Albumin and globulins are present at levels of less than 2% on these nanoparticle coronas. Fibrinogen, which presents in the plasma but not in the serum, preferably binds to negatively charged gold nanoparticles. These observations demonstrate the specific plasma protein binding pattern of silver and gold nanoparticles, as well as the importance of the surface charge and core in determining the protein corona compositions. The potential downstream biological impacts of the corona proteins were also investigated.

  13. Binding Energy and Enzymatic Catalysis.

    Science.gov (United States)

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  14. Cooperative binding: a multiple personality.

    Science.gov (United States)

    Martini, Johannes W R; Diambra, Luis; Habeck, Michael

    2016-06-01

    Cooperative binding has been described in many publications and has been related to or defined by several different properties of the binding behavior of the ligand to the target molecule. In addition to the commonly used Hill coefficient, other characteristics such as a sigmoidal shape of the overall titration curve in a linear plot, a change of ligand affinity of the other binding sites when a site of the target molecule becomes occupied, or complex roots of the binding polynomial have been used to define or to quantify cooperative binding. In this work, we analyze how the different properties are related in the most general model for binding curves based on the grand canonical partition function and present several examples which highlight differences between the cooperativity characterizing properties which are discussed. Our results mainly show that among the presented definitions there are not two which fully coincide. Moreover, this work poses the question whether it can make sense to distinguish between positive and negative cooperativity based on the macroscopic binding isotherm only. This article shall emphasize that scientists who investigate cooperative effects in biological systems could help avoiding misunderstandings by stating clearly which kind of cooperativity they discuss.

  15. Observation of Androgen Receptor Gene and Sex Hormone Binding Protein Gene in PCOS Patients%PCOS患者雄激素受体基因和性激素结合蛋白基因情况观察

    Institute of Scientific and Technical Information of China (English)

    马娟; 周俊; 田贵聪; 石华

    2016-01-01

    目的:研究观察多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者的雄激素受体基因和性激素结合蛋白基因的情况。方法:选取2014年11月-2015年7月本院接诊的62例PCOS患者为观察组,同一时期由于生殖系统发生异常导致不孕的62例患者为对照组。提取所有患者血液标本的DNA进行基因扩增、琼脂糖凝胶、毛细管电泳等检测,观察研究PCOS患者的雄激素受体和性激素结合蛋白基因的情况。结果:观察组SHBG-TAAAA基因型多态性与胰岛素抵抗的研究中,发现9/9基因型的分布在胰岛素抵抗和非胰岛素抵抗两组中存在统计学差异(P<0.05);观察组中,短重复组在高雄激素血症组的分布为52.94%,在雄激素正常组分布为42.86%;而长重复组在高雄激素血症组的分布为61.76%,在雄激素正常组的分布为39.29%,两组数据比较差异有统计学意义(P<0.05)。结论:雄激素受体基因和性激素结合蛋白基因与PCOS相关,可对PCOS的检查指标、PCOS防治、及早诊断起重要作用。%Objective:To investigate the status of androgen receptor gene and sex hormone binding protein gene in patients with polycystic ovary syndrome(PCOS).Method:A total of 62 PCOS patients were selected as the observation group from November 2014 to July 2015 in our hospital,the control group were choosed from the same period due to the occurrence of reproductive system abnormalities lead to infertility in 62 patients.DNA gene amplification,agarose gel electrophoresis and capillary electrophoresis were performed to detect the expression of androgen receptor and sex hormone binding protein gene in PCOS patients.Result:SHBG-TAAAA gene type of polymorphic and insulin resistance of the observation group in the study,found that 9/9 genotype distribution in insulin resistance and insulin resistance had a significant difference in two groups(P<0.05).In the observation group

  16. 7S球蛋白水解物对猪肉糜凝胶的影响%Effect of Alcalase Hydrolysates of Soybean 7S Globulin on Gel Properties of Minced Pork

    Institute of Scientific and Technical Information of China (English)

    段春红; 潘思轶

    2012-01-01

    In this study, the influence of soybean 7S globulin hydrolysates with different degree of hydrolysis (DH) on gel properties of minced pork was investigated. Soybean 7S globulin was first hydrolyzed to different DH (3%, 6%, 9%, 12%, 15%) using alcalase. Hydrolysates were then added to minced pork to make pork sausage. Interactions to stabilize the gel structure of pork sausage were finally analyzed to determine the influence of hydrolysates on gel properties of minced pork. The results obtained showed that hydrophobic interaction was not significantly related to the gel strength of pork sausage, indicating it was not a principle interaction in maintaining the gel network of mined pork. While, disulfide bond and hydrophobic interactions were significantly related to the springiness and chewiness of pork sausage (P 〈 0.01). Hydrogen bond was also significantly related to springiness of the pork sausage (P 〈 0.05), indicating that disulfide bonds, hydrophobic interactions and hydrogen bonds were the principle forces to maintain pork gel network. Scanning electron microscopy (SEM) revealed that hydrolysates of soybean 7S globulin improved the gel properties of minced pork. With increasing DH added hydrolysates, the pork gel became more compact and uniform, with no noticeable pores in it.%以大豆为原料,提取7s球蛋白,并采用碱性蛋白酶对其进行限制性酶解,控制其水解度,得到水解度为3%、6%、9%、12%、15%的酶解产物,将酶解产物与猪肉糜混合制备猪肉肠,分析添加不同水解度的酶解产物所形成的猪肉糜凝胶的化学作用力的变化。结果表明:静电作用与猪肉糜凝胶强度相关性不显著,不是维持猪肉糜凝胶网络结构的主要作用力;疏水作用与猪肉糜凝胶的回复性和咀嚼性呈现极显著的正相关性;氢键与猪肉糜凝胶的弹性呈现极显著的正相关性,二硫键与猪肉糜凝胶的弹性、内聚性

  17. 小儿破伤风应用静脉丙种球蛋白的免疫力效果观察%Observation on immune effect of intravenous immune globulin in the treatment of pediatric tetanus

    Institute of Scientific and Technical Information of China (English)

    龚德彰

    2013-01-01

    Objective To preliminarily study and discuss the specific clinical effect of intravenous immune globulin in the treatment of pediatric tetanus, in order to increase the clinical effect of treatment to the pediatric tetanus and guarantee their life safety. Methods 28 pediatric patients with tetanus treated in this hospital from October 2010 to December 2012 were randomly divided into the observation group and control group, including 14 cases in each group. Pediatric patients in the control group received the routine treatment of tetanus antitoxin; while pediatric patients in the observation group received the routine treatment and intravenous immune globulin. Observed and made statistics for the clinical effect of pediatric patients in two groups. Results After receiving the treatment, the clinical effect in the observation group was significantly better than the one in the control group, with the significant difference (P<0.05). Conclusion Tetanus has a great impact on the immune function of pediatric patients. Based upon the routine treatment, the intravenous immune globulin will have a significant clinical effect in the treatment to pediatric tetanus, which will significantly increase the clinical effect, guarantee patients' life safety, reduce the pains of disease to them and thus is worthy to be propularized.%  目的为了进一步提高我院治疗小儿破伤风的临床疗效,保障患儿的生命安全,本资料就小儿破伤风应用静脉丙种球蛋白的免疫力的具体临床效果进行了浅显的研究和探讨。方法将我院在2010年10月~2012年12月期间收治的28例破伤风患儿随机分为观察组和对照组,两组患者均14例、给予对照组患儿采用破伤风抗毒素进行常规治疗;给予观察组患儿在常规治疗的基础上加用静脉丙种球蛋白进行治疗,对两组患儿的治疗效果进行观察和统计。结果两组患儿在接受治疗后,观察组患儿的治疗效果要明显的

  18. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    and KCN, are selectively bound to the catalyst, providing exceptionally high enantioselectivities for kinetic resolutions, elimination reactions (fluoride base), and Strecker synthesis (cyanide nucleophile). Asymmetric cation-binding catalysis was recently expanded to silicon-based reagents, enabling...... solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...

  19. Serum LBP Is Associated with Insulin Resistance in Women with PCOS

    Science.gov (United States)

    Zhu, Qibo; Zhou, Huang; Zhang, Aipin; Gao, Rufei; Yang, Shumin; Zhao, Changhong; Wang, Yue; Hu, Jinbo; Goswami, Richa; Gong, Lilin; Li, Qifu

    2016-01-01

    Introduction Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. Participants and Design In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson’s correlation and multiple linear regression was used to analyze the associations between M value and LBP level. Settings The study was performed in a clinical research center. Results Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. Conclusion Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS. PMID:26799617

  20. Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

    Directory of Open Access Journals (Sweden)

    Qibo Zhu

    Full Text Available Lipopolysaccharide-binding protein (LBP is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS. The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR in PCOS.In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP. Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level.The study was performed in a clinical research center.Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001, and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001. Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI, fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c, free testosterone, high sensitive C reactive protein (hs-CRP and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c and sex hormone binding globulin (SHBG. Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP.Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

  1. Androgen Receptor CAG Repeat Length Is Associated With Body Fat and Serum SHBG in Boys

    DEFF Research Database (Denmark)

    Mouritsen, Annette; Hagen, Casper P; Sørensen, Kaspar;

    2013-01-01

    was to evaluate associations between the AR (CAG)n polymorphism and development of pubic hair, levels of androgens, and body fat content in healthy boys. Methods: A longitudinal study of 78 healthy boys (age 6.2-12.4 years at inclusion) from the COPENHAGEN Puberty Study was conducted with clinical examinations...

  2. Estradiol, SHBG and leptin interplay with food craving and intake across the menstrual cycle.

    Science.gov (United States)

    Objective: To understand the association between ovarian hormones, non-acute satiety hormones and craving calorie dense foods in the luteal phase. Methods: 17 premenopausal women, mean age 23.2 y, mean BMI 22.4 kg/m2 with regular menstrual cycles were studied during late follicular (FP) and luteal ...

  3. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan

    2014-02-01

    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  4. The prion protein binds thiamine.

    Science.gov (United States)

    Perez-Pineiro, Rolando; Bjorndahl, Trent C; Berjanskii, Mark V; Hau, David; Li, Li; Huang, Alan; Lee, Rose; Gibbs, Ebrima; Ladner, Carol; Dong, Ying Wei; Abera, Ashenafi; Cashman, Neil R; Wishart, David S

    2011-11-01

    Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 μM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data, in conjunction with computer-aided docking and molecular dynamics, were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.

  5. Galectin-3-Binding and Metastasis

    Science.gov (United States)

    Nangia-Makker, Pratima; Balan, Vitaly; Raz, Avraham

    2013-01-01

    i. Summary Galectin-3 is a member of a family of carbohydrate-binding proteins. It is present in the nucleus, the cytoplasm and also extracellular matrix of many normal and neoplastic cell types. Arrays of reports show an upregulation of this protein in transformed and metastatic cell lines (1, 2). Moreover, in many human carcinomas, an increased expression of galectin-3 correlates with progressive tumor stages (3–6). Several lines of analysis have demonstrated that the galectins participate in cell-cell and cell-matrix interactions by recognizing and binding complimentary glycoconjugates and thereby play a crucial role in normal and pathological processes. Elevated expression of the protein is associated with an increased capacity for anchorage-independent growth, homotypic aggregation, and tumor cell lung colonization (7–9). In this chapter we describe the methods of purification of galectin-3 from transformed E. coli and some of the commonly used functional assays for analyzing galectin-3 binding. PMID:22674139

  6. Computational Prediction of RNA-Binding Proteins and Binding Sites.

    Science.gov (United States)

    Si, Jingna; Cui, Jing; Cheng, Jin; Wu, Rongling

    2015-01-01

    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.

  7. 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.

  8. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  9. Cellulose binding domain fusion proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  10. Protein binding assay for hyaluronate

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, B.E.; Underhill, C.B.

    1986-11-01

    A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity, and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, they used a competition assay in which the binding of a set amount of (/sup 3/H)hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. They have found that this method is sensitive to 1 ..mu..g or less of hyaluronate, and is unaffected by the presence of proteins.

  11. The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans.

    Science.gov (United States)

    Allen, Naomi E; Appleby, Paul N; Davey, Gwyneth K; Kaaks, Rudolf; Rinaldi, Sabina; Key, Timothy J

    2002-11-01

    The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.

  12. Clinical pharmacokinetics of contraceptive steroids. An update.

    Science.gov (United States)

    Shenfield, G M; Griffin, J M

    1991-01-01

    The present article should be read in conjunction with the original review published in the Journal in 1983. There is no new information of major significance about the pharmacokinetics of levonorgestrel, norethisterone (norethindrone) or ethinylestradiol, although it has been shown that the concentrations of these hormones secreted in breast milk are small and mothers taking combined oral contraceptive steroids may breast-feed safely. Both levonorgestrel and ethinylestradiol can be successfully administered from appropriate vaginal formulations, but no clear advantages over oral administration have been demonstrated. Several new progestogens have been investigated. Desogestrel is a prodrug for its active metabolite 3-keto-desogestrel, gestodene is itself an active progestogen and norgestimate is a prodrug acting by conversion to norgestrel and its metabolites. All 3 compounds have good bioavailability with wide intersubject variation. The newer progestogens, like norethisterone and levonorgestrel, are bound to sex hormone binding globulin (SHBG). This causes their plasma concentrations to increase with time, since SHBG is induced by ethinylestradiol even in doses of 30 micrograms daily. The binding capacity and affinity of SHBG do not increase in direct proportion to its concentration. Further drug interactions with oral contraceptive steroids have been described. Contraceptive steroids may inhibit hepatic microsomal enzyme metabolism and increase the plasma concentration and effect of some tricyclic antidepressants, the hydroxylated benzodiazepines, some beta-blocking drugs, methylxanthines, prednisolone and cyclosporin. There are no significant effects on vitamins. Oral contraceptive steroids induce glucuronidation and hence decrease plasma concentrations of some benzodiazepines, clofibric acid, paracetamol (acetaminophen) and possibly morphine. The plasma concentration of ethinylestradiol may be increased by competitive sulphation with paracetamol. Plasma

  13. Functional characterization of acetylated Brazil nut (Bertholletia excelsa HBK kernel globulin Caracterizaçao funcional das globulinas de amêndoa de castanha-do-Pará após a acetilação

    Directory of Open Access Journals (Sweden)

    Cíntia Maria Pinto Ramos

    2004-03-01

    Full Text Available Defatted Brazil nut kernel flour, a rich source of high quality proteins, is presently being utilized in the formulation of animal feeds. One of the possible ways to improve its utilization for human consumption is through improvement in its functional properties. In the present study, changes in some of the functional properties of Brazil nut kernel globulin were evaluated after acetylation at 58.6, 66.2 and 75.3% levels. The solubility of acetylated globulin was improved above pH 6.0 but was reduced in the pH range of 3.0-4.0. Water and oil absorption capacity, as well as the viscosity increased with increase in the level of acetylation. Level of modification also influenced the emulsifying capacity: decreased at pH 3.0, but increased at pH 7.0 and 9.0. Highest emulsion activity (approximately 62.2% was observed at pH 3.0 followed by pH 9.0 and pH 7.0 and least (about 11.8% at pH 5.0. Emulsion stability also followed similar behavior as that of emulsion activity.Farinha desengordurada de amêndoa de castanha-do-Pará, fonte rica de proteína de alta qualidade, vem sendo, atualmente, aproveitada apenas na formulação de ração animal. Uma das possíveis maneiras de melhorar seu aproveitamento para o consumo humano é através do melhoramento de suas propriedades funcionais. No presente trabalho, mudanças em algumas propriedades funcionais da globulina de castanha-do-Pará, após acetilação, aos níveis de 58,6, 66,2 e 75,3% foram estudadas. A solubilidade da globulina acetilada aumentou acima de pH 6,0, porém diminuiu na faixa de pH 3,0 a 4,0. As capacidades de absorção de água e de óleo como também a viscosidade, melhoraram com o aumento de grau de acetilação. O grau de modificação também influenciou a capacidade de emulsificação: reduziu em pH 3,0, e aumentou nos pHs 7,0 e 9,0. A máxima atividade de emulsão (aproximadamente 62,2% foi observada em pH 3,0 seguida de pH 9,0 e a mínima foi observada (11,8% em pH 5,0. A

  14. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    Science.gov (United States)

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.).

  15. In vitro digestibility of globulins from sapucaia (Lecythis pisonis Camb. nuts by mammalian digestive proteinases Digestibilidade in vitro de globulinas das amêndoas de sapucaia (Lecythis pisonis Camb. por proteinases digestivas de mamíferos

    Directory of Open Access Journals (Sweden)

    Sandra Maria Silveira Denadai

    2007-09-01

    Full Text Available Sapucaia (Lecythis pisonis Camb. raw nuts collected from Brazil were analyzed to determine the proximate composition, amino acid profile of protein fractions, in vitro protein digestibility and antinutritional factors in order to evaluate their potential as a protein alimentary complement. The nuts contained adequate amounts of essential amino acids, fatty acids and minerals. In the present study, no hemagglutinating or inhibitory activities were observed in any of the samples investigated, indicating low or non-detectable levels of proteinase inhibitors or lectins in the samples. In vitro digestibility of in natura and heated nut globulins by mammalian digestive proteinases was carried out using trypsin + chymotrypsin + peptidase, with resulting mean values of approximately 70.30 and 71.35%, respectively. Taken together, the results suggest that sapucaia nuts may provide a new source of protein to use as a potential nutritional agent.Amêndoas cruas de Sapucaia (Lecythis pisonis Camb. colhidas no Brasil foram analisadas para se determinar a composição centesimal, o perfil de aminoácidos de suas proteínas, a digestibilidade protéica in vitro e a presença de fatores antinutricionais, para avaliar o seu potencial como complemento alimentar protéico. As amêndoas apresentaram quantidades adequadas de aminoácidos essenciais, ácidos graxos e minerais; no entanto, baixo teor de fibra foi observado. No presente estudo, a presença de lectinas ou inibidores de proteinases, quando detectada, apresentou baixos níveis. A digestibilidade in vitro de globulinas, in natura ou aquecidas, por proteinases digestivas de mamíferos foi realizada utilizando-se tripsina + quimotripsina + peptidase, obtendo-se valores aproximados de 71,5 e 73,5%, respectivamente. Estes resultados sugerem que as amêndoas de sapucaia podem ser utilizadas como complemento alimentar de proteínas, sendo um potencial agente nutricional.

  16. National Institutes of Health classification for chronic graft-versus-host disease predicts outcome of allo-hematopoietic stem cell transplant after fludarabine-busulfan-antithymocyte globulin conditioning regimen.

    Science.gov (United States)

    Saillard, Colombe; Crocchiolo, Roberto; Furst, Sabine; El-Cheikh, Jean; Castagna, Luca; Signori, Alessio; Oudin, Claire; Faucher, Catherine; Lemarie, Claude; Chabannon, Christian; Granata, Angela; Blaise, Didier

    2014-05-01

    Abstract In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk (p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe.

  17. Effect of gamma globulin applied in patients with peripartum cardiomyopathy%人血丙种球蛋白治疗围产期心肌病的疗效评价

    Institute of Scientific and Technical Information of China (English)

    俞子恒; 韦凡平

    2012-01-01

    Objectives To evaluate the treatment effects of applying human gamma globulin in patients with peripartum cardiomyopathy after the gestation. Methods Forty nine females diagnosed as peripartum cardiomyopathy in Zhejiang Province Huzhou Central Hospital were divided into two groups: treatment group and control group. Patients in treatment group were treated with standard treatments plus gamma globulin [continuous intravenous injection of 400 trig/(kg-d) for 5 d]. Left ventricular end diastolic dimension (LVEDd) and left ventricular ejection fraction (LVEF) before and after treatment in two groups were measured by ultrasonic cardiogram. Meanwhile, serum concentrations of immunoglobulin G, A and M were measured and compared. Results LVEDd and LYEF in treatment group were significanlty improved after treatment [(5.8±0.4) mm w.(6.2±0.7) mm,p<0.05: 58%±13% vs. 39%±11%, p<0.05=: Only LVEF was significantly improved in control group (52%±6%vs. 40%±7%,P<0.05). LVEDd and LVEF in treatment group after treatment were significantly better improved than those in control group [(5.8±0.4) mm vs. (6.0±0.2) mm, P<0.05: 58%±13% vs. 52%±6%, p<0.05]. Serum concentrations of immunoglobulin G, A and M obviously descreased after treatment in both treatment group and control group, and serum concentration of immunoglobulin G in treatment group decreased more obviously than that in control group[(9.58±1.14)g/L vs.(10.98±1.16)g/L,P<0.05]. Conclusions It can obtain obvious curative effect when giving a big amount of human gamma globulin to treat patients with peripartum cardiomyopathy. LVEDd, LVEF and immunoglobulin G can be the effective index signs.%目的 探讨应用人血丙种球蛋白治疗产后围产期心肌病的疗效评价.方法 选取浙江省湖州市中心医院确诊的产后围产期心肌病患者49例,分为治疗组和对照组.治疗组在标准化治疗基础上加用人血丙种球蛋白治疗,用法为400 mg/(kg.d)连续静脉注射5d.利用超声心

  18. The hormonal response of older men to sub-maximum aerobic exercise: the effect of training and detraining.

    Science.gov (United States)

    Lovell, Dale I; Cuneo, Ross; Wallace, Jennifer; McLellan, Chris

    2012-04-01

    The hormonal response of 32 older men (70-80years) to a bout of sub-maximum aerobic exercise was examined before, after 16weeks of resistance or aerobic training and again after 4weeks of detraining. Blood samples were obtained at rest and immediately post sub-maximum exercise (30min @ 70% VO(2) max) to determine the concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone (Test), sex hormone-binding globulin (SHBG) and the calculation of free testosterone (FT). Both training groups had significant increases in leg strength and VO(2) max after 16weeks training but leg strength and VO(2) max returned to pre-training levels in the aerobic training and resistance training groups, respectively. During the 20week study there was no change in resting concentrations of any hormones among the three groups. There was no increase in GH, IGF-1 or SHBG immediately post sub-maximum exercise in any of the groups before training, after 16weeks training or after 4weeks detraining. Testosterone and FT increased immediately post sub-maximum exercise within all groups before training, after 16weeks training and after 4weeks detraining with the increase in Test and FT higher after 16weeks of resistance training compared to before training and after 4weeks detraining within the resistance training group. The increased responsiveness of Test and FT after 16weeks of resistance training was lost after 4weeks of detraining. Our results indicate that some physiological and hormonal adaptations gained after 16weeks training are lost after only 4weeks detraining.

  19. Testosterone and metabolic syndrome.

    Science.gov (United States)

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  20. Testosterone and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  1. 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 )

  2. Male patients with terminal renal failure exhibit low serum levels of antimüllerian hormone

    Directory of Open Access Journals (Sweden)

    Dag Eckersten

    2015-02-01

    Full Text Available Male reproductive function is impaired during end-stage renal disease (ESRD. Disturbance of the hypothalamic-pituitary-gonadal axis, and therefore the regulation of sex hormones, is one of the major causes. Our focus was to include antimüllerian hormone (AMH and inhibin B concentrations. Twenty male patients on hemodialysis, median age 40 (26-48 years, were analyzed for follicle-stimulating hormone (FSH, luteinizing hormone (LH, prolactin, sex hormone-binding globulin (SHBG, testosterone, estradiol, AMH and inhibin B levels. We used 144 proven fertile men, median age 32 (19-44 years as a control group and analyzed differences using multiple linear regression. Males with ESRD demonstrated higher mean values for prolactin, 742 versus normal 210 mIE l−1 (95% confidence interval (CI: 60.3, 729, LH, 8.87 versus normal 4.5 IE l−1 (95% CI: 2.75, 6.14, and estradiol 89.7 versus normal 79.0 pmol l−1 (95% CI: −1.31, −0.15. Mean value for AMH was lower, 19.5 versus normal 47.3 pmol l−1 (95% CI: −37.6, −11.6. There were no differences found for FSH, SHBG, inhibin B and testosterone. The most important difference was found for AMH, a marker of Sertoli cell function in the testes, which decreased by close to 60% when compared with controls. Combined with an increase in LH, these findings may indicate a dysfunction of Sertoli cells and an effect on Leydig cells contributing to a potential mechanism of reproductive dysfunction in men with ESRD.

  3. Male patients with terminal renal failure exhibit low serum levels of antimüllerian hormone

    Institute of Scientific and Technical Information of China (English)

    Dag Eckersten; Aleksander Giwercman; Anders Christensson

    2015-01-01

    Male reproductive function is impaired during end‑stage renal disease (ESRD). Disturbance of the hypothalamic‑pituitary‑gonadal axis, and therefore the regulation of sex hormones, is one of the major causes. Our focus was to include antimüllerian hormone (AMH) and inhibin B concentrations. Twenty male patients on hemodialysis, median age 40 (26–48) years, were analyzed for follicle‑stimulating hormone (FSH), luteinizing hormone (LH), prolactin, sex hormone‑binding globulin (SHBG), testosterone, estradiol, AMH and inhibin B levels. We used 144 proven fertile men, median age 32 (19–44) years as a control group and analyzed differences using multiple linear regression. Males with ESRD demonstrated higher mean values for prolactin, 742 versus normal 210 mIE l−1 (95% confidence interval (CI): 60.3, 729), LH, 8.87 versus normal 4.5 IE l−1 (95% CI: 2.75, 6.14), and estradiol 89.7 versus normal 79.0 pmol l−1 (95% CI: −1.31, −0.15). Mean value for AMH was lower, 19.5 versus normal 47.3 pmol l−1 (95% CI: −37.6,−11.6). There were no differences found for FSH, SHBG, inhibin B and testosterone. The most important difference was found for AMH, a marker of Sertoli cell function in the testes, which decreased by close to 60% when compared with controls. Combined with an increase in LH, these findings may indicate a dysfunction of Sertoli cells and an effect on Leydig cells contributing to a potential mechanism of reproductive dysfunction in men with ESRD.

  4. Pharmacokinetics of continuous once-a-week combination 17β-Estradiol/Low- or high-dose levonorgestrel transdermal delivery systems in postmenopausal women.

    Science.gov (United States)

    Karara, Adel H; Harrison, Lester I; Melikian, Armen P; Poola, Nagaraju; Morrison, Dennis; Bourg, Dale; Bourg, Linda; Zurth, Christian

    2014-05-01

    Two open-label, randomized, two-period, crossover studies were performed to determine the safety, delivery rates, and pharmacokinetic properties of a combination estradiol (E2)/levonorgestrel (LNG) transdermal delivery system (TDS). Study 1 enrolled 24 postmenopausal women who received a single TDS containing 4.4 mg E2 and 1.39 mg of LNG (E2/LNG Low) or E2 0.050 mg/24 hours TDS and 0.090 mg LNG oral tablet. Study 2 enrolled 44 postmenopausal women who received either E2/LNG Low or TDS containing 4.4 mg E2 and 2.75 mg LNG (E2/LNG High) weekly for a period of 4 weeks. E2, estrone (E1), LNG, and sex hormone-binding globulin (SHBG) serum concentrations were determined. Overall, both E2/LNG TDS were well tolerated and had excellent adhesion properties. The average daily delivery for E2/LNG Low was 0.045 mg for E2 and 0.0132 mg for LNG. Following weekly delivery of E2/LNG Low or High for 4 weeks, the combination of E2 with two different strengths of LNG did not alter the pharmacokinetic profile of E2. SHBG, total cholesterol, and triglycerides concentrations significantly decreased compared to baseline. Both E2/LNG Low and High TDSs were well tolerated and provided continuous drug delivery over 7 days supporting the benefits of the transdermal route of administration in optimally delivering hormonal therapy.

  5. Associations between brominated flame retardants in house dust and hormone levels in men

    Science.gov (United States)

    Johnson, Paula I.; Stapleton, Heather M.; Mukherjee, Bhramar; Hauser, Russ; Meeker, John D.

    2013-01-01

    Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octaand deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men. PMID:23333513

  6. The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study.

    Science.gov (United States)

    Hart, Roger; Doherty, Dorota A; Frederiksen, Hanne; Keelan, Jeffrey A; Hickey, Martha; Sloboda, Deborah; Pennell, Craig E; Newnham, John P; Skakkebaek, Niels E; Main, Katharina M

    2014-01-01

    We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989-1991, 1377 had antenatal serum stored without thawing at -80 °C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Müllerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography-tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 samples available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche (P=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (P=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) were protective against PCOS in adolescence (P=0.001 and P=0.005 respectively). There were negative associations of MEP with PCO (P=0.022) and of MEP with serum AMH (P=0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.

  7. Evidence that treatment with monophasic oral contraceptive formulations containing ethinylestradiol plus gestodene reduces bone resorption in young women.

    Science.gov (United States)

    Paoletti, A M; Orrù, M; Floris, S; Mannias, M; Vacca, A M; Ajossa, S; Guerriero, S; Melis, G B

    2000-04-01

    The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound (gestodene, GES, 75 microg) but different doses of ethinylestradiol (EE2) (20 or 30 microg) differently influences specific markers of bone resorption (urinary levels of pyridinoline (PYR) and dexoxypyridinoline (D-PYR)). During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women (subjects of the same age group with normal menstrual cycle who did not use contraception). In women taking pills with 20 or 30 microg EE2, the levels of sex hormone-binding globulin (SHBG) significantly increased during treatment in comparison with baseline, whereas in the same time period no changes occurred in control women. These findings suggest that similar to the pill containing 30 microg EE2, the lower dosage of the EE2 pill (20 microg) is also capable of reducing bone resorption. Twenty and 30 microg EE2 pills exert the same biological estrogenic effect. In fact, SHBG levels significantly increased with both pills. However, an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone cannot be excluded. Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects, these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice.

  8. Associations between brominated flame retardants in house dust and hormone levels in men

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Paula I. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Stapleton, Heather M. [Nicholas School of the Environment, Box 90328, Duke University, Durham, NC 27708 (United States); Mukherjee, Bhramar [Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Hauser, Russ [Department of Environmental Health, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115 (United States); Meeker, John D., E-mail: meekerj@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

    2013-02-15

    Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octa- and deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men. - Highlights: ► Brominated flame retardants (BFRs) including PBDEs and alternates were measured. ► Exposure to BFRs is characterized from concentrations in participant vacuum bag dust. ► Exposure to PBDEs and

  9. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B;

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

  10. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen;

    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...... around the phosphorylated residue are important for the binding affinity of ILKAP. We conclude that solid-phase affinity pull-down of proteins from complex mixtures can be applied in phosphoproteomics and systems biology....

  11. 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.

  12. 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.

  13. Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class switch DNA recombination, and somatic hypermutation.

    Science.gov (United States)

    Mai, Thach; Zan, Hong; Zhang, Jinsong; Hawkins, J Seth; Xu, Zhenming; Casali, Paolo

    2010-11-26

    Estrogen enhances antibody and autoantibody responses through yet to be defined mechanisms. It has been suggested that estrogen up-regulates the expression of activation-induced cytosine deaminase (AID), which is critical for antibody class switch DNA recombination (CSR) and somatic hypermutation (SHM), through direct activation of this gene. AID, as we have shown, is induced by the HoxC4 homeodomain transcription factor, which binds to a conserved HoxC4/Oct site in the AICDA/Aicda promoter. Here we show that estrogen-estrogen receptor (ER) complexes do not directly activate the AID gene promoter in B cells undergoing CSR. Rather, they bind to three evolutionarily conserved and cooperative estrogen response elements (EREs) we identified in the HOXC4/HoxC4 promoter. By binding to these EREs, ERs synergized with CD154 or LPS and IL-4 signaling to up-regulate HoxC4 expression, thereby inducing AID and CSR without affecting B cell proliferation or plasmacytoid differentiation. Estrogen administration in vivo significantly potentiated CSR and SHM in the specific antibody response to the 4-hydroxy-3-nitrophenylacetyl hapten conjugated with chicken γ-globulin. Ablation of HoxC4 (HoxC4(-/-)) abrogated the estrogen-mediated enhancement of AID gene expression and decreased CSR and SHM. Thus, estrogen enhances AID expression by activating the HOXC4/HoxC4 promoter and inducing the critical AID gene activator, HoxC4.

  14. Engineering RNA-binding proteins for biology

    OpenAIRE

    Chen,Yu; Varani, Gabriele

    2013-01-01

    RNA-binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA-binding proteins has shown that RNA-binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA-binding proteins with tailored sequenc...

  15. Feature-Based Binding and Phase Theory

    Science.gov (United States)

    Antonenko, Andrei

    2012-01-01

    Current theories of binding cannot provide a uniform account for many facts associated with the distribution of anaphors, such as long-distance binding effects and the subject-orientation of monomorphemic anaphors. Further, traditional binding theory is incompatible with minimalist assumptions. In this dissertation I propose an analysis of…

  16. Clinical Analysis of Thrombocytopenic Purpura Given Different Measurement of Gamma Globulin Combined with Prednisone%血小板减少性紫癜给予不同剂量丙种球蛋白联合强的松治疗的临床分析

    Institute of Scientific and Technical Information of China (English)

    何飞

    2016-01-01

    目的:观察并探讨血小板减少性紫癜给予不同剂量丙种球蛋白联合强的松治疗的临床疗效分析。方法:选取2013年12月至2015年12月来我院治疗的90例血小板减少性紫癜患儿进行回顾性分析,随机分成两组:给予观察组患儿静注400mg/(kg·d)丙种球蛋白,治疗5d后联合强的松2mg/(kg·d)(每日3次),30d为一疗程;给予观察组患儿静注200mg/(kg·d)丙种球蛋白,联合强的松的用量及疗程均为观察组相同。观察两组患者在经过各自治疗后的血小板上升、达峰值以及止血时间对比。结果:经比较得知,两组患者在血小板上升时间、止血时间以及临床疗效上无明显差异(P<0.05),观察组在达峰值时间上要少于对照组,两组患者存在显著差异(P<0.05),具有统计学意义。结论:丙种球蛋白联合强的松治疗临床血小板减少性紫癜的临床疗效明确,不良反应少,大剂量丙种球蛋白联合强的松的达峰值时间更短,小剂量丙种球蛋白联合强的松的临床疗效基本等同于大剂量,疗效可靠。%Objective: To observe and evaluate the effect of thrombocytopenic purpura given different measurement of gamma globulin combined with methylprednisolone therapy.Methods: 90 cases of platelet from December 2013 to December 2015 in our hospital for treatment of idiopathic thrombocytopenic purpura were retrospectively analyzed, were randomly divided into two groups. The observation group were given intravenous injection of 400mg/kg·d gamma globulin (1 times daily), for 5d 2mg/kg·d combined with prednisone (3 times daily), 40d for a course of treatment. Observation group were given intravenous injection of 200mg/kg·d globulin (1 times daily), dosage and treatment combined with prednisone were same as observation group. Patients in two groups were observed on the rise after the treatment of platelets, peak and hemostasis time comparison. Results: By comparison

  17. Isolamento da globulina majoritária, digestibilidade in vivo e in vitro das proteínas do tremoço-doce (Lupinus albus L., var. Multolupa Isolation of major globulin, in vivo and in vitro digestibility of proteins from sweet lupin (Lupinus albus L. var. Multolupa

    Directory of Open Access Journals (Sweden)

    Valdir Augusto Neves

    2006-12-01

    Full Text Available Os objetivos do trabalho foram isolar, purificar e estudar algumas propriedades da fração globulina majoritária de tremoço-doce, var. Multolupa; assim como avaliar as características de digestibilidade da farinha e frações isoladas. As frações protéicas foram separadas por fracionamento diferencial com uso de diferentes solventes. A globulina majoritária de tremoço-doce foi isolada, purificada por cromatografia em Q-Sepharose, revelando um único pico de proteína. Apresentou um peso molecular de 162,5 ± 10,0 kDa, determinado por cromatografia em Sephacryl S-300, e subunidades entre 20-70 kDa em PAGE-SDS. A solubilidade em função do pH e concentrações de NaCl revelaram curva típica dessa fração. A digestibilidade da proteína da farinha e das frações albumina, globulina e glutelina foi avaliada por experimentos in vitro e in vivo e se revelou alta para a fração globulina, seguida pela glutelina, albumina e farinha. A digestibilidade in vivo da fração globulina, tanto aparente quanto verdadeira, não diferiu significativamente daquela determinada para a caseína. Apesar da alta digestibilidade da fração majoritária e frações protéicas, a utilização como única fonte de proteína nas dietas revelou valores baixos de RPLR (razão protéica líquida relativa, indicando ser insuficiente para sustentar o crescimento dos animais, comparativamente à caseína.The aim of the present work was to isolate, purify and study some properties of the major globulin fraction from sweet lupin, var. Multolupa; as well as to evaluate the digestibility features of flour and isolated fractions. The protein fractions were separated by differential fractionation with different solvents. The lupin major globulin was isolated, purified by Q-Sepharose chromatography when it showed only one protein peak. The major protein presented a molecular weight of 162.5 ± 10.0 kDa, determined on Sephacryl S-300 chromatography; and subunits between 20

  18. Synthetic heparin-binding factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  19. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper

    2015-01-01

    phosphatases. The main objective of this study was to quantify the binding affinity of different enzymes that are involved in this cyclic process. We established a protocol to quickly, reproducibly, and quantitatively measure the binding of the enzymes to glucans utilizing Affinity Gel Electrophoresis (AGE...... glucan phosphatases showed similar affinities for the short oligosaccharide β-cyclodextrin. We performed structure-guided mutagenesis to define the mechanism of these differences. We found that the carbohydrate binding module (CBM) domain provided a stronger binding affinity compared to surface binding...

  20. Statistics for Transcription Factor Binding Sites

    OpenAIRE

    2008-01-01

    Transcription factors (TFs) play a key role in gene regulation. They interact with specific binding sites or motifs on the DNA sequence and regulate expression of genes downstream of these binding sites. In silico prediction of potential binding of a TF to a binding site is an important task in computational biology. From a statistical point of view, the DNA sequence is a long text consisting of four different letters ('A','C','G', and 'T'). The binding of a TF to the sequence corresponds to ...

  1. Caracterização e hidrólise in vitro da globulina principal de grão-de-bico (Cicer arietinum L., var. IAC-Marrocos Characterization and in vitro tryptic hydrolysis of the major globulin from chickpea (Cicer arietinum L.

    Directory of Open Access Journals (Sweden)

    Valdir A. Neves

    2004-03-01

    Full Text Available No presente estudo procedeu-se ao isolamento e caracterização da fração globulina majoritária (11 S de grão-de-bico, var. IAC-Marrocos. A globulina majoritária extraída foi isolada por cromatografia de filtração em gel e de troca-iônica mostrando apenas uma banda de proteína na eletroforese em gel de poliacrilamida. A globulina majoritária, após passagem em coluna de Sephadex, revelou duas bandas protéicas de 55 e 52,5kDa e três bandas menores em gel de poliacrilamida dodecilsulfato de sódio. Na presença de 2-mercaptoetanol 6 polipeptídios na faixa de 18 a 42kDa foram revelados na eletroforese. A globulina isolada foi submetida à ação da tripsina e quimotripsina onde a forma nativa mostrou-se resistente à ação enzimática enquanto o aquecimento (96 e 121°C/15min não foi suficiente para aumentar a susceptibilidade à hidrólise, significativamente. Adição de NaCl 0,3M levou a um aumento da estabilidade estrutural com menor susceptibilidade à digestão proteolítica, fato em parte perdido com o aquecimento. As hidrólises foram acompanhadas por eletroforese em gel de poliacrilamida dodecilsulfato de sódio.The isolation and characterization of the major globulin fraction (11 S from Chickpea, vc IAC-Marrocos, were evaluated. The major globulin was extracted, isolated by gel filtration and ion-exchange chromatography showing only one protein band on PAGE. The globulin, after Sephadex elution, revealed two protein bands of 55 and 52.5kDa and three minor bands on SDS-PAGE. In the presence of 2-mercaptoethanol six polypeptides were revealed on SDS-PAGE in the range of 18 to 42kDa. The isolated native globulin shown to be resistant to trypsin and chymotrypsin however heating at 96 and 121ºC/15min was not sufficient to increase the hydrolysis significantly. The proteolytic susceptibility of the enzymes was reduced by 0.3M NaCl addition at the assay. The salt concentration was sufficient to stabilize the native protein

  2. A Study of Bone Mineral Density and Its Determinants in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Ameya Joshi

    2013-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM has been inconsistently associated with low bone mineral density (BMD and increased fracture risk. 86 consecutive T1DM cases and 140 unrelated age and sex matched healthy nondiabetic controls were included in the study. After history and examination, BMD and body composition were assessed by dual energy X-ray absorptiometry (DXA. Serum samples were analyzed for calcium, phosphorus, albumin, creatinine, alkaline phosphatase, 25 (OH vitamin D3, intact parathormone (PTH levels (both cases and controls and HbA1c, antimicrosomal and IgA tissue transglutaminase (IgA TTG antibodies, cortisol, follicle stimulating hormone (FSH, testosterone, sex hormone binding globulin (SHBG, tetraiodothyronine (T4, thyroid stimulating hormone (TSH, growth hormone (GH, insulin-like growth factor-1 (IGF-1, and insulin-like growth factor binding protein 3 (IGFBP3 (cases only. T1DM cases had a lower BMD as compared to controls at both total body (TB and lumbar spine (LS (. Patients with celiac autoimmunity (CA had significantly, lower BMD as compared to age, sex, and body mass index (BMI matched T1DM controls. Linear regression analysis showed that low BMD in T1DM patients was associated with poor glycaemic control, lower IGF-1 levels, less physical activity (in total population as well as in male and female subgroups, and lower body fat percentage (in females and higher alkaline phosphatase level (in males (.

  3. Indices of Free Testosterone And Hyperandrogenemia in Relation To Hirsutism in Middle Aged Egyptian females

    Directory of Open Access Journals (Sweden)

    *Kandil H.T., * Hassan Z.A., * Abaza D.M. ** Abd. El Fattah . A.M

    2003-12-01

    Full Text Available Hirsutism is an androgen excess related disorder that commonly affects women causing a variety of negative metabolic disturbances. Early and accurate diagnoses of androgen over-production or hypersensitivity to normal circulating androgen have an important implication for treatment and follow up of patients. The aim of this work is to study the validity of hyperandrogonemic index (HAI and index of free testosterone (IFT in, diagnosis of hirsute Egyptian women, and its correlation to hair score as a clinical marker for hirsutism. Twenty-four hirsute women aged 19-32 y's, median (24.25 ± 4.3 were studied. Ten age matched nonhirsute females, were studied as controls. Patients and control were subjected to the following, full history and clinical examination. Biochemical and hormonal parameters were measured, fasting blood sugar (FBLS, 2 hours post prandial blood sugar (2h pp BL. S, serum total testosterone (TT, free testosterone (FT, dihydroepiandrosterone (DHEA, Dihydroepiandrosterone sulphate (DHEAS androstenedion (ADION, prolactin (PL and sex hormone binding globulin (SHBG. Index of free testosterone (IFT and index of hyperandrogenemia (IHA were calculated. Results showed significant higher BMI (P< 0.009, 2hrs PPBLS. (P< 0.001, TT (P< 0.005, FT (P< 0.000, SHBG (P< 0.02 and (ADION (P< 0.000 in hirsute females compared to controls. Hair score was positively correlated with IFT only while it was not correlated with all of the measured hormones. FT was positively correlated with BMI (P< 0.004, FBLS (P< 0.001 and 2hrs PPBL.S (P< 0.000. While TT was positively correlated with BMI (P< 0.001. Androstenedion was positively correlated with systolic BL.P (P< 0.000, diastolic BL.P (P< 0.02, FBL.S (P< 0.001 and 2hrs PPBL.S (P< 0.000. IFT was positively correlated with hair score (P< 0.05, BMI (P< 0.01, systolic BL.P (P< 0.004, FBL.S (P< 0.001 and 2hrs PPBL.S (P< 0.01. SHBG was negatively correlated with systolic BL.P (P< 0.04, FBL.S (P< 0.05 and 2hrs PPBL

  4. Attenuation of mild hyperandrogenic activity in postpubertal acne by a triphasic oral contraceptive containing low doses of ethynyl estradiol and d,l-norgestrel.

    Science.gov (United States)

    Lemay, A; Dewailly, S D; Grenier, R; Huard, J

    1990-07-01

    The effect of a low dose triphasic oral contraceptive (OC) was evaluated during a 6-month treatment period in 41 patients (mean age, 25.4 +/- 0.7 yr) who had grade I-IV postpubertal acne and normal menses. The OC contained three dose levels of ethynyl estradiol and dl-norgestrel. Acne lesions were assessed, and serum androgen levels were measured during a control cycle and between days 17-21 of treatment cycles 1, 2, 3, and 6. Four patients dropped out after 3 months of treatment. Acne was significantly improved after the first OC cycle. After six cycles, the number of comedones had decreased by 79.6 +/- 3.2% (range, 50-100%) in 69.4% of the patients. Mean baseline levels of testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were in the upper third of the normal range, with elevated individual values in 18.9%, 36.5%, and 26.8% of the women, respectively. Mean baseline levels of androstenedione, free testosterone (T), and 3 alpha-androstanediol glucuronide (3 alpha-diol-G) were above the normal range, with elevated individual values in 51.2%, 75.0%, and 85.4% of the patients, respectively. Sex hormone-binding globulin (SHBG) levels were below the normal range in 26.8% of the cases. At the end of the first OC cycle, there was a significant (P less than 0.01) decrease in all androgen precursors and a 2-fold increase in SHBG. Androstenedione and free T decreased into the normal range during OC intake. Serum 3 alpha-diol-G levels remained elevated, but had decreased by 34.5% at cycle 6 (P less than 0.05). These results show that the triphasic OC has significantly improved acne in postpubertal women for whom acne was the main manifestation of mild hyperandrogenic activity. The improvement in acne corresponded to a decrease in adrenal/ovarian androgens and free T, which led to a decreased metabolism to 3 alpha-diol-G, presumably by the sebaceous glands. The increase in SHBG is considered an estrogenic effect, and the triphasic formulation containing

  5. DBD2BS: connecting a DNA-binding protein with its binding sites

    OpenAIRE

    2012-01-01

    By binding to short and highly conserved DNA sequences in genomes, DNA-binding proteins initiate, enhance or repress biological processes. Accurately identifying such binding sites, often represented by position weight matrices (PWMs), is an important step in understanding the control mechanisms of cells. When given coordinates of a DNA-binding domain (DBD) bound with DNA, a potential function can be used to estimate the change of binding affinity after base substitutions, where the changes c...

  6. Infinite sets and double binds.

    Science.gov (United States)

    Arden, M

    1984-01-01

    There have been many attempts to bring psychoanalytical theory up to date. This paper approaches the problem by discussing the work of Gregory Bateson and Ignacio Matte-Blanco, with particular reference to the use made by these authors of Russell's theory of logical types. Bateson's theory of the double bind and Matte-Blanco's bilogic are both based on concepts of logical typing. It is argued that the two theories can be linked by the idea that neurotic symptoms are based on category errors in thinking. Clinical material is presented from the analysis of a middle-aged woman. The intention is to demonstrate that the process of making interpretations can be thought of as revealing errors in thinking. Changes in the patient's inner world are then seen to be the result of clarifying childhood experiences based on category errors. Matte-Blanco's theory of bilogic and infinite experiences is a re-evaluation of the place of the primary process in mental life. It is suggested that a combination of bilogic and double bind theory provides a possibility of reformulating psychoanalytical theory.

  7. Total body irradiation and cyclophosphamide plus antithymocyte globulin regimen is well tolerated and promotes stable engraftment as a preparative regimen before T cell-replete haploidentical transplantation for acute leukemia.

    Science.gov (United States)

    Fu, Haixia; Xu, Lanping; Liu, Daihong; Liu, Kaiyan; Zhang, Xiaohui; Chen, Huan; Chen, Yuhong; Han, Wei; Wang, Yu; Wang, Jingzhi; Wang, Fengrong; Huang, Xiaojun

    2014-08-01

    We compared total body irradiation (TBI, 700 cGy)/cyclophosphamide (Cy, 3.6 g/m(2))/simustine (250 mg/m(2)) plus antithymocyte globulin (ATG) (TBI/Cy plus ATG) with cytarabine (8 g/m(2))/i.v. busulfan (Bu, 9.6 mg/kg)/Cy (3.6 g/m(2))/simustine (250 mg/m(2)) plus ATG (modified Bu/Cy plus ATG) as preparative therapy in T cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive patients using TBI/Cy plus ATG regimen for T cell-replete haplo-HSCT (TBI group) at our center were eligible, which contained 28 high-risk and 10 standard-risk patients. A nested case-control study was designed. Seventy-seven patients using modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1 to 3:1 ratio matching for age, disease and status, year of HSCT (±2 years), and length of follow-up. Only 1 graft failure occurred in the TBI group. The incidence and time of neutrophil and platelet engraftment were comparable between the 2 groups. Severe grades III/IV graft-versus-host disease was observed in 13.4% of Bu group and only 2.6% of TBI group (P = .083). More toxicity of the liver (37.7% versus 10.5%; P = .002) and more hemorrhagic cystitis occurred in the Bu group (49.3% versus 23.7%, P = .008). Diarrhea was more common in the TBI group (44.7% versus 22.1%; P = .031). No significant differences were found in the 2-year incidences of relapse (26.5% for TBI group versus 32.3% for Bu group, P = .742), 1-year transplant-related mortality (12.6% versus 16.2%, P = .862), 2-year overall survival (60.2% versus 57.0%, P = .937), and 2-year incidence of disease-free survival (57.9% versus 56.6%, P = .845) between the 2 groups. We conclude that the TBI/Cy plus ATG regimen seems to be feasible in T cell-replete haplo-HSCT, which promotes stable engraftment and a lower incidence of liver toxicity and hemorrhagic cystitis. However, longer follow-up is necessary to

  8. Surveys of serum reproductive hormone levels and the prevalence rates of late onset of hypogonadism in Chinese aging males

    Institute of Scientific and Technical Information of China (English)

    Zhou Shan-jie; Li Xian-kun; Lu Wen-hong; Liang Xiao-wei; Yuan Dong; Li Hong; Gu Yi-qun; Zhang Bao-long; Ji Yu-dang; Wang Can-gang

    2011-01-01

    Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism (LOH) in males in Chinese middle and aging males.Methods:Subjects included 1,498 men aged 40 to 69 from a county,and the serum reproductive hormones of 434 subjects were measured and calculated.In addition,the prevalence rates of LOH were analyzed by cut-off point of total testosterone (TT) and free testosterone (cFT),and screening scales (a questionnaire of androgen deficiency in the aging males (ADAM) and a scale of aging males' symptoms (AMS)).TT,cFT,bio-available testosterone (Bio-T),luteinizing hormone (LH),sex hormone binding globulin (SHBG),testosterone secretion index (TSI),free testosterone index (FTI),the positive rates of LOH screening,androgen deficiency rates and the clinical prevalence rates of LOH were measured or calculated.Results:The serum TT levels did not change significantly with male aging while serum LH and SHBG levels gradually increased,but cFT,Bio-T,TSI and FTI levels gradually decreased with male aging.There was very significant difference in other six parameters of reproductive hormones (P<0.01),except for serum TT among the four age brackets(P>0.05).There was no correlation between serum TT levels and aging,LH levels(P>0.05).However,there was significantly a positive correlation between serum LH,SHBG and age (P<0.01),while there were negative correlation between cFT,Bio-T,TSI,FTI and age,LH levels (P<0.01).Moreover,SHBG level was positively correlated with LH level (P<0.01).Utilizing the Questionnaire of ADAM and AMS to screen subjects aged 40 to 69 years,mean positive rates of LOH screening were 80.77% and 32.34% respectively.Mean androgen deficiency rates were 14.02% and 43.69%by using TT and cFT cut-off point.In addition,mean LOH clinical prevalence rates of subjects on positive questionnaire results were 37.85% and 15.42

  9. Estudo da atividade hormonal de mulheres tratadas com tamoxifeno no menacme A study of hormone activity in premenopausal tamoxifen-treated women

    Directory of Open Access Journals (Sweden)

    Júlio Roberto de M. Bernardes Jr

    1998-10-01

    Full Text Available Objetivos: Avaliar o efeito do tamoxifeno nos níveis séricos de progesterona, estradiol, prolactina, hormônio luteinizante (LH, hormônio folículo-estimulante (FSH e da globulina transportadora dos hormônios sexuais (SHBG, quando administrado a mulheres no menacme, nas doses de 10 e 20 mg/dia por 22 dias. Métodos: Estudo aleatório e duplo-cego. Foram incluídas 43 mulheres pré-menopausadas e eumenorréicas. Foram distribuídas em 3 grupos: A (N = 15; placebo, B (N = 15; 10 mg/dia e C (N = 13; 20 mg/dia. Foram realizadas duas dosagens hormonais, sendo a primeira no 22º dia do ciclo menstrual que precedeu o uso da droga e a segunda após 22 dias de uso do medicamento. Utilizaram-se os testes de Levene e t-pareado para avaliar a homogeneidade da amostra e a variação das dosagens hormonais, respectivamente. Resultados: As concentrações séricas de estradiol, progesterona e SHBG aumentaram significantemente nos grupos B e C. No grupo C, observou-se ainda elevação no nível sérico de FSH (p Purpose: to evaluate the effects of tamoxifen (TAM on plasma levels of estradiol, progesterone, prolactin, luteinizing hormone (LH, follicle-stimulating hormone (FSH and steroid hormone-binding globulin (SHBG when given to premenopausal women in the doses of 10 and 20 mg/day for 22 days. Patients and Methods: a randomized double-blind study was performed with 43 premenopausal eumenorrheic women. The patients were divided into three groups: A (N = 15, placebo; B (N = 15, TAM 10 mg/day and C (N = 13, 20 mg/day. They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Two hormone determinations were performed, both on the 22nd day of the menstrual cycle: the first in the cycle that preceded the use of the drug and the second, in the following cycle, after 22 days of using the medication. We used the Levine and Student tests in order to evaluate the homogeneity of the sample and the variation of the hormone

  10. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  11. Gamma Oscillations and Visual Binding

    Science.gov (United States)

    Robinson, Peter A.; Kim, Jong Won

    2006-03-01

    At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

  12. DNA binding hydroxyl radical probes

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Vicky J.; Konigsfeld, Katie M.; Aguilera, Joe A. [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States); Milligan, Jamie R., E-mail: jmilligan@ucsd.edu [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States)

    2012-01-15

    The hydroxyl radical is the primary mediator of DNA damage by the indirect effect of ionizing radiation. It is a powerful oxidizing agent produced by the radiolysis of water and is responsible for a significant fraction of the DNA damage associated with ionizing radiation. There is therefore an interest in the development of sensitive assays for its detection. The hydroxylation of aromatic groups to produce fluorescent products has been used for this purpose. We have examined four different chromophores, which produce fluorescent products when hydroxylated. Of these, the coumarin system suffers from the fewest disadvantages. We have therefore examined its behavior when linked to a cationic peptide ligand designed to bind strongly to DNA. - Highlights: > Examined four aromatic groups as a means to detect hydroxyl radicals by fluorescence. > Coumarin system suffers from the fewest disadvantages. > Characterized its reactivity when linked to a hexa-arginine peptide.

  13. Why tight-binding theory?

    Science.gov (United States)

    Harrison, Walter A.

    2002-12-01

    In the context of computational physics other methods are more accurate, but tight-binding theory allows very direct physical interpretation and is simple enough to allow much more realistic treatments beyond the local density approximation. We address several important questions of this last category: How does the gap enhancement from Coulomb correlations vary from material to material? Should the enhanced gap be used for calculating the dielectric constant? For calculating the effective mass in k-dot-p theory? How valid is the scissors approximation? How does one line up bands at an interface? How should we match the envelope function at interfaces in effective-mass theory? Why can the resulting quantum-well states seem to violate the uncertainty principle? How should f-shell electrons be treated when they are intermediate between band-like and core-like? The answers to all of these questions are given and discussed.

  14. 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

  15. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.;

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit......Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length...... and composition. A large set of available synthetic peptides (n=127) was tested for binding to calreticulin and the results analysed by multivariate data analysis. The parameter that correlated best with binding was hydrophobicity while beta-turn potential disfavoured binding. Only hydrophobic peptides longer...... a peptide-binding specificity for hydrophobic sequences and delineate the fine specificity of calreticulin for hydrophobic amino acid residues....

  16. The helical structure of DNA facilitates binding

    Science.gov (United States)

    Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-09-01

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

  17. 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...

  18. 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.

  19. 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.

  20. Lead-Binding Proteins: A Review

    Directory of Open Access Journals (Sweden)

    Harvey C. Gonick

    2011-01-01

    Full Text Available Lead-binding proteins are a series of low molecular weight proteins, analogous to metallothionein, which segregate lead in a nontoxic form in several organs (kidney, brain, lung, liver, erythrocyte. Whether the lead-binding proteins in every organ are identical or different remains to be determined. In the erythrocyte, delta-aminolevulinic acid dehydratase (ALAD isoforms have commanded the greatest attention as proteins and enzymes that are both inhibitable and inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD-1, appears to bind lead in a less toxic form. What may be of greater significance is that a low molecular weight lead-binding protein, approximately 10 kDa, appears in the erythrocyte once blood lead exceeds 39 μg/dL and eventually surpasses the lead-binding capacity of ALAD. In brain and kidney of environmentally exposed humans and animals, a cytoplasmic lead-binding protein has been identified as thymosin β4, a 5 kDa protein. In kidney, but not brain, another lead-binding protein has been identified as acyl-CoA binding protein, a 9 kDa protein. Each of these proteins, when coincubated with liver ALAD and titrated with lead, diminishes the inhibition of ALAD by lead, verifying their ability to segregate lead in a nontoxic form.

  1. 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...

  2. 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.

  3. 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.

  4. Tissue specificity of endothelin binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bolger, G.T.; Liard, F.; Krogsrud, R.; Thibeault, D.; Jaramillo, J. (BioMega, Inc., Laval, Quebec (Canada))

    1990-09-01

    A measurement was made of the binding of 125I-labeled endothelin (125I-ET) to crude membrane fractions prepared from rat aorta, atrium, ventricle, portal vein, trachea, lung parenchyma, vas deferens, ileum, bladder, and guinea-pig taenia coli and lung parenchyma. Scatchard analysis of 125I-ET binding in all tissues indicated binding to a single class of saturable sites. The affinity and density of 125I-ET binding sites varied between tissues. The Kd of 125I-ET binding was approximately 0.5 nM for rat aorta, trachea, lung parenchyma, ventricle, bladder, and vas deferens, and guinea-pig taenia coli and lung parenchyma, 1.8 nM for rat portal vein and atrium, and 3.3 nM for ileum. The Bmax of 125I-ET binding had the following rank order of density in rat tissues: trachea greater than lung parenchyma = vas deferens much greater than aorta = portal vein = atrium greater than bladder greater than ventricle = ileum. The properties of 125I-ET endothelin binding were characterized in rat ventricular membranes. 125I-ET binding was time dependent, reaching a maximum within 45-60 min at 25 degrees C. The calculated microassociation constant was 9.67 x 10(5) s-1 M-1. Only 15-20% of 125I-ET dissociated from its binding site even when dissociation was studied as long as 3 h. Preincubation of ventricular membranes with ET prevented binding of 125I-ET. 125I-ET binding was destroyed by boiling of ventricular membranes and was temperature, pH, and cation (Ca2+, Mg2+, and Na+) dependent.

  5. Binding of (/sup 3/H)imipramine to human platelet membranes with compensation for saturable binding to filters and its implication for binding studies with brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, O.M.; Wood, K.M.; Williams, D.C.

    1984-08-01

    Apparent specific binding of (/sup 3/H)imipramine to human platelet membranes at high concentrations of imipramine showed deviation from that expected of a single binding site, a result consistent with a low-affinity binding site. The deviation was due to displaceable, saturable binding to the glass fibre filters used in the assays. Imipramine, chloripramine, desipramine, and fluoxetine inhibited binding to filters whereas 5-hydroxytryptamine and ethanol were ineffective. Experimental conditions were developed that eliminated filter binding, allowing assay of high- and low-affinity binding to membranes. Failure to correct for filter binding may lead to overestimation of binding parameters, Bmax and KD for high-affinity binding to membranes, and may also be misinterpreted as indicating a low-affinity binding component in both platelet and brain membranes. Low-affinity binding (KD less than 2 microM) of imipramine to human platelet membranes was demonstrated and its significance discussed.

  6. Binding Principle for Long-Distance Anaphors.

    Science.gov (United States)

    Choi, Dong-Ik

    1997-01-01

    An analysis of long-distance anaphora, a binding phenomenon in which reflexives find their antecedents outside their local domain, is presented, using data from English, Chinese, Japanese, Korean, Russian, Icelandic, and Italian. It is found that no approach deals with long-distance anaphors exclusively and elegantly. The binding domain…

  7. Binding of anandamide to bovine serum albumin

    DEFF Research Database (Denmark)

    Bojesen, I.N.; Hansen, Harald S.

    2003-01-01

    The endocannabinoid anandamide is of lipid nature and may thus bind to albumin in the vascular system, as do fatty acids. The knowledge of the free water-phase concentration of anandamide is essential for the investigations of its transfer from the binding protein to cellular membranes, because...

  8. Triazatriangulene as binding group for molecular electronics

    DEFF Research Database (Denmark)

    Wei, Zhongming; Wang, Xintai; Borges, Anders

    2014-01-01

    The triazatriangulene (TATA) ring system was investigated as a binding group for tunnel junctions of molecular wires on gold surfaces. Self-assembled monolayers (SAMs) of TATA platforms with three different lengths of phenylene wires were fabricated, and their electrical conductance was recorded ...... with its high stability and directionality make this binding group very attractive for molecular electronic measurements and devices. (Figure Presented)....

  9. 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...

  10. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  11. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  12. Anthropometric Measurements, Serum Reproductive Hormonal Levels and Sexual Development among Boys in the Rural Western Cape, South Africa

    Directory of Open Access Journals (Sweden)

    Jun Mao

    2016-11-01

    Full Text Available Data on growth and sexual maturation among boys from the rural Western Cape in South Africa is limited. A cross-sectional study of 269 school boys was conducted testing for serum luteinizing hormone (LH, follicle stimulating hormone (FSH, testosterone, sex hormone binding globulin (SHBG and estradiol (E2; height, weight and body mass index (BMI; sexual maturity (using Tanner Stages and a questionnaire (demographic and medical history. The median age at pubertal onset (Tanner Stage 2 and Tanner Stage 5 was 11.6 and 14.7 years, respectively. The median testicular volume was 5.5 mL at Tanner Stage 2 increasing from 2.5 mL at Tanner Stage 1 to 14.7 mL at Tanner Stage 5. Height and weight measurements were <25th & 50th percentile references at Tanner Stages 1–3. Controlling for confounders, serum FSH and LH increased (p < 0.05 from Tanner Stage 1 to 4 (by 4.1 and 3 mL respectively, and serum testosterone and estradiol increased after Tanner Stage 2 (by 12.7 nmol/L and 59.5 pmol/L respectively. These results indicate some delays in pubertal development of boys in the rural Western Cape when compared to boys from other settings possibly due to nutritional, socio-economic and environmental exposures. Changes in serum hormone levels were consistent with other populations. Initiatives to improve nutrition amongst Western Cape rural communities are recommended.

  13. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene

    2014-01-01

    and predictive value of PSA in HIV+ men. METHODS: Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count...... at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed....../L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5-1.4) and 0.2 (0.2-0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.7-12.9) and 5.4 (1.7-17.4)]. Elevated tPSA values in cases were...

  14. Association entre les hormones sexuelles, les marqueurs de remodelage osseux et la densité minérale osseuse chez des femmes ménopausées d'origine marocaine (étude transversale)

    Science.gov (United States)

    El Maataoui, Aissam; Biaz, Asmae; El Boukhrissi, Fatima; El Machtani, Si; Dami, Abdellah; Bouhsain, Sanae; Bamou, Youssef; El Maghraoui, Abdellah; Ouzzif, Zhor

    2015-01-01

    Introduction Le présent travail se propose d’étudier la relation entre les hormones sexuelles, notamment l’œstradiol et l'indice de l’œstradiol libre, le sulfate de déhydroépiandrosterone et la sex hormone binding globulin, les marqueurs de remodelage osseux et la densité minérale osseuse chez une population de femmes marocaine ménopausées. Méthodes Il s'agit d'une étude transversale, menée sur une période de 6 mois d'octobre 2012 à fin avril 2013 et ayant fait participer deux cent deux (202). Résultats L’œstradiol et l'indice d’œstradiol libre (IEL) ont montré une corrélation négative respectivement à l'ostéocalcine (OC), à la crosslaps (β-CTX) et l'OC (ptravail montre que l'augmentation de l’âge et la diminution de l’œstradiol libre expliquent la diminution de la DMO au niveau du col du fémur, alors que l'augmentation du taux sérique de la SHBG et la diminution du poids expliquent la diminution de la DMO au rachis lombaire. PMID:26848353

  15. Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS

    Directory of Open Access Journals (Sweden)

    Kushner Harvey

    2011-11-01

    Full Text Available Abstract Background Recent evidence suggests that there may be a bidirectional, physiological link between hypogonadism and metabolic syndrome (MetS, and testosterone replacement therapy (TRT has been shown to improve some symptoms of MetS in small patient populations. We examined the effect of 12 months of TRT on MetS components in a large cohort of hypogonadal men. Methods Data were obtained from TRiUS (Testim® Registry in the United States, a 12-month, multicenter, prospective observational registry (N = 849 of hypogonadal men prescribed Testim 1% testosterone gel (5-10 g/day. Data analyzed included age, total testosterone (TT, free testosterone (FT, sex hormone-binding globulin (SHBG, and MetS components: waist circumference, blood pressure, fasting blood glucose, plasma triglycerides, and HDL cholesterol. Results Of evaluable patients (581/849 at baseline, 37% were MetS+ (n = 213 and 63% were MetS- (n = 368. MetS+ patients had significantly lower TT (p Conclusion Hypogonadal MetS+ patients were more likely than their MetS- counterparts to have lower baseline TT levels and present with more comorbid conditions. MetS+ patients and those in the lowest TT quartile showed improvement in some metabolic syndrome components after 12 months of TRT. While it is currently unclear if further cardiometabolic benefit can be seen with longer TRT use in this population, testing for low testosterone may be warranted in MetS+ men with hypogonadal symptoms.

  16. Prostaglandin treatment is associated with a withdrawal of progesterone and androgen at the receptor level in the uterine cervix

    Directory of Open Access Journals (Sweden)

    Ekman-Ordeberg Gunvor

    2009-10-01

    Full Text Available Abstract Treatment with prostaglandin(PG-E2 is clinically efficient for cervical priming. The aim of this study was to evaluate the impact of PG-E2 on the expression of the progesterone (PR, androgen (AR and glucocorticoid (GR receptors in human uterine cervix in prolonged pregnancy. The study groups were postterm nulliparous women with unripe cervices undergoing cervical priming with PG-E2 before labor induction. Responders (n = 12 who delivered vaginally were compared with non-responders (n = 10, who underwent cesarean section due to failure to progress to the active phase of labor. Controls (n = 18 with vaginal partus at a normal gestational age served as a reference group. Cervical levels of PR-A and PR- B isoforms, AR and GR, serum levels of their ligands and sex hormone-binding globulin (SHBG were quantified. The responder group displayed lower total PR-AB and AR protein levels as compared to non-responders, and lower PR-B and AR protein levels as compared to controls. In addition, the PR mRNA level was lower in responders as compared to non-responders. The GR protein level did not differ between the groups. We conclude that successful PG-E2 priming was followed by a progesterone and androgen withdrawal at the receptor level in the uterine cervix.

  17. Anthropometric Measurements, Serum Reproductive Hormonal Levels and Sexual Development among Boys in the Rural Western Cape, South Africa.

    Science.gov (United States)

    Mao, Jun; Dalvie, Mohamed Aqiel

    2016-11-29

    Data on growth and sexual maturation among boys from the rural Western Cape in South Africa is limited. A cross-sectional study of 269 school boys was conducted testing for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and estradiol (E2); height, weight and body mass index (BMI); sexual maturity (using Tanner Stages) and a questionnaire (demographic and medical history). The median age at pubertal onset (Tanner Stage 2) and Tanner Stage 5 was 11.6 and 14.7 years, respectively. The median testicular volume was 5.5 mL at Tanner Stage 2 increasing from 2.5 mL at Tanner Stage 1 to 14.7 mL at Tanner Stage 5. Height and weight measurements were development of boys in the rural Western Cape when compared to boys from other settings possibly due to nutritional, socio-economic and environmental exposures. Changes in serum hormone levels were consistent with other populations. Initiatives to improve nutrition amongst Western Cape rural communities are recommended.

  18. Current insights into gonadotropic pituitary function in the polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    JacklyneSilvaBarbosa; EvelynBarzotto daSilva; Sebastião Freitas de Medeiros

    2014-01-01

    Objective:To assess the gonadotrope cell function in patients with polycystic ovary syndrome(PCOS). Methods:This study included42 patients with polycystic ovary syndrome, aged26.6±5.9 years, and13 eumenorrheic controls, aged30.1±4.6 years.Gonadotropins, sex steroids, sex hormone binding globulin(SHBG), cortisol, thyroid stimulating hormone(TSH), prolactin, free thyroxin, and insulin were measured.Gonadotrope cell function was assessed at baseline and at30 and 60 min after gonadotropin releasing hormone(GnRH) injection.Results:Luteinizante hormone (LH), prolactin(PRL), total testosterone(T), androstenedione(A), and17- hidroxyprogesterone(17-OHP4) levels were higher(P0.05).Positive correlation between insulin and theAUC ofLH was identified in controls.Conclusion:The current study confirms the hypersecretion ofLH inPCOS patients after the newest diagnostic systematization.The gonadotrope response toGnRH stimulation inPCOS patients was associated with the baseline levels ofLH,P4, insulin.

  19. Interactions between antiepileptic drugs and hormones.

    Science.gov (United States)

    Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

    2015-05-01

    Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation.

  20. Associations between peripheral androgens and cortisol in infertile women.

    Science.gov (United States)

    Gleicher, Norbert; Seier, Kenneth; Kushnir, Vitaly A; Weghofer, Andrea; Wu, Yan-Guang; Wang, Qi; Albertini, David F; Barad, David H

    2016-04-01

    Testosterone has in recent years been proven essential for normal growth and maturation of small growing follicles. Concomitantly, low functional ovarian reserve (LFOR), characterized by a small growing follicle pool, has been associated with low testosterone levels, which can be of ovarian and/or adrenal origin. In this study we, therefore, investigated whether peripheral sex steroid precursors and testosterone levels potentially reflect on adrenal function. In a retrospective cohort study of 355 consecutive infertile women, who presented to an academically affiliated fertility center in New York City, we investigated in a series of statistical models whether low peripheral sex steroid precursors and testosterone are associated with peripheral cortisol (C) levels, reflecting adrenal function. To determine potential correlations, we investigated the dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (AD), total testosterone (TT), free testosterone (FT); sex hormone binding globulin (SHBG), anti-Müllerian hormone (AMH), thyroid stimulating hormone (TSH) and C in a series of multivariate and logistic regression analyses, utilizing C either as a continuous variable or with cut off infertile women peripheral sex hormone precursors, especially DHEA, reflect C levels and, therefore, adrenal function. In infertile women, at all ages low levels of sex hormone precursors, therefore, should be considered indications for further adrenal assessments.

  1. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.

    Science.gov (United States)

    Ali, Imran; Engström, Annette; Vahter, Marie; Skerfving, Staffan; Lundh, Thomas; Lidfeldt, Jonas; Samsioe, Göran; Halldin, Krister; Åkesson, Agneta

    2014-10-01

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.

  2. Does metformin affect ovarian morphology in patients with polycystic ovary syndrome? A retrospective cross-sectional preliminary analysis

    Directory of Open Access Journals (Sweden)

    Falbo Angela

    2009-05-01

    Full Text Available Abstract Background The significance of polycystic ovarian morphology and its relation to polycystic ovary syndrome (PCOS is unclear, but probably it is associated with higher androgen and insulin levels and lower sex hormone binding globulin (SHBG in absence of identifiable differences in gonadotropin dynamics. The aim of this study was to evaluate ovarian morphology in patients affected by PCOS with different ovulatory responses to metformin. Methods In this cross-sectional analysis, we studied 20 young normal-weight PCOS patients who had received a six-month course of metformin treatment. Ten of these patients remained anovulatory (anovulatory group, whereas other ten became ovulatory, but failed to conceive (ovulatory group. Other ten age- and body mass index (BMI-matched PCOS subjects were also enrolled as controls and observed without any treatment (control group. Results After six months of metformin, in both PCOS treated groups, a similar improvement in testosterone (T and insulin resistance indexes was observed. Moreover, in one (10.0% and nine (90.0% subjects from anovulatory and ovulatory PCOS groups, respectively, ovarian morphology changed, whereas a significant reduction in ovarian dimension was observed in the PCOS ovulatory group only. Conclusion PCOS patients under metformin administration demonstrate a change in ovarian morphology closely related to ovulatory response.

  3. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome.

    Science.gov (United States)

    Enli, Yasar; Fenkci, Semin Melahat; Fenkci, Veysel; Oztekin, Ozer

    2013-12-01

    This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.

  4. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Imran; Engström, Annette; Vahter, Marie [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Skerfving, Staffan; Lundh, Thomas [Division of Occupational and Environmental Medicine, University Hospital, Lund (Sweden); Lidfeldt, Jonas [Department of Community Health, Malmö University Hospital, Malmö (Sweden); Samsioe, Göran [Department of Gynecology and Obstetrics, University Hospital, Lund (Sweden); Halldin, Krister [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Åkesson, Agneta, E-mail: agneta.akesson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2014-10-15

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.

  5. Erectile Dysfunction and Low Sex Drive in Men with Type 2 DM: The Potential Role of Diabetic Pharmacotherapy

    Science.gov (United States)

    Al-Gareeb, Ali I.

    2016-01-01

    Introduction Diabetic men with erectile dysfunction have not been widely studied. They have low testosterone levels, causing low sex drive and erectile dysfunction. Aim To assess the erectile dysfunction and sex drive in relation to testosterone serum levels in type 2 Diabetes Mellitus (DM) patients. Materials and Methods A total of 64 patients with type 2 DM were enrolled in this cross-sectional study, according to the treatment types they were divided into three groups, group (A): 34 patients treated with metformin, group (B): 30 patients treated with sulfonylurea and group (C): 27 healthy normal non-diabetic men are taken as control. Total testosterone (TT), Free Testosterone (FT), Free Androgenic Index (FAI), Sex Hormone Binding Globulin (SHBG), lipid profile and anthropometric parameters in metformin and sulfonylurea treated patients were compared to normal healthy men along with Sexual Health Inventory for Men (SHIM). Results Total testosterone serum levels were high in sulfonylurea treated patients as compared to metformin treated patients’ p elevation in testosterone levels, sex drive and erectile function. PMID:28208875

  6. Role of diet in the treatment of polycystic ovary syndrome

    Science.gov (United States)

    Douglas, Crystal C.; Gower, Barbara A.; Darnell, Betty E.; Ovalle, Fernando; Oster, Robert A.; Azziz, Ricardo

    2013-01-01

    Objective To determine whether eucaloric diets either enriched with monounsaturated fatty acids (MUFA; 17% energy) or low in carbohydrates (Low CHO; 43% energy) would increase insulin sensitivity (Si) and decrease circulating insulin concentrations, relative to a standard diet (STD; 56% CHO, 31% fat, 16% protein), among women with polycystic ovary syndrome (PCOS). Design Crossover. Setting Academic research environment. Patient(s) Healthy women with PCOS not on hormonal or insulin-sensitizing therapy. Intervention(s) Subjects consumed three, 16-day, eucaloric diets, each separated by a 3-week washout period. A frequently sampled, intravenous, glucose tolerance test was administered at baseline and following each diet. Main Outcome Measure(s) Fasting glucose, insulin, the acute insulin response to glucose (AIRg), Si, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, A4, total cholesterol, high-density lipoprotein cholesterol (HDL-C), tryglycerides (TG), and free fatty acids (FFA). Result(s) Fasting insulin was lower following the Low CHO diet relative to the STD diet; AIRg was lower following the Low CHO diet relative to the MUFA diet. Fasting glucose, Si, and the circulating concentrations of reproductive hormones were not significantly affected by the intervention. Conclusion(s) A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS, which, over time, may improve reproductive/endocrine outcomes. PMID:16500338

  7. 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......-CoA esters containing more than eight carbon atoms and that the 3'-phosphate of the ribose accounts for almost half of the binding energy. Binding of acyl-CoA esters, with increasing chain length, to ACBP was clearly enthalpically driven with a slightly unfavorable entropic contribution. Accessible surface...... areas derived from the measured enthalpies were compared to those calculated from sets of three-dimensional solution structures and showed reasonable correlation, confirming the enthalphically driven binding. Binding of dodecanoyl-CoA to ACBP was studied at various temperatures and was characterized...

  8. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    Energy Technology Data Exchange (ETDEWEB)

    Serck-Hanssen, G.; Soevik, O.

    1987-12-28

    Insulin binding was studied in subpopulations of bovine chromaffin cells enriched in adrenalin-producing cells (A-cells) or noradrenalin-producing cells (NA-cells). Binding of /sup 125/I-insulin was carried out at 15/sup 0/C for 3 hrs in the absence or presence of excess unlabeled hormone. Four fractions of cells were obtained by centrifugation on a stepwise bovine serum albumin gradient. The four fractions were all shown to bind insulin in a specific manner and the highest binding was measured in the cell layers of higher densities, containing mainly A-cells. The difference in binding of insulin to the four subpopulations of chromaffin cells seemed to be related to differences in numbers of receptors as opposed to receptor affinities. The authors conclude that bovine chromaffin cells possess high affinity binding sites for insulin and that these binding sites are mainly confined to A-cells. 24 references, 2 figures, 1 table.

  9. The Observation Effects of Immune Globulin and Conventional Therapy in Guillain-Barre Syndrome%免疫球蛋白和常规方法治疗格林巴利综合征患者的疗效对比观察

    Institute of Scientific and Technical Information of China (English)

    余鸽鸽

    2015-01-01

    目的:对格林巴利综合征治疗中常规方法与免疫球蛋白的使用效果进行对比观察。方法将本院于2013年6月~2015年6月收治的格林巴利综合征患者74例纳为研究对象,随机分成对照组与治疗组,分别采取常规综合治疗与免疫球蛋白治疗。进行两组生活活动能力、起效时间、总有效率的对比观察。结果治疗组的总有效率(94.59%)高于对照组(78.38%),治疗组的起效时间较快,且治疗后生活活动能力较好,组间对比,P<0.05,差异有统计学意义。结论格林巴利综合征治疗中免疫球蛋白的使用效果突出。%Objective To compare the effect of immune globulin and conventional therapy for Guillain-Barre syndrome patients.Methods The hospital in June 2013 to June 2015, 74 cases of Guillain-Barre syndrome were satisfied for the study, were randomly divided into control and treatment groups, were taken to routine treatment with immune globulin therapy. Two sets of living activity, onset time, total contrast observation efficiency.Results The total efficiency of the treatment group (94.59%) higher (78.38%), onset time faster treatment group, and the ability to better treatment after living activities, group comparison,P<0.05, the difference was statistically signiifcant. Conclusion Guillain-Barre syndrome treatment effect immune globulin prominent.

  10. 丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎60例临床分析%Clinical analysis of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis in 60 cases

    Institute of Scientific and Technical Information of China (English)

    郭书霞

    2015-01-01

    目的:探讨丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎的临床效果。方法:收治重症毛细支气管炎患儿60例,随机分为对照组和观察组,对照组采用常规对症支持治疗,观察组在常规治疗的基础上加用丙种球蛋白+沙丁胺醇+孟鲁司特钠治疗,比较两组的治疗效果及不良反应。结果:观察组总有效率显著高于对照组(P<0.05)。结论:丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎总有效率显著高于常规治疗,不良反应少,使用方便。%Objective:To explore the clinical effect of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis.Methods:60 children with severe bronchiolitis were selected.They were randomly divided into the control group and the observation group.The control group was given conventional symptomatic and supportive treatment.The observation group was given gamma globulin,salbutamol combined with montelukast sodium treatment on the basis of conventional treatment.The treatment effects and adverse reactions of two groups were compared.Results:The total effective rate of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The total effective rate of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis is significantly higher than that of the conventional treatment.Its adverse reaction is less.It is easy to use.

  11. Clinical efficacy of methylprednisolone combined with gamma globulin for severe hand-foot-mouth disease%甲基强的松龙联合丙种球蛋白治疗重症手足口病的疗效分析

    Institute of Scientific and Technical Information of China (English)

    李冰

    2014-01-01

    ObjectiveTo discuss clinical efficacy of methylprednisolone combined with gamma globulin for severe hand-foot-mouth disease. Methods Selected 214 cases with severe hand-foot-mouth disease were retrospectively analyzed,and all cases were divided into combined therapy group and conventional therapy group according to different treatment.Combined therapy group was treated by full dose,early phase methylprednisolone combined with gamma globulin bases on conventional therapy. Clinical efficacy of two groups was compared. Results Clinical efficacy of combined therapy group was better than that of conventional therapy group(P<0.05). Temperature returned to normal time, skin rash disappearing time, neurological sign and pneumonia performance disappearing time, white blood cell, blood glucose returned to normal time of combined therapy group were shorter than those of conventional therapy group(P<0.01).ConclusionFull dose,early phase methylprednisolone combined with gamma globulin for severe hand-foot-mouth disease can improve clinical efficacy, worthy of clinical application.%目的:探讨甲基强的松龙联合丙种球蛋白治疗重症手足口病的临床疗效。方法回顾性分析重症手足口病患儿214例的临床资料,根据治疗方法分为常规治疗组与联合治疗组。联合治疗组在常规治疗的基础上给予足量、早期甲基强的松龙联合丙种球蛋白治疗。比较两组临床疗效。结果联合治疗组的临床疗效显著优于常规治疗组(P<0.05)。联合治疗组体温恢复正常时间、皮疹消退时间、神经症状和肺炎表现消失时间、白细胞、血糖降至正常时间显著短于常规治疗组(P<0.01)。结论早期、足量甲基强的松龙联合丙种免疫球蛋白治疗重症手足口病能够显著提高临床疗效,值得临床推广。

  12. Predicted metal binding sites for phytoremediation.

    Science.gov (United States)

    Sharma, Ashok; Roy, Sudeep; Tripathi, Kumar Parijat; Roy, Pratibha; Mishra, Manoj; Khan, Feroz; Meena, Abha

    2009-09-05

    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 not appear in the essential oil and that some of these species are able to grow in metal contaminated sites. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high specificity of the motifs designed for the ions of nickel, lead, molybdenum, manganese, cadmium, zinc, iron, cobalt and xenobiotic compounds. Motifs were also studied against PDB structures. Results of the study suggested the presence of binding sites on the surface of protein molecules involved. PDB structures of proteins were finally predicted for the binding sites functionality in their respective phytoremediation usage. This was further validated through CASTp server to study its physico-chemical properties. Bioinformatics implications would help in designing strategy for developing transgenic plants with increased metal binding capacity. These metal binding factors can be used to restrict metal update by plants. This helps in reducing the possibility of metal movement into the food chain.

  13. [Binding to chicken liver lactatedehydrogenase (author's transl)].

    Science.gov (United States)

    Lluís, C; Bozal, J

    1976-06-01

    Some information about the lactate dehydrogenase NAD binding site has been obtained by working with coenzymes analogs of incomplete molecules. 5'AMP, 5'-ADP, ATP, 5'-c-AMP and 3'(2)-AMP inhibit chicken liver LDH activity competitively with NADH. 5"-AMP and 5'-ADP show a stronger inhibition power than ATP, suggesting that the presence of one or two phosphate groups at the 5' position of adenosine, is essential for the binding of the coenzyme analogs at the enzyme binding site. Ribose and ribose-5'-P do not appear to inhibit the LDH activity, proving that purine base lacking mononucleotides do not bind to the enzyme. 5"-ADPG inhibits LDH activity in the exactly as 5'-ADP, showing that ribose moiety may be replaced by glucose, without considerable effects on the coenzyme analog binding. 2'-desoxidenosin-5'-phosphate proves to be a poorer inhibitor of the LDH activity than 5'-AMP, indicating that an interaction between the--OH groups and the amino-acids of the LDH active center takes place. Nicotinamide does not produce any inhibition effect, while NMN and CMP induce a much weaker inhibition than the adenine analogues, thus indicating a lesser binding capacity to the enzyme. Therefore, the LDH binding site seems to show some definite specificity towards the adenina groups of the coenzyme.

  14. Measuring Binding Affinity of Protein-Ligand Interaction Using Spectrophotometry: Binding of Neutral Red to Riboflavin-Binding Protein

    Science.gov (United States)

    Chenprakhon, Pirom; Sucharitakul, Jeerus; Panijpan, Bhinyo; Chaiyen, Pimchai

    2010-01-01

    The dissociation constant, K[subscript d], of the binding of riboflavin-binding protein (RP) with neutral red (NR) can be determined by titrating RP to a fixed concentration of NR. Upon adding RP to the NR solution, the maximum absorption peak of NR shifts to 545 nm from 450 nm for the free NR. The change of the absorption can be used to determine…

  15. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  16. 不同剂量丙种球蛋白联合地塞米松治疗小儿特发性血小板减少性紫癜的临床疗效分析%Effect observation of different doses Dexamethasone combined with gamma globulin in the treatment of idiopathic thrombocytopenic purpura with children

    Institute of Scientific and Technical Information of China (English)

    覃黄正

    2014-01-01

    Objective To explore the clinical effect of different dose Dexamethasone combined with gamma globulin in the treatment of idiopathic thrombocytopenic purpura with children. Methods 120 patients with Idiopathic thrombocytopenic purpura in our hosipta were randomly divided intocontrol group, low-dose group and high dose group, each group had 40 cases. All patients were received treatment using dexamethasone injection, children with high-dose group were given Globulin 400mg/(kg·d), 1 times a day, once every 5d;children withlow-dose group were given Globulin 200mg/(kg·d), 1 times a day, once every 5d;the clinical efficacy, platelets rise time, platelet recovery time, time to stop bleeding of three group were observation and compared. Results The clinical efficacy of high-dose group, the rise time of platelets and platelet recovery time, time to stop the bleeding was compared between low-dose group and high dose group, the difference was not statistically significant (P > 0.05), compared with control group, the differences were statistically significant (P < 0.05). Conclusion Gamma globulin and dexamethasone can significantly improve pediatric idiopathic thrombocytopenic purpura clinical symptoms, the rapid increase platelet count, and small doses of gamma globulinhad similartreatment effect with high dose, it is worthy of wide application in clinical.%目的:探讨不同剂量丙种球蛋白联合地塞米松治疗小儿重症特发性血小板减少性紫癜的疗效观察。方法将120例小儿特发性血小板减少性紫癜患儿随机分为对照组,小剂量组和大剂量组,每组各40例,所有患者均接受采用地塞米松注射液治疗,大剂量组患儿给予丙种球蛋白400mg/(kg·d),1次/d,连用5d;小剂量组患儿给予丙种球蛋白200mg/(kg·d),1次/d,连用5d,观察比较三组临床疗效,血小板上升时间,血小板恢复正常时间,出血停止时间。结果小剂量组与大剂量组临床疗

  17. An effect analysis of different doses of gamma globulin combined with prednisone in the treatment of idiopathic thrombocytopenic purpura%不同剂量的丙种球蛋白联合强的松治疗特发性血小板减少性紫癜的效果分析

    Institute of Scientific and Technical Information of China (English)

    潘凤娟; 钟翠鸣; 钟华

    2015-01-01

    Objective To compare the efficacy of low dose and high dose gamma globulin combined with prednisone in the treatment of idiopathic thrombocytopenic purpura for obtaining a better cost - effect ratio treatment scheme. Methods Between March 2010 and May 2014 a total of 64 pediatric patients with idio-pathic thrombocytopenic purpura cared at Pediatrics Department of our hospital were enrolled in this study,a hidden random number table method was used to allocate the patients to two groups.Thirty- two cases in group A were given 400 mg/(kg · d)gamma globulin for 5 days,after that they received oral prednisone. Thirty-two cases in group B were given 200 mg/(kg·d)gamma globulin for 5 days,after that they received oral prednisone,after drug administration,platelet count was measured,and the platelet elevating time,mean hemostasis time,time to platelet peak and the platelet value were all recorded every day.The efficacy rate was compared between the two groups. Results After treatment,comparison of mean platelet elvating time,av-erage hemostasis time,mean platelet peak value between the two groups of pediatric children showed no signif-icant differences (P > 0.05 ).Group A patients had shorter average peak time than group B,group paired comparison yielded statistical difference (P 0.05 ). Conclusion Low dose gamma globulin combined with prednisone in treatment of idiopathic thrombocytopenic purpura can obtain high potency ratio,can quickly increase platelet and control of hemorrhage.%目的:比较大剂量和小剂量丙种球蛋白联合强的松治疗特发性血小板减少性紫癜(ITP)的效果,寻求效价比高的治疗方案。方法选择我院儿科2010年3月~2014年5月住院的64例特发性血小板减少性紫癜患儿,采用隐匿数字随机法分为两组,A 组32例患儿给予400 mg/(kg·d)丙种球蛋白治疗5 d 后口服强的松,B 组32例患儿给予200 mg/(kg·d)丙种球蛋白治疗5 d 后口服强的松,用药后每天检测血小板计数,

  18. On Reflexive Binding in North Sami

    Directory of Open Access Journals (Sweden)

    Hanna Outakoski

    2004-01-01

    Full Text Available Principle A of the Binding Theory states that an anaphor must be A-bound in the local domain containing it, its governor and an accessible subject. However, if the anaphor is contained in an infinitival complement clause, it may, in North Sami, be bound either by the clause-mate subject or by the subject of the tensed clause. Thus, it appears that there is a larger binding domain for anaphors in addition to that determined by the condition A of standard binding theory. This domain can in some languages, as in North Sami, be defined by the notion of Tense whereas in other languages this need not be case, as in English. This supports the approach that the characterization of binding domains is parameterized and that languages pick different values of the parameter.

  19. System Support for Managing Invalid Bindings

    CERN Document Server

    Das, Lachhman; Shah, Azhar; Khoumbati, Khalil; 10.5121/iju.2011.2303

    2011-01-01

    Context-aware adaptation is a central aspect of pervasive computing applications, enabling them to adapt and perform tasks based on contextual information. One of the aspects of context-aware adaptation is reconfiguration in which bindings are created between application component and remote services in order to realize new behaviour in response to contextual information. Various research efforts provide reconfiguration support and allow the development of adaptive context-aware applications from high-level specifications, but don't consider failure conditions that might arise during execution of such applications, making bindings between application and remote services invalid. To this end, we propose and implement our design approach to reconfiguration to manage invalid bindings. The development and modification of adaptive context-aware applications is a complex task, and an issue of an invalidity of bindings further complicates development efforts. To reduce the development efforts, our approach provides ...

  20. Motion transparency promotes synchronous perceptual binding.

    Science.gov (United States)

    Clifford, Colin W G; Spehar, Branka; Pearson, Joel

    2004-12-01

    While identified regions of human extrastriate visual cortex are functionally specialized for processing different attributes of an object, the cognitive and neural mechanisms by which these attributes are dynamically bound into integrated percepts are still largely mysterious. Here, we report that perceptual organization influences the dynamics of binding. Specifically, the perception of motion transparency promotes the synchronous perceptual binding of colour and motion, which otherwise exhibits considerable asynchronies. In addition, we demonstrate that perceptual asynchrony can be reinstated by manipulating stereoscopic disparity or speed within the stimulus. Our findings suggest that the phenomenology of colour-motion binding parallels the known physiology of motion processing in area MT of primate visual cortex, supporting the view that the dynamics of perceptual binding is a direct reflection of the time course of the underlying neural processing.

  1. Hardware device binding and mutual authentication

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04

    Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

  2. Acyl-coenzyme A binding protein (ACBP)

    DEFF Research Database (Denmark)

    Kragelund, B B; Knudsen, J; Poulsen, F M

    1999-01-01

    Acyl-coenzyme A binding proteins are known from a large group of eukaryote species and to bind a long chain length acyl-CoA ester with very high affinity. Detailed biochemical mapping of ligand binding properties has been obtained as well as in-depth structural studies on the bovine apo-protein...... and of the complex with palmitoyl-CoA using NMR spectroscopy. In the four alpha-helix bundle structure, a set of 21 highly conserved residues present in more that 90% of all known sequences of acyl-coenzyme A binding proteins constitutes three separate mini-cores. These residues are predominantly located...... at the helix-helix interfaces. From studies of a large set of mutant proteins the role of the conserved residues has been related to structure, function, folding and stability....

  3. Acyl-coenzyme A binding protein, ACBP

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Knudsen, J.; Poulsen, Flemming

    1999-01-01

    Acyl-coenzyme A binding proteins are known from a large group of eukaryote species and to bind a long chain length acyl-CoA ester with very high affinity. Detailed biochemical mapping of ligand binding properties has been obtained as well as in-depth structural studies on the bovine apo-protein...... and of the complex with palmitoyl-CoA using NMR spectroscopy. In the four a-helix bundle structure, a set of 21 highly conserved residues present in more that 90% of all known sequences of acyl-coenzyme A binding proteins constitutes three separate mini-cores. These residues are predominantly located at the helix......-helix interfaces. From studies of a large set of mutant proteins the role of the conserved residues has been related to structure, function, folding and stability....

  4. Tau Induces Cooperative Taxol Binding to Microtubules

    Science.gov (United States)

    Ross, Jennifer; Santangelo, Christian; Victoria, Makrides; Fygenson, Deborah

    2004-03-01

    Taxol and tau are two ligands which stabilize the microtubule (MT) lattice. Taxol is an anti-mitotic drug that binds β tubulin in the MT interior. Tau is a MT-associated protein that binds both α and β tubulin on the MT exterior. Both taxol and tau reduce MT dynamics and promote tubulin polymerization. Tau alone also acts as a buttress to bundle, stiffen, and space MTs. A structural study recently suggested that taxol and tau may interact by binding to the same site. Using fluorescence recovery after photobleaching, we find that tau induces taxol to bind MTs cooperatively depending on the tau concentration. We develop a model that correctly fits the data in the absence of tau and yields a measure of taxol cooperativity when tau is present.

  5. Imidazole binding to human serum albumin.

    Science.gov (United States)

    Rodrigo, M C; Ceballos, A; Mariño, E; Cachaza, J M; Domínguez-Gil, A; Kuemmerle, H P

    1988-06-01

    Imidazole is a substance released by the organism when a new salicylate derivative, imidazole salicylate is administered. A study was made of the binding of imidazole to human serum albumin by an in vitro assay employing an ultrafiltration technique. For the concentration range that imidazole was found in plasma following administration of the drug to healthy volunteers, the mean binding percentages were: 12.1 +/- 1.8 and 19.7 +/- 3.1 at 37 degrees C and 25 degrees C, respectively. The results obtained in the study follow a model entailing three equal and independent binding sites of imidazole to serum albumin and the values of the corresponding constants were determined. Apparently, the presence in the plasma samples of sodium salicylate at a concentration of 100 micrograms/ml does not affect the binding of imidazole to human serum albumin.

  6. Adjustment of legally binding local plans

    DEFF Research Database (Denmark)

    Hvingel, Line Træholt; Aunsborg, Christian; Christensen, Finn Kjær

    2012-01-01

    Traditionally, and by law, new urban areas in Denmark are regulated and planned through legally binding local plans. Recently a tendency has occurred: The municipalities make the legally binding local plans quite open for future adjustment, and they are using a substantial amount of ‘empowerment......, which seem to be beyond the scope of the Danish Planning Act. This paper deals with this problem through case studies and a legal analysis of present law. If the combination of the legally binding local plan and subsequent added requirements is misused, it will weaken the legal rights of the citizens...... the considerations of legal rights, the extend of the legal use of empowerment provisions and the combination of the use of legal binding local plans and other legal instruments such as easements and sales agreements....

  7. HEAVY QUARK POTENTIALS AND QUARKONIA BINDING.

    Energy Technology Data Exchange (ETDEWEB)

    PETRECZKY,P.

    2004-11-04

    The author reviews recent progress in studying in-medium modification of inter-quark forces at finite temperature in lattice QCD. Some applications to the problem of quarkonium binding in potential models is also discussed.

  8. Binding capacity: cooperativity and buffering in biopolymers.

    Science.gov (United States)

    Di Cera, E; Gill, S J; Wyman, J

    1988-01-01

    The group of linkage potentials resulting from the energy of a physicochemical system expressed per mol of a reference component, say a polyfunctional macromolecule, leads to the concept of binding capacity. This concept applies equally to both chemical and physical ligands and opens the way to consideration of higher-order linkage relationships. It provides a means of exploring the consequences of thermodynamic stability on generalized binding phenomena in biopolymers. PMID:3422436

  9. Fractal aspects of calcium binding protein structures

    Energy Technology Data Exchange (ETDEWEB)

    Isvoran, Adriana [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)], E-mail: aisvoran@cbg.uvt.ro; Pitulice, Laura [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania); Craescu, Constantin T. [INSERM U759/Institute Curie-Recherche, Centre Universitaire Paris-Sud, Batiment 112, 91405 Orsay (France); Chiriac, Adrian [West University of Timisoara, Department of Chemistry, Pestalozzi 16, 300115 Timisoara (Romania)

    2008-03-15

    The structures of EF-hand calcium binding proteins may be classified into two distinct groups: extended and compact structures. In this paper we studied 20 different structures of calcium binding proteins using the fractal analysis. Nine structures show extended shapes, one is semi-compact and the other 10 have compact shapes. Our study reveals different fractal characteristics for protein backbones belonging to different structural classes and these observations may be correlated to the physicochemical forces governing the protein folding.

  10. Predicting zinc binding at the proteome level

    Directory of Open Access Journals (Sweden)

    Rosato Antonio

    2007-02-01

    Full Text Available Abstract Background Metalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, for regulation of their activities or for structural purposes. Metal-binding properties remain difficult to predict as well as to investigate experimentally at the whole-proteome level. Consequently, the current knowledge about metalloproteins is only partial. Results The present work reports on the development of a machine learning method for the prediction of the zinc-binding state of pairs of nearby amino-acids, using predictors based on support vector machines. The predictor was trained using chains containing zinc-binding sites and non-metalloproteins in order to provide positive and negative examples. Results based on strong non-redundancy tests prove that (1 zinc-binding residues can be predicted and (2 modelling the correlation between the binding state of nearby residues significantly improves performance. The trained predictor was then applied to the human proteome. The present results were in good agreement with the outcomes of previous, highly manually curated, efforts for the identification of human zinc-binding proteins. Some unprecedented zinc-binding sites could be identified, and were further validated through structural modelling. The software implementing the predictor is freely available at: http://zincfinder.dsi.unifi.it Conclusion The proposed approach constitutes a highly automated tool for the identification of metalloproteins, which provides results of comparable quality with respect to highly manually refined predictions. The ability to model correlations between pairwise residues allows it to obtain a significant improvement over standard 1D based approaches. In addition, the method permits the identification of unprecedented metal sites, providing important hints for the work of experimentalists.

  11. Comparison of low dose and high dose human gamma globulin in therapy for acute Guillain-Barre syndrome in infants%不同剂量丙种球蛋白治疗儿童吉兰-巴雷综合征的疗效比较

    Institute of Scientific and Technical Information of China (English)

    唐军

    2013-01-01

    目的 观察不同剂量丙种球蛋白(IVIG)治疗儿童吉兰-巴雷综合征(GBS)的临床疗效.方法 将符合GBS诊断的141例患者分为三组,分别给予不同剂量IVIG,并对疗效进行对比观察.结果 三种给药方式对轻、中、重度患者的疗效差异无统计学意义(均P> 0.05),不同程度患者总有效率分别为95.83%、95.74%、82.85%.结论 IVIG治疗儿童吉兰-巴雷综合征具有良好的效果,低剂量组和大剂量组差异无统计学意义,低剂量IVIG治疗儿童GBS亦有效.%Objective To observe the therapy effect of different dosages human gamma globulin (IVIG) for acute Guillain-Barre syndrome.Methods 134 cases of acute Guillain-Barre syndrome were divided into three groups.They were given different dosages of IVIG.Clinical effects were compared and observed.Results The curative effect of three kinds of drug ways for light, medium and severe patients had no significant differences (all P > 0.05).The total effective rate of patients with different level was 95.83%, 95.74%, 82.85% respectively.Conclusion IVIG in the treatment of children with Guillain-Barre syndrome has a good effect.There is no significant difference between low dose and high dose human gamma globulin for acute Guillain-Barre syndrome.Low dosage IVIG in treating children with Guillain-Barre syndrome is also effective.

  12. DNA-Aptamers Binding Aminoglycoside Antibiotics

    Directory of Open Access Journals (Sweden)

    Nadia Nikolaus

    2014-02-01

    Full Text Available Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

  13. Electrostatically biased binding of kinesin to microtubules.

    Directory of Open Access Journals (Sweden)

    Barry J Grant

    2011-11-01

    Full Text Available The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.

  14. Comparative serum protein binding of anthracycline derivatives.

    Science.gov (United States)

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P

    1996-01-01

    The binding of doxorubicin, iododoxorubicin, daunorubicin, epirubicin, pirarubicin, zorubicin, aclarubicin, and mitoxantrone to 600 microM human serum albumin and 50 microM alpha 1-acid glycoprotein was studied by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by high-performance liquid chromatography (HPLC) with fluorometric detection. Binding to albumin (600 microM) varied from 61% (daunorubicin) to 94% (iododoxorubicin). The binding to alpha 1-acid glycoprotein (50 microM) was more variable, ranging from 31% (epirubicin) to 64% (zorubicin), and was essentially related to the hydrophobicity of the derivatives. Simulations showed that the total serum binding varied over a broad range from 71% (doxorubicin) to 96% (iododoxorubicin). We recently reported that the binding to lipoproteins of a series of eight anthracycline analogues could be ascribed to chemicophysical determinants of lipophilicity [2]. The present study was conducted to evaluate in vitro the contribution of albumin and alpha 1-acid glycoprotein to the total serum binding of these drugs.

  15. The readiness potential reflects intentional binding

    Directory of Open Access Journals (Sweden)

    Han-Gue eJo

    2014-06-01

    Full Text Available When a voluntary action is causally linked with a sensory outcome, the action and its consequent effect are perceived as being closer together in time. This effect is called intentional binding. Although many experiments were conducted on this phenomenon, the underlying neural mechanisms are not well understood. While intentional binding is specific to voluntary action, we presumed that preconscious brain activity (the readiness potential, RP, which occurs before an action is made, might play an important role in this binding effect. In this study, the brain dynamics were recorded with electroencephalography (EEG and analyzed in single-trials in order to estimate whether intentional binding is correlated with the early neural processes. Moreover, we were interested in different behavioral performance between meditators and non-meditators since meditators are expected to be able to keep attention more consistently on a task. Thus, we performed the intentional binding paradigm with twenty mindfulness meditators and compared them to matched controls. Although, we did not observe a group effect on either behavioral data or EEG recordings, we found that self-initiated movements following ongoing negative deflections of slow cortical potentials (SCPs result in a stronger binding effect compared to positive potentials, especially regarding the perceived time of the consequent effect. Our results provide the first direct evidence that the early neural activity within the range of SCPs affects perceived time of a sensory outcome that is caused by intentional action.

  16. Zinc Binding by Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    Jasna Mrvčić

    2009-01-01

    Full Text Available Zinc is an essential trace element in all organisms. A common method for the prevention of zinc deficiency is pharmacological supplementation, especially in a highly available form of a metalloprotein complex. The potential of different microbes to bind essential and toxic heavy metals has recently been recognized. In this work, biosorption of zinc by lactic acid bacteria (LAB has been investigated. Specific LAB were assessed for their ability to bind zinc from a water solution. Significant amount of zinc ions was bound, and this binding was found to be LAB species-specific. Differences among the species in binding performance at a concentration range between 10–90 mg/L were evaluated with Langmuir model for biosorption. Binding of zinc was a fast process, strongly influenced by ionic strength, pH, biomass concentration, and temperature. The most effective metal-binding LAB species was Leuconostoc mesenteroides (27.10 mg of Zn2+ per gram of dry mass bound at pH=5 and 32 °C, during 24 h. FT-IR spectroscopy analysis and electron microscopy demonstrated that passive adsorption and active uptake of the zinc ions were involved.

  17. The readiness potential reflects intentional binding.

    Science.gov (United States)

    Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo; Schmidt, Stefan

    2014-01-01

    When a voluntary action is causally linked with a sensory outcome, the action and its consequent effect are perceived as being closer together in time. This effect is called intentional binding. Although many experiments were conducted on this phenomenon, the underlying neural mechanisms are not well understood. While intentional binding is specific to voluntary action, we presumed that preconscious brain activity (the readiness potential, RP), which occurs before an action is made, might play an important role in this binding effect. In this study, the brain dynamics were recorded with electroencephalography (EEG) and analyzed in single-trials in order to estimate whether intentional binding is correlated with the early neural processes. Moreover, we were interested in different behavioral performance between meditators and non-meditators since meditators are expected to be able to keep attention more consistently on a task. Thus, we performed the intentional binding paradigm with 20 mindfulness meditators and compared them to matched controls. Although, we did not observe a group effect on either behavioral data or EEG recordings, we found that self-initiated movements following ongoing negative deflections of slow cortical potentials (SCPs) result in a stronger binding effect compared to positive potentials, especially regarding the perceived time of the consequent effect. Our results provide the first direct evidence that the early neural activity within the range of SCPs affects perceived time of a sensory outcome that is caused by intentional action.

  18. Curative Effect of Intravenous Immune Globulin Drug on Severe Adenovirus Pneumonia in Children%静脉用丙种球蛋白佐治重症腺病毒肺炎84例疗效评价

    Institute of Scientific and Technical Information of China (English)

    崔艳杰; 程军; 孙雯

    2015-01-01

    Objective To investigate the curative effect of intravenous immune-enhancing drug on the severe adenovirus pneumonia (SAP)in children. Methods 168 children cases of SAP in the hospital from April 2009 to May 2014 were selected and randomly di-vided into the observation group and control group,84 cases in each group. The control group adopted the traditional routine therapy mode,while on this basis the observation group was given the intravenous immune-enhancing drug immunoglobulin(IG). Results The average fever time and average length of hospital stay were (5. 17 ± 2. 58) d and (11. 17 ± 5. 11) d in the observation group and (6. 78 ± 4. 02) d and (12. 71 ± 5. 75) d in the control group,the differences between the two groups were statistically significant( t=2. 281,2. 181,P < 0. 05). 21 cases (25. 00%) in the two groups used the breathing machine,including 11 cases in the observation group with the average use time of(4. 58+1. 39)d and 10 cases in the control group with the average use time of(5. 96+3. 39)d,the differences between the two groups showed statistical significance ( t=1. 992,P=0. 047);68 cases in the observation group appeared complications,while all the cases in the control group suffered from complications,in which the occurrence rates of atelectasis,pleural effusion,myocarditis,tozic encephalopathy and diarrhea in the observation group were significantly lower than those in the control group;the effective rate in the observation group was 22. 62%,which was significantly higher than 10. 71% in the control group(χ2=7. 872, P=0. 002 ),and the ineffective rate in the control group was significantly higher than that in the observation group(χ2=4. 421 , P=0. 037). Conclusion The assisted therapy of intravenous immune globulin in the treatment of children SAP can reduce the occur-rence of some complications,improve the curative effect and prognosis,shorten the hospitalization time,breathing machine using time and persistent fever time.%目的:探

  19. Mannose-Binding Lectin Binds to Amyloid Protein and Modulates Inflammation

    Directory of Open Access Journals (Sweden)

    Mykol Larvie

    2012-01-01

    Full Text Available Mannose-binding lectin (MBL, a soluble factor of the innate immune system, is a pattern recognition molecule with a number of known ligands, including viruses, bacteria, and molecules from abnormal self tissues. In addition to its role in immunity, MBL also functions in the maintenance of tissue homeostasis. We present evidence here that MBL binds to amyloid β peptides. MBL binding to other known carbohydrate ligands is calcium-dependent and has been attributed to the carbohydrate-recognition domain, a common feature of other C-type lectins. In contrast, we find that the features of MBL binding to Aβ are more similar to the reported binding characteristics of the cysteine-rich domain of the unrelated mannose receptor and therefore may involve the MBL cysteine-rich domain. Differences in MBL ligand binding may contribute to modulation of inflammatory response and may correlate with the function of MBL in processes such as coagulation and tissue homeostasis.

  20. To Bind or not to Bind: It’s in the Contract

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.

    2015-01-01

    discusses, in a theoretical perspective, the legal reasoning behind the different partnering approaches, both from a historical and contract law perspective, and furthermore applies a game theoretical approach in evaluating binding versus non-binding partnering contracts. The analysis focuses on private......This article discusses the formalization of collaboration through partnering contracts in the construction industry in the USA, Great Britain and Denmark. The article compares the different types of collaborative partnering contracts in the three countries, and provides a conclusion on whether...... the collaborative partnering contract should be binding or non-binding, based on the three empirical contracts analyzed in this article. The partnering contracts in Great Britain and Denmark are legally binding, while in the USA the partnering agreements are non-binding charters or letters of intent. This article...

  1. Theoretical studies of binding of mannose-binding protein to monosaccharides

    Science.gov (United States)

    Aida-Hyugaji, Sachiko; Takano, Keiko; Takada, Toshikazu; Hosoya, Haruo; Kojima, Naoya; Mizuochi, Tsuguo; Inoue, Yasushi

    2004-11-01

    Binding properties of mannose-binding protein (MBP) to monosaccharides are discussed based on ab initio molecular orbital calculations for cluster models constructed. The calculated binding energies indicate that MBP has an affinity for N-acetyl- D-glucosamine, D-mannose, L-fucose, and D-glucose rather than D-galactose and N-acetyl- D-galactosamine, which is consistent with the biochemical experimental results. Electrostatic potential surfaces at the binding site of four monosaccharides having binding properties matched well with that of MBP. A vacant frontier orbital was found to be localized around the binding site of MBP, suggesting that MBP-monosaccharide interaction may occur through electrostatic and orbital interactions.

  2. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  3. Automatic Binding Time Analysis for a Typed Lambda-Calculus

    DEFF Research Database (Denmark)

    Nielson, Hanne Riis; Nielson, Flemming

    1988-01-01

    analysis of the binding times of a typed lambda-calculus with products, sums, lists and general recursive types. Given partial information about the binding times of some of the subexpressions it will complete that information such that (i) early bindings may be turned into late bindings but not vice versa......, (ii) the resulting two-level lambda-expression reflects our intuition about binding times, e.g. that early bindings are performed before late bindings, and (iii) as few changes as possible have been made compared with the initial binding information. The results can be applied in the implementation...

  4. Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species.

    Directory of Open Access Journals (Sweden)

    Robert K Bradley

    2010-03-01

    Full Text Available Changes in gene expression play an important role in evolution, yet the molecular mechanisms underlying regulatory evolution are poorly understood. Here we compare genome-wide binding of the six transcription factors that initiate segmentation along the anterior-posterior axis in embryos of two closely related species: Drosophila melanogaster and Drosophila yakuba. Where we observe binding by a factor in one species, we almost always observe binding by that factor to the orthologous sequence in the other species. Levels of binding, however, vary considerably. The magnitude and direction of the interspecies differences in binding levels of all six factors are strongly correlated, suggesting a role for chromatin or other factor-independent forces in mediating the divergence of transcription factor binding. Nonetheless, factor-specific quantitative variation in binding is common, and we show that it is driven to a large extent by the gain and loss of cognate recognition sequences for the given factor. We find only a weak correlation between binding variation and regulatory function. These data provide the first genome-wide picture of how modest levels of sequence divergence between highly morphologically similar species affect a system of coordinately acting transcription factors during animal development, and highlight the dominant role of quantitative variation in transcription factor binding over short evolutionary distances.

  5. Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R.; Stevens, Raymond C. (Scripps); (UW)

    2011-11-02

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-{angstrom} X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.

  6. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men.

    Directory of Open Access Journals (Sweden)

    Amy C Reynolds

    Full Text Available BACKGROUND: Sleep restriction is associated with development of metabolic ill-health, and hormonal mechanisms may underlie these effects. The aim of this study was to determine the impact of short term sleep restriction on male health, particularly glucose metabolism, by examining adrenocorticotropic hormone (ACTH, cortisol, glucose, insulin, triglycerides, leptin, testosterone, and sex hormone binding globulin (SHBG. METHODOLOGY/PRINCIPAL FINDINGS: N = 14 healthy men (aged 27.4±3.8, BMI 23.5±2.9 underwent a laboratory-based sleep restriction protocol consisting of 2 baseline nights of 10 h time in bed (TIB (B1, B2; 22:00-08:00, followed by 5 nights of 4 h TIB (SR1-SR5; 04:00-08:00 and a recovery night of 10 h TIB (R1; 22:00-08:00. Subjects were allowed to move freely inside the laboratory; no strenuous activity was permitted during the study. Food intake was controlled, with subjects consuming an average 2000 kcal/day. Blood was sampled through an indwelling catheter on B1 and SR5, at 09:00 (fasting and then every 2 hours from 10:00-20:00. On SR5 relative to B1, glucose (F(1,168 = 25.3, p<0.001 and insulin (F(1,168 = 12.2, p<0.001 were increased, triglycerides (F(1,168 = 7.5, p = 0.007 fell and there was no significant change in fasting homeostatic model assessment (HOMA determined insulin resistance (F(1,168 = 1.3, p = 0.18. Also, cortisol (F(1,168 = 10.2, p = 0.002 and leptin (F(1,168 = 10.7, p = 0.001 increased, sex hormone binding globulin (F(1,167 = 12.1, p<0.001 fell and there were no significant changes in ACTH (F(1,168 = 0.3, p = 0.59 or total testosterone (F(1,168 = 2.8, p = 0.089. CONCLUSIONS/SIGNIFICANCE: Sleep restriction impaired glucose, but improved lipid metabolism. This was associated with an increase in afternoon cortisol, without significant changes in ACTH, suggesting enhanced adrenal reactivity. Increased cortisol and reduced sex hormone binding globulin

  7. Endocytosis of integrin-binding human picornaviruses.

    Science.gov (United States)

    Merilahti, Pirjo; Koskinen, Satu; Heikkilä, Outi; Karelehto, Eveliina; Susi, Petri

    2012-01-01

    Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9), echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1) has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses.

  8. An extended database of keratin binding.

    Science.gov (United States)

    Hansen, Steffi; Selzer, Dominik; Schaefer, Ulrich F; Kasting, Gerald B

    2011-05-01

    Diffusion modeling of dermal absorption relies in large part on high quality input data. Currently, estimates of corneocyte-phase partitioning are based on an analysis of a dataset of limited size and diversity. Therefore, we have updated and broadened the analysis. For this purpose, binding coefficients to different keratins, namely, bovine hoof and horn, human delipidized callus, human delipidized stratum corneum (SC), human nail, human hair, and sheep wool were collected from the literature. In addition, binding coefficients to hoof/horn and delipidized SC were measured for eight hydrophilic compounds including three ionizable compounds that were measured at different pH values. Important results are: (i) only hoof/horn, callus, and delipidized SC are suitable keratins for estimating corneocyte protein binding; (ii) binding coefficients to hoof/horn, callus, and delipidized SC can be predicted from the octanol-water partition coefficients log K(o/w) confirming the analysis of the limited dataset; (iii) binding of ionizable compounds can be predicted by correcting log K(o/w) for pH; (iv) the correlation derived for the extended database is steeper than the relationship derived for the limited dataset. This has consequences for the estimates of SC partition and diffusion coefficients for diffusion modeling of dermal absorption. .

  9. Optical binding between dielectric nanowires (Conference Presentation)

    Science.gov (United States)

    Hanna, Simon; Simpson, Stephen H.

    2016-09-01

    Optical binding occurs when micron-sized particles interact through the exchange of scattered photons. It has been observed both in systems of colloidal dielectric particles and between metallic nanoparticles, and can result in the formation of clusters and coupled dynamical behaviour. Optical binding between spherical particles has been studied in some detail, but little work has appeared in the literature to describe binding effects in lower symmetry systems. In the present paper we discuss recent theoretical work and computer simulations of optical binding effects operating between dielectric nanowires in counter propagating beams. The reduction in symmetry from simple spheres introduces new opportunities for binding, including different types of orientational ordering and anisotropies in the spatial arrangements that are possible for the bound particles. Various ordered configurations are possible, including ladder-like structures and oriented lattices. The stability of these structures to thermal perturbations will be discussed. Asymmetric arrangements of the nanowires are also possible, as a consequence of interactions between the nanowires and the underlying counter-propagating laser field. These configurations lead to a diversity of non-conservative effects, including uniform translation in linearly polarised beams and synchronous rotations in circularly polarised beams, suggesting potential applications of such bound structures in micro-machines.

  10. Haptenation: Chemical Reactivity and Protein Binding

    Directory of Open Access Journals (Sweden)

    Itai Chipinda

    2011-01-01

    Full Text Available Low molecular weight chemical (LMW allergens are commonly referred to as haptens. Haptens must complex with proteins to be recognized by the immune system. The majority of occupationally related haptens are reactive, electrophilic chemicals, or are metabolized to reactive metabolites that form covalent bonds with nucleophilic centers on proteins. Nonelectrophilic protein binding may occur through disulfide exchange, coordinate covalent binding onto metal ions on metalloproteins or of metal allergens, themselves, to the major histocompatibility complex. Recent chemical reactivity kinetic studies suggest that the rate of protein binding is a major determinant of allergenic potency; however, electrophilic strength does not seem to predict the ability of a hapten to skew the response between Th1 and Th2. Modern proteomic mass spectrometry methods that allow detailed delineation of potential differences in protein binding sites may be valuable in predicting if a chemical will stimulate an immediate or delayed hypersensitivity. Chemical aspects related to both reactivity and protein-specific binding are discussed.

  11. Conformational heterogeneity of the calmodulin binding interface

    Science.gov (United States)

    Shukla, Diwakar; Peck, Ariana; Pande, Vijay S.

    2016-04-01

    Calmodulin (CaM) is a ubiquitous Ca2+ sensor and a crucial signalling hub in many pathways aberrantly activated in disease. However, the mechanistic basis of its ability to bind diverse signalling molecules including G-protein-coupled receptors, ion channels and kinases remains poorly understood. Here we harness the high resolution of molecular dynamics simulations and the analytical power of Markov state models to dissect the molecular underpinnings of CaM binding diversity. Our computational model indicates that in the absence of Ca2+, sub-states in the folded ensemble of CaM's C-terminal domain present chemically and sterically distinct topologies that may facilitate conformational selection. Furthermore, we find that local unfolding is off-pathway for the exchange process relevant for peptide binding, in contrast to prior hypotheses that unfolding might account for binding diversity. Finally, our model predicts a novel binding interface that is well-populated in the Ca2+-bound regime and, thus, a candidate for pharmacological intervention.

  12. Endocytosis of Integrin-Binding Human Picornaviruses

    Directory of Open Access Journals (Sweden)

    Pirjo Merilahti

    2012-01-01

    Full Text Available Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9, echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1 has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses.

  13. DNA binding studies of tartrazine food additive.

    Science.gov (United States)

    Kashanian, Soheila; Zeidali, Sahar Heidary

    2011-07-01

    The interaction of native calf thymus DNA with tartrazine in 10 mM Tris-HCl aqueous solution at neutral pH 7.4 was investigated. Tartrazine is a nitrous derivative and may cause allergic reactions, with a potential of toxicological risk. Also, tartrazine induces oxidative stress and DNA damage. Its DNA binding properties were studied by UV-vis and circular dichroism spectra, competitive binding with Hoechst 33258, and viscosity measurements. Tartrazine molecules bind to DNA via groove mode as illustrated by hyperchromism in the UV absorption band of tartrazine, decrease in Hoechst-DNA solution fluorescence, unchanged viscosity of DNA, and conformational changes such as conversion from B-like to C-like in the circular dichroism spectra of DNA. The binding constants (K(b)) of DNA with tartrazine were calculated at different temperatures. Enthalpy and entropy changes were calculated to be +37 and +213 kJ mol(-1), respectively, according to the Van't Hoff equation, which indicated that the reaction is predominantly entropically driven. Also, tartrazine does not cleave plasmid DNA. Tartrazine interacts with calf thymus DNA via a groove interaction mode with an intrinsic binding constant of 3.75 × 10(4) M(-1).

  14. On the Orientation Problem in Korean 'CAKI' Binding and the Typology of X Reflexive Binding.

    Science.gov (United States)

    Cho, Mi-Hui

    1994-01-01

    The purpose of this paper is to demonstrate the existence of nonsubject binding of the so-called long distance anaphor in languages like Korean and Japanese and to give a principled account of why and when it happens. The Korean reflexive pronoun "caki" ('self') is bound by local and long-distance antecedents. Nonsubject binding occurs…

  15. Ancestral Protein Reconstruction Yields Insights into Adaptive Evolution of Binding Specificity in Solute-Binding Proteins.

    Science.gov (United States)

    Clifton, Ben E; Jackson, Colin J

    2016-02-18

    The promiscuous functions of proteins are an important reservoir of functional novelty in protein evolution, but the molecular basis for binding promiscuity remains elusive. We used ancestral protein reconstruction to experimentally characterize evolutionary intermediates in the functional expansion of the polar amino acid-binding protein family, which has evolved to bind a variety of amino acids with high affinity and specificity. High-resolution crystal structures of an ancestral arginine-binding protein in complex with l-arginine and l-glutamine show that the promiscuous binding of l-glutamine is enabled by multi-scale conformational plasticity, water-mediated interactions, and selection of an alternative conformational substate productive for l-glutamine binding. Evolution of specialized glutamine-binding proteins from this ancestral protein was achieved by displacement of water molecules from the protein-ligand interface, reducing the entropic penalty associated with the promiscuous interaction. These results provide a structural and thermodynamic basis for the co-option of a promiscuous interaction in the evolution of binding specificity.

  16. The interrelationship between ligand binding and self-association of the folate binding protein

    DEFF Research Database (Denmark)

    Holm, Jan; Schou, Christian; Babol, Linnea N.

    2011-01-01

    The folate binding protein (FBP) regulates homeostasis and intracellular trafficking of folic acid, a vitamin of decisive importance in cell division and growth. We analyzed whether interrelationship between ligand binding and self-association of FBP plays a significant role in the physiology...

  17. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization

    DEFF Research Database (Denmark)

    Kalamajski, Sebastian; Aspberg, Anders; Lindblom, Karin

    2009-01-01

    The interactions of the ECM (extracellular matrix) protein asporin with ECM components have previously not been investigated. Here, we show that asporin binds collagen type I. This binding is inhibited by recombinant asporin fragment LRR (leucine-rich repeat) 10-12 and by full-length decorin, but...

  18. Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. (Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge (England))

    1991-07-01

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

  19. A review of albumin binding in CKD.

    Science.gov (United States)

    Meijers, Björn K I; Bammens, Bert; Verbeke, Kristin; Evenepoel, Pieter

    2008-05-01

    Hypoalbuminemia is associated with excess mortality in patients with kidney disease. Albumin is an important oxidant scavenger and an abundant carrier protein for numerous endogenous and exogenous compounds. Several specific binding sites for anionic, neutral, and cationic ligands were described. Overall, the extent of binding depends on the ligand and albumin concentration, albumin-binding affinity, and presence of competing ligands. Chronic kidney disease affects all these determinants. This may result in altered pharmacokinetics and increased risk of toxicity. Renal clearance of albumin-bound solutes mainly depends on tubular clearance. Dialytic clearance by means of conventional hemodialysis/hemofiltration and peritoneal dialysis is limited. Other epuration techniques combining hemodialysis with adsorption have been developed. However, the benefit of these techniques remains to be proved.

  20. Conformation-controlled binding kinetics of antibodies

    Science.gov (United States)

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

  1. Predicting binding free energies in solution

    CERN Document Server

    Jensen, Jan H

    2015-01-01

    Recent predictions of absolute binding free energies of host-guest complexes in aqueous solution using electronic structure theory have been encouraging for some systems, while other systems remain problematic for others. In paper I summarize some of the many factors that could easily contribute 1-3 kcal/mol errors at 298 K: three-body dispersion effects, molecular symmetry, anharmonicity, spurious imaginary frequencies, insufficient conformational sampling, wrong or changing ionization states, errors in the solvation free energy of ions, and explicit solvent (and ion) effects that are not well-represented by continuum models. While the paper is primarily a synthesis of previously published work there are two new results: the adaptation of Legendre transformed free energies to electronic structure theory and a use of water clusters that maximizes error cancellation in binding free energies computed using explicit solvent molecules. While I focus on binding free energies in aqueous solution the approach also a...

  2. ABP: a novel AMPA receptor binding protein.

    Science.gov (United States)

    Srivastava, S; Ziff, E B

    1999-04-30

    We review the cloning of a novel AMPA receptor binding protein (ABP) that interacts with GluR2/3 and is homologous to GRIP. ABP is enriched in the PSD with GluR2 and is localized to the PSD by EM. ABP binds GluR2 via the C-terminal VXI motif through a Class I PDZ interaction. ABP and GRIP can also homo- and heteromultimerize. Thus, ABP and GRIP may be involved in AMPA receptor regulation and localization, by linking it to other cytoskeletal or signaling molecules. We suggest that the ABP/GRIP and PSD-95 families form distinct scaffolds that anchor, respectively, AMPA and NMDA receptors. We are currently investigating proteins that bind ABP and that may regulate the AMPA receptor.

  3. Arsenic binding to Fucus vesiculosus metallothionein.

    Science.gov (United States)

    Merrifield, Maureen E; Ngu, Thanh; Stillman, Martin J

    2004-11-05

    The seaweed Fucus vesiculosus is a member of the brown algae family. Kille and co-workers [Biochem. J. 338 (1999) 553] reported that this species contains the gene for metallothionein. Metallothionein is a metalloprotein having low molecular weight, and high cysteine content, which binds a range of metals. F. vesiculosus bioaccumulates arsenic from the aquatic environment [Mar. Chem. 18 (1986) 321]. In this paper we describe arsenic binding to F. vesiculosus metallothionein, characterized by electrospray ionization mass spectrometry. Five arsenic-MT species were detected with increasing As to protein ratios. These results provide important information about the metal-chelation behaviour of this novel algal metallothionein which is a putative model for arsenic binding to F. vesiculosus in vivo.

  4. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper;

    2015-01-01

    Starch is a vital energy molecule in plants that has a wide variety of uses in industry, such as feedstock for biomaterial processing and biofuel production. Plants employ a three enzyme cyclic process utilizing kinases, amylases, and phosphatases to degrade starch in a diurnal manner. Starch...... is comprised of the branched glucan amylopectin and the more linear glucan amylose. Our lab has determined the first structures of these glucan phosphatases and we have defined their enzymatic action. Despite this progress, we lacked a means to quickly and efficiently quantify starch binding to glucan...... phosphatases. The main objective of this study was to quantify the binding affinity of different enzymes that are involved in this cyclic process. We established a protocol to quickly, reproducibly, and quantitatively measure the binding of the enzymes to glucans utilizing Affinity Gel Electrophoresis (AGE...

  5. Heavy quark interactions and quarkonium binding

    Science.gov (United States)

    Satz, Helmut

    2009-06-01

    We consider heavy quark interactions in quenched and unquenched lattice QCD. In a region just above the deconfinement point, non-Abelian gluon polarization leads to a strong increase in the binding. Comparing quark-antiquark and quark-quark interaction, the dependence of the binding on the separation distance r is found to be the same for the colorless singlet Q{\\skew3\\bar{Q}} and the colored anti-triplet QQ state. In a potential model description of in-medium J/ψ behavior, this enhancement of the binding leads to a survival up to temperatures of 1.5 Tc or higher; it could also result in J/ψ flow. Based on joint work with O Kaczmarek and F Karsch.

  6. Mercury-binding proteins of Mytilus edulis

    Energy Technology Data Exchange (ETDEWEB)

    Roesijadi, G.; Morris, J. E.; Calabrese, A.

    1981-11-01

    Mytilus edulis possesses low molecular weight, mercury-binding proteins. The predominant protein isolated from gill tissue is enriched in cysteinyl residues (8%) and possesses an amino acid composition similar to cadmium-binding proteins of mussels and oysters. Continuous exposure of mussels to 5 ..mu..g/l mercury results in spillover of mercury from these proteins to high molecular weight proteins. Antibodies to these proteins have been isolated, and development of immunoassays is presently underway. Preliminary studies to determine whether exposure of adult mussels to mercury will result in induction of mercury-binding proteins in offspring suggest that such proteins occur in larvae although additional studies are indicated for a conclusive demonstration.

  7. Presence of a highly efficient binding to bacterial contamination can distort data from binding studies

    Energy Technology Data Exchange (ETDEWEB)

    Balcar, V.J. (Department of Anatomy, University of Sydney, N.S.W. (Australia))

    1990-12-01

    {sup 3}HGABA at low concentrations (5-10 nM) was bound by what appeared to be a GABA receptor binding site in bacterial contamination originating from a batch of distilled water. Under experimental conditions similar to those usually employed in {sup 3}HGABA binding studies, the apparent binding displayed a very high specific component and a high efficiency in terms of {sup 3}HGABA bound per mg of protein. The binding was blocked by muscimol but not by isoguvacine, SR95531 and nipecotic acid. These characteristics suggest that the presence of such spurious binding in the experiments using 3H-labeled ligands in brain homogenates may not always be very obvious and, moreover, it can result in subtle, but serious, distortions of data from such studies, which may not be immediately recognized.

  8. Potential of goat probiotic to bind mutagens.

    Science.gov (United States)

    Apás, Ana Lidia; González, Silvia Nelina; Arena, Mario Eduardo

    2014-08-01

    The mutagen binding ability of the goat probiotics (Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39, and Bifidobacterium bifidum DDBA) was evaluated. The oral administration of these probiotics reduced fecal mutagens and intestinal cancer markers in goats. Secondly, the effects of probiotics against the mutagenesis induced by sodium azide (SA), and Benzopyrene (B[α]P) by performing the modified Ames test using Salmonella typhimurium TA 100 was investigated. The capacity to bind benzopyrene and the stability of the bacterial-mutagen complex was analyzed by HPLC. The dismutagenic potential against both mutagens was proportional to probiotic concentration. Results showed that probiotic antimutagenic capacity against SA was ranging from 13 to 78%. The mixture of four goat probiotics (MGP) displayed higher antimutagenic activity against SA than any individual strains at the same cell concentration. This study shows that the highest diminution of mutagenicity in presence of B[α]P (74%) was observed in presence of MGP. The antimutagenic activity of nearly all the individual probiotic and the MGP were in concordance with the B[α]P binding determined by HPLC. According to our results, the B[α]P binding to probiotic was irreversible still after being washed with DMSO solution. The stability of the toxic compounds-bacterial cell binding is a key consideration when probiotic antimutagenic property is evaluated. MGP exhibits the ability to bind and detoxify potent mutagens, and this property can be useful in supplemented foods for goats since it can lead to the removal of potent mutagens and protect and enhance ruminal health and hence food safety of consumers.

  9. 多囊卵巢综合征患者肥胖、高胰岛素和高雄激素血症的相关性研究%Correlation of obesity and hyper-insulinemia with hyperandrogenemia in the patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    时照明; 吴道爱; 张士荣; 周静; 孙卫华; 席玉玲; 张晓梅

    2012-01-01

    目的 探讨多囊卵巢综合征(PC(O)S)患者胰岛素水平的变化及对雄激素的影响.方法 选择新诊断PCOS患者46例和对照(NC)组30名,测定糖脂代谢指标、基础性激素、硫酸脱氢表雄酮(DHEAS)、性激素结合球蛋白(SHBG),计算游离雄激素指数(FAI).根据BMI和胰岛素抵抗指数(HO-MA-IR)进行分组,比较各组间生化指标的差异.结果 总体PCOS组、Ob-PCOS组和IR-PCOS组BMI、FIns、HOMA-IR、FPG、血脂、睾酮(T)、DHEAS、FAI、黄体生成素(LH)均高于NC组(P均<0.05),SHBG低于NC组(P<0.01).Ob-PCOS组和IR-PCOS组BMI、FIns、HOMA-IR、FAI分别高于NOb-PCOS组和NIR-PCOS组(P<0.05).BMI与FIns、HOMA-IR呈正相关(P<0.01);BMI、FIns与T、DHEAS、FAI呈正F相关(P<0.05),且BMI与SHBG呈负相关(P<0.01).结论 肥胖PCOS患者存在明显的高胰岛素血症和IR,肥胖、高胰岛素血症与PCOS患者高雄激素血症密切相关.%Objective To explore the changes of plasma insulin levels and its effect on androgenic hormones in patients with polycystic ovary syndrome (PCOS). Methods Glucose and lipid metabolism indices, basal sexual hormones! Dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured in 46 women initially diagnosed as PCOS and 30 normal controls. Free androgen index (FAI) was calculated. The PCOS patients and normal controls were divided into groups according to their body mass index (BMI) and homeostasis model assessment-insulin resistance (HOMA-IR). And the differences in the biochemical indices among all the groups were compared. Results Compared with the control group, the total PCOS group, obese PCOS group and IR PCOS group showed an increase in the levels of BMI, fasting insulin (Fins), HOMA-IR, fasting plasma glucose (FPG), blood lipids, testosterone (T), DHEAS, FAI, and luteinizing hormone (LH) (P<0. 05), but showed a decrease in the level of SHBG (P<0. 01). The obese PCOS group and IR PCOS group had higher levels

  10. Binding energy of two-dimensional biexcitons

    DEFF Research Database (Denmark)

    Singh, Jai; Birkedal, Dan; Vadim, Lyssenko;

    1996-01-01

    Using a model structure for a two-dimensional (2D) biexciton confined in a quantum well, it is shown that the form of the Hamiltonian of the 2D biexciton reduces into that of an exciton. The binding energies and Bohr radii of a 2D biexciton in its various internal energy states are derived...... analytically using the fractional dimension approach. The ratio of the binding energy of a 2D biexciton to that of a 2D exciton is found to be 0.228, which agrees very well with the recent experimental value. The results of our approach are compared with those of earlier theories....

  11. Perceptual-binding and persistent surface segregation.

    Science.gov (United States)

    Moradi, Farshad; Shimojo, Shinsuke

    2004-11-01

    Visual input is segregated in the brain into subsystems that process different attributes such as motion and color. At the same time, visual information is perceptually segregated into objects and surfaces. Here we demonstrate that perceptual segregation of visual entities based on a transparency cue precedes and affects perceptual binding of attributes. Adding an irrelevant transparency cue paradoxically improved the pairing of color and motion for rapidly alternating surfaces. Subsequent experiments show: (1) Attributes are registered over the temporal window defined by the perceptual persistence of segregation, resulting in asynchrony in binding, and (2) attention is necessary for correct registration of attributes in the presence of ambiguity.

  12. The binding energy and bonding in dialane.

    Science.gov (United States)

    Goebbert, Daniel J; Hernandez, Heriberto; Francisco, Joseph S; Wenthold, Paul G

    2005-08-24

    The binding energy of dialane, Al2H6, has been measured using mass spectrometric techniques to be 33 +/- 5 kcal/mol. This represents the first measurement of the thermochemical properties of dialane, which has only recently been observed in low-temperature matricies. High-level quantum mechanical calculations give a binding energy in agreement with the measured value. Experimental and quantum mechanical calculations show that dialane is chemically similar to diborane, B2H6, even though the bonding for these two systems shows significant differences.

  13. Binding energies of hypernuclei and hypernuclear interactions

    Energy Technology Data Exchange (ETDEWEB)

    Bodmer, A.R. [Argonne National Lab., IL (United States)]|[Univ. of Illinois, Chicago, IL (United States). Dept. of Physics; Murali, S.; Usmani, Q.N. [Jamia Millia Islamia, New Delhi (India). Dept. of Physics

    1996-05-01

    In part 1 the effect of nuclear core dynamics on the binding energies of {Lambda} hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the {Lambda} single-particle energy in terms of basic {Lambda}-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body {Lambda}NN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei.

  14. Binding Energy Distribution Analysis Method: Hamiltonian Replica Exchange with Torsional Flattening for Binding Mode Prediction and Binding Free Energy Estimation.

    Science.gov (United States)

    Mentes, Ahmet; Deng, Nan-Jie; Vijayan, R S K; Xia, Junchao; Gallicchio, Emilio; Levy, Ronald M

    2016-05-10

    Molecular dynamics modeling of complex biological systems is limited by finite simulation time. The simulations are often trapped close to local energy minima separated by high energy barriers. Here, we introduce Hamiltonian replica exchange (H-REMD) with torsional flattening in the Binding Energy Distribution Analysis Method (BEDAM), to reduce energy barriers along torsional degrees of freedom and accelerate sampling of intramolecular degrees of freedom relevant to protein-ligand binding. The method is tested on a standard benchmark (T4 Lysozyme/L99A/p-xylene complex) and on a library of HIV-1 integrase complexes derived from the SAMPL4 blind challenge. We applied the torsional flattening strategy to 26 of the 53 known binders to the HIV Integrase LEDGF site found to have a binding energy landscape funneled toward the crystal structure. We show that our approach samples the conformational space more efficiently than the original method without flattening when starting from a poorly docked pose with incorrect ligand dihedral angle conformations. In these unfavorable cases convergence to a binding pose within 2-3 Å from the crystallographic pose is obtained within a few nanoseconds of the Hamiltonian replica exchange simulation. We found that torsional flattening is insufficient in cases where trapping is due to factors other than torsional energy, such as the formation of incorrect intramolecular hydrogen bonds and stacking. Work is in progress to generalize the approach to handle these cases and thereby make it more widely applicable.

  15. Solution structure and binding specificity of the p63 DNA binding domain.

    Science.gov (United States)

    Enthart, Andreas; Klein, Christian; Dehner, Alexander; Coles, Murray; Gemmecker, Gerd; Kessler, Horst; Hagn, Franz

    2016-05-26

    p63 is a close homologue of p53 and, together with p73, is grouped into the p53 family of transcription factors. p63 is known to be involved in the induction of controlled apoptosis important for differentiation processes, germ line integrity and development. Despite its high homology to p53, especially within the DNA binding domain (DBD), p63-DBD does not show cooperative DNA binding properties and is significantly more stable against thermal and chemical denaturation. Here, we determined the solution structure of p63-DBD and show that it is markedly less dynamic than p53-DBD. In addition, we also investigate the effect of a double salt bridge present in p53-DBD, but not in p63-DBD on the cooperative binding behavior and specificity to various DNA sites. Restoration of the salt bridges in p63-DBD by mutagenesis leads to enhanced binding affinity to p53-specific, but not p63-specific response elements. Furthermore, we show that p63-DBD is capable of binding to anti-apoptotic BclxL via its DNA binding interface, a feature that has only been shown for p53 so far. These data suggest that all p53 family members - despite alterations in the specificity and binding affinity - are capable of activating pro-apoptotic pathways in a tissue specific manner.

  16. Nucleic acids encoding a cellulose binding domain

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1996-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  17. Development of a glucose binding protein biosensor

    Science.gov (United States)

    Dweik, M.; Milanick, M.; Grant, S.

    2007-09-01

    Glucose binding protein (GBP) is a monomeric periplasmic protein. It is synthesized in the cytoplasm of Escherichia coli which functions as a receptor for transport D-glucose. GBP binds glucose with high affinity. The binding mechanism is based on a hinge motion due to the protein conformational change. This change was utilized as an optical sensing mechanism by applying Fluorescence Resonance Energy Transfer (FRET). The wild-type GBP lacks cysteine in its structure, but by introducing a single cysteine at a specific site by site-directed mutagenesis, this ensured single-label attachment at specific sites with a fluorescent probe. The other sites were amino sites, which were labeled with second fluorophore. The near IR FRET pair, Alexa Fluor 680 (AF680) and Alexa Fluor 750(AF750), was utilized. The AF680 targeted the amine sites, which was the donor fluorophore, while the AF750 labeled the single cysteine site, which was the acceptor fluorophore. The sensing system strategy was based on the fluorescence changes of the probe as the protein undergoes a structural change upon binding. This biosensor had the ability to detect down to 10 uM concentrations of glucose. Next the probes were uploaded into red blood cells via hypo osmotic dialysis. The sensor responded to glucose while encapsulated with the red cells. These results showed the feasibility of an intracellular glucose biosensor.

  18. Tension-induced binding of semiflexible biopolymers

    CERN Document Server

    Benetatos, Panayotis; Zippelius, Annette

    2014-01-01

    We investigate theoretically the effect of polymer tension on the collective behavior of reversibly binding cross-links. For this purpose, we employ a model of two weakly bending wormlike chains aligned in parallel by a tensile force, with a sequence of inter-chain binding sites regularly spaced along the contours. Reversible cross-links attach and detach at the sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and find the emergence of a free-energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the tension increases. We show that this transition is related to the cross-over between weak and strong localization of a directed polymer in a pinning potential. The cross-over to the strongly bound state can be interpreted as a mechan...

  19. Oxytocin binding sites in bovine mammary tissue

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  20. Binding of cationic surfactants to humic substances

    NARCIS (Netherlands)

    Ishiguro, M.; Tan, W.; Koopal, L.K.

    2007-01-01

    Commercial surfactants are introduced into the environment either through waste products or site-specific contamination. The amphiphilic nature of both surfactants and humic substances (HS) leads to their mutual attraction especially when surfactant and HS are oppositely charged. Binding of the cati

  1. ALG-2, a multifunctional calcium binding protein?

    DEFF Research Database (Denmark)

    Tarabykina, Svetlana; Mollerup, Jens; Winding Gojkovic, P.;

    2004-01-01

    ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article...

  2. Alkali binding in hydrated Portland cement paste

    NARCIS (Netherlands)

    Chen, W.; Brouwers, H.J.H.

    2010-01-01

    The alkali-binding capacity of C–S–H in hydrated Portland cement pastes is addressed in this study. The amount of bound alkalis in C–S–H is computed based on the alkali partition theories firstly proposed by Taylor (1987) and later further developed by Brouwers and Van Eijk (2003). Experimental data

  3. Binding Hydrated Anions with Hydrophobic Pockets.

    Science.gov (United States)

    Sokkalingam, Punidha; Shraberg, Joshua; Rick, Steven W; Gibb, Bruce C

    2016-01-13

    Using a combination of isothermal titration calorimetry and quantum and molecular dynamics calculations, we demonstrate that relatively soft anions have an affinity for hydrophobic concavity. The results are consistent with the anions remaining partially hydrated upon binding, and suggest a novel strategy for anion recognition.

  4. The Double Bind: The next Generation

    Science.gov (United States)

    Malcom, Lindsey E.; Malcom, Shirley M.

    2011-01-01

    In this foreword, Shirley Malcom and Lindsey Malcom speak to the history and current status of women of color in science, technology, engineering, and mathematics (STEM) fields. As the author of the seminal report "The Double Bind: The Price of Being a Minority Woman in Science", Shirley Malcom is uniquely poised to give us an insightful…

  5. Lipid Binding Proteins from Parasitic Platyhelmithes

    Directory of Open Access Journals (Sweden)

    Gabriela eAlvite

    2012-09-01

    Full Text Available Two main families of lipid binding proteins have been identified in parasitic Platyhelminthes: hydrophobic ligand binding proteins (HLBPs and fatty acid binding proteins (FABPs. Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesise their own lipids, these lipid-binding proteins are important molecules in these organisms.HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates.Despite that the knowledge of their function is scarce, the differences in their molecular organisation, ligand preferences, intra/extracellular localisation, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  6. Binding of cholera toxin to Giardia lamblia.

    OpenAIRE

    McCardell, B. A.; Madden, J M; Stanfield, J T; Tall, B D; Stephens, M. J.

    1987-01-01

    Binding of cholera toxin to Giardia lamblia was demonstrated by two slightly different methods: an immunofluorescence technique using antibody to cholera toxin and anti-rabbit immunoglobulin G conjugated to fluorescein isothiocyanate, and a one-step fluorescence method in which G. lamblia was incubated with the B subunit of cholera toxin conjugated to fluorescein isothiocyanate.

  7. Singular Value Decomposition and Ligand Binding Analysis

    Directory of Open Access Journals (Sweden)

    André Luiz Galo

    2013-01-01

    Full Text Available Singular values decomposition (SVD is one of the most important computations in linear algebra because of its vast application for data analysis. It is particularly useful for resolving problems involving least-squares minimization, the determination of matrix rank, and the solution of certain problems involving Euclidean norms. Such problems arise in the spectral analysis of ligand binding to macromolecule. Here, we present a spectral data analysis method using SVD (SVD analysis and nonlinear fitting to determine the binding characteristics of intercalating drugs to DNA. This methodology reduces noise and identifies distinct spectral species similar to traditional principal component analysis as well as fitting nonlinear binding parameters. We applied SVD analysis to investigate the interaction of actinomycin D and daunomycin with native DNA. This methodology does not require prior knowledge of ligand molar extinction coefficients (free and bound, which potentially limits binding analysis. Data are acquired simply by reconstructing the experimental data and by adjusting the product of deconvoluted matrices and the matrix of model coefficients determined by the Scatchard and McGee and von Hippel equation.

  8. Lipid binding proteins from parasitic platyhelminthes.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2012-01-01

    TWO MAIN FAMILIES OF LIPID BINDING PROTEINS HAVE BEEN IDENTIFIED IN PARASITIC PLATYHELMINTHES: hydrophobic ligand binding proteins (HLBPs) and fatty acid binding proteins (FABPs). Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesize their own lipids, these lipid-binding proteins are important molecules in these organisms. HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates. Despite that the knowledge of their function is scarce, the differences in their molecular organization, ligand preferences, intra/extracellular localization, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  9. Information flow through calcium binding proteins

    Science.gov (United States)

    Bak, Ji Hyun; Bialek, William

    2013-03-01

    Calcium signaling is a ubiquitous mode of biological communication, which regulates a great variety of vital processes in living systems. Such a signal typically begins with an elementary event, in which calcium ions bind to a protein, inducing a change in the protein's structure. Information can only be lost, from what was conveyed through this initial event, as the signal is further transduced through the downstream networks. In the present work we analyze and optimize the information flow in the calcium binding process. We explicitly calculate the mutual information between the calcium concentration and the states of the protein, using a simple model for allosteric regulation in a dimeric protein. The optimal solution depends on the dynamic range of the input as well as on the timescale of signal integration. According to our result, the optimizing strategy involves allowing the calcium-binding protein to be ``activated'' by a partial occupation of its sites, and tuning independently the strengths of cooperative interactions in the binding and unbinding processes.

  10. Binding of flavonoids to staphylococcal enterotoxin B.

    Science.gov (United States)

    Benedik, Evgen; Skrt, Mihaela; Podlipnik, Crtomir; Ulrih, Nataša Poklar

    2014-12-01

    Staphylococcal enterotoxins are metabolic products of Staphylococcus aureus that are responsible for the second-most-commonly reported type of food poisoning. Polyphenols are known to interact with proteins to form complexes, the properties of which depend on the structures of both the polyphenols and the protein. In the present study, we investigated the binding of four flavonoid polyphenols to Staphylococcal enterotoxin B (SEB) at pH 7.5 and 25 °C: (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), kaempferol-3-glucoside (KAM-G) and kaempferol (KAM). Fluorescence emission spectrometry and molecular docking were applied to compare experimentally determined binding parameters with molecular modeling. EGCG showed an order of magnitude higher binding constant (1.4 × 10(5) M(-1)) than the other studied polyphenols. Our blind-docking results showed that EGCG and similar polyphenolic ligands is likely to bind to the channel at the surface of SEB that is responsible for the recognition of the T-cell beta chain fragment and influence the adhesion of SEB to T cells.

  11. Retinoblastoma-binding protein 1 has an interdigitated double Tudor domain with DNA binding activity.

    Science.gov (United States)

    Gong, Weibin; Wang, Jinfeng; Perrett, Sarah; Feng, Yingang

    2014-02-21

    Retinoblastoma-binding protein 1 (RBBP1) is a tumor and leukemia suppressor that binds both methylated histone tails and DNA. Our previous studies indicated that RBBP1 possesses a Tudor domain, which cannot bind histone marks. In order to clarify the function of the Tudor domain, the solution structure of the RBBP1 Tudor domain was determined by NMR and is presented here. Although the proteins are unrelated, the RBBP1 Tudor domain forms an interdigitated double Tudor structure similar to the Tudor domain of JMJD2A, which is an epigenetic mark reader. This indicates the functional diversity of Tudor domains. The RBBP1 Tudor domain structure has a significant area of positively charged surface, which reveals a capability of the RBBP1 Tudor domain to bind nucleic acids. NMR titration and isothermal titration calorimetry experiments indicate that the RBBP1 Tudor domain binds both double- and single-stranded DNA with an affinity of 10-100 μM; no apparent DNA sequence specificity was detected. The DNA binding mode and key interaction residues were analyzed in detail based on a model structure of the Tudor domain-dsDNA complex, built by HADDOCK docking using the NMR data. Electrostatic interactions mediate the binding of the Tudor domain with DNA, which is consistent with NMR experiments performed at high salt concentration. The DNA-binding residues are conserved in Tudor domains of the RBBP1 protein family, resulting in conservation of the DNA-binding function in the RBBP1 Tudor domains. Our results provide further insights into the structure and function of RBBP1.

  12. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

    Science.gov (United States)

    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  13. Chromate Binding and Removal by the Molybdate-Binding Protein ModA.

    Science.gov (United States)

    Karpus, Jason; Bosscher, Michael; Ajiboye, Ifedayo; Zhang, Liang; He, Chuan

    2017-02-02

    Effective and cheap methods and techniques for the safe removal of hexavalent chromate from the environment are in increasingly high demand. High concentrations of hexavalent chromate have been shown to have numerous harmful effects on human biology. We show that the E. coli molybdate-binding protein ModA is a genetically encoded tool capable of removing chromate from aqueous solutions. Although previously reported to not bind chromate, we show that ModA binds chromate tightly and is capable of removing chromate to levels well below current US federal standards.

  14. 大剂量丙种球蛋白治疗儿童重型病毒性脑炎的临床疗效分析%Analysis of Clinical Curative Effect of Large-dose Gamma Globulin in Treatment of Severe Viral Encephalitis in Children

    Institute of Scientific and Technical Information of China (English)

    吴国红; 高振文; 闫冬梅; 石玉梅; 马杰

    2016-01-01

    Objective To observe the clinical curative effect of the intravenous drip of different large-dose gamma globulin in treatment of severe viral encephalitis in children. Methods 67 cases of children with severe viral encephalitis admitted and treated in our hospital from January 2014 to October 2015 were divided into two groups, the treatment group were given the intravenous drip of IVIG 1.0g/(kg•d) for continuous 2d on the basis of the conventional treatment, the control group were given the intravenous drip of IVIG 400mg/(kg•d) for continuous 5d,the two groups had the same total gamma globulin, and the clinical symptoms, sign disappearance time and length of stay of the children were respectively observed. Results The time of fever being brought down, improvement time of conscious disturbance, twitch stop time and length of stay were re-spectively (2.5±0.6), (1.5±0.5), (1.5±0.7) d and (9±3.6) d in the treatment group, which were obviously shorter than those in the control group, and the differences between the two groups had obvious statistical significance by comparison, P<0.01. Conclusion Enhancing the single-dose and early saturated pulse therapy can obviously improve the clinical symptoms and signs of children with severe viral encephalitis and improve the total effective rate on the condition of applying the same large-dose gamma globulin.%目的:探讨静脉滴注不同大剂量丙种球蛋白(IVIG)治疗儿童重型病毒性脑炎的临床疗效。方法整群选取该院于2014年1月—2015年10月收治的67例儿童重型病毒性脑炎分为治疗组和对照组,治疗组在常规治疗的基础上静脉滴注IVIG 1.0 g/(kg•d),连用2 d,对照组在常规治疗的基础上静脉IVIG 400 mg/(kg•d),连用5 d,两组单例患者应用丙种球蛋白总量相同,分别观察患儿的临床症状、体征消失的时间以及统计住院时间。结果治疗组热退时间、意识障碍好转时间、抽动停止时间及住院时间分别为(2

  15. Effect of intravenous infusion of high does gamma globulin therapy on preventing Kawasaki disease children from eoronary artery damage and nursing%大剂量静脉滴注丙种球蛋白防止川崎病患儿冠伏动脉损害的效果评价及护理

    Institute of Scientific and Technical Information of China (English)

    郭志芬

    2012-01-01

    目的 探讨大剂量静脉滴注丙种球蛋白防止川崎病患儿冠状动脉损害的效果.方法 将82例川崎病患儿依据治疗方法分为观察组和对照组各41例,观察组患儿采用大剂量丙种球蛋白冲击治疗,对照组应用常规用量进行治疗.对照组采取常规护理,观察组在对照组的基础上按症状实施针对性的护理措施.比较2组的治疗及护理效果.结果 观察组发生冠状动脉扩张1例,对照组发生8例,观察组发生率显著低于对照组.主要观察指标如发热、淋巴结肿大及皮肤黏膜改变的恢复时间观察组明显较对照组缩短.结论 良好细致的护理和健康教育指导,可增加患儿及家属对川崎病的了解,积极配合医疗各个环节,可减少并发症,加快疾病康复.%Objective To explore the effect and nursing of high dose gamma globulin therapy on preventing Kawasaki disease children from coronary artery damage.Methods 82 cases of children with Kawasaki disease were divided into two groups according to the treatment methods,each with 41 cases.The observation group was treated by high dose shock treatment of gamma globulin,the control group was given conventional dosage of gamma globulin.The control group received routine nursing care.The observation group was given targeted nursing measures according to the symptoms on the basis of the control group.The treatment and nursing effect were compared between two groups.Results 1 cases of coronary artery dilatation appeared in the observation group,while 8 cases in the control group,the difference was statistically significant.The recovery time of main observation index such as fever,lymphadenopathy,skin and mucous membrane alterations was significantly shorter in the observation group than the control group,the differences were statistically significant.Conclusions Careful nursing and health education guidance can increase the understanding of disease for Kawasaki disease children and their

  16. STARD4 Membrane Interactions and Sterol Binding.

    Science.gov (United States)

    Iaea, David B; Dikiy, Igor; Kiburu, Irene; Eliezer, David; Maxfield, Frederick R

    2015-08-01

    The steroidogenic acute regulatory protein-related lipid transfer (START) domain family is defined by a conserved 210-amino acid sequence that folds into an α/β helix-grip structure. Members of this protein family bind a variety of ligands, including cholesterol, phospholipids, sphingolipids, and bile acids, with putative roles in nonvesicular lipid transport, metabolism, and cell signaling. Among the soluble START proteins, STARD4 is expressed in most tissues and has previously been shown to transfer sterol, but the molecular mechanisms of membrane interaction and sterol binding remain unclear. In this work, we use biochemical techniques to characterize regions of STARD4 and determine their role in membrane interaction and sterol binding. Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (Ω1) loop, which covers the sterol binding pocket, attenuates sterol transfer activity. To gain insight into the attenuating mechanism of the L124D mutation, we conducted structural and biophysical studies of wild-type and L124D STARD4. These studies show that the L124D mutation reduces the conformational flexibility of the protein, resulting in a diminished level of membrane interaction and sterol transfer. These studies also reveal that the C-terminal α-helix, and not the Ω1 loop, partitions into the membrane bilayer. On the basis of these observations, we propose a model of STARD4 membrane interaction and sterol binding and release that requires dynamic movement of both the Ω1 loop and membrane insertion of the C-terminal α-helix.

  17. Isothermal titration calorimetry: general formalism using binding polynomials.

    Science.gov (United States)

    Freire, Ernesto; Schön, Arne; Velazquez-Campoy, Adrian

    2009-01-01

    The theory of the binding polynomial constitutes a very powerful formalism by which many experimental biological systems involving ligand binding can be analyzed under a unified framework. The analysis of isothermal titration calorimetry (ITC) data for systems possessing more than one binding site has been cumbersome because it required the user to develop a binding model to fit the data. Furthermore, in many instances, different binding models give rise to identical binding isotherms, making it impossible to discriminate binding mechanisms using binding data alone. One of the main advantages of the binding polynomials is that experimental data can be analyzed by employing a general model-free methodology that provides essential information about the system behavior (e.g., whether there exists binding cooperativity, whether the cooperativity is positive or negative, and the magnitude of the cooperative energy). Data analysis utilizing binding polynomials yields a set of binding association constants and enthalpy values that conserve their validity after the correct model has been determined. In fact, once the correct model is validated, the binding polynomial parameters can be immediately translated into the model specific constants. In this chapter, we describe the general binding polynomial formalism and provide specific theoretical and experimental examples of its application to isothermal titration calorimetry.

  18. A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution.

    Science.gov (United States)

    Sharpe, Belinda K; Matthews, Jacqueline M; Kwan, Ann H Y; Newton, Anthea; Gell, David A; Crossley, Merlin; Mackay, Joel P

    2002-05-01

    Many different zinc binding modules have been identified. Their abundance and variety suggests that the formation of zinc binding folds might be relatively common. We have determined the structure of CH1(1), a 27-residue peptide derived from the first cysteine/histidine-rich region (CH1) of CREB binding protein (CBP). This peptide forms a highly ordered zinc-dependent fold that is distinct from known folds. The structure differs from a subsequently determined structure of a larger region from the CH3 region of CBP, and the CH1(1) fold probably represents a nonphysiologically active form. Despite this, the fold is thermostable and tolerant to both multiple alanine mutations and changes in the zinc-ligand spacing. Our data support the idea that zinc binding domains may arise frequently. Additionally, such structures may prove useful as scaffolds for protein design, given their stability and robustness.

  19. Cooperative binding of copper(I) to the metal binding domains in Menkes disease protein

    DEFF Research Database (Denmark)

    Jensen, P Y; Bonander, N; Møller, L B;

    1999-01-01

    We have optimised the overexpression and purification of the N-terminal end of the Menkes disease protein expressed in Escherichia coli, containing one, two and six metal binding domains (MBD), respectively. The domain(s) have been characterised using circular dichroism (CD) and fluorescence...... spectroscopy, and their copper(I) binding properties have been determined. Structure prediction derived from far-UV CD indicates that the secondary structure is similar in the three proteins and dominated by beta-sheet. The tryptophan fluorescence maximum is blue-shifted in the constructs containing two...... and six MBDs relative to the monomer, suggesting more structurally buried tryptophan(s), compared to the single MBD construct. Copper(I) binding has been studied by equilibrium dialysis under anaerobic conditions. We show that the copper(I) binding to constructs containing two and six domains...

  20. The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

    Directory of Open Access Journals (Sweden)

    Nancy A Stearns

    Full Text Available Antibodies to DNA (anti-DNA ar